A randomised trial of a four-step multidisciplinary approach to the antenatal care of obese pregnant women.
Obesity is common in pregnancy and results in morbidity to mother and newborn. To evaluate whether a four-step multidisciplinary protocol of antenatal care for overweight and obese women would reduce the incidence of gestational diabetes. Pregnant women were approached at their first antenatal visit, and body mass index (BMI) was calculated to determine whether they were overweight or obese (BMI > 25). Eligible women were randomised to standard obstetric antenatal care or four-step multidisciplinary antenatal care. Clinic protocol included (i) continuity of obstetric provider; (ii) weighing on arrival at each visit; (iii) a five brief minute intervention by a food technologist who asked about the women's eating habits of the previous day, provided information on reading food labels, shopping lists of affordable foods available from local shops and recipes for a healthy pregnancy diet; and (iv) clinical psychology management to assess symptoms of depression and anxiety, stressful life events and determine whether psychological factors were involved in eating patterns. Labour and delivery data were audited from the medical records to determine the final incidence of gestational diabetes. The primary outcomes were gestational diabetes and weight gain. The intervention was associated with a significant reduction in the incidence of gestational diabetes (6 versus 29%, OR 0.17 95% CI 0.03-0.95, P = 0.04). It was also associated with reduced weight gain in pregnancy (7.0 versus 13.8 kg, P < 0.0001). Despite this, birthweight of newborns was similar [3.5 (0.1) kg versus 3.4 (0.1) kg P = 0.16]. A four-step management plan adopted with obese women reduces the incidence of gestational diabetes.


[Genetic control of the RecF recombination pathway. II. Effect of recL- and uvrE- mutations].
It was found earlier that the effect of the uvrE- mutation on the yield of recombinants formed via RecF pathway of recombination was mainly due to the decreased viability of the recB-C-sbcB-uvrE- recipient. The results of the present paper show the uvrE- and recL- mutations reduce the recipient ability of the recB-C- sbcB- strains to the same extent. We were unable to find any evidence for complementation between the recL- and uvrE- mutations in transient as well as in stable uvrE-/recL- merozygotes. The recL152 as well as the uvrE502 mutation is lethal for the strains deficient in DNA polymerase I. Both recL- and uvrE- mutations reduce in the recB-C- sbcB- strains the probability of inheritance of the proximal non-selective donor markers as well as selective markers located close to the leading end of the donor chromosome. The former effect however could not be completely due to the latter.


Cardiac sarcolemmal Na+-K+-ATPase: combined effects of propranolol and arachidonyl CoA.
Sarcolemma from adult canine cardiac myocytes (Na+-K+-ATPase activity 71.8 +/- 3.4 mumol . mg protein-1 . h-1) was preincubated (10 min at 37 degrees C, pH 7.2) with 1) 5-250 microM arachidonyl CoA, 2) 2.5 nM- 2.5 mM propranolol, 3) 5-250 microM arachidonyl CoA plus 2.5 mM propranolol or 4) 2.5 nM-2.5 mM propranolol plus 50 microM arachidonyl CoA; after preincubation the Na+-stimulatable activity was assayed. Arachidonyl CoA alone (50 microM, expt 1) elicited maximum stimulation (89% above control), whereas concentrations greater than 125 microM were inhibitory. Preincubation with propranolol alone (expt 2) had no significant effect on activity. However, when membranes were pretreated with both arachidonyl CoA and 2.5 mM propranolol (expt 3) activity was significantly inhibited. Preincubation with concentrations of propranolol greater than 25 microM were required to reverse the stimulatory effect of 50 microM arachidonyl CoA (expt 4). Propranolol and arachidonyl CoA do not have to be present simultaneously to produce an inhibitory effect. Activity was greatly inhibited (87%) when membranes were preincubated with 100 microM arachidonyl CoA followed by addition of 2.5 mM propranolol; no inhibition was observed if preincubation conditions were reversed. These data suggest that propranolol-induced inhibition of the Na+-K+-ATPase is reversible but becomes irreversible when sarcolemma is pretreated with the fatty acyl CoA, either prior to or during propranolol preincubation.


Atomic-level design of metalloenzyme-like active pockets in metal-organic frameworks for bioinspired catalysis.
Natural metalloenzymes with astonishing reaction activity and specificity underpin essential life transformations. Nevertheless, enzymes only operate under mild conditions to keep sophisticated structures active, limiting their potential applications. Artificial metalloenzymes that recapitulate the catalytic activity of enzymes can not only circumvent the enzymatic fragility but also bring versatile functions into practice. Among them, metal-organic frameworks (MOFs) featuring diverse and site-isolated metal sites and supramolecular structures have emerged as promising candidates for metalloenzymes to move toward unparalleled properties and behaviour of enzymes. In this review, we systematically summarize the significant advances in MOF-based metalloenzyme mimics with a special emphasis on active pocket engineering at the atomic level, including primary catalytic sites and secondary coordination spheres. Then, the deep understanding of catalytic mechanisms and their advanced applications are discussed. Finally, a perspective on this emerging frontier research is provided to advance bioinspired catalysis.


Odorant detection in a locust exhibits unusually low redundancy.
Olfactory coding, from insects to humans, is canonically considered to involve considerable across-fiber coding already at the peripheral level, thereby allowing recognition of vast numbers of odor compounds. We show that the migratory locust has evolved an alternative strategy built on highly specific odorant receptors feeding into a complex primary processing center in the brain. By collecting odors from food and different life stages of the locust, we identified 205 ecologically relevant odorants, which we used to deorphanize 48 locust olfactory receptors via ectopic expression in Drosophila. Contrary to the often broadly tuned olfactory receptors of other insects, almost all locust receptors were found to be narrowly tuned to one or very few ligands. Knocking out a single receptor using CRISPR abolished physiological and behavioral responses to the corresponding ligand. We conclude that the locust olfactory system, with most olfactory receptors being narrowly tuned, differs from the so-far described olfactory systems.


Cost-effectiveness of vitamin therapy for age-related macular degeneration.
To determine the cost-effectiveness of vitamin therapy (antioxidants plus zinc) for all indicated patients diagnosed with age-related macular degeneration (AMD). We compared the impacts of vitamin therapy with those of no vitamin therapy using a computerized, stochastic, agent-based model. The model simulated the natural history of AMD and patterns of ophthalmic service use in the United States in a cohort from age 50 years until 100 or death. The model created 20 million simulated individuals. These individuals each received both the intervention (vitamin therapy after diagnosis) and the control (no vitamin therapy). Expected outcomes generated when vitamins were taken after diagnosis were compared with the expected outcomes generated when they were not. The model created individuals representative of patients in the U.S. Incidence of early AMD was based on published studies, as was vision loss and response to choroidal neovascularization therapies. Post-incident disease progression was governed by previously unpublished data drawn from the Age-Related Eye Disease Study. Extent of disease progression, years and severity of visual impairment, cost of ophthalmic care and nursing home services, and quality-adjusted life years (QALYs). Costs and benefits were considered from the health care perspective and discounted using a 3% rate. The analysis was run for 50 years starting in 2003. Compared with no therapy, vitamin therapy yielded a cost-effectiveness ratio of $21,387 per QALY gained and lowered the percentage of patients with AMD who ever developed visual impairment in the better-seeing eye from 7.0% to 5.6%. Our model demonstrates that vitamin therapy for AMD improves quality of life at a reasonable cost.


Maternal exposure to nano-titanium dioxide impedes fetal development via endothelial-to-mesenchymal transition in the placental labyrinth in mice.
Extensive production and usage of commercially available products containing TiO2 NPs have led to accumulation in the human body. The deposition of TiO2 NPs has even been detected in the human placenta, which raises concerns regarding fetal health. Previous studies regarding developmental toxicity have frequently focused on TiO2 NPs < 50 nm, whereas the potential adverse effects of large-sized TiO2 NPs received less attention. Placental vasculature is essential for maternal-fetal circulatory exchange and ensuring fetal growth. This study explores the impacts of TiO2 NPs (100 nm in size) on the placenta and fetal development and elucidates the underlying mechanism from the perspective of placental vasculature. Pregnant C57BL/6 mice were exposed to TiO2 NPs by gavage at daily dosages of 10, 50, and 250 mg/kg from gestational day 0.5-16.5. TiO2 NPs penetrated the placenta and accumulated in the fetal mice. The fetuses in the TiO2 NP-exposed groups exhibited a dose-dependent decrease in body weight and length, as well as in placental weight and diameter. In vivo imaging showed an impaired placental barrier, and pathological examinations revealed a disrupted vascular network of the labyrinth upon TiO2 NP exposure. We also found an increase in gene expression related to the transforming growth factor-β (TGF-β) -SNAIL pathway and the upregulation of mesenchymal markers, accompanied by a reduction in endothelial markers. In addition, TiO2 NPs enhanced the gene expression responsible for the endothelial-to-mesenchymal transition (EndMT) in cultured human umbilical vein endothelial cells, whereas SNAIL knockdown attenuated the induction of EndMT phenotypes. Our study revealed that maternal exposure to 100 nm TiO2 NPs disrupts placental vascular development and fetal mice growth through aberrant activation of EndMT in the placental labyrinth. These data provide novel insight into the mechanisms of developmental toxicity posed by NPs.


Malpractice liability of physicians to nonpatients.
Sometimes physicians assume responsibilities to third parties when undertaking the care of patients. Physicians have been held liable to third parties, though strangers to the patients, for failing to warn regarding the communicability of contagious diseases. Two suits have been allowed against physicians by third parties who were injured by drivers of vehicles who had not been warned by the physician of the danger of driving caused by their medical problem. Hospitals and psychiatrists have been held liable to injured third parties for failing to warn of the dangerous propensities of their patients under psychotherapy. Courts have held that such disclosures do not violate the patient's right to privacy and confidentiality. However, physicians may exercise professional discretion and need not warn if, in their judgment, that would be unreasonable, unnecessary, or harmful. Nevertheless, rights of patients must yield to the public interest when it collides with public safety and welfare.


Interference between conscious and unconscious facial expression information.
There is ample evidence to show that many types of visual information, including emotional information, could be processed in the absence of visual awareness. For example, it has been shown that masked subliminal facial expressions can induce priming and adaptation effects. However, stimulus made invisible in different ways could be processed to different extent and have differential effects. In this study, we adopted a flanker type behavioral method to investigate whether a flanker rendered invisible through Continuous Flash Suppression (CFS) could induce a congruency effect on the discrimination of a visible target. Specifically, during the experiment, participants judged the expression (either happy or fearful) of a visible face in the presence of a nearby invisible face (with happy or fearful expression). Results show that participants were slower and less accurate in discriminating the expression of the visible face when the expression of the invisible flanker face was incongruent. Thus, facial expression information rendered invisible with CFS and presented a different spatial location could enhance or interfere with consciously processed facial expression information.


Risk modifying effect of social capital on measures of heavy alcohol consumption, alcohol abuse, harms, and secondhand effects: national survey findings.
To examine associations between social capital and individual risk for alcohol abuse and harms and identify protective effect mechanisms. Multilevel multivariate analysis with individual level data from a national panel survey of drinking and a contextual measure of social capital reflecting college mean aggregate reports of student volunteerism. Outcomes include heavy episodic (binge) drinking, frequent drinking, frequent drunkenness, diagnosable alcohol abuse, intentional drunkenness, acquisition of binge drinking, harms, secondhand effects from others' drinking. United States, 119 four year colleges. Representative samples of youth ages 18-24 surveyed in 1997 and 1999 using an anonymous mailed questionnaire (total n = 27 687). Students from colleges with higher levels of social capital reported reduced risks for binge drinking (adjusted OR 0.38, 95% CI 0.20 to 0.69, p = 0.002), frequent drunkenness (adjusted OR 0.58, 95% CI 0.34 to 0.98, p = 0.04), acquisition of binge drinking in college (adjusted OR 0.48, 95% CI 0.24 to 0.95, p = 0.03), and alcohol abuse (adjusted OR 0.55, 95% CI 0.34 to 0.91, p = 0.02) in multilevel multivariate analyses that controlled for individual volunteering, the measure on which social capital was based. Higher levels of social capital protected against multiple drinking related harms (adjusted OR 0.51, 95% CI 0.29 to 0.90, p = 0.02) and secondhand drinking effects (adjusted OR, 0.30, 95% CI 0.16 to 0.58, p = 0.0003). Significant cross level interactions exist between fraternity/sorority membership and social capital for measures of risky drinking. Harm reduction primarily reflects consumption modification. Social capital exerts strong protective effects on alcohol abuse and harm in college including among high risk students.


Acupuncture and related interventions for smoking cessation.
Acupuncture and related techniques are promoted as a treatment for smoking cessation in the belief that they may reduce nicotine withdrawal symptoms. The objectives of this review are to determine the effectiveness of acupuncture and the related interventions of acupressure, laser therapy and electrostimulation in smoking cessation, in comparison with no intervention, sham treatment, or other interventions. We searched the Cochrane Tobacco Addiction Group Specialized Register (which includes trials of smoking cessation interventions identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and PsycINFO) and AMED in October 2013. We also searched four Chinese databases in September 2013: Sino-Med, China National Knowledge Infrastructure, Wanfang Data and VIP. Randomized trials comparing a form of acupuncture, acupressure, laser therapy or electrostimulation with either no intervention, sham treatment or another intervention for smoking cessation. We extracted data in duplicate on the type of smokers recruited, the nature of the intervention and control procedures, the outcome measures, method of randomization, and completeness of follow-up.We assessed abstinence from smoking at the earliest time-point (before six weeks) and at the last measurement point between six months and one year. We used the most rigorous definition of abstinence for each trial, and biochemically validated rates if available. Those lost to follow-up were counted as continuing smokers. Where appropriate, we performed meta-analysis pooling risk ratios using a fixed-effect model. We included 38 studies. Based on three studies, acupuncture was not shown to be more effective than a waiting list control for long-term abstinence, with wide confidence intervals and evidence of heterogeneity (n = 393, risk ratio [RR] 1.79, 95% confidence interval [CI] 0.98 to 3.28, I² = 57%). Compared with sham acupuncture, the RR for the short-term effect of acupuncture was 1.22 (95% CI 1.08 to 1.38), and for the long-term effect was 1.10 (95% CI 0.86 to 1.40). The studies were not judged to be free from bias, and there was evidence of funnel plot asymmetry with larger studies showing smaller effects. The heterogeneity between studies was not explained by the technique used. Acupuncture was less effective than nicotine replacement therapy (NRT). There was no evidence that acupuncture is superior to psychological interventions in the short- or long-term. There is limited evidence that acupressure is superior to sham acupressure for short-term outcomes (3 trials, n = 325, RR 2.54, 95% CI 1.27 to 5.08), but no trials reported long-term effects, The pooled estimate for studies testing an intervention that included continuous auricular stimulation suggested a short-term benefit compared to sham stimulation (14 trials, n = 1155, RR 1.69, 95% CI 1.32 to 2.16); subgroup analysis showed an effect for continuous acupressure (7 studies, n = 496, RR 2.73, 95% CI 1.78 to 4.18) but not acupuncture with indwelling needles (6 studies, n = 659, RR 1.24, 95% CI 0.91 to 1.69). At longer follow-up the CIs did not exclude no effect (5 trials, n = 570, RR 1.47, 95% CI 0.79 to 2.74). The evidence from two trials using laser stimulation was inconsistent and could not be combined. The combined evidence on electrostimulation suggests it is not superior to sham electrostimulation (short-term abstinence: 6 trials, n = 634, RR 1.13, 95% CI 0.87 to 1.46; long-term abstinence: 2 trials, n = 405, RR 0.87, 95% CI 0.61 to 1.23). Although pooled estimates suggest possible short-term effects there is no consistent, bias-free evidence that acupuncture, acupressure, or laser therapy have a sustained benefit on smoking cessation for six months or more. However, lack of evidence and methodological problems mean that no firm conclusions can be drawn. Electrostimulation is not effective for smoking cessation. Well-designed research into acupuncture, acupressure and laser stimulation is justified since these are popular interventions and safe when correctly applied, though these interventions alone are likely to be less effective than evidence-based interventions.


Glucose intolerance associated with early-life exposure to maternal cafeteria feeding is dependent upon post-weaning diet.
In addition to being a risk factor for adverse outcomes of pregnancy, maternal obesity may play a role in determining the long-term disease patterns observed in the resulting offspring, with metabolic and dietary factors directly programming fetal development. The present study evaluated the potential for feeding rats an obesogenic cafeteria diet (O) pre-pregnancy, during pregnancy, during lactation and for the offspring post-weaning, to programme glucose tolerance. Early-life exposure to an O diet had no significant effect on offspring food intake. Early-life programming associated with O feeding to induce maternal obesity was associated with reduced adiposity in offspring weaned onto low-fat chow. Adult offspring exposed to an O diet in early life and weaned on a chow diet had low fasting glucose and insulin concentrations and appeared to be more sensitive to insulin during an intraperitoneal glucose tolerance test. When weaned on an O diet, male offspring were more prone to glucose intolerance than females. On the basis of the area under the glucose curve, maternal O feeding at any point from pre-mating to lactation was associated with impaired glucose tolerance. The mechanism for this was not identified, although increased hepatic expression of Akt2 may have indicated disturbance of insulin signalling pathways. The observations in the present study confirm that maternal overnutrition and obesity during pregnancy are risk factors for metabolic disturbance in the resulting offspring. Although the effects on glucose homeostasis were independent of offspring adiposity, the programming of a glucose-intolerant phenotype was only observed when offspring were weaned on a diet that induced greater fat deposition.


Phosphorylation by the stress-activated MAPK Slt2 down-regulates the yeast TOR complex 2.
Saccharomyces cerevisiae target of rapamycin (TOR) complex 2 (TORC2) is an essential regulator of plasma membrane lipid and protein homeostasis. How TORC2 activity is modulated in response to changes in the status of the cell envelope is unclear. Here we document that TORC2 subunit Avo2 is a direct target of Slt2, the mitogen-activated protein kinase (MAPK) of the cell wall integrity pathway. Activation of Slt2 by overexpression of a constitutively active allele of an upstream Slt2 activator (Pkc1) or by auxin-induced degradation of a negative Slt2 regulator (Sln1) caused hyperphosphorylation of Avo2 at its MAPK phosphoacceptor sites in a Slt2-dependent manner and diminished TORC2-mediated phosphorylation of its major downstream effector, protein kinase Ypk1. Deletion of Avo2 or expression of a phosphomimetic Avo2 allele rendered cells sensitive to two stresses (myriocin treatment and elevated exogenous acetic acid) that the cell requires Ypk1 activation by TORC2 to survive. Thus, Avo2 is necessary for optimal TORC2 activity, and Slt2-mediated phosphorylation of Avo2 down-regulates TORC2 signaling. Compared with wild-type Avo2, phosphomimetic Avo2 shows significant displacement from the plasma membrane, suggesting that Slt2 inhibits TORC2 by promoting Avo2 dissociation. Our findings are the first demonstration that TORC2 function is regulated by MAPK-mediated phosphorylation.


Batesian mimics influence mimicry ring evolution.
Mathematical models of mimicry typically involve artificial prey species with fixed colorations or appearances; this enables a comparison of predation rates to demonstrate the level of protection a mimic might be afforded. Fruitful theoretical results have been produced using this method, but it is also useful to examine the possible evolutionary consequences of mimicry. To that end, we present individual-based evolutionary simulation models where prey colorations are free to evolve. We use the models to examine the effect of Batesian mimics on Müllerian mimics and mimicry rings. Results show that Batesian mimics can potentially incite Müllerian mimicry relationships and encourage mimicry ring convergence.


Resolving competing conical intersection pathways: time-resolved X-ray absorption spectroscopy of trans-1,3-butadiene.
Time-resolved X-ray absorption spectroscopy is emerging as a uniquely powerful tool to probe coupled electronic-nuclear dynamics in photo-excited molecules. Theoretical studies to date have established that time-resolved X-ray absorption spectroscopy is an atom-specific probe of excited-state wave packet passage through a seam of conical intersections (CIs). However, in many molecular systems, there are competing dynamical pathways involving CIs of different electronic and nuclear character. Discerning these pathways remains an important challenge. Here, we demonstrate that time-resolved X-ray absorption spectroscopy (TRXAS) has the potential to resolve competing channels in excited-state non-adiabatic dynamics. Using the example of 1,3-butadiene, we show how TRXAS discerns the different electronic structures associated with passage through multiple conical intersections. trans-1,3-Butadiene exhibits a branching between polarized and radicaloid pathways associated with ethylenic "twisted-pyramidalized" and excited-state cis-trans isomerization dynamics, respectively. The differing electronic structures along these pathways give rise to different XAS signals, indicating the possibility of resolving them. Furthermore, this indicates that XAS, and other core-level spectroscopic techniques, offer the appealing prospect of directly probing the effects of selective chemical substitution and its ability to affect chemical control over excited-state molecular dynamics.


Postinduction minimal residual disease monitoring by polymerase chain reaction in children with acute lymphoblastic leukemia.
Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer. Monitoring minimal residual disease (MRD) by using real-time quantitative polymerase chain reaction (RQ-PCR) provides information for patient stratification and individual risk-directed treatment. Cooperative studies have documented that measurement of blast clearance from the bone marrow during and after induction therapy identifies patient populations with different risk of relapse. We explored the possible contribution of measurements of MRD during the course of treatment. We used RQ-PCR to detect MRD in 110 unselected patients treated in Italy in the International Collaborative Treatment Protocol for Children and Adolescents With Acute Lymphoblastic Leukemia (AIEOP-BFM ALL 2000). The trial took place in AIEOP centers during postinduction chemotherapy. Results were categorized as negative, low positive (below the quantitative range [< 5 × 10(-4)]), or high positive (≥ 5 × 10(-4)). Patients with at least one low-positive or high-positive result were assigned to the corresponding subgroup. Patients who tested high positive, low positive, or negative had significantly different cumulative incidences of leukemia relapse: 83.3%, 34.8%, and 8.6%, respectively (P < .001). Two thirds of positive cases were identified within 4 months after induction-consolidation therapy, suggesting that this time frame may be most suitable for cost-effective MRD monitoring, particularly in patients who did not clear their disease at the end of consolidation. These findings provide further insights into the dynamic of MRD and the ongoing effort to define molecular relapse in childhood ALL.


Is lower extremity strength gain associated with improvement in physical performance and disability in frail, community-dwelling elders?
Strength loss is strongly associated with functional decline and is reversible with exercise. The effect of increased strength on function has not been clearly established. The purpose of this study was to determine whether strength gain is associated with improvement in physical performance and disability. One hundred functionally impaired community-dwelling men and women (77.6 +/- 7.6 yrs) were tested at baseline and outcome for lower extremity strength, physical performance, and disability. After random group assignment, exercise participants received strengthening exercises in their homes three times a week for 10 weeks while control subjects continued their normal activities. Using multiple regression techniques, the relationship between strength gain and improvement in physical performance and disability was assessed, controlling for age, depression, and baseline strength. A significant impact of strength gain on mobility skills (p = .0009) was found. The impact of strength gain on chair rise performance was significant in participants who were more impaired (p = .04). Strength gain was associated with gain in gait speed (p = .02) and in falls efficacy (p = .05), but not with other balance, endurance, or disability measures. Lower extremity strength gain is associated with gains in chair rise performance, gait speed, and in mobility tasks such as gait, transfers, stooping, and stair climbing, but not with improved endurance, balance, or disability. Strength gain is also associated with improvement in confidence in mobility. Factors that may influence the ability of strength gain to affect function are initial level of frailty and specificity of exercise. These results support the idea that strength training is an intervention that can potentially improve physical health status in many frail elders.


T-Type calcium channel alpha1G and alpha1H subunits in human retinoblastoma cells and their loss after differentiation.
Human retinoblastoma cells are multipotent retinal precursor cells capable of differentiating into photoreceptors, neurons, and glia. The current-voltage relation of the undifferentiated cells is dominated by a transient inward current that disappears shortly after differentiation. In 20 mM Ba(2+)-containing bath solutions, the current has an activation midpoint near -25 mV and appears to be fully inactivated at -20 mV. Sr(2+) and Ca(2+) are preferred charge carriers relative to Ba(2+), and the current vanishes in the absence of these divalent cations. Cd(2+) blocks the current with an IC(50) of 160 microM, and Ni(2+) blocks in a biphasic manner with IC(50)s of 22 and 352 microM. The current is unaffected when sodium is replaced with other monovalent cations, and it is insensitive to nifedipine, omega-conotoxin GVIA, omega-agatoxin IVA, and omega-conotoxin MVIIC. RT-PCR revealed the presence of alpha 1G and alpha 1H mRNA in undifferentiated cells, but following differentiation, a striking reduction of both alpha 1G and alpha 1H mRNA was found, and this was paralleled by the loss of T-type Ca channel currents. alpha 1I subunit mRNA levels were low in undifferentiated and differentiated cells. These results suggest that T-type Ca channels could play a role in undifferentiated retinoblastoma cell physiology since alpha 1G and alpha 1H Ca channel subunit expression is reduced in cells that have differentiated and exited the cell cycle.


Increased severity associated with tallowamine in acute glyphosate poisoning.
Context: During the re-approval process of glyphosate in Europe, it was mentioned that glyphosate-based products (GBF) were more toxic than glyphosate alone. This phenomenon was attributed to the surfactants and among them, polyethoxylated tallowamine (POEA) has been suspected to significantly contribute to the toxicity of glyphosate products. In animal data acute oral toxicity of POEA has been suggested to be greater than glyphosate toxicity in animal studies. There are no data, however, comparing the clinical signs and severity of acute human poisoning with tallowamine-containing GBF (TA) and non-tallowamine-containing GBF (NTA). The aim of this study was to compare the severity of oral poisoning between TA and NTA cases, reported to the French Poison Control Centres (PCC) over 7 years.Methods: This is a retrospective study of cases of oral exposure to GBF reported to French PCCs between January 1st, 2008 and December 12th, 2014. The formulation of every GBF was reviewed using the PCC national database of products and compositions, to identify cases involving TA, NTA, or GBF with unknown co-formulants.Results: Between 2008 and 2014, 1362 cases of GBF ingestion were registered in the PCC national database of poisoning cases. Among them, 429 were symptomatic acute cases of ingestion of GBF. There were 235 exposures to TA, 105 to NTA, and 89 to unknown GBF. There were more severe cases in the TA group than in the NTA group (p = 0.037).Discussion: The present study shows that POEA rather than other co-formulants leads to more severe symptoms in those patients ingesting GBF. The acute toxicity of POEA might be explained by its irritating properties; in experimental studies, it caused skin irritation and severe eye and mucous membranes irritation.Conclusion: In this study, severe respiratory symptoms were also more frequently reported in the TA group. The surfactant properties of POEA are likely to cause aspiration pneumonitis which is a plausible explanation for the respiratory failure complicating severe GBF poisoning cases.


Long-term anatomical and functional outcomes after autokeratoplasty.
To evaluate the anatomical and functional outcomes of autologous contralateral penetrating keratoplasty (autokeratoplasty). Kaplan-Meier survival analyses were retrospectively performed. Anatomical failure was defined as regraft or graft permanently cloudy at any time during follow-up. Functional failure was defined as the final best-corrected visual acuity (BCVA) <20/400. Thirty-one eyes of 31 patients (19 men), with a mean age of 52±18 years (range 15-81 years) were studied during a mean follow-up of 11.3 years (from 13 months to 48 years). At 12 months postoperatively, all the recipient eyes showed a transparent cornea, but 23% showed functional failure. At the final followup, 16 recipient eyes (52%) showed anatomical and functional success. Twenty-three eyes (74%) showed a clear cornea and 68% reached a better BCVA when compared with preoperative measurements. Nevertheless, 13/31 eyes (42%) displayed functional failure. The accumulative probabilities for anatomical success were 100%, 72% and 48% and 77%, 59% and 29% for functional success at 1, 10 and 40 years, respectively. The most common risk factor for failure was progression of previous glaucoma in 50% of the anatomical failures and in 77% of the functional failures. Autokeratoplasty could be a successful long-term option in patients having one eye with a clear cornea but with irreversible visual dysfunction and the contralateral eye having favourable visual potential limited only by a completely opacified cornea. Progression of previous glaucoma was the most important risk factor for long-term cornea decompensation and visual functional failure in the sample.


Adsorption and Detection of Hazardous Trace Gases by Metal-Organic Frameworks.
The quest for advanced designer adsorbents for air filtration and monitoring hazardous trace gases has recently been more and more driven by the need to ensure clean air in indoor, outdoor, and industrial environments. How to increase safety with regard to personal protection in the event of hazardous gas exposure is a critical question for an ever-growing population spending most of their lifetime indoors, but is also crucial for the chemical industry in order to protect future generations of employees from potential hazards. Metal-organic frameworks (MOFs) are already quite advanced and promising in terms of capacity and specific affinity to overcome limitations of current adsorbent materials for trace and toxic gas adsorption. Due to their advantageous features (e.g., high specific surface area, catalytic activity, tailorable pore sizes, structural diversity, and range of chemical and physical properties), MOFs offer a high potential as adsorbents for air filtration and monitoring of hazardous trace gases. Three advanced topics are considered here, in applying MOFs for selective adsorption: (i) toxic gas adsorption toward filtration for respiratory protection as well as indoor and cabin air, (ii) enrichment of hazardous gases using MOFs, and (iii) MOFs as sensors for toxic trace gases and explosives.


Counterpropagating nematicons in bias-free liquid crystals.
We experimentally investigate the interaction of two counter-propagating spatial optical solitons (nematicons) in bias-free nematic liquid crystals. We demonstrate the existence of vector solitons composed of two nematicons propagating in opposite directions and analyze their stability versus relative distance and input power.We observe the dynamic instability of two counterpropagating nematicons in the form of time-dependent splitting and spatial entanglement.


Through children's eyes: children's experience of living with a parent with an acquired brain injury.
While previous literature on brain injury reports high levels of stress and burden in primary caregivers, the impact on children has been overlooked. This paper reports on an in-depth, qualitative research project exploring the experiences of four children living with fathers with an acquired brain injury (ABI). The findings indicate that these children were negatively impacted and at risk of emotional and behavioural difficulties. The children reported a complexity of feelings associated with the trauma and multiple losses, including profound grief, social isolation and fear of family disintegration and violence. Despite the difficulties they faced, the children also demonstrated resilience and reported positive outcomes such as having greater independence. Although only a small pilot study, the current findings highlight the need for both clinicians and researchers to be more proactive in questioning their clients and families about the level of violence following ABI and that disclosure may be more likely to occur with on-going involvement and support. The study concludes that early intervention and systemic support is required to minimize the trauma for these children. Further research is recommended, not only to replicate these findings in a larger sample, but also to explore in-depth children's experience of living with a parent with a brain injury.


Surgical management of intracranial arteriovenous malformation associated with aneurysms.
The association of intracranial arteriovenous malformation (AVM) with aneurysm(s) is hazardous, and various forms of treatment have been suggested. Most authors agree that surgery for these combined lesions should be directed toward the symptomatic lesion first. This may be difficult, however, especially when the source of the hemorrhage is unclear. Between 1985 and 1996, 12 patients with combined AVM and aneurysm(s) were treated at this institution. Clinical presentations included headache and hemorrhage in all patients, limb weakness in three patients, and seizure in one patient. Hemorrhage types included subarachnoid hemorrhage (SAH), intracerebral hemorrhage (ICH) and intraventricular hemorrhage (IVH). To avoid the intraoperative rupture of aneurysms during resection of the AVM, these were routinely clipped first, followed by total extirpation of the AVM. SAH, ICH and/or IVH simultaneously presented in seven patients (58.3%). According to the surgical findings, bleeding resulted from the aneurysm in 10 patients and AVM in two patients. There was a high incidence of combined lesions in the posterior circulation (67%) in our series. Among the patients with combined lesions in the posterior circulation, half had multiple aneurysms. A total of 21 aneurysms were found in the 12 patients, with five patients harboring multiple aneurysms. Among the 12 patients, 10 had good results. Eight patients received one-stage operations and two received two-stage operations. Two patients died, one of massive rebleeding from multiple giant aneurysms with SAH, IVH and ICH after ventricular drainage, and the other died of massive bleeding during resection of a large AVM. It is difficult to predict bleeding sources preoperatively by radiologic images. Our experience has led to the belief that the safest approach is to treat the aneurysm before microsurgical resection of the AVM. Most of our patients were surgically treated in one approach and showed good results.


Outcomes and use of healthcare resources after an intervention for chronic limb-threatening ischaemia.
The fate of patients with chronic limb-threatening ischaemia undergoing revascularization or a primary amputation is unclear. The aim of this study was to assess the postoperative outcomes and post-procedural healthcare resource use/costs over 1 year after revascularization or a primary amputation for chronic limb-threatening ischaemia. The UK Kent Integrated Dataset, which links primary, community, and secondary care for 1.6 million people, was interrogated. All patients with a new diagnosis of chronic limb-threatening ischaemia undergoing revascularization or a major amputation between January 2016 and January 2019 (3 years) were identified. Postoperative events across all healthcare settings and post-procedure healthcare resource use were analysed over 1 year (until the end of 2019). Overall, 4252 patients with a new diagnosis of chronic limb-threatening ischaemia were identified (65 per cent were male and the mean age was 73 years) between January 2016 and January 2019, of whom 579 (14 per cent) underwent an intervention (studied population); 296 (7 per cent) had an angioplasty, 75 (2 per cent) had bypass surgery, 141 (3 per cent) had a primary major lower limb amputation, 11 had a thrombo-embolectomy (0.3 per cent), and 56 had an endarterectomy (1.3 per cent). Readmissions (median of 2) were similar amongst different procedures within 1 year; bypass surgery was associated with more hospital appointments (median of 4 versus 2; P = 0.002). Patients undergoing a primary amputation had the highest number of cardiovascular events and 1-year mortality. In a linear regression model, index procedure type and Charlson co-morbidity index score were not predictors of appointments in primary/secondary care, community care visits, or readmissions after discharge. There were no statistically significant differences regarding post-procedural healthcare costs between procedures over 1 year. Revascularization is not associated with more hospital, primary/community care appointments or increased post-procedural healthcare costs over 1 year when compared with primary amputation, in people with chronic limb-threatening ischaemia.


Feline struvite crystalluria: a comparison of some commercially available dry cat diets in New Zealand.
Thirteen adult cats were each fed consecutively five test diets: firstly a complete canned diet, and then four commercially available dry cat diets (New Formula Biscats, Cat Chow, Go-Cat and Whiskettes) for 7,13, 5, 4 and 4 weeks respectively. Urine samples were tested for pH and presence of struvite crystals. Body weight was recorded weekly. Urine pH was ranked from acid to alkaline as follows: Whiskettes (pH 5.8), canned diet (pH 5.9), Biscats (pH 6.1), Cat Chow (pH 6.45) and Go-Cat (pH 6.5). The pH of urine when cats were fed Whiskettes, Biscats and canned diet was not significantly different. Biscats produced a urine pH significantly higher than Whiskettes but, in each case, these three diets produced a significantly lower urine pH than Cat Chow and Go-Cat. Struvite crystals occurred spontaneously in 9% of urine samples from cats when fed Whiskettes and Biscats, 71% when fed Cat Chow and 38% when fed Go-Cat: spontaneous struvite was not seen in any cat fed CX9. Haematuria was seen in 2.9% (2/69) urine samples from cats fed Cat Chow. One tom cat had a blocked urethra after 24 days on Go-Cat. No abnormalities were observed in any cat when fed canned diet, Biscats or Whiskettes. It was concluded that of the four dry cat diets tested only Biscats and Whiskettes produce urine with an acceptably low rate of spontaneous struvite crystalluria.


GenDB--an open source genome annotation system for prokaryote genomes.
The flood of sequence data resulting from the large number of current genome projects has increased the need for a flexible, open source genome annotation system, which so far has not existed. To account for the individual needs of different projects, such a system should be modular and easily extensible. We present a genome annotation system for prokaryote genomes, which is well tested and readily adaptable to different tasks. The modular system was developed using an object-oriented approach, and it relies on a relational database backend. Using a well defined application programmers interface (API), the system can be linked easily to other systems. GenDB supports manual as well as automatic annotation strategies. The software currently is in use in more than a dozen microbial genome annotation projects. In addition to its use as a production genome annotation system, it can be employed as a flexible framework for the large-scale evaluation of different annotation strategies. The system is open source.


WRKY Transcription Factors Associated With NPR1-Mediated Acquired Resistance in Barley Are Potential Resources to Improve Wheat Resistance to Puccinia triticina.
Systemic acquired resistance (SAR) in Arabidopsis is established beyond the initial pathogenic infection or is directly induced by treatment with salicylic acid or its functional analogs (SA/INA/BTH). NPR1 protein and WRKY transcription factors are considered the master regulators of SAR. Our previous study showed that NPR1 homologs in wheat (Triticum aestivum L.) and barley (Hordeum vulgare L.) regulated the expression of genes encoding pathogenesis-related (PR) proteins during acquired resistance (AR) triggered by Pseudomonas syringae pv. tomato DC3000. In the present examination, AR induced by P. syringae DC3000 was also found to effectively improve wheat resistance to Puccinia triticina (Pt). However, with more complex genomes, genes associated with this SAR-like response in wheat and barley are largely unknown and no specific WRKYs has been reported to be involved in this biological process. In our subsequent analysis, barley transgenic line overexpressing wheat wNPR1 (wNPR1-OE) showed enhanced resistance to Magnaporthe oryzae isolate Guy11, whereas AR to Guy11 was suppressed in a barley transgenic line with knocked-down barley HvNPR1 (HvNPR1-Kd). We performed RNA-seq to reveal the genes that were differentially expressed among these transgenic lines and the wild-type barley plants during the AR. Several PR and BTH-induced (BCI) genes were designated as downstream genes of NPR1. The expression of few WRKYs was significantly associated with NPR1 expression during the AR events. The transient expression of three WRKY genes, including HvWRKY6, HvWRKY40, and HvWRKY70, in wheat leaves by Agrobacterium-mediated infiltration enhanced the resistance to Pt. In conclusion, a profile of genes associated with NPR1-mediated AR in barley was drafted and WRKYs discovered in the current study showed a substantial potential for improving wheat resistance to Pt.


Harnessing the power of the grassroots to conduct public health research in sub-Saharan Africa: a case study from western Kenya in the adaptation of community-based participatory research (CBPR) approaches.
Community-based participatory research (CBPR) is a collaborative approach to research that involves the equitable participation of those affected by an issue. As the field of global public health grows, the potential of CBPR to build capacity and to engage communities in identification of problems and development and implementation of solutions in sub-Saharan Africa has yet to be fully tapped. The Orphaned and Separated Children's Assessments Related to their Health and Well-Being (OSCAR) project is a longitudinal cohort of orphaned and non-orphaned children in Kenya. This paper will describe how CBPR approaches and principles can be incorporated and adapted into the study design and methods of a longitudinal epidemiological study in sub-Saharan Africa using this project as an example. The CBPR framework we used involves problem identification, feasibility and planning; implementation; and evaluation and dissemination. This case study will describe how we have engaged the community and adapted CBPR methods to OSCAR's Health and Well-being Project's corresponding to this framework in four phases: 1) community engagement, 2) sampling and recruitment, 3) retention, validation, and follow-up, and 4) analysis, interpretation and dissemination. To date the study has enrolled 3130 orphaned and separated children, including children living in institutional environments, those living in extended family or other households in the community, and street-involved children and youth. Community engagement and participation was integral in refining the study design and identifying research questions that were impacting the community. Through the participation of village Chiefs and elders we were able to successfully identify eligible households and randomize the selection of participants. The on-going contribution of the community in the research process has been vital to participant retention and data validation while ensuring cultural and community relevance and equity in the research agenda. CBPR methods have the ability to enable and strengthen epidemiological and public health research in sub-Saharan Africa within the social, political, economic and cultural contexts of the diverse communities on the continent. This project demonstrates that adaptation of these methods is crucial to the successful implementation of a community-based project involving a highly vulnerable population.


Does a serious game increase intrinsic motivation in children receiving urotherapy?
Urotherapy is considered the treatment of choice for children suffering daytime urinary incontinence (DUI). Urotherapy intends to improve bladder dysfunction for children with DUI. For children with refractory DUI, an intensive inpatient bladder training program exists, which focuses on relearning, concentration on, and awareness of the bladder. Children's motivation and adherence are key determinants of a successful training outcome. It is hypothesized that motivation endurance throughout the treatment process may be enhanced by a serious game training tool, which could make the training more appealing and rewarding. The study explores intrinsic motivation in children receiving bladder training for DUI and whether using a serious game improves their intrinsic motivation. In this pragmatic study, 50 children were allowed to choose among receiving bladder training with (intervention group) or without the application of a serious game (control group). At 4, 8, and 12 weeks of training, children and parents were asked to complete the Intrinsic Motivation Inventory (IMI). Children also completed the Pediatric Urinary Incontinence Quality of Life Tool (PinQ) before the start of the training and 6 months thereafter. At 6-month follow-up, patients were ask to participate in two focus groups, wherein the children discussed how they used the serious game and which improvements they would prefer. Children who received standard bladder training with the addition of a serious game did not differ in terms of intrinsic motivation from children who underwent standard bladder training only. Training results were equal in both the groups, with 80% good or improved. Incontinence-related quality of life (QoL) improved accordingly. In contrast to the study expectations, this game did not increase intrinsic motivation. Findings on training and QoL results are consistent with those of previous studies in both interventions. Although a randomized design could have yielded more valid results than this preference-based approach, the latter is more congruent with clinical practice. In contrast to existing bladder diary apps, this game offers a combination of child-friendly instructions, explanation of bladder (dys)function, and keeping a bladder diary. Mobile devices are playing an increasingly important role in health care; therefore, an urotherapy app can be a complementary therapeutic tool. Most children find it attractive to combine bladder training with a serious game. However, no added value was found regarding intrinsic motivation and training results. All children with persistent DUI in this cohort were highly motivated to complete an intensive bladder training program.


Differences in Posttraumatic Stress Disorder, Depression, and Attribution of Symptoms in Service Members With Combat Versus Noncombat Mild Traumatic Brain Injury.
This study compares combat-related mild traumatic brain injury (mTBI) to non-combat-related mTBI in rates of posttraumatic stress disorder (PTSD) and depression after injury, severity of postconcussive symptoms (PCSs), and attribution of those symptoms to mTBI versus PTSD. A total of 371 active duty service members (SMs) with documented history of mTBI, divided into combat and non-combat-related cohorts. Retrospective cohort study. Diagnoses of PTSD and depression based on medical record review and self-report. PCSs measured using Neurobehavioral Symptom Index. Attribution of symptoms based on a rating scale asking how much mTBI, PTSD, depression, deployment, or readjustment stress contributed to current symptoms. Prevalence of PTSD was significantly higher after a combat-related mTBI, compared with a noncombat mTBI (P = .001). Prevalence of depression did not differ between the 2 groups. PCSs were high in both combat and noncombat mTBIs, with no statistical difference between groups. SMs with PTSD reported higher PCS, regardless of combat status. SMs without PTSD attributed symptoms mainly to mTBI, whereas SMs with PTSD, regardless of combat status, were much more likely to attribute symptoms to PTSD, depression, and deployment/readjustment stress. This research contributes to our understanding of the complex interplay between mTBI and PTSD in both combat and noncombat injuries within the military population and the importance of addressing both simultaneously.


Systemic Candidiasis and TLR2 Agonist Exposure Impact the Antifungal Response of Hematopoietic Stem and Progenitor Cells.
We have previously demonstrated that Candida albicans induces differentiation of hematopoietic stem and progenitor cells (HSPCs) toward the myeloid lineage both in vitro and in vivo in a TLR2- and Dectin-1-dependent manner, giving rise to functional macrophages. In this work, we used an ex vivo model to investigate the functional consequences for macrophages derived from HSPCs in vivo-exposed to Pam3CSK4 (a TLR2 agonist) or C. albicans infection. Short in vivo treatment of mice with Pam3CSK4 results in a tolerized phenotype of ex vivo HSPC-derived macrophages, whereas an extended Pam3CSK4 treatment confers a trained phenotype. Early during candidiasis, HSPCs give rise to macrophages trained in their response to Pam3CSK4 and with an increased fungicidal activity; however, as the infection progresses to higher fungal burden, HSPC-derived macrophages become tolerized, while their fungicidal capacity is maintained. These results demonstrate that memory-like innate immune responses, already described for monocytes and macrophages, also take place in HSPCs. Interestingly, extended Pam3CSK4 treatment leads to an expansion of spleen HSPCs and myeloid cells, and drastically reduces the fungal burden in the kidney and spleen during systemic C. albicans infection. This protection against tissue invasion is abrogated by immunodepletion of HSPCs, suggesting their protective role against infection in this model. In addition, HSPCs produce in vitro cytokines and chemokines in response to C. albicans and Pam3CSK4, and these secretomes are capable of inducing myeloid differentiation of HSPCs and modulating peritoneal macrophage cytokine responses. Taken together, these data assign an active role for HSPCs in sensing pathogens during infection and in contributing to host protection by diverse mechanisms.


Perceptions of responsiveness in service delivery.
The delivery of service quality has become a topic of increasing interest especially in the context of health care services marketing. The research investigated the responsiveness component of quality service. Both issues, the customers' perception of time as well as their expectations for responsiveness in quality service delivery were addressed. Specifically, an attempt was made to determine if the patients' perception of bell response time differed from the actual response time. In addition, this paper tried to determine if the difference between patient's perception of bell response time and actual response time had an effect on their perception of the responsiveness of the nurse.


Measurement of Quality of Life in Keratoconus.
To identify and assess the quality of questionnaires used to measure quality of life in keratoconus and guide selection of the most appropriate questionnaire for evaluating the impact of keratoconus. A literature search was carried out in Scopus, Web of Science, PubMed, MEDLINE, Cochrane, and PsycINFO databases. Articles that described a questionnaire to measure quality of life in keratoconus were included. Information on psychometric properties and validity was extracted and analyzed based on a set of quality criteria. Finally, the impact of keratoconus and its management methods on quality of life was reviewed. The search yielded 331 publications, of which 45 articles describing 18 (12 ophthalmic including 2 keratoconus-specific and 6 generic) questionnaires were reviewed. Most of the articles (40, 88.9%) described ophthalmic questionnaires not specific to keratoconus. The National Eye Institute Visual Function Questionnaire was the most frequently used questionnaire (n = 26). Only 4 articles provided information on psychometric properties. The Keratoconus Outcomes Research Questionnaire, the only validated keratoconus-specific questionnaire, had the most superior psychometric properties. However, it consists of items on only 2 domains of quality of life (activity limitation and symptoms). Overall, keratoconus management methods (spectacles, contact lenses, and cross-linking in early stages, corneal transplantation in late stages) improved quality of life. The quality of life scores were associated with clinical measures including visual acuity, corneal topography, pachymetry, and keratoconus severity. There is a need for a comprehensive and high-quality patient-reported outcome measure in keratoconus. A questionnaire should be chosen based on the purpose and the quality of the questionnaire. This review guides selection of an appropriate questionnaire.


Assignment of the human gene for the low density lipoprotein receptor to chromosome 19: synteny of a receptor, a ligand, and a genetic disease.
The availability of a species-specific monoclonal antibody that recognizes the low density lipoprotein (LDL) receptor of human but not hamster origin permitted assignment of the structural gene for the human receptor to chromosome 19. The antibody was used to detect the human LDL receptor in a series of hamster-human somatic cell hybrids by two assays: (i) a structural assay that measured cellular incorporation of [35S]methionine into immunoprecipitable receptor and (ii) a functional assay that measured the rate of receptor-dependent uptake and degradation of the 125I-labeled anti-receptor monoclonal antibody. Both assays showed that the human LDL receptor was expressed in 15 out of 20 hybrid cell lines. Expression of the human LDL receptor was 100% concordant with the presence of human chromosome 19; all other human chromosomes showed at least 25% discordance. As expected, the gene for the LDL receptor (LDLR) is located on the same chromosome as the gene for the disease familial hypercholesterolemia, which has been previously mapped to chromosome 19 by pedigree studies and is caused by allelic mutations at the LDL receptor locus. The gene for apolipoprotein E, a ligand for the LDL receptor, is also known to be located on chromosome 19, raising the possibility of an evolutionary link between a protein ligand and its receptor.


Main Mechanisms of Remote Monitoring Programs for Cardiac Rehabilitation and Secondary Prevention: A SYSTEMATIC REVIEW.
The objective of this report was to identify the main mechanisms of home-based remote monitoring programs for cardiac rehabilitation (RM CR) and examine how these mechanisms vary by context. This was a systematic review using realist synthesis. To be included, articles had to be published in English between 2010 and November 2020 and contain specific data related to mechanisms of effect of programs. MEDLINE All (1946-) via Ovid, Embase (1974-) via Ovid, APA PsycINFO (1806-), CINAHL via EBSCO, Scopus databases, and gray literature were searched. From 13 747 citations, 91 focused on cardiac conditions, with 23 reports including patients in CR. Effective RM CR programs more successfully adapted to different patient home settings and broader lives, incorporated individualized patient health data, and had content designed specifically for patients in cardiac rehabilitation. Relatively minor but common technical issues could significantly reduce perceived benefits. Patients and families were highly receptive to the programs and viewed themselves as fortunate to receive such services. The RM CR programs could be improved via incorporating more connectivity to other patients. No clear negative effects on perceived utility or outcomes occurred by patient age, ethnicity, or sex. Overall, the programs were seen to best suit highly motivated patients and consolidated rather than harmed existing relationships with health care professionals and teams. Remote monitoring CR programs are perceived by patients to be beneficial and attractive. Future RM CR programs should consider adaptability to different home settings, incorporate individualized health data, and contain content specific to patient needs.


Dyskinesia is most centrally situated in an estimated network of extrapyramidal syndrome in Asian patients with schizophrenia: findings from research on Asian psychotropic prescription patterns for antipsychotics.
Network analysis provides a new viewpoint that explicates intertwined and interrelated symptoms into dynamic causal architectures of symptom clusters. This is a process called 'symptomics' and is concurrently applied to various areas of symptomatology. Using the data from Research on Asian Psychotropic Prescription Patterns for Antipsychotics (REAP-AP), we aimed to estimate a network model of extrapyramidal syndrome in patients with schizophrenia. Using data from REAP-AP, extrapyramidal symptoms of 1046 Asian patients with schizophrenia were evaluated using the nine items of the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS). The estimated network of the ordered-categorical DIEPSS items consisted of nodes (symptoms) and edges (interconnections). A community detection algorithm was also used to identify distinctive symptom clusters, and correlation stability coefficients were used to evaluate the centrality stability. An interpretable level of node strength centrality was ensured with a correlation coefficient. An estimated network of extrapyramidal syndrome showed that 26 (72.2%) of all possible 35 edges were estimated to be greater than zero. Dyskinesia was most centrally situated within the estimated network. In addition, earlier antipsychotic-induced extrapyramidal symptoms were divided into three distinctive clusters - extrapyramidal syndrome without parkinsonism, postural instability and gait difficulty-dominant parkinsonism, and tremor-dominant parkinsonism. Our findings showed that dyskinesia is the most central domain in an estimated network structure of extrapyramidal syndrome in Asian patients with schizophrenia. These findings are consistent with the speculation that acute dystonia, akathisia, and parkinsonism could be the risk factors of tardive dyskinesia.


Skill acquisition and competency testing for physical agent modality use.
The use of physical agent modalities is not considered an entry-level skill and requires postprofessional education, according to the American Occupational Therapy Association. The purpose of this survey was to determine how occupational therapy practitioners who use physical agents modalities are trained. Two hundred fifty occupational therapists were randomly selected from the American Occupational Therapy Association's Physical Disabilities Special Interest Section. The practitioners were surveyed about their use of, education in, competency testing for, and opinions on eight physical agent modalities. Results were based on 100 responses (40% response rate). Of the eight modalities, the most commonly used were hot and cold packs, and the least were transcutaneous electrical nerve stimulators. The most common means of education was on-the-job training, and the least common was higher level accredited education. A majority (71) of respondents reported that no competency testing was being performed at their facilities. In the remaining facilities (29), the majority performed competency tests with no routine frequency, using no particular guidelines for testing and no formal methods for maintaining standards for physical agent modality use. Eighty-five respondents indicated they would be interested in attending continuing education programs on the use of physical agent modalities, and 88 believed that functional activities should follow the use of physical agent modalities within the same treatment session. The occupational therapy profession may need specific educational and competency guidelines to assure the qualifications of therapists using physical agent modalities.


Effects of the surface pH on interfacial interactions of collagen-elastin matrix.
This study is aimed to elucidate the effects of surface pH of bioprosthetic heart valve (BHV) on their binding property to calcium and protein. It is hypothesized that the binding affinities of the BHV for calcium and protein are surface pH dependent. To test this hypothesis, collagen-elastin matrix (CEM) made of varying ratios of collagen and elastin were used as calcifiable matrices to simulate the calcium binding process of BHV. The calcium binding profiles of CEM, whose surface pHs were adjusted at 3.4, 5.0 or 7.4, were examined by either incubating CEM in the buffer solutions containing various calcium concentrations or implanting CEM in the rat subcutaneous model. The amounts of calcium and protein bound to CEM decreased as the surface pH of CEM decreased. The calcium level in the CEM (pH 7.4) was 2.32+/-0.8 as compared with 1.23+/-0.35 (microg/mg) in CEM (pH 3.4). The equilibrium dissociation constant (Kd) was in a reciprocal relationship with the surface pH. This study demonstrated that the affinity of CEM for calcium is surface pH dependent and provided basic information about the role of surface properties in BHV calcification.


Time-Dependent Hypotensive Effect of Aspirin in Mice.
Objective- Evening but not morning administration of low-dose aspirin has been reported to lower blood pressure in hypertensive patients. The present study was designed to determine whether this phenomenon could be replicated in mice, and if so, whether a time-dependent effect of aspirin on blood pressure was because of alteration of circadian clock function. Approach and Results- We recapitulated the protective effect of aspirin (50 μg/d for 7 days) at zeitgeber time 0 (active-to-rest transit), but not at zeitgeber time 12, on a high-salt diet-induced increase of blood pressure. However, the time of aspirin administration did not influence expression of canonical clock genes or their acetylation. We used mouse Bmal1 and Per2-luciferase reporters expressed in U2OS cells to determine the real-time effect of aspirin on circadian function but found that the oscillation of bioluminescence was unaltered. Timing of aspirin administration also failed to alter urinary prostaglandin metabolites or catecholamines, or the acetylation of its COX-1 (cyclooxygenase-1) target in platelets. Conclusions- The time-dependent hypotensive effect of aspirin in humans has been recapitulated in hypertensive mice. However, this does not seem to reflect a direct impact of aspirin on circadian clocks or on acetylation of platelet COX-1.


Effect of pH on Fenton process using estimation of hydroxyl radical with salicylic acid as trapping reagent.
This study estimates the yield of hydroxyl radical using salicylic acid as the trapping reagent and investigates the relationship between hydroxyl radical and pH value. The formation and variation of hydroxyl radical under different pH values were evaluated using reaction products, 2,3-DHBA, 2,5-DHBA, and catechol. The formation rate of hydroxyl radical was dependent on the ratio of ferrous ion to hydrogen peroxide and pH values. The difference between various pH values was explored. The kinetics and mechanisms of hydroxyl radical reactions were established in the Fenton process. Experimental results showed that the best reaction conditions were 8.5 mM H(2)O(2), 1.25 mM Fe(2 + ), Fe(2 + )/H(2)O(2) = 0.147 at pH 3 and the formation rate constant of hydroxyl radical was 1.12 x 10(11) M(-1) s(-1).


Retrospective cohort study of 4,591 dental implants: Analysis of risk indicators for bone loss and prevalence of peri-implant mucositis and peri-implantitis.
Due to the risk of peri-implantitis, following dental implant placement, this study aimed to evaluate risk indicators associated with marginal bone loss from a retrospective open cohort study of 4,591 dental implants, placed in private practice, with 5- to 10-year follow-up. Furthermore, the prevalence of mucositis and peri-implantitis among the study cohort was evaluated, comparing strict versus relaxed criteria for bleeding on probing. Periapical radiographs were used to evaluate changes in crestal bone level. Peri-implant soft tissue was evaluated using an ordinal mucosal index in comparison with the conventional binary threshold for bleeding (i.e., present or not). Periodontal probing depth was not evaluated. Linear mixed models were used to evaluate bone level over time, and other risk indicators, at the patient and implant level. Risk indicators found to have a significant impact on bone level included: autoimmune disease, heavy smoking, bisphosphonate therapy, implant location, diameter and design, and the presence of a bone defect at site of implantation. The prevalence of mucositis at the implant level was 38.6% versus 14.2% at 6 to 7 years, when using strict versus relaxed criteria, respectively. The prevalence of peri-implantitis after 6 to 7 years was 4.7% and 3.6% when using strict versus relaxed criteria, respectively. The results of this study identify several risk factors associated with bone loss. Furthermore, the prevalence of mucositis and peri-implantitis was shown to be lower at both the implant and the patient when using strict versus relaxed criteria based on the assessment of oral health surrounding dental implants.


Recent advances in externally controlled ring-opening polymerisations.
Switchable catalysis is a powerful tool in the polymer chemist's toolbox as it allows on demand access to a variety of polymer architectures. Switchable catalysts operate by the generation of a species which is chemically distinct in behaviour and structure to the precursor. This difference in catalytic activity has been exploited to allow spatiotemporal control over polymerisations in the synthesis of (co)polymers. Although switchable methodologies have been applied to other polymerisation mechanisms for quite some time, for ring opening polymerisation (ROP) reactions it is a relatively young area of research. Despite its infancy, the field is accelerating rapidly. Here, we review recent developments for selected external stimuli for ROP, including redox chemistry, light, allosteric and mechanical control. Furthermore, a brief review on switch catalysis involving exogeneous gases will also be provided, although this area differs from traditional switchable catalysis techniques. An outlook on the future of switchable catalysis is also provided.


Autocrine CCL3 and CCL4 induced by the oncoprotein LMP1 promote Epstein-Barr virus-triggered B cell proliferation.
Epstein-Barr virus (EBV) alters the regulation and expression of a variety of cytokines in its host cells to modulate host immune surveillance and facilitate viral persistence. Using cytokine antibody arrays, we found that, in addition to the cytokines reported previously, two chemotactic cytokines, CCL3 and CCL4, were induced in EBV-infected B cells and were expressed at high levels in all EBV-immortalized lymphoblastoid cell lines (LCLs). Furthermore, EBV latent membrane protein 1 (LMP1)-mediated Jun N-terminal protein kinase activation was responsible for upregulation of CCL3 and CCL4. Inhibition of CCL3 and CCL4 in LCLs using a short hairpin RNA approach or by neutralizing antibodies suppressed cell proliferation and caused apoptosis, indicating that autocrine CCL3 and CCL4 are required for LCL survival and growth. Importantly, significant amounts of CCL3 were detected in EBV-positive plasma from immunocompromised patients, suggesting that EBV modulates this chemokine in vivo. This study reveals the regulatory mechanism and a novel function of CCL3 and CCL4 in EBV-infected B cells. CCL3 might be useful as a therapeutic target in EBV-associated lymphoproliferative diseases and malignancies.


Basal energy expenditure in southern Chinese healthy adults: measurement and development of a new equation.
The objective of the present study is to measure basal energy expenditure (BEE) using the Cosmed K₄b² portable metabolic system (Rome, Italy) and to develop a new predictive equation for BEE in southern Chinese adults. A total of 165 healthy Chinese adults aged 18-45 years with normal body weight were involved in the present study. BEE was measured by Cosmed K₄b². Body composition was determined by body composition analysers (ImpediMed DF50, QLD, Australia). Multiple linear regression analysis and correlation analysis were applied to develop a new optimal equation for predicting BEE of southern healthy Chinese adults. Measured BEE (mBEE) of southern Chinese healthy adults was 5513 (sem 96) kJ/d, which was similar to the results predicted by the equation developed by of Liu 5579 (sem 57) kJ/d (P = 0·37) and significantly lower than those from equations developed by Henry (5763 (sem 54) kJ/d), Schofield (5898 (sem 58) kJ/d) and Harris-Benedict (HB; 5863 (sem 51) kJ/d) (all P = 0·001). The optimal equation developed by our data was BEE (kJ/d) = 277+89 weight (kg)+600 sex (male = 1 and female = 0) (r² = 0·48, n 165). For males, BEE (kJ/d) = 105 weight (kg) - 58 (r² = 0·27, n 79); for females, BEE (kJ/d) = 69 weight (kg)+1335 (r² = 0·24, n 86). In conclusion, the mBEE of southern Chinese healthy adults was 5513 (sem 96) kJ/d. The BMR of Chinese adults of normal weight is overestimated by widely used prediction equations developed by Henry, Schofield and HB. The equation developed in the present study (equation 7) can be used in predicting BEE for Chinese adults aged 18-45 years with normal body weight.


[Health and sickness as sociological concepts].
Health and illness, as widely used terms in scientific literature, leave a wide scope as to their definition and conceptual interpretation. The medicotechnical perspective refers to health and illness as objective changes in the structure and/or functioning of the human body and mind, as a result of which the bodily and mental integrity of the human organism is affected detrimentally. On the contrary, the social sciences, and especially medical sociology, define health and illness essentially in terms of the social system within which they occur. The main task of medical sociology is to pay attention to those social systemic and sociocultural aspects of health and illness which are sometimes grossly neglected or insufficiently understood by the medical sciences, thereby to contribute to a comprehensive approach to these phenomena.


Small for Gestational Age Preterm Neonates Exhibit Defective GH/IGF1 Signaling Pathway.
Objective: To investigate the impact of fetal growth restriction (FGR) on hormonal regulation of post-natal growth and glucose metabolism [via insulin and growth hormone (GH)/Insulin-like Growth factor 1 (IGF1) axis pathways] in small for gestational age (SGA) neonates. Methods: We conducted a monocentric observational prospective comparative study on 73 singleton babies born with a weight inferior to 2,000 g. We analyzed auxological (weight, height and head circumference), and hormonal (GH, IGF1, and insulin plasma concentrations) data comparing SGA and appropriate for gestational age (AGA) neonates, between day 1 and 60. Results: One third (23/73) of the neonates were SGA. Twenty-five percent (18/73) required insulin for idiopathic hyperglycemia of prematurity and were smaller in weight and head circumference at discharge. In the SGA group compared with the AGA group, GH plasma concentrations were higher at day 3 (70.1 vs. 38.0 mIU/L) and IGF1 plasma concentrations were higher at day 10 (29.0 vs. 18.7 ng/ml). Conclusions: SGA neonates displayed resistance to GH and IGF1, concomitant to insulin resistance. This could partially explain the initial defective catch-up growth and, later in life, the higher prevalence of metabolic syndrome in this population.


Using behavior as an early predictor of sickness in veal calves.
The objective of this study was to analyze whether changes in behavior can be a good early predictor of sickness in calves. Friesian males calves (n = 325; 30 ± 9 d of age; 65 ± 15 kg) were monitored with an activity-monitoring device from 30 to 90 d of life in 4 periods corresponding to 4 seasons. The activity-monitoring device measured number of steps, number of lying bouts, lying time, and frequency and time of visits to the feed bunk. Calf health status was monitored daily and all incidences were recorded. To compare sick and healthy calves, a matched pair design was used to assign calves into the healthy group. Day 0 was defined as the day of sickness diagnosis. For each sick calf, 3 calves with no signs of sickness during the entire period (healthy calves) on the same date, in the same season, and of similar age (±4 d) and weight at entry were identified. A multivariate linear mixed model was used from d -10 to +10 relative to the sickness diagnosis to describe differences between sick and healthy calves. A multivariate logistic regression model was used for predicting sick calves on the days before the diagnosis. Significance was declared at P < 0.05. Daily, healthy calves had 1,476 ± 195 steps, spent 185 ± 32.5 min at the feed bunk, consumed 10 ± 1.1 meals, had 19.5 ± 1.8 lying bouts, and spent an average of 978 ± 30.5 min lying. The difference in behavior between sick (n = 33) and healthy calves (n = 99) began to be evident on d -10. Sick calves had fewer steps and numbers of visits to the feed bunk on d -1 and 0 and spent less time at the feed bunk on d -10 and -1 compared with healthy calves. From d -2 to d 9, sick calves had 15% fewer lying bouts, with no difference in lying time except on d -10, when sick calves spent more time lying. The best prediction model was for d -1 and included season and age at entry as qualifying variables, and frequency of visits to the feed bunk, steps, and lying time as behavior predictors (69% sensitivity, 72% specificity, 72% accuracy, 55% false discovery rate, and 12% false omission rate). However, an earlier prediction would be more useful to reduce the negative effect of sickness on production and welfare. The prediction model for d -10 had 67% sensitivity, 67% specificity, 67% accuracy, 60% false discovery rate, and 14% false omission rate. Results indicate that the occurrence of sickness can be predicted in advance, and an automated alarm system could be used to identify calves at risk of becoming sick and apply a preventive treatment.


Plasmodium falciparum adhesion on human brain microvascular endothelial cells involves transmigration-like cup formation and induces opening of intercellular junctions.
Cerebral malaria, a major cause of death during malaria infection, is characterised by the sequestration of infected red blood cells (IRBC) in brain microvessels. Most of the molecules implicated in the adhesion of IRBC on endothelial cells (EC) are already described; however, the structure of the IRBC/EC junction and the impact of this adhesion on the EC are poorly understood. We analysed this interaction using human brain microvascular EC monolayers co-cultured with IRBC. Our study demonstrates the transfer of material from the IRBC to the brain EC plasma membrane in a trogocytosis-like process, followed by a TNF-enhanced IRBC engulfing process. Upon IRBC/EC binding, parasite antigens are transferred to early endosomes in the EC, in a cytoskeleton-dependent process. This is associated with the opening of the intercellular junctions. The transfer of IRBC antigens can thus transform EC into a target for the immune response and contribute to the profound EC alterations, including peri-vascular oedema, associated with cerebral malaria.


Perceptions and Attitudes Toward Dementia in Predominantly African American Congregants.
The purpose of this study was to identify the perceptions and attitudes of African American congregants toward dementia before and after attending a dementia-focused workshop. Six churches in Metropolitan Atlanta, Georgia, hosted the workshops. Attendees (N = 171) participated in a free association exercise to evaluate their perceptions and attitudes toward dementia. Before and after the workshop, participants wrote words and phrases that occurred to them when they thought of dementia. Content analysis was used to identify themes. Before the workshop, participants' responses tended to include negative language (e.g., fear, memory loss, sadness). After the workshop, participants expressed more positive words (e.g., support, hopefulness, caring). These findings suggest that education can change congregants' perceptions about dementia and potentially reduce dementia-associated stigma. This change will allow families to feel comfortable both interacting with and seeking help from those in their faith communities.


[Prevention and treatment of congenital syphilis].
Due to uncertainties about the treatment of their mothers' syphilis infections, in three neonates congenital syphilis was suspected. The mother of the first newborn, a girl, had treated herself for a syphilis infection. The second mother, who gave birth to a son, was treated adequately for her infection, but there was no record of this available at the time of birth. The third mother, who gave birth to a girl, had also been treated for syphilis, but within the month before delivery. None of the neonates had any clinical manifestations of congenital syphilis. These obscurities resulted in serological examination of all three neonates and in treatment in the first and third cases. The reported increase in the incidence of syphilis infections in The Netherlands poses a risk of more cases of congenital syphilis infection in newborns. It is crucial to be aware of the consequences of syphilis infection in the neonate and fetus, and also of the various measures available for its prevention and treatment. In The Netherlands, screening for syphilis is routinely carried out during pregnancy. If a pregnant woman is found to be infected, the therapy of choice is penicillin. The Treponema pallidum agglutination test (TPA) and the venereal disease research laboratory (VDRL) test should be performed on the mother and the newborn after birth. All infants born to seropositive but insufficiently treated mothers require careful physical examinations. Infants with proven infection or with a high index of suspicion should be treated with aqueous crystalline penicillin G for a total of 10 days. After discharge, all infants should be followed up with physical and serological examinations up to the first year of life.


Correlating the three-dimensional atomic defects and electronic properties of two-dimensional transition metal dichalcogenides.
The electronic, optical and chemical properties of two-dimensional transition metal dichalcogenides strongly depend on their three-dimensional atomic structure and crystal defects. Using Re-doped MoS2 as a model system, here we present scanning atomic electron tomography as a method to determine three-dimensional atomic positions as well as positions of crystal defects such as dopants, vacancies and ripples with a precision down to 4 pm. We measure the three-dimensional bond distortion and local strain tensor induced by single dopants. By directly providing these experimental three-dimensional atomic coordinates to density functional theory, we obtain more accurate electronic band structures than derived from conventional density functional theory calculations that relies on relaxed three-dimensional atomic coordinates. We anticipate that scanning atomic electron tomography not only will be generally applicable to determine the three-dimensional atomic coordinates of two-dimensional materials, but also will enable ab initio calculations to better predict the physical, chemical and electronic properties of these materials.


The epidemiology and genetics of smoking initiation and persistence: crosscultural comparisons of twin study results.
We examined whether there are crosscultural differences in the magnitude of genetic and environmental contributions to risk of becoming a regular smoker and of persistence in smoking in men and women. Standard methods of epidemiologic and genetic analysis were applied to questionnaire data on history of cigarette use obtained from large samples of male and female like-sex twins from three different countries: Australia (N = 2284 pairs), Sweden (N = 8651 pairs), and Finland (N = 10,948 pairs). Samples were subdivided into three age groups (AG), 18-25 years, 26-35 years, and 36-46 years of age. The magnitude of genetic influence for lifetime smoking was found to be consistent across country and AG for women (46%) and men (57%), and estimates of the contribution from environmental influences shared by twin and co-twin could be equated across all countries by AG for the women (from youngest to oldest AG: 45%, 35%, and 26%), but not for men, with separate estimates obtained for the Scandinavian (33%, 29%, and 19%) and the Australian men (26%, 9%, and 11%). There was no evidence for an important role for shared environmental influences on persistent smoking, and the genetic contribution was found to be consistent in magnitude in men and women, and the same across country and AG (52%). There are strong genetic influences on smoking behavior, and that risk of becoming a smoker (but not persistence in smoking) may be modified by experiences shared by twins that differ by AG and, at least for men, cultural background.


Sex differences in cognitive impairment in Alzheimer's disease.
Sex differences in neurocognitive abilities have been extensively explored both in the healthy population and in many disorders. Until recently, however, little work has examined such differences in people with Alzheimer's disease (AD). This is despite clear evidence that AD is more prevalent in women, and converging lines of evidence from brain imaging, post-mortem analyses, hormone therapy and genetics suggesting that AD affects men and women differently. We provide an overview of evidence attesting to the poorer cognitive profiles in women than in men at the same stage of AD. Indeed, men significantly outperform women in several cognitive domains, including: Language and semantic abilities, visuospatial abilities and episodic memory. These differences do not appear to be attributable to any differences in age, education, or dementia severity. Reasons posited for this female disadvantage include a reduction of estrogen in postmenopausal women, greater cognitive reserve in men, and the influence of the apolipoprotein E ε4 allele. Assessment of cognitive abilities contributes to the diagnosis of the condition and thus, it is crucial to identify the role of sex differences if potentially more accurate diagnoses and treatments are to emerge.


Lymphadenectomy for early-stage mucinous ovarian carcinoma.
There is evidence to suggest that the rate of lymph node metastases in patients with ovarian mucinous tumors is rare. The objective of this study was to investigate the prevalence of regional lymph node metastases among patients with apparent stage IA and IC mucinous ovarian carcinoma. A retrospective cohort study was performed and included patients from the National Cancer Database with apparent stage IA and IC mucinous ovarian tumors who underwent surgery between January 1, 2004 and December 31, 2015. Data collected included demographics, surgical procedures, and pathologic characteristics. The primary outcome was the effect of tumor stage, grade, and size on the risk of lymph node metastases. Categorical and continuous variables were compared using the χ2 and Mann-Whitney U tests, respectively. A total of 4379 patients were identified: 3088 and 1213 with stage IA and IC disease, respectively, with an additional 78 patients who were stage I Not Otherwise Specified (NOS). Lymphadenectomy was performed in 70.6% of patients with stage IA and 70.3% of patients with stage IC cancers. Stratifying by grade, 68.4%, 71.3%, and 72.8% of patients with grades 1, 2, and 3 tumors underwent a lymphadenectomy, respectively. Furthermore, lymphadenectomy was performed in 64.9% of patients with tumors <10 cm and 72.4% with tumors >10 cm. Lymph node metastases were identified in 1.2% and 1.6% of patients with stage IA and IC disease, respectively (p=0.063). Additionally, metastases were present in 0.6% of patients with grade 1 tumors, 1.1% of patients with grade 2 tumors, and 5.3% of patients with grade 3 tumors (p<0.001). Lastly, 0.9% of patients with tumors <10 cm and 1.4% of patients with tumors >10 cm had lymph node metastases (p=0.19). Among patients with mucinous ovarian carcinoma, lymph node metastases are rare. However, metastases are significantly more common in patients with higher grade tumors. These factors may be considered when making decisions regarding the need for lymphadenectomy in early-stage mucinous ovarian tumors.


Early recovery properties of sevoflurane and desflurane in patients undergoing total hip replacement surgery.
The pharmacokinetic properties of sevoflurane and desflurane differ from those of other volatile anesthetics. For example, both agents allow more rapid emergence than traditional volatile anesthetics. However, few direct comparisons of the 2 agents have been made. The aim of this study was to compare the early recovery properties of desflurane and sevoflurane in patients with American Society of Anesthesiologists physical status I or II undergoing total hip replacement (THR) surgery. This open-label study was performed at the Department of Anesthesiology, Erciyes University School of Medicine, Kayseri, Turkey. Early recovery was assessed in the surgical suite by measuring the time to 50% decline of end-tidal volatile concentration of desflurane or sevoflurane; time to extubation, eye opening, orientation, and a modified Aldrete Scale (MAS) score >8 (ie, safe to discharge from the surgical suite); and time to discharge from the postanesthesia recovery room. Time to 50% decline of end-tidal volatile concentration of desflurane or sevoflurane, tracheal extubation, eye opening, orientation, and an MAS score >8 occurred significantly more rapidly in the desflurane group than in the sevoflurane group (P<0.001). However, the groups did not differ significantly in duration of anesthesia; time to discharge from the postanesthesia recovery room; or incidences of nausea, vomiting, dizziness, and drowsiness in the first 24 hours after anesthesia. In this study population, desflurane provided significantly more rapid early recovery than sevoflurane, but we did not find any beneficial effects of desflurane on intermediate recovery. The rapid emergence from anesthesia may facilitate more efficient surgical suite use and may be associated with more benefits after prolonged anesthesia. We suggest that both volatile agents may be acceptable anesthetics for use during THR surgery.


The Chitranjan Ranawat Award: Running Subcuticular Closure Enables the Most Robust Perfusion After TKA: A Randomized Clinical Trial.
Maintaining robust perfusion is an important physiologic parameter in wound healing. The effect of different closure techniques on wound perfusion after total knee arthroplasty (TKA) has not been established previously and may have implications for wound healing. We asked whether a running subcuticular, vertical mattress, or skin staple closure technique enables the most robust wound perfusion after TKA as measured by laser-assisted indocyanine green angiography (LA-ICGA) in patients without specific risk factors for wound healing complications. Forty-five patients undergoing primary TKA without comorbidities known to impact wound healing and perfusion were prospectively randomized to receive superficial skin closure with one of the following techniques: (1) running subcuticular (3-0 monofilament); (2) vertical mattress (2-0 nylon); or (3) skin staples. Twenty procedures were performed by RTT, 15 by RJS, and 10 by FHS. All surgeons used an anterior skin incision over the medial third of the patella in combination with a median parapatellar arthrotomy. Perfusion was assessed with a LA-ICGA device and software system immediately after closure to quantify fluorescence. Twenty-seven points were assessed immediately after closure in the operating room in each patient (nine along the incision and nine pairs medial and lateral to the incision). Mean incision perfusion was determined from the nine points along the incision with higher values indicating greater blood flow. Mean perfusion impairment was determined by calculating the difference between the nine pairs of surrounding skin and the nine points along the incision with smaller values indicating less perfusion impairment. These parameters were compared with analysis of variance (ANOVA) and subsequent pairwise comparisons with an unadjusted analysis as well as a multivariate analysis that adjusted for age, sex, and body mass index. Patients were followed for a mean of 7 months after surgery (range, 3-12 months) for possible incision-related complications. No patents were lost to followup. Running subcuticular closure demonstrated the best overall perfusion. Mean incision perfusion in fluorescent units with SD was as follows: running subcuticular, 64 (16); vertical mattress, 32 (18); and staples, 19 (7) (ANOVA p < 0.001). The running subcuticular closure demonstrated the least impairment of perfusion among the closures compared. Mean perfusion impairment was as follows: running subcuticular, 21 (12); vertical mattress, 37 (24); and staples, 69 (27) (ANOVA p < 0.001). All Tukey-adjusted pairwise comparisons from both metrics likewise favored the subcuticular closure (p < 0.001) both before and after adjusting for age, sex, and body mass index. One patient in the vertical mattress cohort experienced a surgical site infection; no other wound-related complications were observed in this study. The method of closure can influence skin and soft tissue perfusion after TKA. Running subcuticular closure enables the most physiologic robust blood flow, which may improve wound healing. However, the clinical importance of these findings remains uncertain, because patients in this study were selected because they lacked risk factors for wound healing complications. Studies with this modality in specific patient populations at higher risk for wound complications will be necessary to quantify the clinical advantage of using running subcuticular closure. Level I, therapeutic study.


Performance-based measures: the early results are in.
Pay for performance (P4P) initiatives are designed to foster and reward improvement in health care delivery. These programs promote "value-based health care" by rewarding quality care that is characterized by a reduced amount of disproportionate spending. To review the intent and design of P4P initiatives as well as the design and results of P4P programs in current practice. Three key principles are fundamental to building a value-based health care system: measurement, transparency, and accountability. There are several levers currently driving P4P, each influencing the movement in its own way. Among these are employers, federal agencies such as the Centers for Medicare & Medicaid Services and the Department of Health and Human Services, health plans, providers, accreditors, and Congress. One key player in the P4P movement, the National Committee for Quality Assurance (NCQA), is a private, independent nonprofit health care quality oversight organization that measures and reports on health care quality and unites diverse groups around a common goal: improving health care quality. NCQA, has demonstrated several successful provider-level measurement initiatives connected to P4P programs, notable among them Bridges to Excellence programs in several markets, physician recognition programs, the Integrated Healthcare Association's P4P initiative in California, the National Forum on Performance Benchmarking of Physician Offices and Organizations, and health plan accreditation. The initial data from developmental P4P programs across the nation have indicated that both financial and nonfinancial incentives motivate significant change in health care delivery, but the return on investment of these initiatives is not yet known.


Three-dimensional organization of Rift Valley fever virus revealed by cryoelectron tomography.
Rift Valley fever virus (RVFV) is a member of the Bunyaviridae virus family (genus Phlebovirus) and is considered to be one of the most important pathogens in Africa, causing viral zoonoses in livestock and humans. Here, we report the characterization of the three-dimensional structural organization of RVFV vaccine strain MP-12 by cryoelectron tomography. Vitrified-hydrated virions were found to be spherical, with an average diameter of 100 nm. The virus glycoproteins formed cylindrical hollow spikes that clustered into distinct capsomeres. In contrast to previous assertions that RVFV is pleomorphic, the structure of RVFV MP-12 was found to be highly ordered. The three-dimensional map was resolved to a resolution of 6.1 nm, and capsomeres were observed to be arranged on the virus surface in an icosahedral lattice with clear T=12 quasisymmetry. All icosahedral symmetry axes were visible in self-rotation functions calculated using the Fourier transform of the RVFV MP-12 tomogram. To the best of our knowledge, a triangulation number of 12 had previously been reported only for Uukuniemi virus, a bunyavirus also within the Phlebovirus genus. The results presented in this study demonstrate that RVFV MP-12 possesses T=12 icosahedral symmetry and suggest that other members of the Phlebovirus genus, as well as of the Bunyaviridae family, may adopt icosahedral symmetry. Knowledge of the virus architecture may provide a structural template to develop vaccines and diagnostics, since no effective anti-RVFV treatments are available for human use.