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Abstract Background Febrile neutropenia (FN) occurs following myelosuppressive chemotherapy and is associated with morbidity, mortality, costs, and chemotherapy reductions and delays. Granulocyte colony-stimulating factors (G-CSFs) stimulate neutrophil production and may reduce FN incidence when given prophylactically following chemotherapy. Methods A systematic review and meta-analysis assessed the effectiveness of G-CSFs (pegfilgrastim, filgrastim or lenograstim) in reducing FN incidence in adults undergoing chemotherapy for solid tumours or lymphoma. G-CSFs were compared with no primary G-CSF prophylaxis and with one another. Nine databases were searched in December 2009. Meta-analysis used a random effects model due to heterogeneity. Results Twenty studies compared primary G-CSF prophylaxis with no primary G-CSF prophylaxis: five studies of pegfilgrastim; ten of filgrastim; and five of lenograstim. All three G-CSFs significantly reduced FN incidence, with relative risks of 0.30 (95% CI: 0.14 to 0.65) for pegfilgrastim, 0.57 (95% CI: 0.48 to 0.69) for filgrastim, and 0.62 (95% CI: 0.44 to 0.88) for lenograstim. Overall, the relative risk of FN for any primary G-CSF prophylaxis versus no primary G-CSF prophylaxis was 0.51 (95% CI: 0.41 to 0.62). In terms of comparisons between different G-CSFs, five studies compared pegfilgrastim with filgrastim. FN incidence was significantly lower for pegfilgrastim than filgrastim, with a relative risk of 0.66 (95% CI: 0.44 to 0.98). Conclusions Primary prophylaxis with G-CSFs significantly reduces FN incidence in adults undergoing chemotherapy for solid tumours or lymphoma. Pegfilgrastim reduces FN incidence to a significantly greater extent than filgrastim.

Abstract The anaphase promoting complex is a highly conserved E3 ligase complex that mediates the destruction of key regulatory proteins during both mitotic and meiotic divisions. In order to maintain ploidy, this destruction must occur after the regulatory proteins have executed their function. Thus, the regulation of APC/C activity itself is critical for maintaining ploidy during all types of cell divisions. During mitotic cell division, two conserved activator proteins called Cdc20 and Cdh1 are required for both APC/C activation and substrate selection. However, significantly less is known about how these proteins regulate APC/C activity during the specialized meiotic nuclear divisions. In addition, both budding yeast and flies utilize a third meiosis-specific activator. In Saccharomyces cerevisiae, this meiosis-specific activator is called Ama1. This review summarizes our knowledge of how Cdc20 and Ama1 coordinate APC/C activity to regulate the meiotic nuclear divisions in yeast.

Abstract Background A variety of different approaches to the synthesis of qualitative data are advocated in the literature. The aim of this paper is to describe the application of a pragmatic method of qualitative evidence synthesis and the lessons learned from adopting this "best fit" framework synthesis approach. Methods An evaluation of framework synthesis as an approach to the qualitative systematic review of evidence exploring the views of adults to the taking of potential agents within the context of the primary prevention of colorectal cancer. Results Twenty papers from North America, Australia, the UK and Europe met the criteria for inclusion. Fourteen themes were identified a priori from a related, existing conceptual model identified in the literature, which were then used to code the extracted data. Further analysis resulted in the generation of a more sophisticated model with additional themes. The synthesis required a combination of secondary framework and thematic analysis approaches and was conducted within a health technology assessment timeframe. Conclusion The novel and pragmatic "best fit" approach to framework synthesis developed and described here was found to be fit for purpose. Future research should seek to test further this approach to qualitative data synthesis.

Background: Outpatient prescriptions for postoperative pain play an important role in the opioid epidemic. Prescribing guidelines are an effective target for intervention but require procedure-specific data to be successful. The aim of this study was to examine opioid prescribing patterns and pain control after primary cleft lip and palate repair at a large academic center., Methods: Children undergoing cleft lip and palate repair from April of 2018 to July of 2019 were included in a prospective cohort study. Data on discharge prescriptions, refills, and emergency room visits were obtained from the medical record. Caregivers were surveyed 7 to 21 days after surgery regarding pain control, opioid use, education exposure, storage, and disposal. Chi-square tests and one-way analysis of variance were used to examine predictors of pain control, opioid consumption, safe storage, and disposal., Results: After screening, 59 children were included in the study. Patients were 55.8 percent male with a median age of 12 months (interquartile range, 5 to 15). Ninety percent of patients received an opioid prescription at discharge with a mean quantity of 10 doses (interquartile range, 5 to 15). Ninety-seven percent of caregivers used adjunct medication. Opioids were given for a median of 3 days (interquartile range, 2 to 6.5). Seventy-six percent of caregivers gave less opioid than prescribed. There was no association between pain control and opioid quantity ( p = 0.68). Twenty-four percent of caregivers used locked storage. Thirty-four percent of respondents with leftover medication reported disposal., Conclusions: Opioids are often overprescribed after cleft lip and palate repair. Providers should consider limiting prescriptions to a 3-day supply to help reduce the quantity of opioids available in the community., (Copyright © 2022 by the American Society of Plastic Surgeons.)

Rhodoquinone (RQ) is a close analogue of ubiquinone (UQ) that confers diverse bacterial and eukaryotic taxa the ability to utilize fumarate as an electron acceptor in hypoxic conditions. The RquA protein, identified in a Rhodospirillum rubrum RQ-deficient mutant, has been shown to be required for RQ biosynthesis in bacteria. In this report, we demonstrate that RquA, homologous to SAM-dependent methyltransferases, is necessary and sufficient to catalyze RQ biosynthesis from UQ in vitro. Remarkably, we show that RquA uses SAM as the amino group donor in a substitution reaction that converts UQ to RQ. In contrast to known aminotransferases, RquA does not use pyridoxal 5'-phosphate (PLP) as a coenzyme, but requires the presence of Mn 2+ as a cofactor. As these findings reveal, RquA provides an example of a non-canonical SAM-dependent enzyme that does not catalyze methyl transfer, instead it uses SAM in an atypical amino transfer mechanism., (© 2022. The Author(s).)

The protonation state of lanthanide-ligand complexes, or lanthanide-containing porous materials, with many Brønsted acid sites can change due to proton loss/gain reactions with water or other heteroatom-containing compounds. Consequently, variations in the protonation state of lanthanide-containing species affect their molecular structure and desired properties. Lanthanide(III) aqua ions undergo hydrolysis and form hydroxides; they are the best characterized lanthanide-containing species with multiple Brønsted acid sites. We employed constrained ab initio molecular dynamics simulations and electronic structure calculations to determine all acidity constants of the lanthanide(III) aqua ions solely from computation. The first, second, and third acidity constants of lanthanide(III) aqua ions were predicted, on average, within 1.2, 2.5, and 4.7 absolute p K a units from experiment, respectively. A table includes our predicted p K a values alongside most experimentally measured p K a values known to date. The approach presented is particularly suitable to determine the Brønsted acidity of lanthanide-containing systems with multiple acidic sites, including those whose measured acidity constants cannot be linked to specific acid sites.

Background: Novice nurses, occupational and physical therapist's injury rates are alarming., Objective: To test for differences in peak elbow flexion forces (PEFF) by profession using different forearm positions., Methods: Entry-level RN, OT, and PT students performed 3-repetitions of standing PEFF in forearm supination, pronation, and neutral. A one-way repeated measures ANOVA determined the forearm position with the greatest PEFF. A one-way ANOVA assessed differences in PEFF between professions. The alpha level was set at p≤0.05 for all analyses., Results: Thirty 30 RN, 25 OT, and 30 PT students (x = 23.27 + /-3.29 yrs.) were studied. A one-way repeated measures ANOVA revealed a significant difference in PEFF between positions (F(2,168) = 144.3, p < 0.0001). A significant (p < 0.0001) pairwise comparison revealed neutral produced the greatest (28.15 + /-12.64 kg) and pronation the least PEFF (17.27 + /-7.40). PEFF was significantly different between position by profession (supination: F(2,82) = 10.14, p < 0.0001; pronation: F(2,82) = 10.33, p < 0.0001; neutral: F(2,82) = 13.39, p < 0.0001). PTs were significantly stronger than OTs and RN students in all forearm positions (p < 0.01)., Conclusions: Neutral PEFF was greatest and PT students demonstrated greater PEFF than OT and RN students.

Objective: To examine whether a service guideline reducing postoperative opioid prescription quantities and caregiver-reported education to use nonopioid analgesics first are associated with caregiver-reported pain control after pediatric tonsillectomy., Study Design: Prospective cohort study (July 2018-April 2019)., Setting: Pediatric otolaryngology service at a tertiary academic children's hospital., Subjects and Methods: Caregivers of patients aged 1 to 11 years undergoing tonsillectomy (N = 764) were surveyed 7 to 21 days after surgery regarding pain control, education to use nonopioid analgesics first, and opioid use. Respondents who were not prescribed opioids or had missing data were excluded. Logistic regression modeled caregiver-reported pain control as a function of service guideline implementation (December 2018) recommending 20 rather than 30 doses for postoperative opioid prescriptions and caregiver-reported analgesic education, adjusting for patient demographics., Results: Among 430 respondents (56% response), 387 patients were included. The sample was 43% female with a mean age of 5.0 years (SD, 2.5). Pain control was reported as good (226 respondents, 58%) or adequate/poor (161 respondents, 42%). Mean opioid prescription quantity was 27 doses (SD, 7.9) before and 21 doses (SD, 6.1) after guideline implementation ( P < .001). Education to use nonopioids first was reported by 308 respondents (80%). In regression, prescribing guideline implementation was not associated with pain control (adjusted odds ratio, 1.3; 95% CI, 0.9-2.0; P = .22), but caregiver-reported education to use nonopioids first was associated with a higher odds of good pain control (adjusted odds ratio, 1.9; 95% CI, 1.1-3.2; P = .02)., Conclusion: Caregiver education to use nonopioid analgesics first may be a modifiable health care practice to improve pain control as postoperative opioid prescription quantities are reduced.

Importance: Practice guidelines recommend nonopioid medications in children after tonsillectomy, but to date, studies have not used recent national data to assess perioperative opioid prescribing patterns or the factors associated with these patterns in this population. Closing this knowledge gap may help in assessing whether such prescribing and prescription duration could be safely reduced., Objective: To assess national perioperative opioid prescribing patterns, clinical and demographic factors associated with these patterns, and association between these patterns and complications in children after tonsillectomy compared with children not using opioids., Design, Setting, and Participants: This cohort analysis used the 2016 to 2017 claims data from the database of a large national private insurer in the United States. Opioid-naive children aged 1 to 18 years with a claims code for tonsillectomy with or without adenoidectomy between April 1, 2016, and December 15, 2017, were identified (n = 22 567) and screened against the exclusion criteria. The final sample included 15 793 children., Main Outcomes and Measures: The percentage of children with 1 or more perioperative fills (prescription drug claims for opioids between 7 days before to 1 day after tonsillectomy) was calculated, along with the duration of perioperative prescriptions (days supplied). Linear regression was used to identify the demographic and clinical factors associated with the duration of perioperative opioid prescriptions. Logistic regression was used to assess the association between having 1 or more perioperative fills and their duration and the risk of return visits 2 to 14 days after tonsillectomy for pain or dehydration, secondary hemorrhage, and constipation compared with children not using opioids., Results: Among 15 793 children, the mean (SD) age was 7.8 (4.2) years, 12 807 (81.1%) were younger than 12 years, 2986 (18.9%) were between 12 and 18 years of age, and 8289 (52.6%) were female. In total, 9411 (59.6%) children had 1 or more perioperative fills, and the median (25th-75th percentile) duration was 8 (6-10) days; 6382 had no perioperative fills. The probability of having 1 or more perioperative fills and the duration of prescription varied across US census divisions. Having 1 or more perioperative fills was not associated with return visits for pain or dehydration (adjusted odds ratio [AOR], 1.13; 95% CI, 0.95-1.34) or secondary hemorrhage (AOR, 0.90; 95% CI, 0.73-1.10) compared with children not using opioids, but it was associated with increased risk of return visits for constipation (AOR, 2.02; 95% CI, 1.24-3.28). Duration was not associated with return visits for complications., Conclusions and Relevance: These findings suggest that reducing perioperative opioid prescribing and the duration of perioperative opioid prescriptions may be possible without increasing the risk of these complications.

Objective: This study aimed to evaluate magnetic resonance imaging (MRI) features and interobserver agreement of endometrial polyps., Methods: After institutional review board approval, our database was searched for women older than 18 years who underwent MRI pelvis and pelvic surgical intervention from 2012 to 2016. Seventy-two patients with polyps and 75 controls composed the study cohort. Two radiologists evaluated the MRIs retrospectively for polyps. Polyp characteristics and enhancement were assessed., Results: Sensitivity and specificity of readers 1 and 2 were 59.7% and 88.0%, and 44.4 and 96.0%, respectively. There was moderate agreement for presence of polyps (κ = 0.556, P ≤ 0001), T2 fibrous core, and intratumoral cysts, with slight agreement for T2 signal and enhancement. Polyp size moderately correlated with pathology (κ = 0.465 [P = 0.025] for reader 1, κ = 0.562 [P = 0.029] for reader 2). The most common enhancement was same as myometrium., Conclusion: Magnetic resonance imaging is moderately sensitive for detecting endometrial polyps, demonstrating features that are not sensitive but can be specific, with moderate interobserver agreement.

Objective: To quantify the performance of food products in a sustainable diet based on the balance of their contribution to nutrient intake and environmental impact, within the context of the Dutch diet. Design: While fixing the quantity of a specific food group at different levels, optimized diets that met nutrient requirements and stayed as close as possible to the current Dutch diet were calculated, in order to understand its potential environmental impact and its nutritional quality. Bread & breakfast cereals, dairy, and meat were compared between 0 and 250% of current intake. Their performance is expressed in the relationship between the quantity of these food products and (1) the environmental impact of diets and (2) the nutrient balance of the diets. Setting: The Netherlands. Subjects: Women aged 31-50. Results: The amount of bread & breakfast cereals in the optimized diets were inversely correlated with their environmental impact. The nutrient balance of the optimized diets was maintained despite varying cereal content, with the expected improvement over the current diet. Increasing amounts of dairy in the optimized diet were associated with an increase in environmental impact and meat with a steep increase. The nutrient balance of optimized diets with varying dairy and meat contents was also maintained at high levels, even at 0% content. Conclusions: Bread and breakfast cereals are sources of nutrients with a better environmental performance compared to dairy or meat within the context of the Dutch diet. It is possible to optimize diets for environmental impact whilst maintaining a high nutrient balance.

The UK currently has the most detailed, directly measured data for food wasted in the home. This includes information on the exact types of food wasted. These data allow calculation of the nutrients within that waste, as well as its environmental impact. The results progress the conversation beyond how much food is wasted or its energy content; it permits the implications for nutrition and sustainability to be assessed in detail. Data for UK household food waste were expressed as an average waste per capita for each type of food. Each food type was matched with an item (or group of items) from the UK Composition of Foods (7th Ed). The level of nutrients wasted was compared to UK Reference Nutrient Intakes (RNIs) for adult women (19-50 years, used as a proxy for general population requirements). The data were normalized into "nutrient days" wasted per capita per year, then into the number of complete diet days (for 21 nutrients plus energy). Results show that approximately 42 daily diets were discarded per capita per year. By individual nutrient, the highest losses were vitamin B 12 , vitamin C, and thiamin (160, 140, and 130 nutrient days/capita/year, respectively). For protein, dietary energy and carbohydrates, 88, 59, and 53 nutrient days/capita/year, respectively, were lost. Substantial losses were also found for under-consumed nutrients in the UK: calcium, which was mostly lost via bakery (27%) and dairy/eggs (27%). Food folate was mainly lost through fresh vegetables/salads (40%) and bakery (18%), as was dietary fiber (31 and 29%, respectively). Environmental impacts were distributed over the food groups, with wasted meat and fish the single largest contribution. For all environmental impacts studied, the largest contribution came from agricultural production. This paper shows that there are areas where interventions preventing food waste and promoting healthy eating could work together (e.g., encouraging consumption of vegetables or tackling overbuying, especially of unhealthy foods). Food manufacturers and retailers, alongside governments and NGOs, have a key role to minimize waste of environmentally impactful, nutrient-dense foods, for instance, by helping influence people's behaviors with appropriate formulation of products, packaging, portioning, use of promotions, or public education.

Aim: To determine the association between use of therapeutic hypothermia (TH) after resuscitation from out-of-hospital cardiac arrest (OHCA) and neurological outcome., Method: Retrospective observational cohort study in a tertiary university-associated Level III general ICU of 179 ICU patients in three cohorts ('pre' hypothermia: 58 patients, 'post' hypothermia 69 patients, 'recent' 52 patients) admitted between 1 January, 2009, and 15 April, 2011, after resuscitation from OHCA., Interventions: TH to 33C for 12 hours., Main Outcome Measures: Favourable neurological outcome (transferred home) at hospital discharge., Results: The frequency of bystander CPR increased (38/58, 56/69, 47/52, p=0.04), as did the use of TH (0/58, 25/69, 39/52, p<0.00001) and the frequency of favourable neurological outcome between the three cohorts (21/58, 28/69, 32/52, p=0.02). The cohorts were similar in age, gender, shockable rhythm and time to ROSC. In multivariate analysis, favourable neurological outcome was independently associated with younger age (in 5-year intervals, OR 0.78 [0.67-0.90], p=0.001), bystander CPR (OR 4.8 [1.5-15], p=0.007), shockable rhythm (OR 3.5 [1.1-11], p=0.04), time to ROSC (OR 0.90 [0.86-0.94], p<0.0005) and use of TH (OR 2.8 [1.2-6.2], p=0.01)., Conclusions: The use of TH in patients admitted to ICU after resuscitation following OHCA was independently associated with favourable neurological outcome.

Consumption of cocoa-enriched dark chocolate (DC) has been shown to alter glucose and insulin concentration during rest and exercise compared with cocoa-depleted control (CON). However, the impact of DC consumption on exercise metabolism and performance is uncertain. Therefore, we investigated carbohydrate metabolism via stable isotope tracer techniques during exercise after subjects ingested either DC or CON. Sixteen overnight-fasted male cyclists performed a single-blinded, randomized, crossover design trial, after consuming either DC or CON at 2 h prior to 2.5 h of steady-state (SS) exercise (∼45% peak oxygen uptake). This was followed by an ∼15-min time-trial (TT) and 60 min of recovery. [6,6-(2)H2]Glucose and [U-(13)C]glucose were infused during SS to assess glucose rate of appearance (Ra) and disappearance (Rd). After DC consumption, plasma (-)-glucose and insulin concentrations were significantly (p < 0.001) elevated throughout vs. CON. During SS, there was no difference in [6,6-(2)H2]glucose Ra between treatments, but towards the end of SS (last 60 min) there was a ∼16% decrease in Rd in DC vs. CON (p < 0.05). Accordingly, after DC there was an ∼18% significant decrease in plasma glucose oxidation (trial effect; p = 0.032), and an ∼15% increase in tracer-derived muscle glycogen utilization (p = 0.045) late during SS exercise. The higher blood glucose concentrations during exercise and recovery after DC consumption coincided with high concentrations of epicatechin and (or) theobromine. In summary, DC consumption altered muscle carbohydrate partitioning, between muscle glucose uptake and glycogen oxidation, but did not effect cycling TT performance.

Purpose: Acute antioxidant supplementation may modulate oxidative stress and some immune perturbations that typically occur following prolonged exercise. The aims of the present study were to examine the effects of acutely consuming dark chocolate (high polyphenol content) on plasma antioxidant capacity, markers of oxidative stress and immunoendocrine responses to prolonged exercise., Methods: Fourteen healthy men cycled for 2.5 h at ~60% maximal oxygen uptake 2 h after consuming 100 g dark chocolate (DC), an isomacronutrient control bar (CC) or neither (BL) in a randomised-counterbalanced design., Results: DC enhanced pre-exercise antioxidant status (P = 0.003) and reduced by trend (P = 0.088) 1 h post-exercise plasma free [F₂-isoprostane] compared with CC (also, [F₂-isoprostane] increased post-exercise in CC and BL but not DC trials). Plasma insulin concentration was significantly higher pre-exercise (P = 0.012) and 1 h post-exercise (P = 0.026) in the DC compared with the CC trial. There was a better maintenance of plasma glucose concentration on the DC trial (2-way ANOVA trial × time interaction P = 0.001), which decreased post-exercise in all trials but was significantly higher 1 h post-exercise (P = 0.039) in the DC trial. There were no between trial differences in the temporal responses (trial × time interactions all P > 0.05) of hypothalamic-pituitary-adrenal axis stress hormones, plasma interleukin-6, the magnitude of leukocytosis and neutrophilia and changes in neutrophil function., Conclusion: Acute DC consumption may affect insulin, glucose, antioxidant status and oxidative stress responses, but has minimal effects on immunoendocrine responses, to prolonged exercise.

We conducted a dietary feeding study with juvenile chinook salmon (Oncorhynchus tshawytscha) to assess the potential for tributyltin (TBT) to elicit the obesogen response that has been described for mammals. The results show increases in whole-body lipid content, which is consistent with the obesogen response; however, we also observed associated parameters that were dissimilar. We found increases in body mass and alterations to several physiological parameters at doses between 0.4 and 3.5 ng/g fish/day (1.4-12 pmol/g fish/day) and reduced body mass at the highest dose after 55 days of exposure. Lipid related plasma parameters (plasma triacylglycerols, cholesterol, and lipase) exhibited monotonic increases over all doses while other values (glucose and insulin-like growth factor (IGF)) exhibited increases only for the low-dose treatments. The increases noted for several parameters in fish were opposite to those reported for the obesogen metabolic syndrome, which is characterized by a reduction in serum glucose, free fatty acids, and triglycerides. This is the first report of growth stimulation resulting from low-dose exposure to this pesticide, which is an unusual response for any animal exposed to an organic or organometallic xenobiotic. Because a number of environmental contaminants act as metabolic disruptors at very low doses, these results are noteworthy for a variety of species. Intuitively, enhanced growth and lipid storage may appear beneficial; however, for salmonids there are numerous potentially negative consequences for populations., (Copyright © 2010 Elsevier Inc. All rights reserved.)

We examined postprandial changes in circulating growth hormone (GH), insulin, insulin-like growth factor (IGF)-I, and IGF-binding proteins (IGFBPs) in yearling coho salmon under different feeding regimes. Fish were initially fasted for 1 day, 1 wk, or 3 wk. Fasted fish were then fed, and blood was collected at 4-h intervals over 26 h. After the various periods of fasting, basal levels of insulin were relatively constant, whereas those of IGF-I, IGFBPs and GH changed in proportion to the duration of the fast. A single meal caused a rapid, large increase in the circulating insulin levels, but the degree of the increase was influenced by the fasting period. IGF-I showed a moderate increase 2 h after the meal but only in the regularly fed fish. Plasma levels of 41-kDa IGFBP were increased in all groups within 6 h after the single meal. The fasting period did not influence the response of 41-kDa IGFBP to the meal. IGFBP-1 and GH decreased after the meal to the same extent among groups regardless of the fasting period. The present study shows that insulin and IGF-I respond differently to long (weeks)- and short (hours)-term nutritional changes in salmon; insulin maintains its basal level but changes acutely in response to food intake, whereas IGF-I adjusts its basal levels to the long-term nutritional status and is less responsive to acute nutritional input. IGFBPs maintain their sensitivity to food intake, even after prolonged fasting, suggesting their critical role in the nutritional regulation of salmon growth.

The aim of this study was to explore the effects of preoperative and postoperative lateralized mesial temporal damage on three measures of spatial learning: navigation, object location and plan drawing, and to determine the relationship between volumetry of the hippocampus and memory performance. Fifteen patients with well-characterized unilateral hippocampal sclerosis, 15 patients who had undergone unilateral anterior temporal lobectomy (ATL), and a comparison group consisting of 15 patients with idiopathic generalized epilepsy and 25 neurologically healthy participants explored a novel virtual environment. Volumetric analyses of both hippocampi were conducted on unilateral hippocampal sclerosis and idiopathic generalized epilepsy patients' T(1)-weighted magnetic resonance imaging scans. Performance of temporal lobe epilepsy (TLE) patients (either unilateral hippocampal sclerosis or anterior temporal lobectomy) on the different spatial memory variables, namely navigation, object location and plan drawing, was significantly worse relative to the comparison groups (either idiopathic generalized epilepsy or controls). Patients with right TLE did not differ from patients with left TLE on any of the spatial memory measures. An index of absolute hippocampal asymmetry did not correlate with any of the spatial memory measures. Together, our lesion and volumetry findings suggest that the domain of spatial memory is systematically related to the integrity of both right and left mesial temporal lobe, and is unlikely to be a strongly lateralized function. From the standpoint of cerebral organization (lateralization), the notion of material-specificity, which postulates that all components of verbal and spatial memory are lateralized in their entirety to the left and right hemispheres, respectively, requires modification. Instead it would appear that the notion of task-specificity is a more accurate description of patterns of lateralization of spatial memory.

Chocolate is often labeled with percent cocoa solids content. It is assumed that higher cocoa solids contents are indicative of higher polyphenol concentrations, which have potential health benefits. However, cocoa solids include polyphenol-free cocoa butter and polyphenol-rich nonfat cocoa solids (NFCS). In this study the strength of the relationship between NFCS content (estimated by theobromine as a proxy) and polyphenol content was tested in chocolate samples with labeled cocoa solids contents in the range of 20-100%, grouped as dark (n = 46), milk (n = 8), and those chocolates containing inclusions such as wafers or nuts (n = 15). The relationship was calculated with regard to both total polyphenol content and individual polyphenols. In dark chocolates, NFCS is linearly related to total polyphenols (r2 = 0.73). Total polyphenol content appears to be systematically slightly higher for milk chocolates than estimated by the dark chocolate model, whereas for chocolates containing other ingredients, the estimates fall close to or slightly below the model results. This shows that extra components such as milk, wafers, or nuts might influence the measurements of both theobromine and polyphenol contents. For each of the six main polyphenols (as well as their sum), the relationship with the estimated NFCS was much lower than for total polyphenols (r2 < 0.40), but these relationships were independent of the nature of the chocolate type, indicating that they might still have some predictive capabilities.

Chocolate and other cocoa-containing products are a rich source of polyphenols. This paper describes an ultra-performance liquid chromatography (UPLC) method that can separate and quantify in 3 min six of the major chocolate polyphenols: catechin; epicatechin; B2 (epicatechin-4beta-8-epicatechin); B5 (epicatechin-4beta-6-epicatechin); C1 (epicatechin-4beta-8-epicatechin-4beta-8-epicatechin); and tetramer D (epicatechin-4beta-8-epicatechin-4beta-8-epicatechin-4beta-8-epicatechin). A survey of 68 chocolate samples indicated that there was a strongly predictive relationship between epicatechin and the other individual polyphenols, especially procyanidin B2 (R 2 = 0.989), even though the chocolates came from varied sources and manufacturers. The relationship was less strong with catechin, and so further work to explore the reasons for this difference was performed. Chiral analysis on a subset of 23 chocolates showed that (-)-epicatechin had a predictive relationship with (+)-catechin in line with the other polyphenols, but not with (-)-catechin (the predominant form). This indicates that (-)-catechin is the most affected by manufacturing conditions, possibly formed through epimerization from (-)-epicatechin during processing. The results show that epicatechin concentrations can be used to predict the content of other polyphenols, especially B2 and C1, and total polyphenols content. Finally, the (-)-catechin content is not predictable from the epicatechin content, and it is concluded that this is the main form of polyphenol that varies according to manufacturing conditions and cocoa origin.

Aim: This study assessed if upright cycling is preferable to semi-recumbent cycling during pregnancy., Method: Healthy women with low risk singleton pregnancies were tested at 34-38 weeks gestation. They cycled for 12 min, either semi-recumbent (45 degrees, n = 27) or upright (n = 23), at 135-145 beats min(-1)., Results: When semi-recumbent, minute ventilation was greater (p<0.03) at rest and systolic blood pressure and pulse pressure were greater during exercise (p<0.05). Exercise maternal heart rate, oxygen consumption, oxygen consumption per kilogram, minute ventilation, cardiac output, stroke volume, mean and diastolic blood pressures and arterio-venous oxygen difference were posture-independent. All increased with exercise (p<0.01), except stroke volume when semi-recumbent (p>0.05). Small post-exercise fetal heart rate increases (by 8 beats min(-1), p<0.05) were similar in both postures (n = 11 in each sub-group), with no adverse changes. Fetal heart rate accelerations and uterine activity (n = 11 in each sub-group) were not influenced by posture or exercise., Conclusions: (1) Neither posture had a distinct advantage. (2) Both postures were safe for short duration cycling. (3) The same target maternal heart rates are suitable for both postures because they resulted in similar oxygen consumptions and fetal heart rates.

Catechin is a flavonoid present in fruits, wine and cocoa products. Most foods contain the (+)-enantiomer of catechin but chocolate mainly contains ( - )-catechin, in addition to its major flavanol, ( - )-epicatechin. Previous studies have shown poor bioavailability of catechin when consumed in chocolate. We compared the absorption of ( - ) and (+)-catechin after in situ perfusion of 10, 30 or 50 micromol/l of each catechin enantiomer in the jejunum and ileum in the rat. We also assayed 23 samples of chocolate for (+) and ( - )-catechin. Samples were analyzed using HPLC with a Cyclobond I-2000 RSP chiral column. At all concentrations studied, the intestinal absorption of ( - )-catechin was lower than the intestinal absorption of (+)-catechin (p < 0.01). Plasma concentrations of ( - )-catechin were significantly reduced compared to (+)-catechin (p < 0.05). The mean concentration of ( - )-catechin in chocolate was 218 +/- 126 mg/kg compared to 25 +/- 15 mg/kg (+)-catechin. Our findings provide an explanation for the poor bioavailability of catechin when consumed in chocolate or other cocoa containing products.

Among many species of salmonids, fast growing fish mature earlier than slow growing fish, and maturing males grow faster than non-maturing ones. To study the potential endocrine basis for this reciprocal relationship we examined the in vivo effects of the androgens, testosterone (T) and 11-ketotestosterone (11-KT), on plasma growth hormone (GH), insulin-like growth factor-I (IGF-I) and 41-kDa IGF binding protein (41-kDa IGFBP) (putative IGFBP-3) in coho salmon, Oncorhynchus kisutch. Immature male and female, two-year old fish (avg. wt. 31.7 +/- 0.63 g) were injected with coconut oil containing T or 11-KT at a dose of 0.1, 0.25, or 1 microg/g body weight. Blood samples were taken 1 and 2 weeks postinjection, and analyzed by immunoassay for T, 11-KT, GH, IGF-I, and 41-kDa IGFBP. Steroid treatments elevated the plasma T and 11-KT levels to physiological ranges typical of maturing fish. Plasma IGF-I and 41-kDa IGFBP levels increased in response to both T and 11-KT in a significant and dose-dependent manner after 1 and 2 weeks, but GH levels were not altered. These data suggest that during reproductive maturation, in addition to the previously demonstrated effects of the IGFs on steroidogenesis, the gonadal steroids may in turn play a significant role in regulating IGF-I and its binding proteins in fish. The interaction between the reproductive and growth axes may provide a regulatory mechanism for bringing about the dimorphic growth patterns observed between maturing and non-maturing salmonids and other species of fish.

Calcium pyrophosphate dihydrate deposition (CPDD) disease is a disorder that occasionally affects the temporomandibular joint (TMJ) and temporal bone, causing pain (66.6% of cases), swelling (50%), trismus (36.8%), and hearing loss (22.2%). Diagnosis of CPDD is challenging because clinical symptoms and imaging features are not characteristic and may mimic a chondrosarcoma. When the diagnosis of CPDD of the TMJ is under consideration, conventional radiographs of the wrist or the knee may contribute to the final diagnosis. Imaging features of CPDD are discussed with a review of the literature.

The effect of different feeding levels on plasma levels of insulin-like growth factor-I (IGF-I), 41 kDa insulin-like growth factor binding protein (41 kDa IGFBP), and growth hormone (GH) were assessed in post-smolt coho salmon. Fish were fed at either stable (1 and 2% body weight/day) or varying (1-0.5-1%, 2-0.5-2% body weight/day) feeding rates and plasma was sampled from 10 fish/treatment at 2-3 week intervals over five dates from June to September, resulting in a total of 200 samples. Fish fed at higher rates grew faster and had higher plasma IGF-I and 41 kDa IGFBP levels. Plasma GH levels were variable but generally showed an inverse relationship to feeding rate. Both plasma IGF-I and 41 kDa IGFBP increased seasonally, average IGF-I levels doubled from June to September, regardless of feeding rate. On any one date both IGF-I and 41 kDa IGFBP were highly related to growth rate with regression coefficients ranging from 0.36 to 0.68 (IGF-I) and from 0.33 to 0.70 (41 kDa IGFBP). No relationship was found between IGF-I:41 kDa IGFBP ratio and individual growth rate. Overall, both feeding rate and date were important in explaining variation in IGF-I and 41 kDa IGFBP levels.

Vitamin A supplements are reported to reduce febrile episodes of malaria and parasite counts, especially in children aged 12-36 months. Red palm oil (RPO) is a good source of vitamin A, is rich in alpha- and beta-carotene and is as effective as high-dose retinyl palmitate supplements in improving vitamin A status. In western Nigeria, where malaria is endemic, RPO is widely used and consumption can be measured using plasma alpha-carotene as a proxy biomarker since there are few other prominent sources of this carotene in the diet. The influence of RPO consumption on malaria was investigated in 207 children (aged 0-60 months) who presented with fever in August-October 1999 at several hospital clinics around Ile-Ife. Medical and anthropometric data, body temperature, parasitaemia and plasma C-reactive protein (CRP), retinol, carotenoids and tocopherols were measured in the children. Mothers were interviewed on usage of cooking oil and mosquito nets in the home, education and occupation. Most families used RPO and median plasma concentrations of both alpha-carotene (0.518 mumol/L) and beta-carotene (0.698 mumol/L) in the children were high. Using body temperature, parasite density and plasma CRP as markers of disease severity, multiple linear regression analysis was carried out on those for whom complete data were available (n = 138), separated into 3 age-groups of < 12 months (n = 37), 12-36 months (n = 68) and > 36 months (n = 33). In the absence of plasma retinol, plasma alpha-carotene explained 13.9% of the variance in parasite density (P = 0.013) but only in children aged > 36 months. The relationship with disease severity was negative, i.e., there was some evidence that RPO usage protected against malaria, and other dietary indices generally indicated that better nutritional status was associated with a lower severity of malaria.

Sub-yearling spring chinook salmon were fed either a LoFat or HiFat diet from February to November. Fish were sampled over 2 days in November, following 24- and 48-h fasts. Length vs. weight relationships between fish fed the two diets were similar; however, fish fed the HiFat diet had roughly twice the body lipid as fish fed the LoFat diet (9% vs. 4.5%, respectively). Plasma IGF-I vs. length relations between fish fed the two diets were similar; overall, there was a strong relation between plasma IGF-I and length (r(2)=0.53). Similarly, plasma log (insulin) vs. length relations did not vary between the two diets; however, the relationship of log (insulin) vs. length was weak (r(2)=0.2). There was little or no relationship between plasma IGF-I or log (insulin) and body adiposity. Finally, there was a weak relationship between plasma IGF-I and log (insulin) (r(2)=0.23).

Objectives: To measure and compare postoperative erythema after laser cutaneous resurfacing using 2 carbon dioxide laser systems and varying postoperative treatment methods., Design: Carbon dioxide laser systems are used as cutaneous resurfacing tools. The continuous-wave lasers have been associated with postoperative erythema, but the short-pulsed lasers reportedly result in less postoperative erythema because of shorter pulse durations. Although subjective evaluations of results have been published, a side-by-side comparison with digital photography has not been performed. Furthermore, postoperative treatment varies among physicians, and objective data about this treatment are scarce., Subjects: To compare postoperative erythema, we created 240 resurfacing wounds on 8 piglets with continuous-wave and short-pulsed lasers, using the manufacturers' suggested settings. By using photography and computed color analysis, we measured the resultant erythema after 1, 3, and 5 laser passes at days 0, 1, 3, 5, 7, and 14. Tissue samples were obtained for histological analysis on days 0, 3, 7, and 14., Intervention: We compared the resolution of erythema after postoperative treatment with petroleum jelly (Vaseline), a wound dressing (Vigilon), partially hydrogenated vegetable oil (Crisco), or a combination drug, bacitracin zinc-neomycin sulfate-polymyxin B sulfate on the wounds., Results: The short-pulsed carbon dioxide laser resulted in an average of 22% less erythema compared with the continuous-wave laser (P<.001). No statistically significant difference in erythema was found among the postoperative treatment methods (P>.10)., Conclusions: Compared with the continuous-wave laser, the short-pulsed carbon dioxide laser results in less postoperative erythema. However, the type of postoperative treatment has little, if any, beneficial effect for reducing erythema.

Background: Standard mitral valve replacement (MVR) in patients with chronic mitral regurgitation results in consistent reductions in resting postoperative ejection fraction. This has been attributed to removal of the low-impedance ejection pathway into the left atrium or to disruption of the chordal apparatus. Mitral valve repair (MVP) does not reduce ejection fraction at rest. However, whether MVP confers any advantages with regard to dynamic left ventricular performance has not been investigated. The aim of this study was to directly compare standard MVR with MVP and to determine their respective influences on ventricular ejection performance during bicycle exercise., Methods and Results: Ten consecutive patients with pure chronic mitral regurgitation who underwent MVP and 10 patients matched for age, sex, and preoperative ejection fraction who underwent standard MVR for pure chronic mitral regurgitation performed symptom-limited, graded upright bicycle exercise with simultaneous Doppler and quantitative two-dimensional echocardiography. Patients with MVP had significantly greater rest (55 +/- 12%) and exercise (63 +/- 11%) ejection fractions than matched patients with MVR (40 +/- 13% [P < .0001] and 42 +/- 17% [P < .005], respectively). End-systolic circumferential wall stress was significantly lower at rest (190 +/- 36 versus 244 +/- 46; P < .03) and at peak exercise (231 +/- 46 versus 300 +/- 52; P < .02) in patients with MVP. At peak exercise, left ventricular shape was significantly more spherical in patients with MVR than those with MVP (1.84 +/- 0.31 versus 2.45 +/- 0.59; P < .02)., Conclusions: MVR with chordal transection resulted in significant reductions in rest and exercise ejection fraction. This was caused in part by a significant increase in end-systolic circumferential wall stress. MVP resulted in improved rest and exercise ejection indexes, primarily due to a marked reduction in end-systolic stress and maintenance of a more ellipsoidal chamber geometry.

In order to test whether trained (n = 10) and sedentary (n = 29) pregnant women have different responses to weight-bearing exercise in the second trimester (range 23 to 28 weeks of gestation), subjects walked continuously on a treadmill for 26 minutes: at low intensity for 10 minutes, then an intermediate stage, followed by moderate intensity for 10 minutes. In the trained group, the mean heart rate was lower (p < 0.02) with both low [104.0 +/- 4.5 (SD) versus 117.4 +/- 2.3 bpm] and moderate intensity exercise (128.4 +/- 5.7 versus 145.2 +/- 2.9 bpm) and the associated mean stroke volume was higher (105 +/- 16 versus 84 +/- 17 ml; 103 +/- 15 versus 86 +/- 18 ml, respectively) (p < 0.02). The mean cardiac output, blood pressure and oxygen consumption were the same in the two groups (p > 0.02) at the same absolute workloads. The potential implications of these findings for exercise prescriptions for pregnant women, research evaluation and exercise testing are discussed.

When using Borg's 6-20 scale during pregnancy, ratings of perceived exertion (RPE) did not significantly correlate with exercise heart rates (HR) (P greater than 0.05). The HR predicted from RPE significantly (P less than 0.05) underestimated the exercise HR in the second trimester during walking (Group 1: mean difference 16 beats min-1, n = 11), aerobics classes (Group 4: mean 15 beats min-1, n = 48) and circuit training (Group 3: mean 18 beats min-1, n = 24); and in the third trimester during cycling (Group 2: mean 16 beats min-1, n = 12) and aerobics classes (Group 5: mean 11 beats min-1, n = 29). Maximal individual HR under-estimations were large for each physical activity during pregnancy, with values up to 54 beats min-1. Consequently, exercise intensity should not be monitored solely with RPE during pregnancy.

Moderate-duration exercise increases serum catecholamine and serum calcium levels and might as a result be also expected to increase the levels of circulating serum immunoreactive human calcitonin (HCT). To explore this possibility, HCT was studied during and after moderate duration symptom-limited dynamic exercise in 13 healthy males, mean age 28 +/- 6.9 (SD) years. The mean duration of exercise using the Bruce treadmill protocol was 14.1 +/- 2.2 (SD) minutes. The mean heart rate (HR) peaked at 185 +/- 6 (SD) bpm which was 96.1% of the predicted maximal HR for age. Values for HCT, uncorrected for changes in plasma volume, showed a minimal decrease in the recovery phase, whilst HCT corrected for changes in plasma volume did not alter during exercise or recovery. The serum parathyroid hormone (PTH) also did not change. At peak exercise, uncorrected but not corrected values for plasma noradrenaline, adrenaline and dopamine had increased significantly. Corrected plasma total calcium increased during recovery. In summary, dynamic weight-bearing moderate-duration exercise did not elevate HCT in healthy males.

Twenty-two patients with Zollinger-Ellison syndrome were managed by a combined medical and surgical approach. Patients were treated initially with cimetidine or ranitidine. A laparotomy was performed to remove easily resectable tumors and to carry out a proximal gastric vagotomy. Tumors were found in 9 patients (41%) and all visible tumors were removed from 6 of the 9 patients. Fasting serum gastrin concentrations and serum gastrin responses to intravenous secretin were normal 6 wk after surgery in each of the patients from whom all visible tumors were resected and are normal in 4 patients, 6 wk to 5 yr after surgery. Acid secretion was reduced after vagotomy in each patient, even when tumors were not found or completely resected. Thus, vagotomy decreased the acid secretory response to endogenous hypergastrinemia. In addition, vagotomy augmented the inhibitory effect of H2-receptor antagonists on acid secretion. Follow-up has ranged from 6 wk to 6 yr (median, 2 yr). Dosages of cimetidine or ranitidine have been reduced, compared with preoperative amounts, in all but 1 patient. Two patients are taking no antisecretory drugs. Only 3 patients have had occasional symptoms of ulcer disease. Complications such as bleeding, perforation, or obstruction have not occurred in any patient. Endoscopy was performed in all patients to estimate the point prevalence of active ulcers and an ulcer was found in 1 patient. Based on these results, it is our opinion that this combined medical and surgical approach is an effective treatment for patients with Zollinger-Ellison syndrome.

These experiments were performed to determine the importance of cephalic-vagal stimulation in the acid secretory response to eating in normal human subjects. Cephalic stimulation was induced by a modified sham feeding (MSF) technique, during which subjects chewed and expectorated appetizing food. The response to MSF was compared with that to gastric distention with 600 ml NaCl, glucose, or food. In addition, we measured the extent to which cephalic stimulation augments acid secretion that has been stimulated simultaneously by these other mechanisms. Our conclusions are as follows: (a) cephalic stimulation accounts for approximately one-third of the acid secreted when all mechanisms act simultaneously (food-distention plus MSF); (b) within the limits imposed by the maximal secretory capacity, the response to MSF is approximately the same, regardless of whether acid secretion is otherwise unstimulated or is stimulated simultaneously by gastric distention with NaCl, glucose, or food; and (c) gastric distention prolongs the response to cephalic stimulation.

We studied effects of selective proximal vagotomy on food-stimulated acid secretion and gastrin release in 7 duodenal ulcer patients. Food-stimulated acid secretion was evaluated by sham feeding patients and by infusing food directly into their stomachs. Vagotomy reduced sham feeding-stimulated acid secretion from 28.2 +/- 4.6 to 1.2 +/- 0.7 meq/hr (95% reduction) whereas infused food-stimulated secretion was decreased from 36.1 +/- 4.6 to 17.9 +/- 5.5 meq/hr (50% reduction). In contrast to the reductions in acid secretion, the gastrin response to infused food doubled after surgery. Although selective proximal vagotomy reduced the rate of acid secretion in response to infused food and also reduced by 64% the peak secretory capacity (peak acid output to pentagastrin), fractional secretion (i.e., the secretion rate in response to infused food expressed as a percentage of the peak secretory capacity) increased significantly after vagotomy from 63 +/- 7% to 91 +/- 11%. This increased fractional secretion in response to infused food was probably a result of exaggerated gastrin release after vagotomy.

The charts of all patients over 30 for whom an adequate smoking history was available and an arteriogram or DIVA was done, specifically looking for renal artery stenosis, were reviewed to evaluate the role of cigarette smoking in contributing to the development of atherosclerotic renovascular hypertension. A patient was considered to be a "case" if the angiographic study demonstrated a typical stenotic lesion and a procedure (surgery or angioplasty) cured or definitely improved the patient's hypertension. If the study was negative, the patient was considered to be a "control." Twenty-one cases and 27 controls were found. The cases were older (57.5 vs. 49.25 years) and all were white (100% vs. 89%). Both groups had severe hypertension, but the cases had disproportionate systolic elevations (premedication BP 226 +/- 32/126 +/- 24 mmHg vs. 193 +/- 30/121 +/- 24 mmHg) and did not respond as well to drug treatment (180 +/- 30/99 +/- 6 vs. 139/85 +/- 10 mmHg) as the controls. There were significantly more smokers (19/21 vs. 16/27, p less than 0.04; odds ratio 6.53) among the cases, and 17 of the 19 were heavy smokers (greater than 25 pack-years). We conclude that cigarette smoking may contribute to the development of atherosclerotic renovascular hypertension.

Fourteen women performed treadmill exercise for continuous 10-minute periods at levels of 2, 3 and 4 mets in the second and third trimester of pregnancy and again postpartum. The percentage increase in heart rate in response to exercise was similar during pregnancy and postpartum while systolic blood pressure was increased only during pregnancy. Maternal plasma noradrenaline levels at peak exercise increased 64% (p less than 0.005), 42% (p less than 0.005) and 29% (NS) in the 3 studies respectively compared to resting levels at these times. Ten women experienced increased uterine activity during the exercise or recovery periods. Fetal heart rate was increased (p less than 0.05) by exercise but this was independent of uterine contractions and plasma noradrenaline levels.