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Preening cups are a semi-open water source for Pekin duck enrichment. To evaluate the ducks' affective state, we combined measuring welfare by walking a transect in the barn with mass spectrometry and qRT-PCR to measure brain neurotransmitter levels and gene expression for serotonin (5-HT) and dopamine (DA) synthesis and metabolism. 5-HT and DA have been established as indicators of mental state and emotions. We visited 4 standard commercial barns that housed approximately 6000-9000 ducks (one preening cup per 1500 ducks) and collected samples on d21 prior to preening cup placement, d28 one week after preening cup placement, and d35 one day prior to processing. Litter samples (n = 3/barn/day) were collected and transect walks were conducted to evaluate the welfare of the birds. Brain samples (n = 8/day/barn) were collected from two locations: ducks actively using the preening cups (PC) and ducks across the barn not actively using the preening cups (CON). The brains were hemisected and dissected in three brain areas: caudal mesencephalon (CM), rostral mesencephalon (RM), and diencephalon (DI). Litter samples showed no significant differences between collection dates. The transect showed significant differences in feather quality, feather cleanliness, and eye due to age, but not preening cups. The right hemisphere showed no differences in 5-HT turnover. For DA turnover, there are differences in CM (p < 0.05) and DI (p < 0.001) over time, but no differences between PC and CON. The left hemisphere measured TPH1, TPH2, and TH. CM and DI brain areas are not significantly different. Within the RM, there is a significant increase in TPH1 expression for ducks on d35 when compared to ducks on d28 and d21. These results suggest that 5-HT and DA do not differ due to duck location. However, DA activity increases as these ducks age. DA is an important neurotransmitter and activity increases as an animal grows allowing for behavioral development. Our data shows that commercial preening cups do not negatively impact ducks' welfare or affective state., Competing Interests: Disclosures The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Previous studies from our lab suggest that transportation of early adulthood ducks can have long lasting physiological effects. To better understand how transportation affects the ducks' physiology, we evaluated several central and peripheral parameters. Thirty-six, 23-week-old ducks were collected at a commercial breeder facility and randomly assigned to one of three treatment groups (n = 6/sex/treatment): 1) caught and euthanized (control), 2) caught and put in a crated in the pen for 90 min (crate), or 3) caught, crated, and transported in a truck for 90 min (transport) to simulate actual transportation. Blood was collected for serum corticosterone and blood smear analyses. Brains were hemisected and each half was dissected into three brain areas: caudal mesencephalon (CM), rostral mesencephalon (RM), and diencephalon (DI). Mass spectrometry was run on the right half of the brain, and gene expression of TPH1, TPH2, TH, CRH, and NPY were measured on the left half of brain using qRT-PCR. Serum corticosterone levels were increased (p = 0.01) in crated hens and in transported hens and drakes (p = 0.0084) when compared to control. HLR was increased (p = 0.035) in crated hens and transported hens and drakes compared to control. No differences in serotonin turnover were observed in drakes but increased in hens within the CM and RM from control to crate (p = 0.01) and crate to transport (p = 0.016). There were no differences in DA turnover or in gene expression for all brain areas for drakes and CM and RM for hens. Within the DI, hens showed a decrease (p = 0.03) in TPH1 for transport compared to crate. Overall, transportation elicits an acutely stressful event that increases corticosterone and HLR in a sex dependent manner where hens appear to be more reactive to the stressor than drakes. Our data supports that when assessing a stress response, care must be given to the sex of the bird and to the relative timepoint of sampling compared to the perceived onset of the stressor., Competing Interests: Conflict of interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Preening cups are a form of environmental enrichment that provides Pekin ducks a semi-open water source to express their natural behaviors. We recently observed that preening cups may increase feather pecking behaviors in ducks. Thus, we set out to determine if this form of enrichment can impact the affective state of Pekin ducks. To accomplish this goal, we evaluated the effect of preening cups on serotonin (5-HT) and dopamine (DA) turnover via mass spectrometry and their respective synthetic enzyme gene expression via qRT-PCR. Our study investigated the link between aggressive pecking with levels and activity of brain 5-HT and DA. Brain 5-HT and DA levels and activity have been established for decades to be associated with affective states. Grow-out Pekin ducks (n = 260) were housed at Purdue and raised per industry standards. On day 18, brains were collected from ducks in pens before preening cups were placed (PRE, n = 6) and, again on day 43, in pens with (PC, n = 6) and without (CON, n = 6) preening cups. Brains were dissected into right and left halves, then further microdissected into 4 brain areas: caudal mesencephalon (CM), rostral mesencephalon (RM), diencephalon (DI), and forebrain (FB). The right hemisphere was used for mass spectrometry to determine the neurotransmitter concentration (ng/mg of tissue) and those concentrations were applied to neurotransmitter turnover equations. There were no differences across treatments for 5-HT turnover in any brain area. There were differences in DA turnover across age (P = 0.0067) in the CM and across treatments (P = 0.003) in the RM. The left hemisphere of the brain was used to perform qRT-PCR on the genes of 5-HT and DA production enzymes. Within the CM, day 43 duck brains had increased (P = 0.022) tryptophan hydroxylase and tyrosine hydroxylase relative mRNA levels. All other brain areas showed no differences. Our data suggest that ducks housed with preening cups and that showed increased feather pecking are associated with increased brain DA activity. The increased DA in the brain may lead to a predisposition for increased aggression in the form of feather pecking., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Recent studies have demonstrated considerable interindividual variability in postprandial glucose response (PPGR) to the same foods, suggesting the need for more precise methods for predicting and controlling PPGR. In the Personal Nutrition Project, the investigators tested a precision nutrition algorithm for predicting an individual's PPGR., Objective: This study aimed to compare changes in glycemic variability (GV) and HbA1c in 2 calorie-restricted weight loss diets in adults with prediabetes or moderately controlled type 2 diabetes (T2D), which were tertiary outcomes of the Personal Diet Study., Methods: The Personal Diet Study was a randomized clinical trial to compare a 1-size-fits-all low-fat diet (hereafter, standardized) with a personalized diet (hereafter, personalized). Both groups received behavioral weight loss counseling and were instructed to self-monitor diets using a smartphone application. The personalized arm received personalized feedback through the application to reduce their PPGR. Continuous glucose monitoring (CGM) data were collected at baseline, 3 mo and 6 mo. Changes in mean amplitude of glycemic excursions (MAGEs) and HbA1c at 6 mo were assessed. We performed an intention-to-treat analysis using linear mixed regressions., Results: We included 156 participants [66.5% women, 55.7% White, 24.1% Black, mean age 59.1 y (standard deviation (SD) = 10.7 y)] in these analyses (standardized = 75, personalized = 81). MAGE decreased by 0.83 mg/dL per month for standardized (95% CI: 0.21, 1.46 mg/dL; P = 0.009) and 0.79 mg/dL per month for personalized (95% CI: 0.19, 1.39 mg/dL; P = 0.010) diet, with no between-group differences (P = 0.92). Trends were similar for HbA1c values., Conclusions: Personalized diet did not result in an increased reduction in GV or HbA1c in patients with prediabetes and moderately controlled T2D, compared with a standardized diet. Additional subgroup analyses may help to identify patients who are more likely to benefit from this personalized intervention. This trial was registered at clinicaltrials.gov as NCT03336411., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Background: Pleural biopsy findings offer greater diagnostic sensitivity in malignant pleural effusions compared with pleural fluid. The adequacy of pleural biopsy techniques in achieving molecular marker status has not been studied, and such information (termed "actionable" histology) is critical in providing a rational, efficient, and evidence-based approach to diagnostic investigation., Research Question: What is the adequacy of various pleural biopsy techniques at providing adequate molecular diagnostic information to guide treatment in malignant pleural effusions?, Study Design and Methods: This study analyzed anonymized data on 183 patients from four sites across three countries in whom pleural biopsy results had confirmed a malignant diagnosis and molecular profiling was relevant for the diagnosed cancer type. The primary outcome measure was adequacy of pleural biopsy for achieving molecular marker status. Secondary outcomes included clinical factors predictive of achieving a molecular diagnosis., Results: The median age of patients was 71 years (interquartile range, 63-78 years), with 92 of 183 (50%) male. Of the 183 procedures, 105 (57%) were local anesthetic thoracoscopies (LAT), 12 (7%) were CT scan guided, and 66 (36%) were ultrasound guided. Successful molecular marker analysis was associated with mode of biopsy, with LAT having the highest yield and ultrasound-guided biopsy the lowest (LAT vs CT scan guided vs ultrasound guided: LAT yield, 95%; CT scan guided, 86%; and ultrasound guided, 77% [P = .004]). Biopsy technique and size of biopsy sample were independently associated with successful molecular marker analysis. LAT had an adjusted OR for successful diagnosis of 30.16 (95% CI, 3.15-288.56; P = .003) and biopsy sample size an OR of 1.18 (95% CI, 1.02-1.37) per millimeter increase in tissue sample size (P < .03)., Interpretation: Although previous studies have shown comparable overall diagnostic yields, in the modern era of targeted therapies, this study found that LAT offers far superior results to image-guided techniques at achieving molecular profiling and remains the optimal diagnostic tool., (Copyright © 2022 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Objectives: To describe challenges and lessons learned in conducting a remote behavioral weight loss trial., Methods: The Personal Diet Study is an ongoing randomized clinical trial which aims to compare two mobile health (mHealth) weight loss approaches, standardized diet vs. personalized feedback, on glycemic response. Over a six-month period, participants attended dietitian-led group meetings via remote videoconferencing and were encouraged to self-monitor dietary intake using a smartphone app. Descriptive statistics were used to report adherence to counseling sessions and self-monitoring. Challenges were tracked during weekly project meetings., Results: Challenges in connecting to and engaging in the videoconferencing sessions were noted. To address these issues, we provided a step-by-step user manual and video tutorials regarding use of WebEx, encouraged alternative means to join sessions, and sent reminder emails/texts about the WebEx sessions and asking participants to join sessions early. Self-monitoring app-related issue included inability to find specific foods in the app database. To overcome this, the study team incorporated commonly consumed foods as "favorites" in the app database, provided a manual and video tutorials regarding use of the app and checked the self-monitoring app dashboard weekly to identify nonadherent participants and intervened as appropriate. Among 135 participants included in the analysis, the median attendance rate for the 14 remote sessions was 85.7% (IQR: 64.3%-92.9%)., Conclusions: Experience and lessons shared in this report may provide critical and timely guidance to other behavioral researchers and interventionists seeking to adapt behavioral counseling programs for remote delivery in the age of COVID-19., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Effects of resveratrol on metabolic health have been studied in several short-term human clinical trials, with conflicting results. Next to dose, the duration of the clinical trials may explain the lack of effect in some studies, but long-term studies are still limited., Objectives: The objective of this study was to investigate the effects of 6-mo resveratrol supplementation on metabolic health outcome parameters., Methods: Forty-one overweight men and women (BMI: 27-35 kg/m2; aged 40-70 y) completed the study. In this parallel-group, double-blind clinical trial, participants were randomized to receive either 150 mg/d of resveratrol (n = 20) or placebo (n = 21) for 6 mo. The primary outcome of the study was insulin sensitivity, using the Matsuda index. Secondary outcome measures were intrahepatic lipid (IHL) content, body composition, resting energy metabolism, blood pressure, plasma markers, physical performance, quality of life, and quality of sleep. Postintervention differences between the resveratrol and placebo arms were evaluated by ANCOVA adjusting for corresponding preintervention variables., Results: Preintervention, no differences were observed between the 2 treatment arms. Insulin sensitivity was not affected after 6 mo of resveratrol treatment (adjusted mean Matsuda index: 5.18 ± 0.35 in the resveratrol arm compared with 5.50 ± 0.34 in the placebo arm), although there was a significant difference in postintervention glycated hemoglobin (HbA1c) between the arms (P = 0.007). The adjusted means showed that postintervention HbA1c was lower on resveratrol (35.8 ± 0.43 mmol/mol) compared with placebo (37.6 ± 0.44 mmol/mol). No postintervention differences were found in IHL, body composition, blood pressure, energy metabolism, physical performance, or quality of life and sleep between treatment arms., Conclusions: After 6 mo of resveratrol supplementation, insulin sensitivity was unaffected in the resveratrol arm compared with the placebo arm. Nonetheless, HbA1c was lower in overweight men and women in the resveratrol arm. This trial was registered at Clinicaltrials.gov as NCT02565979., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.)

Weight loss reduces the risk of type 2 diabetes mellitus (T2D) in overweight and obese individuals. Although the physiological response to food varies among individuals, standard dietary interventions use a "one-size-fits-all" approach. The Personal Diet Study aims to evaluate two dietary interventions targeting weight loss in people with prediabetes and T2D: (1) a low-fat diet, and (2) a personalized diet using a machine-learning algorithm that predicts glycemic response to meals. Changes in body weight, body composition, and resting energy expenditure will be compared over a 6-month intervention period and a subsequent 6-month observation period intended to assess maintenance effects. The behavioral intervention is delivered via mobile health technology using the Social Cognitive Theory. Here, we describe the design, interventions, and methods used., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: Oral anticoagulants (OAC) are effective in the prevention of thromboembolic events but are underused. The 1st year following the beginning of vitamin K antagonists is associated with higher bleeding rate, especially in patients with international normalized ratio (INR) of >4, leading to discontinuation of OAC. We hypothesized that the decision to discontinue OAC during the 1st year in patients with events of overanticoagulation is not fully justified., Setting: A retrospective study of the association between warfarin overanticoagulation during the 1st year of treatment and the outcome and complications in patients admitted to an internal medicine department with INR>4., Subjects: A cohort of 249 patients was divided according to OAC treatment duration: ≤12 months (group I, n=72; mean age, 79.1 years) and >12 months (group II, n=177; mean age, 78.3 years)., Results: International normalized ratio upon admission was higher in group I (INR, 6.88 versus 6.16; P=0.003). Patients in group I were overanticoagulated for a longer period (46.4% versus 18.5%; P<0.001) but had lower time in therapeutic range (39.0% versus 60.2%; P=0.001). The frequency of INR monitoring was higher in group I. The incidence of major and minor bleeding events and survival was similar., Conclusions: Patients who are admitted with INR>4 during the 1st year of OAC therapy are overanticoagulated for a longer period, have lower time in therapeutic range, but do not present with higher incidence of bleeding events, all compared with patients treated for longer than 12 months. Stricter INR monitoring and careful patient selection may prevent the discontinuation of OAC.

Background: In epidemiological studies, Helicobacter pylori infection is usually detected by enzyme-linked immunosorbent assay (ELISA). However, infection can spontaneously clear from the mucosa during the progression of atrophy and could lead to substantial under-detection of infection and underestimation of its effect on gastric cancer (GC) risk. Antibodies detected by western blot are known to persist longer after the loss of the infection., Methods: In a nested case-control study from the Eurogast-EPIC cohort, including 88 noncardia GC cases and 338 controls, we assessed the association between noncardia GC and H. pylori infection comparing antibodies detected by western blot (HELICOBLOT2.1) to those detected by ELISA (Pyloriset EIA-GIII(®))., Results: By immunoblot, 82 cases (93.2%) were H. pylori positive, 10 of these cases (11.4%) were negative by ELISA and only 6 cases (6.8%) were negative by both ELISA and immunoblot. Multivariable odds ratio (OR) for noncardia GC comparing immunoglobulin G positive versus negative by ELISA was 6.8 [95% confidence interval (CI) 3.0-15.1], and by immunoblot, the OR was 21.4 (95% CI 7.1-64.4)., Conclusions: Using a western blot assay, nearly all noncardia GC were classified as H. pylori positive and the OR was more than threefold higher than the OR assessed by ELISA, supporting the hypothesis that H. pylori infection is a necessary condition for noncardia GC.

Residual renal function (RRF) remains important even after beginning of dialysis. RRF contributes significantly to the overall health and well-being of patients on dialysis. It plays an important role in maintaining fluid balance, phosphorus control, nutrition, and removal of middle molecular uremic toxins and shows inverse relationships with valvular calcification and cardiac hypertrophy in patients on dialysis. RRF may allow for a reduction in the duration of hemodialysis sessions and the need for dietary and fluid restrictions in both patients on peritoneal dialysis and hemodialysis. More importantly, the loss of RRF is a powerful predictor of mortality. This article will review the evidence supporting the importance of RRF on outcome and outline potential strategies that may better preserve RRF in patients on dialysis.

Macrolide antibiotics inhibit the metabolism of hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) that may result in myopathy and rhabdomyolysis. We report the first case of rhabdomyolysis related to the administration of clarithromycin without concurrent use of other medications. Inhibition of cytochrome P450 could be one of the potential causative mechanisms of myopathy in our case. Clinicians should be aware of this potential adverse effect of a widely used drug.

A novel sequential injection method for the determination of nitrite at nanomolar level in seawater samples has been developed. The pink azo compound was formed based on the Griess reaction and quantitatively adsorbed onto a Sep-Pak C18 cartridge. The enriched azo compound was rinsed with water and ethanol (28%, v/v) in turn, and then eluted with an eluent containing 26.6% (v/v) ethanol and 0.108 mol L(-1) H(2)SO(4). Finally the azo compound was measured using a spectrophotometer at 543 nm. Under the optimized conditions, the linear calibration ranges were 0.71-42.9 nmol L(-1) for a 150-mL sample and 35.7-429 nmol L(-1) for a 15-mL sample. The relative standard deviation of 8 measurements was 1.44% for 14.3 nmol L(-1) nitrite. For the 150 mL sample, the detection limit was estimated to be 0.1 nmol L(-1). The throughput of the method was about 4 samples per hour. The proposed method has been successfully applied to the in-field determination of nanomolar concentrations of nitrite in seawater.

The cucurbitacins are of great interest because of the wide range of biological activities they exhibit in plants and animals. We studied the antioxidant properties of cucurbitacin B + E glucosides (cucurbitacin glucoside combination, CGC) and their direct free-radical scavenging properties, using ESR spectroscopy. Antioxidant activity was measured by the ability of the CGC to reduce preformed ABTS*+ into its native form and to inhibit MDA formation during the oxidation of linoleic acid. In both methods, the CGC exhibited antioxidant activity in a dose-dependent manner as expected from antioxidants. Using ESR spectroscopy, we found that the CGC inhibited *OH-dependent DEPMPO-OH adduct formation, O2*--dependent DEPMPO-OOH adduct formation, and the 1O2-dependent TEMPO adduct generated in the photoradiation-porphin system. The IC50 values were 0.38, 8, and 11 mM, respectively. Together, these data demonstrate that the CGC exhibits antioxidant properties, probably through the involvement of a direct scavenging effect on several free radicals.

Cardiac involvement is uncommon and important clinical finding during an anaphylactic reaction, and it occurs primarily in subjects with underlying ischemic heart disease. The main mechanism proposed is the vasospasm of coronary arteries. We report a rare case of acute ST-elevation myocardial injury after penicillin-induced anaphylaxis in a patient with normal coronary arteries. Physicians should be alert for such a serious complication in order to diagnose it early and treat properly. We suggest that cardiac monitoring and appropriate therapy should be available for patients with severe allergic reactions especially during parenteral administration of epinephrine.

Weeks or months following Campylobacter infection, a small proportion of infected individuals develop Guillain-Barré syndrome (GBS) or reactive arthritis (ReA). Stool culture for Campylobacter is often negative in these patients, and serology is therefore the method of choice for diagnosing a recent infection with Campylobacter. This study developed a capture ELISA system to detect anti-Campylobacter IgA and IgM antibodies indicative of a recent infection. The sensitivity of the assay was 82.0% in uncomplicated Campylobacter enteritis patients, 96.2% in GBS patients who were culture-positive for Campylobacter, and 93.1% in culture-positive ReA patients, with a specificity of 93.0%. The assay allows identification of Campylobacter infection in patients with post-infectious neurological and rheumatological complications.

A continuous quality improvement approach is proposed for the assessment and management of patients with rheumatoid arthritis (RA) based on scores on a one-page patient self-report multidimensional health assessment questionnaire (MDHAQ), without formal joint counts. The approach includes five simple steps before the patient is seen by the physician: (1) an MDHAQ is completed by every patient at every visit; (2) scores are calculated for patient function, pain, and global estimate, with options for a self-report joint count and other scales; (3) scores are entered on flow sheets with data from prior visits, which might also include laboratory and medication information; (4) scores are compiled into an index termed Routine Assessment of Patient Index Data (RAPID), analogous to a Disease Activity Score (DAS); (5) RAPID scores are classified to guide treatment decisions. RAPID 3 includes the three patient-reported outcome (PRO) measures in the RA Core Data Set - physical function, pain, and global estimate. RAPID 4 adds a self-report joint count, and RAPID 5, a physician global estimate. RAPID 3 can be calculated in about 10 seconds, RAPID 4 in about 19 seconds, and RAPID 5 in about 20 seconds. RAPID 3, RAPID 4, and RAPID 5 give similar results to distinguish active from control treatments in RA clinical trials, at levels similar to American College of Rheumatology or DAS improvement criteria, and are all correlated significantly with DAS28 (rho=0.62-0.64, P<0.001). A proposed classification of RAPID scores, analogous to four DAS28 categories, includes: 'near remission' (0-1), 'low severity' (1.01-2), 'moderate severity' (2.01-4), and 'high severity' (>4). RAPID scoring is feasible in standard clinical care to support continuous quality improvement.

The American College of Rheumatology Core Data Set for rheumatoid arthritis (RA) includes 3 measures which are found on a patient self-report questionnaire, physical function, pain, and patient estimate of global status. These measures are included in all clinical trials, but not assessed at most encounters in standard rheumatology care. Rheumatologists may have experience with lengthy research questionnaires in clinical trials and other clinical research, which (appropriately) are regarded as relatively cumbersome research tools and do not contribute to clinical care. A format of a questionnaire known as the multidimensional health assessment questionnaire (MDHAQ) has been developed for standard rheumatology care to contribute to rheumatology clinical care in daily practice. The 3 scores for physical function, pain, and global status can be "eyeballed" in a second or two and formally scored into a composite index known as rheumatology assessment patient index data (RAPID) in about 10 seconds. This chapter provides a brief tutorial designed to instruct rheumatologists and their staffs regarding how to use and score the MDHAQ and RAPID in standard clinical care.

Background: The optimal treatment of locally advanced non-small-cell lung cancer remains a challenge. Although the benefit of combined chemoradiation has been established, the optimal chemotherapy regimen, timing of full-dose chemotherapy, and how best to combine chemotherapy with radiation to maximize systemic and radiosensitizing effects remain unclear., Patients and Methods: Twenty-nine patients with pathologically confirmed stage IIIA/IIIB non-small-cell lung cancer were included in a phase II trial of sequential carboplatin/paclitaxel followed by chemoradiation, surgery, and postoperative gemcitabine. Twenty-five patients (86%) completed the concurrent chemotherapy and radiation therapy phase and were eligible for surgery. At restaging, 7 patients (21%) showed disease progression. Seventeen patients (59%) went on to surgery. Few were able to tolerate full postoperative chemotherapy., Results: The 1-year overall survival rate was 61%, with a 2-year survival rate of 56%. Median overall survival was 25.2 months. Seven of the patients are alive and without recurrence at the time of this writing. Our median follow-up time was 22.2 months. Reversible grade 3/4 toxicities were fairly common, experienced in 45% of patients., Conclusion: Our results with this combined modality approach are comparable with those of previous, similar studies. Postoperative chemotherapy after initial combined modality therapy is often not feasible, reinforcing the value of initial systemic therapy. Long-term results are still suboptimal and await studies adding targeted therapies to our usual chemotherapy/radiation approaches.

This report describes a unique case of prolonged hypoglycemia in a nondiabetic patient with end-stage renal disease and chronic liver disease. Following a less-than-24-hour period of being NPO (nothing per oral), the patient developed hypercapnic respiratory failure. Severe hypoglycemia in such a patient leading to respiratory failure provides major challenges in identification and management of his illness. To our knowledge, this is the first ever reported case of severe hypoglycemia leading to hypercapnic respiratory failure. We believe that the pathogenic basis for this patient's severe hypoglycemia is failure of contribution by the kidneys and liver to glucose production.

Since cholesterol and lipid content may affect cell membrane fluidity, we assumed that treatment of mice with lipid lowering statins would enhance the engulfing capacity of their macrophages. Four groups of animals were examined. Group I-treated with pravastatin, group II--with simvastatin--both drugs in a dosage of 40 mg/kg daily, 5 days/week for a total of 3 weeks. Mice in group III received atorvastatin 5 mg/kg for the same time period. Group IV--untreated animals serving as controls. The phagocytic capacity of the peritoneal macrophages was evaluated by their ability to engulf latex particles. In addition, the mitogen response of the peripheral blood mononuclear cells (PBMC) and splenocytes to Con A and PHA was examined. Compared to the controls, the percentage of phagocyting cells in pravastatin-treated mice was enhanced by 18%, with simvastatin--by 24% and in atorvastatin-treated animals by 8%. The three statins increased the phagocytic index by 79.5%, 88.8% and 62%, respectively. The mitogen response of splenocytes from mice treated with the three statins to Con A increased by 68%, 48% and by 40%, respectively. Compared with the controls the response to PHA was higher in animals treated with pravastatin (84%), simvastatin (73%) and atorvastatin (57%). The response of PBMC from statin-treated animals to both mitogens did not differ from that of the controls. The results suggest that statins, at least those hereby investigated, may exert a beneficial effect on the immune function of the macrophages.

c-Myc is an oncogenic transcription factor involved in the regulation of cell proliferation, differentiation and apoptosis. The direct targets of c-Myc mediating these various processes are slowly being unravelled. This study indicates that the ornithine decarboxylase (ODC) gene is a physiological transcriptional target of c-Myc in association with induction of cell proliferation and transformation, but not with induction of apoptosis. In addition to the two conserved CACGTG c-Myc-binding sites in the first intron, the CATGTG motif in the 5'-flanking region of the murine odc is also shown to be a functional c-Myc response element. odc is thus a c-Myc target with three binding sites a distance apart. Transient transfection studies with different c-Myc, Max and Mad constructs in COS-7 cells showed that the balance between c-Myc/Max, Max/Max and Max/Mad complexes is crucial for the regulation, resulting in either transactivation or transrepression of an ODC-CAT reporter gene. Transcription of both ODC-CAT and endogenous odc was strongly induced in HeLa cells expressing tetracycline-regulated c-Myc, concomitant with c-Myc promoting the S-phase entry of the cells. Transformation of NIH3T3 cells by c-Ha-ras-(Val12) oncogene was reversed by expression of transcriptionally inactive c-Myc, which was associated with repression of ODC-CAT expression. Further, the c-Myc-induced transactivation of ODC-CAT in COS-7 cells was suppressed by co-expression of the retinoblastoma tumor suppresser pRb, evidently as a result of pRb directly or indirectly interacting with c-Myc. Importantly, the endogenous c-Myc and pRb proteins were also found to associate in Colo 320HSR cells under physiological conditions. These results suggest that c-Myc and pRb can interact in vivo, and may in part control some aspects of cell proliferation and transformation through modulation of odc expression.

NAO is a natural water soluble antioxidant that was isolated and purified from spinach leaves. Using HPLC, NMR, and CMR spectroscopy, the main components were identified as flavonoids and p-coumaric acid derivatives. The NAO was found to be a very effective antioxidant in several in vivo and in vitro biological systems. In the present study, the antioxidant activity of the novel antioxidant glucurinated flavonoid (GF) isolated and characterized from NAO, is compared to well-known antioxidants. In addition, the direct free radical scavenging properties of the purified component GF were studied using the electron spin resonance (ESR) technique. GF and NAO were found to be superior to EGCG and NAC and to the Vitamin E homologue Trolox in inhibiting reactive oxygen species (ROS) formation in the autooxidation system of linoleic acid and in fibroblasts exposed to metal oxidation. GF and NAO were found to inhibit the ESR signal intensity of DMPO-O(2) radical formation during the riboflavin photodynamic reaction. 10 mM GF caused approximately 90% inhibition in the intensity of the ESR signal, while NAO at a concentration of 60 microg/ml caused an inhibition of about 50%. Using the Fenton reaction, GF and NAO were found to inhibit DMPO-OH radical formation. A concentration of 2 mM GF caused a 70% inhibition in the intensity of the DMPO-OH radical ESR signal, while propyl gallate at the same concentration caused only 50% inhibition. Furthermore, both GF and NAO also inhibited the (1)O(2) dependent TEMPO radical generated in the photoradiation TPPS4 system. About 80% inhibition was obtained by 4 mM GF. The results obtained indicate that the natural antioxidants derived from spinach may directly affect the scavenging of ROS and, as a consequence, may be considered as effective sources for combating oxidative damage.

In previous studies we have elucidated the presence of powerful, natural antioxidants (NAO) in water extracts of spinach leaves and demonstrated their biological activity in both in vitro and in vivo systems. In the present study, the chemical identity of several of these antioxidant components is presented. Spinach leaves were extracted with water and the 20,000 g supernatant which contained the antioxidant activity was extracted with a water:acetone (1:9) solution. The 20,000 g supernatant obtained was further purified on reverse phase HPLC using C-8 semi-preparative column. Elution with 0.1% TFA resulted in five hydrophilic peaks. Elution with acetonitrile in TFA resulted in seven additional hydrophobic peaks. All the peaks were detected at 250 nm. All the fractions obtained showed antioxidant activity when tested using three different assays. Based on 1H and 13C NMR spectroscopy four of the hydrophobic fractions were identified as glucuronic acid derivatives of flavonoids and three additional fractions as trans and cis isomers of p-coumaric acid and others as meso-tartarate derivatives of p-coumaric acid. The present study demonstrates for the first time the presence of both flavonoids and p-coumaric acid derivatives as antioxidant components of the aqueous extract of spinach leaves.

Oxidative damage plays a key role in septic shock induced by lipopolysaccharide (LPS) which is known to enhance the formation of reactive oxygen species (ROS). In this study, biochemical parameters indicative of oxidative stress were tested in the rat heart following LPS challenge, with and without pretreatment with the antioxidants NAO (natural antioxidant) and apocynin. NAO is a natural antioxidant isolated and purified from spinach and its main components are flavonoids and coumaric acid derivatives. Treatment with LPS alone significantly (P<0.05) increased the malondialdehyde (MDA) level in heart, both in cytosolic and mitochondrial fractions by 1.5- and 2.4-fold, respectively, and in plasma (2.66 fold). In the heart homogenate, the level of hydroperoxides also increased significantly (P<0.05). In addition, LPS treatment significantly (P<0.05) increased NADPH oxidase activity in the heart microsomal fraction by approximately 10-fold compared to control. Pretreatment for 7 days with either apocynin or NAO prior to the LPS challenge significantly (P<0.05) improved rat survival, decreased MDA levels in both fractions and decreased microsomal NADPH-oxidase activity, compared to LPS alone. Catalase (CAT) activity slightly increased at 24 h post-LPS injection in LPS group and returned to the control level in the apocynin treated group. No meaningful changes were indicated for glutathione peroxidase activity among all the treatment groups. The activities of cytosolic and mitochondrial superoxide dismutase (SOD) enzymes significantly (P<0.05) increased approximately 20% in the LPS-treated group, compared to control. Apocynin significantly (P<0.05) decreased SOD level in the mitochondrial fraction with no effect on the cytosolic fraction; whereas, NAO had no important effect on SOD level in both fractions. The beneficial pretreatment effects of the antioxidants against oxidative stress in the rat heart presented in this study may suggest a potential chemopreventive effect of this compound in sepsis prevention.

The Tg.AC mouse carrying the v-Ha-ras structural gene is a useful model for the study of chemical carcinogens, especially those acting via non-genotoxic mechanisms. This study evaluated the efficacy of the non-toxic, water-soluble antioxidant from spinach, natural antioxidant (NAO), in reducing skin papilloma induction in female hemizygous Tg.AC mice treated dermally five times over 2.5 weeks with 2.5 microg 12-O-tetradecanoylphorbol-13-acetate (TPA). The TPA-only group was considered as a control; the other two groups received, additionally, NAO topically (2 mg) or orally (100 mg/kg), 5 days/week for 5 weeks. Papilloma counts made macroscopically during the clinical observations showed a significant decrease in multiplicity (P<0.01) in the NAO topically treated group. According to histological criteria, papilloma multiplicity were lower in both topical-NAO and oral-NAO groups, but significantly so only in the oral-NAO mice (P<0.01). The beneficial effect of NAO in the Tg.AC mouse is reported.

In this paper we use the 1994-1997 Youth Surveys of the British Household Panel Study to examine the wellbeing of young adolescents. We conceptualize wellbeing as a multi-dimensional construct and we develop and test models of gender and age differences. Using confirmatory factor analysis, we find clear gender differences in self-esteem, self-efficacy, unhappiness and worries. We confirm that wellbeing and some health-risk behaviours (fighting and smoking) are linked. We test models that examine how family structure, father's occupation, tenure, and household income, affect adolescent wellbeing. While socio-economic factors affect health-risk behaviours and also adolescents' reported worries, they have little impact on other aspects of youth wellbeing. The implications of these findings are discussed., (Copyright 2001 The Association for Professionals in Services for Adolescents.)

Hypothermia affects various components of the immune system, leading to impaired immune resistance. To examine the in vitro effect of low temperature on the ultrastructure and phagocytic function of rat peritoneal macrophages, cells were incubated at 4, 10, 24, and 37 degrees C for 60 min. Subsequently, their ultrastructure and capacity to engulf latex particles and generate superoxide anions were evaluated. The results showed a close inverse relationship between incubation temperature and ultrastructural changes, i.e., the lower the temperature, the higher the number of altered cells. In addition, at lower temperatures the number of cells capable of phagocytosis was reduced; the cells engulfed fewer particles per cell and generated less superoxide anions. These findings may be relevant for explaining the increased susceptibility to bacterial infections under hypothermic conditions., (Copyright 2000 Academic Press.)

The cost of medical care is constantly increasing. Therefore, ways of saving expenses should be considered. The aim of the present study is to evaluate the possibility than an awareness of the cost of drugs for treatment of hypertension may affect physicians' prescription decisions. A questionnaire containing the clinical data of a young and an elderly imaginary patient with moderate hypertension was given to 30 family physicians and 30 hospital physicians together with a list of appropriate drugs (phase I). This was repeated as phase II except that for this stage the cost of the drugs was brought to the participants' attention. Knowing the cost of the drugs caused a decrease in prescription of the more expensive drugs for the younger patients; of 60% (family physicians) and 87% (hospital physicians). For their elderly patients family physicians preferred the less expensive drugs at both phases. 25% of the hospital doctors changed their preference towards less expensive drugs at phase II. For the younger patient, no correlation was found between the number of years of physicians' practice and the cost of the drugs chosen. For the elderly patient, physicians from both groups preferred less expensive drugs at phase II without any relation to their years of practice. The results of this study indicate that a knowledge of the price of the drugs may affect physicians' prescription decisions, a fact that may result in considerable saving by health providing organizations.

To elucidate the effect of sodium thiopentone anesthesia on the function of phagocytic cells, albino rats were anesthetized with 60 mg/kg. of sodium thiopentone. After 90 min., peritoneal macrophages were harvested and their capacity for superoxide anion generation was detected. Following anesthesia for 90 min. latex particles were injected intraperitoneally, and after additional 30 min. the macrophages were derived, embedded in agar and the number of cells engaged in phagocytosis, as well as the number of latex particles engulfed by each individual cell were counted in semi-thick sections. Macrophages of anesthetized animals showed a statistically significant decrease of both superoxide anion generation and mean number of phagocytic cells, and engulfed fewer particles than those of the controls. Similar results were obtained following incubation of the cells with sodium thiopentone in vitro. The serum corticosterone level in anesthetized rats was significantly higher than that of the control animals. The results indicate that impaired phagocytosis following anesthesia induced by sodium thiopentone, in addition to alterations of the immune system caused by surgical trauma, may be one of the reasons for increased susceptibility to infections of surgical patients during the postoperative period.

Neuroendocrine changes contribute to female reproductive aging, but changes in other tissues also play a role. In C57BL/6J mice, neuroendocrine changes contribute to estrous cycle lengthening and reduced plasma estradiol levels, but the midlife loss of cyclicity is mainly due to ovarian failure. Hypothalamic estrogen receptor dynamics and estrogenic modulation of gene expression are altered in middle-aged cycling mice. Although insufficient to arrest cyclicity, these neuroendocrine changes may contribute to other reproductive aging phenomena, such as altered gonadotropin secretion and lengthened estrous cycles. In women, the loss of ovarian oocytes, the cause of menopause, accelerates in the decade before menopause. Accelerated oocyte loss may in turn be caused by a selective elevation of plasma follicle stimulating hormone, and neuroendocrine involvement may thus be implicated in menopausal oocyte loss. Chronic calorie restriction retards both neural and ovarian reproductive aging processes, as well as age-related change in many other physiological systems. The diverse effects of food restriction raises the possibility of an underlying coordinated regulatory response of the organism to reduced caloric intake, possibly effected through alterations of neural and/or endocrine signalling. We are therefore attempting to identify neuroendocrine changes that may coordinate the life prolonging response of animals to food restriction. Our initial focus is on the glucocorticoid system. Food restricted rats exhibit daily periods of hyperadrenocorticism, manifest as elevated free corticosterone during the diurnal peak. We hypothesize that this hyperadrenocortical state potentiates cellular and organismic homeostasis throughout life in a manner similar to that achieved during acute stress, thereby retarding aging processes and extending life span.

It is clearly established that dental restorative materials, like all other foreign materials introduced into the human body, may cause pathological changes both local and general in type. However, in a proper evaluation of the side-effects occurring, their type, severity and frequency have to be considered. Local side-effects of dental restorative materials on oral mucosa are of either irritative or allergic nature while systemic effects are mainly due to allergic and other kinds of hypersensitivity reactions. Most side-effects of dental restorative materials seem to be insignificant and of short duration, although systemic hypersensitivity reactions may be most harmful to those affected. Although the frequency of side-effects seems to be low in comparison with the vast number of restorations that are placed, it is reasonable to assume that the more complex and diverse application of an increasing number of dental materials will increase the frequency. Study of a group of patients, referred for investigation of possible side-effects of dental materials, revealed that several of these patients showed allergic reactions to constituents of their dental restorations. Environmental problems associated with the handling of waste amalgam are discussed.

The main current-generating corrosion cells in the oral cavity are the bimetallic cell and the concentration cell, the latter mainly occurring due to differences in access to oxygen in the various parts of the metallic material. Corrosion resistance is not an intrinsic property of a metal or an alloy for it depends on an interaction with the environment. Thus, the contents of the oral cavity, have a decisive influence. This implies that corrosion tests in vitro are of limited value in predicting the clinical corrosion behaviour of a metallic material. Results from a series of clinical studies concerning a possible relationship between galvanic currents and certain oral and other symptoms in a group of patients who had been referred to the Faculty of Odontology, University of Umeå, are briefly presented. The possibility of local and systemic effects of intra-oral galvanic cells is discussed.

We present a mathematical model for cell growth, which takes into account cell-cell interactions and leads to non-exponential inhibited growth of number of cells. The resulting difference equation is solved and extended to a differential equation which turns out to be of a non-linear diffusion type.

Five patients undergoing extensive cerebral monitoring during cardiopulmonary bypass (CPB) procedures were subjected to studies on cerebral CO2 reactivity during nonpulsatile CPB. The cerebral monitoring included recording of arterial blood pressure (BP), central venous pressure (CVP), epidural intracranial pressure (EDP), cerebral electrical activity by a cerebral function monitor (CFM), and middle cerebral artery (MCA) flow velocity by transcranial Doppler technique. The cerebral perfusion pressure (CPP) was thus continuously recorded (CPP = BP - EDP). During steady-state CPB with constant hematocrit, temperature, and arterial carbon dioxide tension (PaCO2), MCA flow velocity varied with changing CPP in a pressure-passive manner, indicating that the cerebral autoregulation was not operative. During moderately hypothermic (28 to 32 degrees C), nonpulsatile CPB, with steady-state hematocrit, temperature, and pump flow, we deliberately and rapidly changed PaCO2 for periods of 1 or 2 minutes by increasing gas flow to the membrane oxygenator, thereby testing the cerebral CO2 reactivity. Nineteen CO2 reactivity tests, performed at CPP levels ranging from 17 to 75 mm Hg, disclosed that the cerebral CO2 reactivity decreased with CPP, especially with CPP levels below 35 mm Hg. In these patients, concomitant changes in CPP during the CO2 reactivity test could be compensated for by adjusting the observed change in MCA flow velocity. The corrected CO2 reactivity values obtained in this way ranged from below 1.0 (observed at CPP levels below 20 mm Hg) to a 3.0 to 4.5% X mm Hg-1 change in PaCO2 (observed at CPP levels above 35 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)