Search

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2005.06.017 Byline: Sanne Kuijper, Harma Feitsma, Rushikesh Sheth, Jeroen Korving, Mark Reijnen, Frits Meijlink Keywords: Limb development; Alx4; Gli3; Antero-posterior patterning; Gene regulation; Sonic hedgehog; FGF4; Polydactyly Abstract: The role of the aristaless-related homeobox gene Alx4 in antero-posterior (AP-) patterning of the developing vertebrate limb has remained somewhat elusive. Polydactyly of Alx4 mutant mice is known to be accompanied by ectopic anterior expression of genes like Shh, Fgf4 and 5'Hoxd. We reported previously that polydactyly in Alx4 mutant mice requires SHH signaling, but we now show that in early Alx4.sup.-/- limb buds the anterior ectopic expression of Fgf4 and Hoxd13, and therefore disruption of AP-patterning, occurs independently of SHH signaling. To better understand how Alx4 functions in the pathways that regulate AP-patterning, we also studied genomic regulatory sequences that are capable of directing expression of a reporter gene in a pattern corresponding to endogenous Alx4 expression in anterior limb bud mesenchyme. We observed, as expected for authentic Alx4 expression, expansion of reporter construct expression in a Shh.sup.-/- background. Total lack of reporter expression in a Gli3.sup.-/- background confirms the existence of Gli3-dependent and -independent Alx4 expression in the limb bud. Apparently, these two modules of Alx4 expression are linked to dissimilar functions. Author Affiliation: Hubrecht Laboratory, The Netherlands Institute for Developmental Biology, Uppsalalaan 8, 3584CT Utrecht, The Netherlands Article History: Received 8 March 2005; Revised 6 June 2005; Accepted 11 June 2005

The effects of ageing and physical fitness on shiftwork tolerance are reviewed. Ageing is one of the most cited factors decreasing the health of shiftworkers. Although long-term prospective studies on ageing are few, shiftworkers over 40-45 years of age seem to sleep worse after night, but not after morning shifts. Sleepiness after successive night shifts is also decreased by age although older shiftworkers' ability to resist acute sleep loss seems to be even better. The reasons for the altered sleep and wakefulness of older shiftworkers are probably related to changes in circadian rhythms, especially higher 'morningness'. Sleep need may also decrease with age which could explain some of the differences found in sleep length. Physical fitness as a factor increasing tolerance to shiftwork is a recent finding. Although the effects of physical activity on sleep have been studied in detail, the relationship of physical fitness to sleep is still a controversial issue. In shiftworkers, moderate physical training has been shown to increase sleep length and night-time alertness. It has not been shown, however, that exercise would quicken the circadian adjustment to night work. It is recommended that work time arrangements should take account of the older workers' changing personal references. Continuous night work should be voluntary after 40 years of age. Moderate physical exercise a few hours before the main sleep period is recommended.

Hypertonic milk replacers are commonly used in animal production systems and their effect on the gastrointestinal system of young animals is insufficiently studied. Total lactose inclusion or its partial replacement with dextrose increases intestinal osmotic pressure, which may compromise gastrointestinal barrier function. In this experiment, we investigated the effect of increased osmolality of calf milk replacer (CMR) on gastrointestinal permeability in 30 Holstein Friesian (n = 17) or crossbred (n = 13) bull calves. The osmolality of CMR increased as result of a gradual replacement of lactose by monosaccharides (dextrose and galactose). Calves were acquired from dairy farms that followed a standardized protocol for colostrum management, including 3 feedings of colostrum in the first 24 h. Calves were then transported to the research facility between 0 and 3 d of age, fed a milk replacer with 0% dextrose twice daily for the first 2 wk of age, and subsequently exposed to their respective treatments from 3 until 7 wk of age. Meal size was 3.2 L at 3 wk of age and increased to 3.5 L at 7 wk of age. No solids were provided throughout the study and calves had ad libitum access to water. Treatments included 4 levels of dextrose inclusion (replacing lactose): 0% (L1, n = 5), 13.3% (L2, n = 5), 26.7% (L3, n = 5), and 40% (L4, n = 5) and an additional treatment (G+D, n = 10) that included 20% galactose and 20% dextrose and matched the galactose supply of L1 and the osmolality of L4. Carbohydrates were exchanged based on hexose equivalents. Across treatments, the estimated osmolality ranged from 439 (L1) to 611 mOsm/kg (L4 and G+D). Gastrointestinal permeability was assessed by fractional urinary recovery of indigestible markers (lactulose, d-mannitol, and Cr-EDTA) delivered as a single dose at 3 and 7 wk of age. Marker recoveries were expressed as percentage of oral dose and assessed in 6-h and 24-h quantitative urinary collections. Increasing the osmolality of the CMR linearly increased urinary Cr-EDTA and lactulose recoveries at 3 and 7 wk of age. Lactulose and Cr-EDTA recoveries did not differ between G+D and L4, suggesting that the source of monosaccharide (dextrose and galactose) in CMR had no effect on gastrointestinal permeability. The observed increase in gastrointestinal permeability to large molecules (Cr-EDTA and lactulose) with increased osmolality suggests that hypertonic CMR may compromise gastrointestinal barrier function. [ABSTRACT FROM AUTHOR]

Introduction Models of attention suggest that endogenous and exogenous factors can bias attention. However, recent data suggest that reward can also enhance attention towards relevant stimulus features as a function of involuntary biases. In this study, we utilized the additional singleton task to determine the neural circuitry that biases perceptual processing as a function of reward history. Methods Participants searched for a unique shape amongst an array of differently shaped objects. All shapes, including the target shape, had the same color except one distractor shape. Participants randomly received a low or high reward after correct trials. From one trial to the next, target colors could stay the same or swap with the distractor color. Interestingly, and despite the irrelevancy of reward magnitude for task accuracy, the difference in reaction time between swap and non-swap trials usually is more pronounced following a high compared to a low reward. Results In the current study, we showed that reward modulated attention is larger for individuals with enhanced reward magnitude sensitivity in the ventral striatum. In addition, connectivity data shows that ventral striatum was more positively connected with visual cortex during high reward non-swap trials compared to high reward swap trials for participants showing stronger reward modulated attention. Conclusions This suggests that involuntary reward modulated attention might be implemented by direct influences of the ventral striatum on visual cortex. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate whether there is a difference in human papillomavirus (HPV), smear, and cervical biopsy results between patients with and without diabetes mellitus (DM). Retrospectively, 136 patients with positive high risk (HR) HPV screening results with and without DM who underwent colposcopy between 2015 and 2019 were identified. The clinicopathological characteristics and HR HPV screening results were reported and analyzed. The results of the patients with and without DM were compared. HPV 16 positivity, Atypical Squamous Cells of Undetermined Significance (ASCUS), and Cervical Intraepithelial Neoplasia 1 (CIN 1) in smear and biopsy results were higher in patients with DM than patients without DM. The higher HPV positivity in patients with diabetes may require reforming the frequency and method of cervical cancer screening to be applied to this patient group. • In diabetes mellitus, human papillomavirus elimination is challenging. • Human papillomavirus and Atypical Squamous Cells of Undetermined Significance are higher in patients with diabetes. • Cervical Intraepithelial Neoplasia 1 in biopsy results is higher in patients with diabetes. [ABSTRACT FROM AUTHOR]

Abstract: The mature cystic teratomas (MCT) constitute the majority of ovarian germ cell tumors. It is uncommon seen postmenopausal period and thyroid tissues are found in 3.5–20% of these tumors on pathologic examinations. Multiple biliary hamartomas (MBH) or von Meyenburg complexes are rare benign neoplasms of the liver, composed of disorganized bile ducts and ductules and fibrocollagenous stroma. We present a postmenopausal women presenting with abdominal mass. Abdominal US and CT of the case revealed a contrast enhanced cystic mass with solid component within pelvis. Besides, multiple hypodense lesions, which were thought initially as metastasis, were detected in the liver. Abdominal MR, MRCP and liver biopsy revealed that the lesions within the liver are multiple biliary hamartomas. Pathological investigation of the mass after the operation revealed that the pelvic mass is a mature cystic teratoma composed of mostly mature thyroid tissue. To our knowledge, there is no report on association of MBH and MCT in the literature. [Copyright &y& Elsevier]

Abstract: Objective: This study assessed the effect of intranasal administration of 17β-estradiol (Aerodiol®) on plasma levels of homocysteine, Vitamin B12 and folate in postmenopausal women. Methods: In all, 26 symptomatic postmenopausal women who had undergone hysterectomy and oophorectomy at least 12 months previously participated in this 6-month randomized prospective clinical study. Menopause was determined by serum FSH level >30μIU/ml and serum estradiol concentration <30pg/ml. Intranasal 17β-estradiol treatment was given once daily at a standard daily dose of 300μg to 16 women, and 10 did not receive any treatment. Results: In the group receiving intranasal 17β-estradiol, mean (±S.D.) plasma homocysteine level decreased significantly from pre-treatment values (from 16.68±4.33 to 14.15±1.18nmol/ml, p=0.029) and the mean folate level increased (from 4.11±0.80 to 5.64±1.87ng/ml, p=0.012). Vitamin B12 levels showed a tendency towards increasing. In the treated group, significant negative correlations were observed between homocysteine and folate values (r=-0.586, p=0.017) and between homocysteine and Vitamin B12 values (r=-0.672, p=0.004). No significant changes were observed in the untreated group. Conclusion: The reduction in plasma homocysteine levels observed after 6 months’ treatment with intranasal 17β-estradiol may reflect an alteration in folate and Vitamin B12 homeostasis. [Copyright &y& Elsevier]

Objectives: Preeclampsia is one of the most serious complications of pregnancy. Free radical damage has been implicated in the pathophysiology of this condition. In this study, we aimed to measure the antioxidant capacity in plasma samples from normotensive and preeclamptic pregnant women to evaluate their antioxidant status using a more recently developed automated measurement method. Study design: Our study group contained 42 women, 24 of whom had preeclampsia, while 18 had normotensive pregnancies. We measured the total plasma antioxidant capacity for all patients, as well as the levels of four major individual plasma antioxidant components; albumin, uric acid, ascorbic acid and bilirubin, and as a reciprocal measure, their total plasma peroxide levels. Results: Statistically significant differences (determined using Student’s t-test) were noted between the normotensive and the preeclamptic groups for their total antioxidant responses and their vitamin C levels (1.31±0.12 mmol versus 1.06±0.41 mmol Trolox eq./L; 30.2±17.83 μmol/L versus 18.1±11.37 μmol/L, respectively), which were both considerably reduced in the preeclamptic patients. In contrast, the total plasma peroxide levels were significantly elevated in this group (49.8±14.3 μmol/L versus 38.8±9.6 μmol/L). Conclusions: We found a decreased total antioxidant response in preeclamptic patients using a simple, rapid and reliable automated colorimetric assay, which may suitable for use in any routine clinical biochemistry laboratory, and considerably facilitates the assessment of this useful clinical parameter. We suggest that this novel method may be used as a routine test to evaluate and follow up of the levels of oxidative stress in preeclampsia. [Copyright &y& Elsevier]

: ObjectiveTo evaluate the effectiveness of sibutramine therapy alone and in combination with ethinyl estradiol-cyproterone acetate (EE-CPA) on the clinical and metabolic parameters of obese women with polycystic ovary syndrome (PCOS).: DesignProspective randomized, controlled study.: SettingEndocrinology and gynecology clinics.: Patient(s)Forty obese women with PCOS.: Intervention(s)Group 1 was treated with oral EE-CPA (35 μg-2 mg/day), group 2 with oral sibutramine (10 mg/day), and group 3 with a combination of EE-CPA plus sibutramine for 6 months. All groups were advised to consume a diet of 1,200 kcal/day.: Main outcome measure(s)Measurements were performed before and 6 months after treatment of body mass index, waist-to-hip ratio, systolic and diastolic blood pressure, Ferriman-Gallwey hirsutism score, total testosterone, free testosterone, sex hormone–binding globulin, dihydroepiandrosterone sulfate (DHEAS), total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, glucose and insulin during oral glucose tolerance test, and insulin sensitivity index; area under the curve for glucose and insulin were obtained from OGTT.: Result(s)Body mass index, Ferriman-Gallwey hirsutism score, serum total testosterone, free testosterone, and DHEAS levels were significantly decreased and SHBG was significantly increased in all groups at the end of the study. WHR, diastolic blood pressure, and serum triglyceride level were significantly reduced only in the sibutramine group.: Conclusion(s)Sibutramine might have a positive effect on hyperandrogenemia, and clinical and metabolic risk factors for cardiovascular disease in obese women with PCOS. [Copyright &y& Elsevier]

Although Moral Foundations Theory (MFT) is claimed to be universally applicable, the data brought to bear in its support come from a self-selected population with mostly English-speaking participants. To the best of our knowledge, the theory has not been hitherto tested in a predominantly Muslim country with non-western moral and religious sensibilities. In Study 1 , we replicated previous findings using Turkish participants by showing through confirmatory factor analyses that the 5-factor structure of MFT provided a better fit than alternative models. In Study 2 , the participants' cultural schemas of individualism and collectivism were experimentally manipulated to see the distinctness and separate manipulability of the five individual foundations. The individualism prime led to an increased concern with the harm dimension whereas the collectivism manipulation led to an increased concern with the loyalty dimension. Taken together, the findings suggest that the 5-factor model of morality is the best fitting model in Turkey as well and that it is useful in predicting the results of cultural prime manipulations. [ABSTRACT FROM AUTHOR]

Background: Several malnutrition screening tools have been advocated for use in pediatric inpatients. Objective: We evaluated how 3 popular pediatric nutrition screening tools [i.e., the Pediatric Yorkhill Malnutrition Score (PYMS), the Screening Tool for the Assessment of Malnutrition in Pediatrics (STAMP), and the Screening Tool for Risk of Impaired Nutritional Status and Growth (STRONGKIDS)] compared with and were related to anthropometric measures, body composition, and clinical variables in patients who were admitted to tertiary hospitals across Europe. Design: The 3 screening tools were applied in 2567 inpatients at 14 hospitals across 12 European countries. The classification of patients into different nutritional risk groups was compared between tools and related to anthropometric measures and clinical variables [e.g., length of hospital stay (LOS) and infection rates]. Results: A similar rate of completion of the screening tools for each tool was achieved (PYMS: 86%; STAMP: 84%; and STRONGKIDS: 81%). Risk classification differed markedly by tool, with an overall agreement of 41% between tools. Children categorized as high risk (PYMS: 25%; STAMP: 23%; and STRONGKIDS: 10%) had a longer LOS than that of children at low risk (1.4, 1.4, and 1.8 d longer, respectively; P < 0.001). In high-risk patients identified with the PYMS, 22% of them had low (<–2) body mass index (BMI) SD-scores (SDSs), and 8% of them had low height-for-age SDSs. For the STAMP, the percentages were 19% and 14%, respectively, and for the STRONGKIDS, the percentages were 23% and 19%, respectively. Conclusions: The identification and classification of malnutrition risk varied across the pediatric tools used. A considerable portion of children with subnormal anthropometric measures were not identified with all of the tools. The data obtained do not allow recommending the use of any of these screening tools for clinical practice. This study was registered at clinicaltrials.gov as NCT01132742. [ABSTRACT FROM AUTHOR]

Background: The proportion of starch disappearing from the small intestinal lumen is generally lower in ruminants than in monogastric animals, and there are indications that the starch digestion capacity in ruminants is limited. Objectives: Milk-fed calves were used to study the rate-limiting enzyme in starch hydrolysis and to quantify starch fermentation in ruminants. Methods: Forty male Holstein-Friesian calves were fed milk replacer containing either lactose (control) or 1 of 4 corn starch products. The following starch products differed in the enzyme ratios required for their complete hydrolysis to glucose: gelatinized starch [α-amylase and (iso)maltase], maltodextrin [(iso)maltase and α-amylase], maltodextrin with α-1,6-branching (isomaltase, maltase, and α-amylase), and maltose (maltase). In the adaptation period, calves were stepwise exposed to an increasing dose of the starch product for 14 wk to allow maximal adaptation of all enzyme systems involved. In the experimental period, apparent total tract and ileal starch product disappearance, total tract starch product fermentation, and α-amylase, maltase, and isomaltase activities were determined at 18% inclusion of the starch product. Results: Maltase and isomaltase activities in the brush border did not increase for any of the starch product treatments. Luminal a-amylase activity was lower in the proximal (3.9 ± 3.2 and 2.7 ± 1.7 U/mg Co for control and starch product calves, respectively) but greater in the distal small intestine of starch-fed calves than in control calves (0.0 ± 0.0 and 6.4 ± 1.5 U/mg Co for control and starch product calves, respectively; means 6 SEs for control and means 6 pooled SEMs for starch product treatments). Apparent ileal (61.6% 6 6.3%) and total tract (99.1 % 6 0.4%) starch product disappearance did not differ between starch product treatments, suggesting that maltase activity limits starch digestion in ruminants. Total tract starch product fermentation averaged 414 ± 43 g/d, corresponding to 89% of intake, of which half was fermented before the terminal ileum, regardless of starch product treatment. Conclusion: Fermentation, rather than enzymatic digestion, is the main reason for small intestinal starch disappearance in milk-fed calves. [ABSTRACT FROM AUTHOR]

Summary Background & aims Previous studies reported a wide range of estimated malnutrition prevalence (6–30%) in paediatric inpatients based on various anthropometric criteria. We performed anthropometry in hospitalised children and assessed the relationship between malnutrition and length of hospital stay (LOS) and complication rates. Methods In a prospective multi-centre European study, 2567 patients aged 1 month to 18 years were assessed in 14 centres in 12 countries by standardised anthropometry within the first 24 h after admission. Body mass index (BMI) and height/length <−2 standard deviation scores (SDS, WHO reference) were related to LOS (primary outcome), frequency of gastrointestinal (diarrhoea and vomiting) and infectious complications (antibiotic use), weight change during stay (secondary outcomes) and quality of life. Results A BMI <−2 SDS was present in 7.0% of the patients at hospital admission (range 4.0–9.3% across countries) with a higher prevalence in infants (10.8%) and toddlers aged 1–2 years (8.3%). A BMI <−2 to ≥−3 SDS (moderate malnutrition) and a BMI <−3 SDS (severe malnutrition) was associated with a 1.3 (CI95: 1.01, 1.55) and 1.6 (CI95: 1.27, 2.10) days longer LOS, respectively ( p = 0.04 and p < 0.001). Reduced BMI <−2 SDS was also associated to lower quality of life, and more frequent occurrence of diarrhoea (22% vs 12%, p < 0.001) and vomiting (26% vs 14%, p < 0.001). Conclusion Disease associated malnutrition in hospitalised children in Europe is common and is associated with significantly prolonged LOS and increased complications, with possible major cost implications, and reduced quality of life. This study was registered at clinicaltrials.gov as NCT01132742 . [ABSTRACT FROM AUTHOR]

Urea recycling, with urea originating from catabolism of amino acids and hepatic detoxification of ammonia, is particularly relevant for ruminant animals, in which microbial protein contributes substantially to the metabolizable protein supply. However, the quantitative contribution of urea recycling to protein anabolism in calves during the transition from preruminants (milk-fed calves) to ruminants [solid feed (SF)-fed calves] is unknown. The aim of this study was to quantify urea recycling in milk-fed calves when provided with low-protein SF. Forty-eight calves [164 ± 1.6 kg body weight (BW)] were assigned to 1 of 4 SF levels [0, 9, 18, and 27 g of dry matter (DM) SF ⋅ kg BW-0.75 ⋅ d-1] provided in addition to an identical amount of milk replacer. Urea recycling was quantified after a 24-h intravenous infusion of [15N2]urea by analyzing urea isotopomers in 68-h fecal and urinary collections. Real-time qPCR was used to measure gene expression levels of bovine urea transporter B (bUTB) and aquaglyceroporin-3 and aquaglyceroporin-7 in rumen wall tissues. For every incremental gram of DMSF intake (g DM ⋅ kg0.75), nitrogen intake increased by 0.70 g, and nitrogen retention increased by 0.55 g (P < 0.01). Of this increase in nitrogen retention, 19% could be directly explained by urea recycling. Additionally, part of the observed increase in nitrogen retention could be explained by the extra protein provided by the SF and likely by a greater efficiency of post-absorptive use of nitrogen for gain. Ruminal bUTB abundance increased (P < 0.01) with SF provision. Aquaglyceroporin-3 expression increased (P < 0.01) with SF intake, but aquaglyceroporin-7 expression did not. We conclude that in addition to the increase in digested nitrogen, urea recycling contributes to the observed increase in nitrogen retention with increasing SF intake in milk-fed calves. Furthermore, ruminal bUTB and aquaglyceroporin-3 expression are upregulated with SF intake, which might be associated with urea recycling. [ABSTRACT FROM AUTHOR]

Introduction and aim: The investigation of new anatomical criteria and revalidation of existing ones in sex determination for different populations are among main research foci of forensic anthropometry. In that context, the pelvis is the most extensively studied bone. A number of qualitative classifications, dimensional measurements and indices have been proposed for investigative anthropometry and forensic studies. Independent use of these parameters generally provided an accuracy rate of 70–75%. In this study, the accuracy rate of the subpubic angle in sex determination was investigated in living Anatolian Caucasians. Material and method: The subpubic angle was identified and measured on three-dimensional computed tomographic images of pelves. Data were obtained using 64-detector computed tomography (MDCT) with an isotrophic resolution of 500 μm. The sample included 66 males (41.6 ± 14.9 years of age) and 43 females (41.1 ± 14.2 years of age). Measurements were taken on a dedicated three-dimensional image analysis workstation. The subpubic angle was electronically measured. The technique and methodology was validated on a standard skeletal model. Intraobserver agreement was analyzed with intraclass correlation coefficient, and intraobserver variability was evaluated with technical error of measurement (inter- and intra-observer TEM), relative technical error of measurement (rTEM) and coefficient of reliability (R) measures. The subpubic angle for the study group and for both sexes was reported as minimum–maximum (mean ± SD). Independent-Samples T Test for equality of means was used to determine the difference between the two sexes regarding the subpubic angle. The correlation between the subpubic angle and the age of subjects were using Pearson Correlation Coefficients in males and in females. Logistic regression model was used to classify subjects according to their sex. Receiver operating characteristic curve analysis was performed to determine a cut-off value for further studies and to test the performance of the binary classification test. Results: Intraclass correlation for the subpubic angle (0.990), TEM (1082), rTEM (1.492), and R (0.990) represented almost complete reliability and accuracy of the measurement method. The subpubic angle was between 48° and 81° (65.9° ± 7.2°) in males and was between 64° and 100° (82.6° ± 7.7°) in females. Statistically significant difference was found between males and females regarding the subpubic angle (p < 0.0001). The subpubic angle was not significantly correlated with age in males (p = 0.953), or in females (r = 0.975). The accuracy of the subpubic angle in sex determination was 90.8%. With a cut-off value of 74°, sensitivity of subpubic angle to detect female phenotype was 88% and its specificity was 95%. Conclusion: The subpubic angle is an accurate parameter in sex determination with high sensitivity and specificity. [ABSTRACT FROM AUTHOR]

Summary: Background & aims: Efforts are directed at reaching the optimal composition of pediatric amino acids (AA) infusions. The goal was to demonstrate the safety and efficacy of a newly developed parenteral AA solution containing alanyl-glutamine (GLN-AA) compared to Standard-AA. Methods: This is a randomized (2:1), double-blind, multicentre clinical pilot trial. Infants after surgical interventions were allocated to receive GLN-AA or Standard-AA over a minimum of 5 days to maximum of 10 days. AA profiles in blood samples obtained at baseline, day 7, and end of treatment were compared to normal ranges. Data regarding safety, and efficacy were also collected. Results: Infants were comparable for (safety population) gestational age at birth (36 vs 38 weeks), birth weight (2460 vs 2955 g), and day of life during start intervention (1 vs 2 days). Plasma AA profiles in infants treated with GLN-AA (n = 13) were closer the normal ranges than those in infants treated with Standard-AA (n = 6). There were no clinical or statistical differences in adverse events, safety and efficacy parameters between both groups. Conclusion: This first-in-man study shows that GLN-AA is safe in infants after surgical interventions, and is well tolerated. Compared to reference values, GLN-AA better reflects the amino acid requirements of the infant. [Copyright &y& Elsevier]

Sirtuin 1 (SIRT1) is a nuclear deacetylase that modulates lipid metabolism and enhances mitochondrial activity. SIRT1 targets multiple transcription factors and coactivators. Thyroid hormone (T3) stimulates the expression of hepatic genes involved in mitochondrial fatty acid oxidation and gluconeogenesis. We reported that T3 induces genes for carnitine palmitoyltransferase (cpt1a), pyruvate dehydrogenase kinase 4 (pdk4), and phosphoenolpyruvate carboxykinase (pepck). SIRT1 increases the expression of these genes via the activation of several factors, including peroxisome proliferator-activated receptor α, estrogen-related receptor α, and peroxisome proliferator-activated receptor γ coactivator (PGC-1α). Previously, we reported that PGC-1α participates in the T3 induction of cpt1a and pdk4 in the liver. Given the overlapping targets of T3 and SIRT1, we investigated whether SIRT1 participated in the T3 regulation of these genes. Resveratrol is a small phenolic compound whose actions include the activation of SIRT1. Addition of resveratrol increased theT3 induction of the pdk4 and cpt1a genes in hepatocytes. Furthermore, expression of SIRT1 in hepatocytes mimicked resveratrol in the regulation of gene expression by T3. The deacetylase activity of SIRT1 was required and PGC-1α was deacetylated following addition of T3. We found that SIRT1 interacted directly with T3 receptor (TRβ). Knockdown of SIRT1 decreased the T3 induction of cpt1a and pdk4 and reduced the T3 inhibition of sterol response element binding protein (srebp-1c) both in isolated hepatocytes and in rat liver. Our results indicate that SIRT1 contributes to the T3 regulation of hepatic genes. [ABSTRACT FROM AUTHOR]

Summary: Defective placentation and resultant oxidative stress are believed to be largely responsible for preeclampsia and early pregnancy loss. In experiments to test the hypothesis that these factors may also be important in complete hydatidiform mole (CHM). CHM cases were found to have significantly higher levels of mean total peroxide, mean oxidative stress index, protein carbonyls and endogenous DNA damage, and lower levels of total antioxidant potential and thiols compared with healthy pregnant patients, pointing to a role for oxidative stress in the condition. Whether this role is primary, secondary or incidental remains to be determined. [Copyright &y& Elsevier]

Abstract: Sub-stock components of highly exploited migratory fish species exhibit different life-history traits and can thus show variation in productivity and vulnerability to fishing pressure. Celtic Sea herring comprises both autumn and winter-spawners that are targeted by the same fishery. The current study investigated if the relative abundances of the two components in the Celtic Sea have changed over time, and whether this could explain marked long-term trends in size-at-age. The study utilized a remarkably long time-series of biological data from commercial landings (1959–2009). Based on the maturity state of the gonads at the time of sampling, herring were assigned to seasonal spawning components. Significant temporal variations in spawning component dominance were found, even after potential bias due to fishing history patterns were accounted for. Strong directional changes in the relative proportion of spawning components consisted of autumn spawning herring proportions reaching a peak in the 1990s before drastically declining. Winter spawning herring had lower mean lengths- and weights-at-age than autumn spawning herring. The recent decline in the autumn spawning component did not fully explain the observed decline in size-at-age in the catches, with both spawning components showing similar decreases in mean-size parameters over time. Response of spawning components to environmental changes may have consequences for the fishery, especially in light of the observed influence of temperature on spawning components. Life-cycle diversity in herring stocks may confer resilience to potential climate-induced changes. Therefore, it is suggested that the relative proportions of spawning components should be monitored and diversity should be preserved as part of the management of fisheries for this species, which is characterized by stock complexity. [Copyright &y& Elsevier]

Abstract: Background: In separate randomized, crossover trials, patients with diabetes reported a preference for durable insulin pen NovoPen® 4 compared with NovoPen 3 and OptiClik®. Objective: This large post-marketing observational study evaluated treatment satisfaction with NovoPen 4 versus previous treatments, which included NovoPen 3 and other devices, in insulin-treated and insulin-naive patients. Methods: During regular clinical practice in Canada, Germany, and the Netherlands, health care professionals assigned adult patients with type 1 or type 2 diabetes to treatment with insulin administered via NovoPen 4 after training according to the device''s instruction manual. The primary end point was change in treatment satisfaction as determined by the Diabetes Treatment Satisfaction Questionnaire given to patients at the beginning and after 12 weeks of treatment. Two additional questionnaires were used at study end to identify why patients preferred either NovoPen 4 or their previously used insulin devices, which included NovoPen 3 and other devices (eg, HumaPen® Ergo and OptiPen® Pro). Adverse events were also recorded. Results: Two thousand eighteen participants (mean age, 55 years; males, 53%; type 1/type 2 diabetes, 28%/71%; mean duration of disease, 13 years; previously on insulin, 89.8%; insulin-naïve, 2.9%) participated. NovoPen 3 was previously used by 1059, HumaPen Ergo by 256, OptiPen Pro by 217, and other devices by 385 patients. Diabetes Treatment Satisfaction Questionnaire scores increased from a mean (SD) baseline of 26.5 (7.2) to 30.5 (5.0) at study end for a median difference of 4.0 (95% CI, 3.5–4.5; Wilcoxon test score: 22.7; P < 0.0001). Over 70% of patients found NovoPen 4 easier to set, read, correct, inject the dose, and change the insulin cartridge than with their previously used device (P < 0.0001). A total of 83.8% rated NovoPen 4 easier to use overall (P < 0.0001). Health care professionals (97.2%) would recommend NovoPen 4 to other patients. No adverse events associated with the device were recorded. Conclusions: Patients reported a significant preference for NovoPen 4 compared with previous treatment with NovoPen 3 or other insulin device. The high ratings NovoPen 4 received for ease of use and learning could potentially lead to improved acceptance of and compliance with prescribed insulin therapy. Further study is warranted to determine the possible health benefits of using this insulin device. [ABSTRACT FROM AUTHOR]

Background: The impact of large vessel extension (LVE) as a prognostic factor for adrenocortical carcinoma (ACC) is not fully understood. This study aimed to assess outcome of ACC in the presence and absence of LVE. Methods: A retrospective review of 57 patients undergoing curative intent resection for ACC over 10 years is presented comparing those with and without LVE. LVE was defined as vascular wall invasion or intraluminal extension of the neoplasm into the inferior vena cava or renal vein. Preoperative diagnostics, operative details, pathology, overall survival (OS), and recurrence-free survival (RFS) were analyzed. Results: Multivariable regression analysis showed a significant association for decreased survival with Stage III and IV disease and LVE. Patients with LVE had more functional neoplasms, greater preoperative serum hormone levels, and more positive margins than those without LVE. Median OS was 6 years and RFS 3 years. Kaplan-Meier analysis demonstrated a significant decrease in OS and RFS with LVE. Median OS with and without LVE was 18 vs 111 months and median RFS was 11 vs 64 months. Three-year OS with and without LVE were 29% vs 93% and 3 year RFS was 15% vs 67%. Conclusion: In addition to systemic and lymph node metastases, LVE is associated with poorer OS and RFS. [ABSTRACT FROM AUTHOR]

Abstract: Investigation of the mechanistic bases and physiological importance of cAMP regulation of HCN channels has exploited an arginine to glutamate mutation in the nucleotide-binding fold, an approach critically dependent on the mutation selectively lowering the channel''s nucleotide affinity. In apparent conflict with this, in intact Xenopus oocytes, HCN and HCN-RE channels exhibit qualitatively and quantitatively distinct responses to the tyrosine kinase inhibitor, genistein — the estrogenic isoflavonoid strongly depolarizes the activation mid-point of HCN1-R538E, but not HCN1 channels (+9.8 mV±0.9 versus +2.2 mV±0.6) and hyperpolarizes gating of HCN2 (−4.8 mV±1.0) but depolarizes gating of HCN2-R591E (+13.2 mV±2.1). However, excised patch recording, X-ray crystallography and modeling reveal that this is not due to either a fundamental effect of the mutation on channel gating per se or of genistein acting as a mutation-sensitive partial agonist at the cAMP site. Rather, we find that genistein equivalently moves both HCN and HCN-RE channels closer to the open state (rendering the channels inherently easier to open but at a cost of decreasing the coupling energy of cAMP) and that the anomaly reflects a balance of these energetic effects with the isoform-specific inhibition of activation by the nucleotide gating ring and relief of this by endogenous cAMP. These findings have specific implications with regard to findings based on HCN-RE channels and kinase antagonists and general implications with respect to interpretation of drug effects in mutant channel backgrounds. [Copyright &y& Elsevier]

Five experiments were implemented to collect information related to the effects of fluazifop-p-butyl (active chemical in grass selective herbicides, Fusilade® and Fusilade Forte™) on seed germination, seedling emergence, growth and health of species native to southwest Australia (a grass and non-grasses), together with several co-occurring introduced species (grasses and a non-grass). Experiments investigated effects of herbicide concentrations, seed burial depths, seed-sowing times since herbicide application and application locations (foliage versus soil). Both herbicides, at half to quadruple strength of recommended field application concentrations, adversely affected development of native and introduced species, both grasses and non-grasses. Herbicidal effects were observed during the seed germination phase, and if germination had occurred, during seedling emergence and, finally, during plant establishment. However, effects were more pronounced after seed germination, particularly on development of seedlings and plants, with retardation and/or discoloration of either radicles or shoots. Not unexpectedly, seedlings from seeds buried deeper in the sand medium (20mm) struggled to emerge. Both herbicides demonstrated residual characteristics by impeding seedling emergence and growth from seeds sown at various dates (up to maximum test duration of 3 weeks) following exposure of the sand medium to the herbicides. Further, herbicide application to sand only, produced effects on 5–6 months old plants that were similar as application to foliage only, demonstrating herbicide uptake from sand. While the findings support independent research, they contradict the purported herbicide characteristics by commercial sources – grass selective, post-emergent, non-residual, rapid breakdown and active through foliar application only. Implications of these herbicides for biodiversity conservation are discussed. [Copyright &y& Elsevier]

Background: Extrathyroidal extension (ETE) is a risk factor for recurrence of papillary thyroid carcinoma (PTC). Although initial data supporting this was based on gross ETE noted at surgery, current treatment regimens group patients with microscopic ETE—identified only on histopathology—similarly to those with macroscopic (gross) ETE. This study was designed to assess the influence of microscopic ETE on disease recurrence. Methods: Retrospective analysis of 212 patients undergoing thyroidectomy for PTC between 1995 and 2004 with minimum 3-year follow-up was conducted. Results: Of 212 patients, 71 had ETE; 32% were macroscopic and 68% microscopic. Patient demographics, tumor variables, and adjuvant therapy were similar between both ETE groups. Recurrence rates were 52% for macroscopic ETE, 21% for microscopic ETE, and 13% without ETE. On multivariate analysis, patients with macroscopic ETE had a 6.4-fold increased relative risk of recurrence compared with patients with microscopic ETE (P < .02; 95% confidence interval, 1.6–25.9) and a significantly decreased disease-free survival (DFS). Furthermore, patients with microscopic ETE had neither a significantly increased risk of recurrence nor different DFS compared with patients without ETE. Conclusion: Macroscopic ETE has a higher incidence of disease recurrence than microscopic ETE, implying they should be considered separately when devising adjuvant treatment regimens. The significance of microscopic ETE is undetermined. [Copyright &y& Elsevier]

Transhydrogenase couples the redox reaction between NADH and NADP+ to proton translocation across a membrane. The protein has three components: dI binds NADH, dIII binds NADP+, and dII spans the membrane. Transhydrogenase is a "dimer" of two dI-dII-dIII "monomers"; x-ray structures suggested that the two catalytic sites alternate during turnover. Invariant Tyr146 in recombinant dI of Rhodospirillum rubrum transhydrogenase was substituted with Phe and Ala (proteins designated dI.Y146F and dI.Y146A, respectively). Analytical ultracentrifuge experiments and differential scanning calorimetry show that dI.Y146A more readily dissociates into monomers than wild-type dI. Analytical ultracentrifuge and Trp fluorescence experiments indicate that the dI.Y146A monomers bind NADH much more weakly than dimers. Wild-type dI and dI.Y146F reconstituted activity to dI-depleted membranes with similar characteristics. However, dI.Y146A reconstituted activity in its dimeric form but not in its monomeric form, this despite monomers retaining their native fold and binding to the dI-depleted membranes. It is suggested that transhydrogenase reconstructed with monomers of dI.Y146A is catalytically compromised, at least partly as a consequence of the lowered affinity for NADH, and this results from lost interactions between the nucleotide binding site and the protein β-hairpin upon dissociation of the dI dimer. The importance of these interactions and their coupling to dI domain rotation in the mechanism of action of transhydrogenase is emphasized. Two peaks in the ¹H NMR spectrum of wild-type dI are broadened in dI.Y146A and are tentatively assigned to S-methyl groups of Met resonances in the E-hairpin, consistent with the segmental mobility of this feature in the structure. [ABSTRACT FROM AUTHOR]

Objective: Femoral nail length can be estimated preoperatively by several methods, but this usually requires an intact contralateral femur. The aim of this study was to determine an alternative method using fibula and femoral head as references. Materials and Methods: Digital radiographic views of the lower limbs of 102 healthy volunteers were used to compare femoral medullary length with the sum of fibular length and transverse head diameter. Results: Femoral medullary length and the estimated length were highly correlated (r=0.942, p<0.0001). Paired samples t-testing has produced a high significance (p<0.002). Conclusion: The formula provides a simple and accurate estimation of femoral medullary length, and may be used in nailing, particularly of bilateral comminuted femoral fractures. [ABSTRACT FROM AUTHOR]

Abstract: Determination of the sex is one of the most important steps when evaluating decomposed bodies or skeletal remnants. However, relevant data exhibit significant ethnic and temporal variation. This study provides information on in vivo femoral dimensions of Anatolian Caucasians. 50 males and 54 females with ages between 18 and 68 years were investigated with computed tomography. For males, mean maximum length (ML) was 448.2mm, mean vertical head diameter (VHD) was 48.8mm, mean midshaft transverse diameter (MTD) was 26.5mm, and mean anterior bowing (AB) was 759.3mm. For females, these were 419.0mm, 43.4mm, 25.6mm, and 779.5mm, respectively. Femoral dimensions of Anatolian Caucasians were not entirely similar to a single racial group that was already reported. There was a significant difference between males and females regarding ML and VHD (p <0.0001 for both). MTD and AB did not exhibit sexual dysmorphism. Discriminant analysis for sex type produced 83.3% accuracy when ML was used, and 76.9% accuracy when VHD was used (p <0.0001). Combined use of both parameters increased overall accuracy to 84.6% (p <0.0001). For VHD, cut-off value of 44.9mm produced 94% sensitivity and 83% specificity. For ML, cut-off value of 428.6 produced 80% sensitivity and 67% specificity. [Copyright &y& Elsevier]

Transhydrogenase couples proton translocation across a membrane to hydride transfer between NADH and NADP+. Previous x-ray structures of complexes of the nucleotide-binding components of transhydrogenase ("dI2dIII1" complexes) indicate that the dihydronicotinamide ring of NADH can move from a distal position relative to the nicotinamide ring of NADP+ to a proximal position. The movement might be responsible for gating hydride transfer during proton translocation. We have mutated three invariant amino acids, Arg-127, Asp-135, and Ser-138, in the NAD(H)-binding site of Rho- dospirillum rubrum transhydrogenase. In each mutant, turnover by the intact enzyme is strongly inhibited. Stopped-flow experiments using dI2dIII1 complexes show that inhibition results from a block in the steps associated with hydride transfer. Mutation of Asp-135 and Ser-138 had no effect on the binding affinity of either NAD+ or NADH, but mutation of Arg-127 led to much weaker binding of NADH and slightly weaker binding of NAD+. X-ray structures of dI2dIII1 complexes carrying the mutations showed that their effects were restricted to the locality of the bound NAD(H). The results are consistent with the suggestion that in wild-type protein movement of the Arg-127 side chain, and its hydrogen bonding to Asp-135 and Ser-138, stabilizes the dihydronicotinamide of NADH in the proximal position for hydride transfer. [ABSTRACT FROM AUTHOR]

Abstract: Objective: This study describes a new technique for treatment of Buerger''s disease, developed to stimulate angiogenesis, using a Kirschner wire placed in the medullary canal of the tibia. The aim of the study was to evaluate clinical and radiological effects of this technique in patients where medical and surgical therapy had failed. Material and methods: Eleven extremities (six patients) with Buerger''s disease were treated with the intramedullary Kirschner wire technique. Inclusion criteria were chronic critical ischemia, Rutherford Grade II or III, with major arterial occlusion shown by Doppler examination and angiography; failure to respond to non-surgical and surgical treatment; and the need for strong analgesics. Results: The mean follow-up time was 19 months (range, 13–25 months). Satisfactory remission in each patient was obtained within 6 weeks of intervention. A significant improvement in clinical manifestations including reduced rest pain and increased claudication distance was observed. Foot ulcers completely healed after Kirschner wire intervention. Conclusion: Despite short-term follow-up and small patient series, the intramedullary Kirschner wire technique can be expected to achieve relief of pain and a decrease in major amputations in patients with Buerger''s disease in whom medical and surgical therapy had failed. However, comparative studies with longer follow-up should be done to confirm the benefits of this new treatment. [Copyright &y& Elsevier]

Environmental change and fishing activity can produce directional trends in exploited fish populations with consequences for stock productivity. For herring in the Celtic Sea, size at age has been in steady decline since the mid 1980's. In the neighbouring herring stock off the Northwest coast of Ireland, reductions in size at age are noted after 1990. Here, gradient boosting regression trees were used to investigate trends in extended time series (1959–2012) of length-at-age across both populations and to identify important variables associated with the observed declines in size. The predominant signal detected was a non-linear negative relationship between adult size and mean Sea Surface Temperature during the first growing season. Herring length was negatively correlated with the Atlantic Multidecadal Oscillation. Weaker associations with indicators of food availability and population size were also detected. Across both populations a marked decline in length was observed at the upper end of the temperature range (~14∘C in the Celtic Sea and ~13∘C in the Northwest). Declines in length and associations with temperature were more pronounced in the Celtic Sea population which may be vulnerable to increasing sea temperatures due to its position at the southern limit of the species distribution. [ABSTRACT FROM AUTHOR]

Abstract: INTRODUCTION: Intraoperative injury of obturator nerve is a rare complication of gynecologic surgeries, it has been reported especially in patients with endometriosis and genitourinary malignancies. Gynecologic patients undergoing open lymphadenectomy are at increased risk of obturator nerve injury. PRESENTATION OF CASE: A 60-year-old woman with FIGO stage II Grade II endometrial adenocarcinoma underwent bilateral pelvic paraaortic lymphadenectomy. During right obturator lymph node dissection, the right obturator nerve was inadvertently transected with Harmonic scalpel sealing system. The graft was used to anastomose epyneurium of distal segment of obturator nerve to its counterpart in the proximal segment with 10–0 prolen suture. DISCUSSION: In case of iatrogenic nerve transection, microsurgical end to end tension-free coaptation is advocated. In case of the obturator nerve is fixed and because of the thermal injury end to end alignment can not be achieved, nerve grafting is necessary. CONCLUSION: According to our knowledge, successful immediate grafting of iatrogenically damaged obturator nerve during pelvic lymphadenectomy in our patient is the third report of such a case, but also it has a unique feature of being the first obturator nerve repairing case after dissected with tissue sealing system which causes large sealed area that does not make it possible to make end-to-end anastomosis without nerve harvesting. [Copyright &y& Elsevier]

Alcohol and cannabis are two of the most commonly used substances by adolescents and are associated with adverse medical and psychiatric outcomes. These adverse psychiatric outcomes may reflect the negative impact of alcohol and/or cannabis abuse on neural systems mediating reward and/or error detection. However, work indicative of this has mostly been conducted in adults with Alcohol and/or Cannabis Use Disorder (i.e., AUD and CUD), with relatively little work in adolescent patients. Furthermore, of the work that has been conducted in adolescents, groups were based on categorical diagnoses of AUD and/or CUD, so the relationship between AUD and/or CUD symptom severity in adolescents and neural dysfunction is unclear. We used a Monetary Incentive Delay (MID) task to examine the relationship between AUDIT and/or CUDIT scores and functional integrity of neuro-circuitries mediating reward processing and error detection within 150 adolescents. Our findings indicate that AUDIT score is negatively related to activity in reward processing neuro-circuitry in adolescents. However, CUDIT score is negatively related to activity in brain regions involved in error detection. Each of these relationships reflected a medium effect size (Partial-η2 0.09-0.14). These data suggest differential impacts of AUD and CUD on reward versus error detection neuro-circuitries within the adolescent brain. [ABSTRACT FROM AUTHOR]