Milk: white elixir or white poison? An examination of the associations between dairy consumption and disease in human subjects

Implications Overall, milk consumption provides health benefits to all age groups. Effects of cheese, butter, and fat-reduced and saturated fat-reduced milk and dairy products are less clear and require more research. Public health nutrition policy related to milk consumption should be based on the evidence presented and not solely on the believed negative effects of dietary fat. Milk is not a white elixir since no study has reported eternal youth from drinking it, but there is certainly no evidence that milk is a white poison!

Plasma free fatty acids do not provide the link between obesity and insulin resistance or β-cell dysfunction: results of the Reading, Imperial, Surrey, Cambridge, Kings (RISCK) study

Aims To investigate the relationship between adiposity and plasma free fatty acid levels and the influence of total plasma free fatty acid level on insulin sensitivity and β-cell function. Methods An insulin sensitivity index, acute insulin response to glucose and a disposition index, derived from i.v. glucose tolerance minimal model analysis and total fasting plasma free fatty acid levels were available for 533 participants in the Reading, Imperial, Surrey, Cambridge, Kings study. Bivariate correlations were made between insulin sensitivity index, acute insulin response to glucose and disposition index and both adiposity measures (BMI, waist circumference and body fat mass) and total plasma free fatty acid levels. Multivariate linear regression analysis was performed, controlling for age, sex, ethnicity and adiposity. Results After adjustment, all adiposity measures were inversely associated with insulin sensitivity index (BMI: β = −0.357; waist circumference: β = −0.380; body fat mass: β = −0.375) and disposition index (BMI: β = −0.215; waist circumference: β = −0.248; body fat mass: β = −0.221) and positively associated with acute insulin response to glucose [BMI: β = 0.200; waist circumference: β = 0.195; body fat mass β = 0.209 (P values <0.001)]. Adiposity explained 13, 4 and 5% of the variation in insulin sensitivity index, acute insulin response to glucose and disposition index, respectively. After adjustment, no adiposity measure was associated with free fatty acid level, but total plasma free fatty acid level was inversely associated with insulin sensitivity index (β = −0.133), acute insulin response to glucose (β = −0.148) and disposition index [β = −0.218 (P values <0.01)]. Plasma free fatty acid concentration accounted for 1.5, 2 and 4% of the variation in insulin sensitivity index, acute insulin response to glucose and disposition index, respectively. Conclusions Plasma free fatty acid levels have a modest negative association with insulin sensitivity, β-cell secretion and disposition index but no association with adiposity measures. It is unlikely that plasma free fatty acids are the primary mediators of obesity-related insulin resistance or β-cell dysfunction.

Rerum cognoscere causas: part I - How do the ideas of system dynamics relate to traditional social theories and the voluntarism/determinism debate?

This is the first half of a two-part paper which deals with the social theoretic assumptions underlying system dynamics. The motivation is that clarification in this area can help mainstream social scientists to understand how our field relates to their literature, methods and concerns. Part I has two main sections. The aim of the first is to answer the question: How do the ideas of system dynamics relate to traditional social theories? The theoretic assumptions of the field are seldom explicit but rather are implicit in its practice. The range of system dynamics practice is therefore considered and related to a framework - widely used in both operational research (OR) and systems science - that organises the assumptions behind traditional social theoretic paradigms. Distinct and surprisingly varied groupings of practice are identified, making it difficult to place system dynamics in any one paradigm with any certainty. The difficulties of establishing a social theoretic home for system dynamics are exemplified in the second main section. This is done by considering the question: Is system dynamics deterministic? An analysis shows that attempts to relate system dynamics to strict notions of voluntarism or determinism quickly indicate that the field does not fit with either pole of this dichotomous, and strictly paradigmatic, view. Part I therefore concludes that definitively placing system dynamics with respect to traditional social theories is highly problematic. The scene is therefore set for Part II of the paper, which proposes an innovative and potentially fruitful resolution to this problem.

Motion of the dayside polar cap boundary during substorm cycles: I. Observations of pulses in the magnetopause reconnection rate

Using data from the EISCAT (European Incoherent Scatter) VHF radar and DMSP (Defense Meteorological Satellite Program) spacecraft passes, we study the motion of the dayside open-closed field line boundary during two substorm cycles. The satellite data show that the motions of ion and electron temperature boundaries in EISCAT data, as reported by Moen et al. (2004), are not localised around the radar; rather, they reflect motions of the open-closed field line boundary at all MLT throughout the dayside auroral ionosphere. The boundary is shown to erode equatorward when the IMF points southward, consistent with the effect of magnetopause reconnection. During the substorm expansion and recovery phases, the dayside boundary returns poleward, whether the IMF points northward or southward. However, the poleward retreat was much faster during the substorm for which the IMF had returned to northward than for the substorm for which the IMF remained southward – even though the former substorm is much the weaker of the two. These poleward retreats are consistent with the destruction of open flux at the tail current sheet. Application of a new analysis of the peak ion energies at the equatorward edge of the cleft/cusp/mantle dispersion seen by the DMSP satellites identifies the dayside reconnection merging gap to extend in MLT from about 9.5 to 15.5 h for most of the interval. Analysis of the boundary motion, and of the convection velocities seen near the boundary by EISCAT, allows calculation of the reconnection rate (mapped down to the ionosphere) from the flow component normal to the boundary in its own rest frame. This reconnection rate is not, in general, significantly different from zero before 06:45 UT (MLT<9.5 h) – indicating that the X line footprint expands over the EISCAT field-of-view to earlier MLT only occasionally and briefly. Between 06:45 UT and 12:45UT (9.5the (large) MLT extent of the reconnection footprint deduced from the DMSP passes. As well as direct control by the IMF on longer timescales, the derived reconnection rate variation shows considerable pulsing on timescales of 2–20 min during periods of steady southward IMF.

The evolution of the Sun's open magnetic flux: I. a single bipole

In this paper the origin and evolution of the Sun’s open magnetic flux are considered for single magnetic bipoles as they are transported across the Sun. The effects of magnetic flux transport on the radial field at the surface of the Sun are modeled numerically by developing earlier work by Wang, Sheeley, and Lean (2000). The paper considers how the initial tilt of the bipole axis (α) and its latitude of emergence affect the variation and magnitude of the surface and open magnetic flux. The amount of open magnetic flux is estimated by constructing potential coronal fields. It is found that the open flux may evolve independently from the surface field for certain ranges of the tilt angle. For a given tilt angle, the lower the latitude of emergence, the higher the magnitude of the surface and open flux at the end of the simulation. In addition, three types of behavior are found for the open flux depending on the initial tilt angle of the bipole axis. When the tilt is such that α ≥ 2◦ the open flux is independent of the surface flux and initially increases before decaying away. In contrast, for tilt angles in the range −16◦ < α < 2◦ the open flux follows the surface flux and continually decays. Finally, for α ≤ −16◦ the open flux first decays and then increases in magnitude towards a second maximum before decaying away. This behavior of the open flux can be explained in terms of two competing effects produced by differential rotation. Firstly, differential rotation may increase or decrease the open flux by rotating the centers of each polarity of the bipole at different rates when the axis has tilt. Secondly, it decreases the open flux by increasing the length of the polarity inversion line where flux cancellation occurs. The results suggest that, in order to reproduce a realistic model of the Sun’s open magnetic flux over a solar cycle, it is important to have accurate input data on the latitude of emergence of bipoles along with the variation of their tilt angles as the cycle progresses.

Fast or slow melting of the Marinoan snowball Earth? The cap dolostone record

The end of the Neoproterozoic era is punctuated by two global glacial events marked by the presence of glacial deposits overlaid by cap carbonates. Duration of glacial intervals is now consistently constrained to 3-12 million years but the duration of the post-glacial transition is more controversial due to the uncertainty in cap dolostone sedimentation rates. Indeed, the presence of several stratabound magnetic reversals in Brazilian cap dolostones recently questioned the short sedimentation duration (a few thousand years at most) that was initially suggested for these rocks. Here, we present new detailed magnetostratigraphic data of the Mirassol d`Oeste cap dolostones (Mato Grosso, Brazil) and ""bomb-spike"" calibrated AMS (14)C data of microbial mats from the Lagoa Vermelha (Rio de Janeiro, Brazil). We also compile sedimentary, isotopic and microbiological data from post-Marinoan outcrops and/or recent depositional analogues in order to discuss the deposition rate of Marinoan cap dolostones and to infer an estimation of the deglaciation duration in the snowball Earth aftermath. Taken together, the various data point to a sedimentation duration in the range of a few 10(5) years. (C) 2010 Elsevier B.V. All rights reserved.

Chronic supplementation of beta-hydroxy-beta methylbutyrate (HM beta) increases the activity of the GH/IGF-I axis and induces hyperinsulinemia in rats

Objective: Beta-hydroxy-beta-methylbutyrate (HM beta) is a metabolite of leucine widely used for improving sports performance. Although limp is recognized to promote anabolic or anti-catabolic effects on protein metabolism, the impact of its long-term use on skeletal muscle and/or genes that control the skeletal protein balance is not fully known. This study aimed to investigate whether chronic HM beta treatment affects the activity of GH/IGF-I axis and skeletal muscle IGF-I and myostatin mRNA expression. Design: Rats were treated with HK beta (320 mg/kg BW) or vehicle, by gavage, for 4 weeks, and killed by decapitation. Blood was collected for evaluation of serum insulin, glucose and IGF-I concentrations. Samples of pituitary, liver, extensor digitorum longus (EDL) and soleus muscles were collected for total RNA or protein extraction to evaluate the expression of pituitary growth hormone (GH) gene (mRNA and protein), hepatic insulin-like growth factor I (IGF-I) mRNA, skeletal muscle IGF-I and myostatin mRNA by Northern blotting/real time-PCR, or Western blotting. Results: Chronic HM beta treatment increased the content of pituitary GH mRNA and GH, hepatic IGF-I mRNA and serum IGF-I concentration. No changes were detected on skeletal muscle IGF-I and myostatin mRNA expression. However, the HIM-treated rats although normoglycemic, exhibited hyperinsulinemia. Conclusions: The data presented herein extend the body of evidence on the potential role of HM beta-treatment in stimulating GH/IGF-I axis activity. In spite of this effect, HM beta supplementation also induces an apparent insulin resistance state which might limit the beneficial aspects of the former results, at least in rats under normal nutritional status and health conditions. (C) 2010 Growth Hormone Research Society. Published by Elsevier Ltd. All rights reserved.

On the synthesis and structures of the complexes [RuCl(L)(dppb)(N-N)]PF(6) (L = CO, py or 4-NH(2)py; dppb=1,4-bis(diphenylphosphino)butane; N-N=2,2 `-bipyridine or 1,10-phenanthroline) and [(dppb)(CO)Cl(2)-Ru-pz-RuCl(2)(CO)(dppb)] (pz = pyrazine)

The ""Ru(P-P)"" unit (P-P = diphosphine) is recognized to be an important core in catalytic species for hydrogenation of unsaturated organic substrates. Thus, in this study we synthesized six new complexes containing this core, including the binuclear complex [(dppb)(CO)Cl(2)Ru-pz-RuCl(2)(CO)(dPPb)] (pz = pyrazine) which can be used as a precursor for the synthesis of cationic carbonyl species of general formula [RuCl(CO)(dppb)(N-N)]PF(6) (N-N = diimine). Complexes with the formula (RuCl(py)(dppb)(N-N)]PF(6) were synthesized by exhaustive electrolysis of these carbonyl compounds or from the precursors [RuCl(2)(dppb)(N-N)]. The new complexes were characterized by microanalysis, conductivity measurements, IR and (31)P{(1)H)} NMR spectroscopy, cyclic voltammetry and X-ray crystallography. (C) 2010 Elsevier Ltd. All rights reserved.

Inhibition of the myotoxic activity of Bothrops jararacussu venom and its two major myotoxins, BthTX-I and BthTX-II, by the aqueous extract of Tabernaemontana catharinensis A. DC. (Apocynaceae)

Partial neutralization of the myotoxic effect of Bothrops jararacussu venom (BV) and two of its myotoxins [bothropstoxin-I (BthTX-I), catalytically inactive, and II (BthTX-II), showing low PLA(2) activity], by the lyophilized aqueous extract of Tabernaemontana catharinensis (AE), was studied in rat isolated soleus muscle preparations (in vitro) and through i.m. injection in the gastrocnemius muscle (in vivo) by determination of creatine kinase (CK) activity and histopathological analysis. Incubation of soleus muscle for 1 h with BV or toxins (20 mug/ml) plus AE (400 mug/ml) added immediately after BV, BthTX-I or BthTX-II reduced CK levels by 53%, 37% and 56%, respectively. The myonecrotic effects of BV (20 mug/ml) upon soleus muscle was reduced 24%, 35% and 36% when AE (400 mug/ml) was added 1 h after BV and CK was evaluated 30 min, 1 and 2 h later, respectively. For BthTX-I these values were 46%, 48% and 47%, while for BthTX-II no inhibitory effect was detected. Histological analysis of soleus muscle after incubation with AE (400 mug/ml, I h) did not reveal any change in muscle fibers, but severe necrosis induced by -BV or toxins (20 mug/ml) was clearly in evidence, and decreased significantly when soleus muscle was protected by AE. This protection was also observed when AE was administered 1 h after BV or BthTX-I, but not after BthTX-II. AE did not inhibit the catalytic PLA(2), activity of BthTX-II or BV and did not change the PAGE pattern of BV, BthTX-I or BthTX-II. In vivo assays were performed in 100-g rats and maximal CK release was attained at a dose of 100 mug of BV, 3 h after injection. AE was not effective when injected 20 s after BV or toxins. However, injecting BV or toxins (100 mug), which were pre-incubated with AE (2 mg) caused an inhibition of 57%, 59% and 51%, respectively, with zero time pre-incubation, but was less effective with I h pre-incubation. This plant represents a potential source of promising myotoxin inhibitors. (C) 2004 Elsevier GmbH. All rights reserved.

DNA methylation in the CTCF-binding site I and the expression pattern of the H19 gene: Does positive expression predict poor prognosis in early stage head and neck carcinomas?

Loss of allele-specific expression by the imprinted genes IGF2 and H19 has been correlated with a differentially methylated region (DMR) upstream to the H19 gene. The H19-DMR contains seven potential CCCTC-binding factor (CTCF) binding sites. CTCF is a chromatin insulator and a multifunctional transcription factor whose binding to the H19-DMR is suppressed by DNA methylation. Our study included a group of 41 head and neck squamous cell carcinoma (HNSCC) samples. The imprinting status of the H19 gene was analyzed in 11 out of 35 positive cases for H19 gene expression, and only 1 of them showed loss of imprinting. We detected a significant correlation (P=0.041, Fisher's exact test) between H19 expression and tumor recurrence. Among H19 positive cases, six were T2, in which five developed recurrence and/or metastasis. Inversely, in the group of tumors that showed no H19 gene expression, 5 out of 24 were T2 and only I presented regional recurrence. These data support the hypothesis that H19 expression could be used as a prognostic marker to indicate recurrence in early stage tumors. We also examined the methylation of the CTCF binding site 1 in a subgroup of these samples. The H19 gene silencing and loss of imprinting were not correlated with the methylation pattern of the CTCF binding site 1. However, the significant correlation between H19 expression and tumor recurrence suggest that this transcript could be a marker for the progression of HNSCC. (c) 2005 Wiley-Liss, Inc.

In situ evaluation of the remineralizing capacity of pit and fissure sealants containing amorphous calcium phosphate and/or fluoride

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Comparative evaluation of the efficacy of occlusal splints fabricated in centric relation or maximum intercuspation in temporomandibular disorders patients

Fabrication of occlusal splints in centric relation for temporomandibular disorders (TMD) patients is arguable, since this position has been defined for asymptomatic stomatognathic system. Thus, maximum intercuspation might be employed in patients with occlusal stability, eliminating the need for interocclusal records. This study compared occlusal splints fabricated in centric relation and maximum intercuspation in muscle pain reduction of TMD patients. Twenty patients with TMD of myogenous origin and bruxism were divided into 2 groups treated with splints in maximum intercuspation (I) or centric relation (II). Clinical, electrognathographic and electromyographic examinations were performed before and 3 months after therapy. Data were analyzed by the Student's t test. Differences at 5% level of probability were considered statistically significant. There was a remarkable reduction in pain symptomatology, without statistically significant differences (p>0.05) between the groups. There was mandibular repositioning during therapy, as demonstrated by the change in occlusal contacts on the splints. Electrognathographic examination demonstrated a significant increase in maximum left lateral movement for group I and right lateral movement for group II (p<0.05). There were no significant differences (p>0.05) in the electromyographic activities at rest after utilization of both splints. In conclusion, both occlusal splints were effective for pain control and presented similar action. The results suggest that maximum intercuspation may be used for fabrication of occlusal splints in patients with occlusal stability without large discrepancies between centric relation and maximum intercuspation. Moreover, this technique is simpler and less expensive.

Monoamine oxidase inhibitory activities of indolylalkaloid toxins from the venom of the colonial spider Parawixia bistriata: Functional characterization of PwTX-I

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)