bluuebunny/crossref_metadata_2025 huggingface dataset:
Spinal disulfide HMGB1, but not all-thiol HMGB1, induces mechanical hypersensitivity in a TLR4-dependent manner
Authors: Agalave N.M. , AbdelMoaty S. , Lundback P. , Andersson U. , Harris H. , Svensson C.I.
Published: July 2015

Aims

Increasing evidence indicates that extracellular high mobility group box-1 protein (HMGB1) is involved in the pathogenesis of inflammatory and autoimmune disease. Data from our laboratory demonstrates that HMGB1 contributes to nociceptive behavior in a model of rheumatoid arthritis-induced pain. HMGB1 binds to multiple receptors, including toll like receptor (TLR) 2, TLR4 and receptor for advanced glycation end products (RAGE). When the cysteine in position C106 is in the reduced thiol form and C23 and C45 are engaged in a disulfide bridge (disulfide HMGB1), the molecule functions as a cytokine-inducing TLR4 ligand. In contrast, when these three cysteines are all reduced (all-thiol HMGB1), HMGB1 exclusively potentiates chemotactic activity via CXCR4. It is currently not well understood which receptor and which redox form of HMGB1 that mediates pain hypersensitivity and is therefore the aim of this study.

Methods

All animal work was carried out in accordance with protocol approved by the local ethics committee for animal experiments in Sweden. Balb/c, C57B/l6 (WT), Tlr2–/–, Tlr4–/– and Rage–/– male mice were used for this study. Disulfide (ds) and all thiol (at) form of HMGB1 were injected intrathecally (1 μg) and mechanical hypersensitivity assessed by von Frey filaments. Lumbar spinal cords were collected after i.t. injection of atHMGB1 and ds HMGB1 and mRNA levels for cytokine and glia markers assessed by quantitative PCR.

Results

In Balb/c and C57Bl/6 WT mice, i.t injection of dsHMGB1, but not atHMGB1, led to a significant reduction in mechanical thresholds. dsHMGB1 induced mechanical hypersensitivity 6 h after i.t. injection, which lasted for 5 days, compared to i.t. injection of saline. When dsHMGB1 was injected i.t. to Tlr4 deficient mice it did not induce mechanical hypersensitivity. In contrast Tlr2 and Rage deficient mice were still susceptible to dsHMGB1-induced mechanical hypersensitivity. Analysis of mRNA for cytokines and glial cell-associated factors in lumbar spinal cords revealed increased levels of Tnf, Ccl2, Cxcl1, Cxcl2, Gfap and Cd11b in mice injected with dsHMGB1, but not atHMGB1, with exception for Il1β and Cxcr3 that was induced also by atHMGB1. Intrathecal injection of dsHMGB1 to Tlr4
–/– deficient mice, did not increase mRNA levels for Tnf, Il1β, Ccl2, Gfap and Cd11b.

Conclusions

We found the i.t. injection of the disulfide, but not the all-thiol, form of HMGB1 to induce pronouncedand long-lasting mechanical hypersensitivity, glial reactivity and cytokine induction in a TLR4-, but not TLR2- or RAGE-dependent manner. Thus our data indicates that, the redox state of HMGB1 is key for determining its nociceptive property and receptor usage and thus also the functional consequences of HMGB1 release. Agents interfering with extracellular HMGB1 may be considered in the development of new pain relieving therapeutics.
Association between chronic pain and the sperm motion characteristics
Authors: Dardmeh F. , Alipour H. , Nielsen H.I. , Rasmussen S. , Yousefi J.T. , Ditlevsen N.E. , Yassin H.A.A.K.T. , Morina E. , Duus R.K. , Gazerani P.
Published: July 2015

Aims

Sex hormones play an important role in pain in many chronic pain conditions. Relationship between chronic pain and sperm quality has not been investigated thoroughly and may provide an insight to better understanding, management and treatment of cases where chronic pain and male sub-fertility co-exist.

Methods

Neat (fresh semen) and processed sperm from 15 males with orthopedic chronic pain (CP) were assessed and compared with 15 healthy age matched controls. Sperm analysis was performed using the SCA computer-aided sperm analyzer.

Results

There was no significant difference in any parameters of the neat semen between the pain and control group. However the percentage of non-progressive motile spermatozoa (type B) was significantly higher in the pain group (27.96) compared to the control group (15.96). Straight line trajectories including linearity, straightness, wobble and beat cross frequency were also significantly higher in the processed sample of the CP group.

Conclusions

This study demonstrated that chronic pain does not affect the sperm morphology, total concentration and motility based on conventional analysis but has significant influence at the level of sperm motion kinetics which could prove to be clinically valuable, prognostic indicators of successful fertilization. Maturation of sperm motility occurs during their transit through the epididymis and vas deferens regulated by androgens. As male gonadal hormones haveaninhibitory, adaptive effectonthe behavioral and neuronal responses to repeated nociceptive stimulation, it can be speculated that the observed difference in sperm kinematic parameters could be related to the alterations in serum sex hormone levels emanating from the chronic pain. Further studies are required to explain the possible mechanism of actionof chronic pain on male fertility.
Spontaneous burrowing behavior as an outcome measure of the global impact of chronic pain in preclinical models of arthritis
Authors: Delaney A. , Su J. , Gao T. , Agalave N. , Svensson C.I.
Published: July 2015

Aims

Arthritis is the leading cause of chronic pain in European adults (painineurope.com). Arthritis-induced chronic pain is a major clinical problem that is frequently inadequately treated by current analgesics and results in significant reduction in the patient’s quality of life. Outcome measures used in pain research to assess injury-induced pain-like behaviours in preclinical models are often dependent on the assessment of withdrawal reflexes, typically evoked by mechanical or thermal stimuli.Advances inpre-dictive validity may be improved by assessing the global impact of pain and the reinstatement of innate behaviours suppressed by injury. Burrowing, an indicator of the global “wellbeing” of the animal can be objectively measured. We aimed to assess the impact of several preclinical modelsof arthritis onburrowing behaviour in mice.

Methods

The collagen antibody-induced arthritis (CAIA) pre-clinical model of rheumatoid arthritis, the complete Freund’s adjuvant (CFA), monosodium iodoacetate (MIA) and partial medial menisectomy (MMT) preclinical models of osteoarthritis were assessed in female and/or male C57/Black6J adult mice, comparing to control (salineorsham-operated) and naïve animals. Mechanical hypersensitivity using von Frey filaments and spontaneous burrowing behaviour were assessed over60days (CAIA), 14days (CFA), 28 days (MIA) and up to 200 days (MMT).

Results

We show the development of mechanical hypersen-sitivity in all preclinical models of arthritis, whereas spontaneous burrowing behaviour was altered differently between the preclin-ical models. A deficit in burrowing behaviour was observed in the preclinical models of osteoarthritis and a gain in burrowing behaviour noted in the preclinical model of rheumatoid arthritis, with no effect seen in the CFA model.

Conclusions

Burrowing behaviour appears more sensitive to detecting variation in preclinical models of arthritis when compared to mechanical hypersensitivity. Burrowing behaviour can detect both gain and deficits in the behaviour, which differs between preclinical models of rheumatoid and osteoarthritis.
Effects of habituation to the testing facility on mechanical nociceptive thresholds of pigs
Authors: Giminiani P. Di , Stausholm J.S. , Viitasaari E. , Petersen L.J. , Herskin M.S.
Published: July 2015

Aims

This study aimed to gain methodological knowledge about quantification of mechanical nociceptive thresholds in pigs stimulated on the hind legs.

Methods

Thirty-two castrated male pigs were used, weighing 50–60kg, 16 weeks of age and housed in standard pens (4.40m×4.40m) with ad libitum access to water and feed. Mechanical nociceptive testing (4 stimulations/pig) was done by an electronic von Frey anesthesiometer (IITC Life Science Inc., CA) with a rigid, hollow plastic tip (cut-off: 1000 gf) and an area of 0.3 mm2. Stimulations targeted caudal aspects of the metatarsus while the pigs were restrained in a cage measuring 35cm×40cm (length×width). During the last 3d before nociceptive testing, half of the pigs were habituated to the experimental set-up twice daily.

Results

Across the three days, the habituation procedure led to a reduction in time required to approach and release the pigs from the home pen (P<0.05) and to increased acceptance of the confinement (P<0.01). The habituated animals had a lower mechanical nociceptive threshold (median: 495gf (302–675) vs 745gf (479–1000); P<0.05), and a decreased occurrence of censored observations (0 vs 25%; P<0.05) compared to animals tested without habituation.

Conclusions

The present experiment focussed on methodological aspects of hand-held tests of mechanical nociceptive thresholds in pigs. The results show that the pigs responded to a 3-day habituation regime by increased ease of handling and tolerance of being confined in a test cage. In addition, habituation to the test environment and handling led to reduced mechanical nociceptive thresholds as well as a lowered proportion of censored observations. The current results reiterate the value of habituation in research involving animal behaviour. Further characterization of the methodology is needed to allow its application in the evaluation of clinical conditions in pigs.
Chronic nonmalignant pain at a mono-disciplinary pain clinic. Identifying the key patient groups for targeted health promotion – A cohort study
Authors: Hansen C.
Published: July 2015

Aims

To identify and describe the most common category of patients in a newly established mono-disciplinary pain clinic, in order to plan, test, evaluate and implement targeted health promotion interventions.

Methods

The study was a register-based retrospective cohort study comprising data from the hospital registration system GS!open. Including chronic non-malignant pain patients in the period January 1st 2013 to December 31st 2014; analysing only patients who underwent a treatment trajectory by the mono-disciplinary pain clinic.

Results

The study population consisted of 300 men and 509 women, mean age 53.6 year. By descriptive statistics the three major patient groups was identified: (1) Long lasting/chronic non-malignant pain – comprising 52% of the cohort, representing 37% male, mean age 54.9 year, mainly labeled nonspecific back pain; (2) Other chronic pain– representing 15% of the cohort, comprising 45% male, mean age 56.0 year; (3) Reflex dystrophy – comprising 8% of the cohort, with 30% male, mean age 43.6 year. The clinic had 4.161 outpatient consultations in the period with an increase of 13.9% from 2013 to 2014; average consultation rate per individual was 5.2 for women both years; for men the average was 5.1 in 2013 and 4.9 in 2014. In addition, the pain clinic patients were referred from: hospital (89.3%); hospital waiting trajectory (1.7%); general practitioner (7.3%) and practitioner specialist (1.7%).

Conclusions

This register-based study revealed that patients with nonspecific back pain were the most frequent patient category treated in the mono-disciplinary pain clinic. This finding suggests that targeted health promotion intervention may advantageously be organized with focus on the large group of patients with chronic nonspecific back pain.
Gender differences in chronic pain related health care utilization
Authors: Jonsdottir T. , Jonsdottir H. , Gunnarsdottir S.
Published: July 2015

Aims

To investigate predictors for health-care utilization for chronic pain and whether there are gender differences in variables predicting chronic pain-related health care utilization.

Methods

A postal questionnaire measuring socio-demographic variables, pain characteristics, health related quality of life (HRQoL) and pain related health care utilization, was sent to a sample of 4500 individuals randomly drawn from the national population of Iceland. The relationships between socio-demographic and pain related variables and pain related health care utilization among participants reporting chronic pain (≥3 months) were tested by using bivariate and multivariate statistical analysis.

Results

The prevalence of chronic pain among respondents was 47.5%. Among participants reporting chronic pain, 53.2% had consulted a health care provider for pain during the previous six months.Predictors for pain related health care utilization were pain interference with daily life and pain pattern (daily pain) as well as physical components of HRQoL. Even though health care utilization was not related to gender, there were gender differences in pain-related predictors for health care utilization. Interference with daily life and pain pattern were the strongest predictors among women, but interference with life and the physical components of HRQoL were the strongest predictors for men. Pain related health care utilization was not related to socio-demographic variables.

Conclusions

Pain related variables are better predictors of chronic pain related health care utilization than socio-demographics. Even though gender does not predict chronic pain-related health care utilization, there are gender differences in the relationships between pain-related variables and health care utilization. These gender differences warrant further exploration.
Cerebrospinal fluid levels of substance P (SP) N-terminal fragment SP1–7 in patients with neuropathic pain
Authors: Jonsson A. , Lind A.-L. , Hallberg M. , Nyberg F. , Gordh T.
Published: July 2015

Aims

Neuropathic pain is a complex and painful condition, which is difficult to treat and causes a lot of suffering. The substance P (SP) system is well known to be involved in nociceptive signaling and it has previously been shown that the cerebrospinal fluid (CSF) level of SP is decreased in neuropathic pain. In this study we analyzed CSF from chronic neuropathic pain patients for the levels of SP1–7, an N-terminal fragment of SP with the ability to alleviate thermal as well as mechanical hypersensitivity in different animal models of chronic neuropathic pain, e.g. [1,2].

Methods

CSF was collected from 11 neuropathic pain patients, treated with SCS, who had refrained from using their spinal cord stimulator for 48h. Control CSF was collected from 11 patients without any known neurological disorder, who underwent minor surgery under spinal anesthesia. The CSF samples were analyzed for the levels of SP1–7 using radioimmunoassay.

Results

The results revealed a decrease in the level of SP1–7 compared to controls. We believe that the lower level ofSP1–7 most likely is a consequence of reduced amount of its precursor SP in the neuropathic pain patients.

Conclusions

Our results indicate that the SP system is changed in patients with neuropathic pain and that SP-related peptides, including SP1–7, might serve as biological markers for the patho-physiology of chronic neuropathic pain.
Characterization of small nerve fibers in painful distal symmetric polyneuropathy and healthy controls
Authors: Karlsson P. , Haroutounian S. , Polydefkis M. , Nyengaard J.R. , Jensen T.S.
Published: July 2015

Aims

The introduction of skin biopsies to examine small nerve fiber morphology together with functional measures such as quantitative sensory testing (QST) has led to an improvement in diagnosing patients with small fiber neuropathy (SFN). Quantification of intraepidermal nerve fiber density (IENFD) is an important measure in SFN. However, the relationship between structure and function is not straightforward and the morphological and functional fiber characteristics are still unclear. This study aimed to combine structural and functional measurements to improve the diagnosis of distal symmetric polyneuropathy and small fiber involvement. Additionally, we investigated whether patients and healthy controls have differential patterns of correlations between structural and functional nerve measurements.

Methods

17 patients with painful distal symmetric polyneu-ropathy (DSP) and 19 controls underwent comprehensive small fiber assessments that included quantitative sensory testing, response to topical capsaicin and analysis of skin biopsy samples (IENFD, epidermal and dermal nerve fiber length densities (eNFLD, dNFLD) and swellings).

Results

DSP patients had reduced sensitivity to cold and heat, diminished capsaicin response, and lower IENFD, eNFLD and dNFLD (all p < 0.0003).The correlation between structural and functional parameters was better in controls than in DSP. A diagnostic approach of combined IENFD and eNFLD utilization, increased DSP diagnostic sensitivity from 82.0% to 100% and specificity from 84.0% to 89.5%.

Conclusions

A correlation is found between functional and structural small fiber parameters for DSP and controls, and an approach to improve diagnostic accuracy in DSP is suggested.
New players in the mechanism of spinal cord stimulation for neuropathic pain
Authors: Lind A. , Emami P. , Sjödin M. , Katila L. , Wetterhall M. , Gordh T. , Kultima K.
Published: July 2015

Aims

The aim of this study was to uncover possible proteins involved in the mechanism for neuropathic spinal cord stimulation (SCS) pain relief in humans.

Methods

Using two different proteomic protocols we compared the protein concentration in cerebrospinal fluid (CSF) from 14 SCS responsive neuropathic pain patients using a shotgun proteomic approach. The comparison was made between samples from the same individual taken when the stimulator had been off for 48 h, and after the stimulator had been used as normal for three weeks. Mass spectrometry raw files from both experimental setups were analysed using MS Quant and DeCyder softwares and proteins were identified using MASCOT search against Swissprot database. After median normalization moderate paired t-test statistics were used in R limma package to find up-and down regulated proteins.

Results

In total, 255 and 216 proteins could be identified by the dimethyl and label free methods respectively and relatively quantified. Of these several were significantly up- and down regulated.

Conclusions

These novel proteins add to the SCS mechanism in patients with neuropathic pain. These results strengthen the evidence for SCS as altering extracellular matrix components and affecting central nervous system plasticity.
Hyperalgesia after experimental and work-related sleep restriction
Authors: Nilsen K.B. , Matrea D.
Published: July 2015

Aims

Sleep restriction (SR) increases pain sensitivity. The aim of this study was to compare the effects of night work on pain sensitivity with experimental SR.

Methods

In study I 22 healthy volunteers (14 females) and in study II 24 nurses (17 females) received pain stimuli in the laboratory twice; after 2 nights with habitual sleep (study I and II) and after 2 nights of experimental 50% SR (study I) or after 2 nights of work (study II). Order of sleep conditions was randomized. Heat pain at intensity 6/10 (pain-6), the pressure pain threshold (PPT), and subjective sleepiness with Karolinska sleepiness scale (KSS) were assessed. A linear mixed model (LMM) with random intercept and random slope was used. Difference scores were compared between study I and II by independent t-tests (PPT and pain-6) and the Mann–Whitney U test (KSS).

Results

Baseline subjective sleepiness (KSS), PPT or pain-6 ratings did not differ between study I and II (p > 0.47). KSS and heat pain ratings increased after both sleep conditions (p < 0.001), but did not differ between study I and II (p > 0.15). PPT was lower after experimental SR (p = 0.007), but unchanged after night work (p = 0.63), but did not differ between study I and II (p = 0.16).

Conclusions

Both experimental and night work-induced SR leads to comparable increased subjective sleepiness and higher pain ratings to heat pain stimuli. PPT was lower after experimental SR, but was not affected by night work-induced SR.
The effect of tail docking in neonatal pigs on the central expression of genes involved in modulating anxiety-like behaviour
Authors: Oberst P. , Sandercock D.A. , Di Giminiani P. , Edwards S.A. , Brunton P.J.
Published: July 2015

Background

Adverse experiences in early life, such as exposure to stress, can have long term detrimental effects on the future physiology and behaviour of the animal. Typically animals exposed to such experiences are more anxious and more reactive to stress in later life. Tail biting is a major problem in modern pig production, both in terms of animal welfare and productivity. Tail docking in early postnatal life is common practice to reduce risk of this problem, but causes pain and may alter pain sensitivity.

Aims

To investigate whether a significant painful experience in early life (tail docking) alters the expression of genes in the amygdala that are linked to an anxiety-prone phenotype.

Methods

Eight female piglets (Landrace/Large White × synthetic sireline) were used. Four piglets were tail docked (amputation of approx. 2/3 of the tail) on post-natal day 3 using hot-iron cautery and four sham-docked piglets served as intact controls. On post-natal day 10, pigs were sedated and then euthanized by barbiturate overdose. Brains were removed, the amygdala grossly dissected and frozen on dry ice. 20 μm sections were cut and subsequently processed using in situ hybridisation with radiolabelled probes complementary to corticotropin-releasing hormone receptor-1 (Crhr1) and CRH receptor-2 (Crhr2) mRNA.

Results

Crhrl mRNA expression was significantly greater in the amygdala of tail-docked piglets compared with the sham-docked animals. There was no significant difference detected in Crhr2 expression in the amygdala between the groups.

Conclusion

Increased expression of Crhrl in the amygdala is associated with an anxiety-prone phenotype in rats and pigs, thus it is likely that tail docking in early life leads to enhanced anxiety which may have a negative impact on pig welfare. Ongoing experiments will determine whether these central changes in gene expression are long-lasting.

[Support: BBSRC/DEFRA, part of ANIWHA ERA-NET initiative].
The effectiveness of a nursing staff development Intervention to improve pain management – A randomized controlled trial
Authors: Zoëga S. , Ward S.E. , Serlin R.C. , Sveinsdottir H. , Gretarsdottir E.Th. , Fridriksdottir N. , Hafsteinsdottir E.J.G. , Gunnarsdóttir S.
Published: July 2015

Aims

To test the effectiveness of the Pain Resource Nurse (PRN) education program in a university hospital.

Methods

This was a randomized controlled trial. Two nurses from each of the 23 participating surgical and medical units were selected to participate in the PRN program. The program consisted of a three day course in pain management with a structured follow up. After a baseline measurement, the units were randomized to either receive the intervention or to serve as a wait-list control. The control group received the intervention following a second data collection 10 months from baseline. Data regarding knowledge and attitudes regarding pain were collected from nurses, but patient data were collected with the American Pain Society Patient Outcome Questionnaire and from medical records. Patients had to be ≥18 years, hospitalized for ≥24 h, alert and able to participate.

Results

Participating patients were 308 at T1 (73% response rate (RR)) and 329 at T2 (79% RR). Participating nurses were 224 (48% RR) at T1 and 176 (38% RR) at T2. No difference was found between the intervention and control groups regarding knowledge and attitudes of nurses, or in any of the patient outcome variables. The only significant effect of the intervention was improvement in documented standardized pain assessment, which increased from 12% at T1 to 24% at T2 on the intervention units, compared to a decrease from 12% at T1 to 9% at T2 on the control units, p < 0.05.

Conclusions

Patient outcomes remained unchanged after the intervention, as were nurses’ knowledge and attitudes. The intervention was, however, successful in changing pain assessment practices. Multifarious efforts to change nursing practice resulted in modest changes. Further studies are needed to advance pain management practices in clinical settings.
Possible adverse effects of frying with vegetable oils
Authors: Dobarganes Carmen , Márquez-Ruiz Gloria
Published: July 2015

The question of whether heated fats in the diet may be detrimental to health is nowadays of the upmost concern, but finding an answer is not easy and requires careful consideration of different aspects of lipid oxidation. This review is divided into two sections. The first part deals with the nature of the new compounds formed at high temperature in the frying process as well as their occurrence in the diet while the second part focuses on their possible nutritional and physiological effects. Oxidation products present in abused frying fats and oils are the compounds most suspected of impairing the nutritional properties of the oils or involving adverse physiological effects. The recent studies on their health implications include those related to their fate and those focused on their effects in metabolic pathways and the most prevalent diseases.
Fermented dairy food and CVD risk
Authors: Tapsell Linda C.
Published: July 2015

Fermented dairy foods such as yoghurt and cheese are commonly found in the Mediterranean diet. Recent landmark research has confirmed the effect of the Mediterranean diet on reducing the CVD risk, but the relative contributions of fermented dairy foods have not been fully articulated. The present study provides a review of the relationship between fermented dairy foods consumption and CVD risk in the context of the whole diet. Studies show that people who eat healthier diets may be more likely to consume yoghurt, so there is a challenge in attributing separate effects to yoghurt. Analyses from large population studies list yoghurt as the food most negatively associated with the risk of weight gain (a problem that may lead to CVD). There is some suggestion that fermented dairy foods consumption (yoghurt or cheese) may be associated with reduced inflammatory biomarkers associated with the development of CVD. Dietary trials suggest that cheese may not have the same effect on raising LDL-cholesterol levels as butter with the same saturated fat content. The same might be stated for yoghurt. The use of different probiotic cultures and other aspects of study design remain a problem for research. Nevertheless, population studies from a range of countries have shown that a reduced risk of CVD occurs with the consumption of fermented dairy foods. A combination of evidence is necessary, and more research is always valuable, but indications remain that fermented dairy foods such as cheese and yoghurt are integral to diets that are protective against CVD.
Relationship between bread and obesity
Authors: Serra-Majem Luis , Bautista-Castaño Inmaculada
Published: July 2015

Some studies have indicated that promoting the Mediterranean diet pattern as a model of healthy eating may help to prevent weight gain and the development of overweight/obesity. Bread consumption, which has been part of the traditional Mediterranean diet, has continued to decline in Spain and in the rest of the world, because the opinion of the general public is that bread fattens. The present study was conducted to assess whether or not eating patterns that include bread are associated with obesity and excess abdominal adiposity, both in the population at large or in subjects undergoing obesity management. The results of the present review indicate that reducing white bread, but not whole-grain bread, consumption within a Mediterranean-style food pattern setting is associated with lower gains in weight and abdominal fat. It appears that the different composition between whole-grain bread and white bread varies in its effect on body weight and abdominal fat. However, the term ‘whole-grain bread’ needs to be defined for use in epidemiological studies. Finally, additional studies employing traditional ways of bread production should analyse this effect on body-weight and metabolic regulation.
Moderate red wine consumption is associated with a lower prevalence of the metabolic syndrome in the PREDIMED population
Authors: Tresserra-Rimbau Anna , Medina-Remón Alexander , Lamuela-Raventós Rosa M. , Bulló Monica , Salas-Salvadó Jordi , Corella Dolores , Fitó Montserrat , Gea Alfredo , Gómez-Gracia Enrique , Lapetra José , Arós Fernando , Fiol Miquel , Ros Emili , Serra-Majem Luis , Pintó Xavier , Muñoz Miguel A. , Estruch Ramón ,   on behalf of the PREDIMED Study Investigators
Published: July 2015

Previous studies on the association between alcohol intake and the development of the metabolic syndrome (MetS) have yielded inconsistent results. Besides, few studies have analysed the effects of red wine (RW) consumption on the prevalence of the MetS and its components. As moderate RW drinkers have a better lipid profile and lower incidence rates of diabetes, hypertension and abdominal obesity, all components of the MetS, it was hypothesised that moderate RW consumption could be associated with a lower prevalence of the MetS. In the present cross-sectional study of 5801 elderly participants at a high cardiovascular risk included in the PREDIMED (Prevención con Dieta Mediterránea) study, 3897 fulfilled the criteria of the MetS at baseline. RW intake was recorded using a validated 137-item FFQ. Multiple logistic regression analysis was carried out to estimate the association between RW intake and the prevalence of the MetS. Compared with non-drinkers, moderate RW drinkers ( ≥ 1 drink/d) were found to have a reduced risk of prevalent MetS (OR 0·56, 95 % CI 0·45, 0·68;P< 0·001), a lower risk of having an abnormal waist circumference (OR 0·59, 95 % CI 0·46, 0·77;P< 0·001), low HDL-cholesterol concentrations (OR 0·42, 95 % CI 0·32, 0·53;P< 0·001), high blood pressure (OR 0·28, 95 % CI 0·17, 0·45;P< 0·001) and high fasting plasma glucose concentrations (OR 0·67, 95 % CI 0·54, 0·82;P< 0·001) after adjusting for several confounders. This association was found to be stronger in female participants, in participants aged < 70 years and in participants who were former or current smokers. No significant association was found between RW intake ( ≥ 1 drink/d) and TAG concentrations. In conclusion, moderate RW consumption is associated with a lower prevalence of the MetS in an elderly Mediterranean population at a high cardiovascular risk.
The Mediterranean diet: health, science and society
Authors: Gerber Mariette , Hoffman Richard
Published: July 2015

The Mediterranean diet (MD) emerged as a healthy food regimen long before it could be recognised which nutrients or foods were responsible for its observed benefits, and it was only in the middle of the last century that the first scientific approach ‘The Seven Countries Study’ appeared. Epidemiological and anthropological studies of the MD converged, first by investigating at single nutrients or foods, then by adopting the more holistic approach of dietary patterns (DP), and now with a molecular approach. These studies resulted in convincing evidence that a MD decreases the risk of all-cause mortality and cardiovascular mortality and incidence. A risk reduction of developing type 2 diabetes is probable. Evidence is less stringent for other metabolic diseases and all cancers but from possible to probable for some cancer sites. Although DP showed that the MD has to be considered in its totality, olive oil could have a specific role. Lifestyle factors such as physical activity for energy balance, outdoor life for vitamin D synthesis and conviviality are also probably partly responsible for the health benefits. The MD is a lifestyle well suited for coping not only with personal health but also with wider societal concerns in relation to environment, public health and economy.
Nuts and CVD
Authors: Ros Emilio
Published: July 2015

Nuts are nutrient-dense foods with complex matrices rich in unsaturated fatty acids and other bioactive compounds, such asl-arginine, fibre, healthful minerals, vitamin E, phytosterols and polyphenols. By virtue of their unique composition, nuts are likely to beneficially affect cardiovascular health. Epidemiological studies have associated nut consumption with a reduced incidence of CHD in both sexes and of diabetes in women, but not in men. Feeding trials have clearly demonstrated that consumption of all kinds of nuts has a cholesterol-lowering effect, even in the context of healthy diets. There is increasing evidence that nut consumption has a beneficial effect on oxidative stress, inflammation and vascular reactivity. Blood pressure, visceral adiposity and the metabolic syndrome also appear to be positively influenced by nut consumption. Contrary to expectations, epidemiological studies and clinical trials suggest that regular nut consumption is not associated with undue weight gain. Recently, the PREvención con DIeta MEDiterránea randomised clinical trial of long-term nutrition intervention in subjects at high cardiovascular risk provided first-class evidence that regular nut consumption is associated with a 50 % reduction in incident diabetes and, more importantly, a 30 % reduction in CVD. Of note, incident stroke was reduced by nearly 50 % in participants allocated to a Mediterranean diet enriched with a daily serving of mixed nuts (15 g walnuts, 7·5 g almonds and 7·5 g hazelnuts). Thus, it is clear that frequent nut consumption has a beneficial effect on CVD risk that is likely to be mediated by salutary effects on intermediate risk factors.
The role of olive oil in disease prevention: a focus on the recent epidemiological evidence from cohort studies and dietary intervention trials
Authors: Buckland Genevieve , Gonzalez Carlos A.
Published: July 2015

Consumption of olive oil within the Mediterranean diet has been long known to have many health benefits. However, only over the last decade has epidemiological research confirmed its protective role against developing several chronic diseases. The objective of this review was to give an overview of the state of art epidemiological evidence concerning the relationship between olive oil and key public health outcomes including mortality, CVD, diabetes, metabolic syndrome (MetS), obesity and cancer, with a particular focus on recent results from cohort studies and dietary intervention trials. Recent epidemiological research has shown that regular consumption of olive oil is associated with increased longevity. This benefit is partly due to the olive oil's unequivocal cardio-protective role. There is converging evidence on the benefits of olive oil for preventing several CVD risk factors, including diabetes, MetS and obesity. Olive oil is also implicated in preventing certain cancers, with the most promising findings for breast and digestive tract cancers, although the data are still not entirely consistent and mainly from case–control studies. These health benefits are supported by strong mechanistic evidence from experimental studies, demonstrating that specific components of olive oil have antihypertensive, antithrombotic, antioxidant, antiinflammatory and anticarcinogenic action. Despite the accumulating epidemiological research, there is still a lack of consistent results from high-quality studies for many health outcomes (i.e. certain cancers and metabolism-related disorders). Further research is mandatory, above all from prospective studies and randomised dietary intervention trials when feasible, to confirm some of the still potential health benefits.
A perspective on vegetarian dietary patterns and risk of metabolic syndrome
Authors: Sabaté Joan , Wien Michelle
Published: July 2015

The vegetarian dietary pattern is traditionally a plant-based diet that includes fruits, vegetables, cereals, legumes, nuts, vegetable oils, soya, and possibly dairy products and/or eggs. Vegetarians and other populations who follow a plant-based dietary pattern enjoy longevity. Specifically, vegetarian dietary patterns have been associated with a lower risk for developing IHD, type 2 diabetes, hypertension, specific cancers, lower all-cause mortality and reduction in cause-specific mortality. The prevalence of the metabolic syndrome (MetS) in the USA is approximately 20 % and is currently increasing in developing countries in line with the obesity epidemic. The health care costs associated with the MetS are on a magnitude of 1·6 overall compared with healthy individuals, which makes it an important public health problem. Current evidence from several cross-sectional and case–control studies shows an association between consumption of a vegetarian dietary pattern and a reduced prevalence or risk of developing the MetS. There is a need for further research to be conducted, particularly prospective cohort studies to evaluate the effect of vegetarian dietary patterns on reducing the incidence of the MetS and, clinical trials should be designed to explore vegetarian dietary patterns for the reversal of the MetS in high-risk populations. This research could contribute to reduce the societal and economic burdens associated with the disorder.
Fruit and vegetables and cancer risk: a review of southern European studies
Authors: Turati Federica , Rossi Marta , Pelucchi Claudio , Levi Fabio , La Vecchia Carlo
Published: July 2015

High intakes of fruit and vegetables may reduce the risk of cancer at several sites. Evidence has been derived mainly from case–control studies. We reviewed the relationship between consumption of vegetables and fruit and the risk of several common cancers in a network of Italian and Swiss case–control studies including over 10 000 cases of fourteen different cancers and about 17 000 controls. Data were suggestive of a protective role of vegetable intake on the risk of several common epithelial cancers. OR for the highest compared with the lowest levels of consumption ranged from 0·2 (larynx, oral cavity and pharynx) to 0·9 (prostate). Inverse associations were found for both raw and cooked vegetables, although for upper digestive tract cancers the former were somewhat stronger. Similar inverse associations were found for cruciferous vegetables. Frequent consumption of allium vegetables was also associated with reduced risk of several cancers. Fruit was a favourable correlate of the risk of several cancers, particularly of the upper digestive tract, with associations generally weaker than those reported for vegetables. A reduced risk of cancers of the digestive tract and larynx was found for high consumption of citrus fruit. Suggestive protections against several forms of cancer, mainly digestive tract cancers, were found for high consumption of apples and tomatoes. High intakes of fibres, flavonoids and proanthocyanidins were inversely related to various forms of cancer. In conclusion, data from our series of case–control studies suggested a favourable role of high intakes of fruit and vegetables in the risk of many common cancers, particularly of the digestive tract. This adds evidence to the indication that aspects of the Mediterranean diet may have a favourable impact not only on CVD, but also on several common (epithelial) cancers, particularly of the digestive tract.
Generalized universal instability: transient linear amplification and subcritical turbulence
Authors: Landreman Matt , Plunk Gabriel G. , Dorland William
Published: July 2015

In this work we numerically demonstrate both significant transient (i.e. non-modal) linear amplification and sustained nonlinear turbulence in a kinetic plasma system with no unstable eigenmodes. The particular system considered is an electrostatic slab with magnetic shear, kinetic electrons and ions, weak collisions and a density gradient, but with no temperature gradient. In contrast to hydrodynamic examples of non-modal growth and subcritical turbulence, here there is no sheared flow in the equilibrium. Significant transient linear amplification is found when the magnetic shear and collisionality are weak. It is also demonstrated that nonlinear turbulence can be sustained if initialized at sufficient amplitude. We prove that these two phenomena are related: when sustained turbulence occurs without unstable eigenmodes, states that are typical of the turbulence must yield transient linear amplification of the gyrokinetic free energy.
Is There a Role for ‘Human Nature’ in Debates About Human Enhancement?
Authors: Groll Daniel , Lott Micah
Published: July 2015

In discussions about the ethics of enhancement, it is often claimed that the concept of ‘human nature’ has no helpful role to play. There are two ideas behind this thought. The first is that nature, human nature included, is a mixed bag. Some parts of our nature are good for us and some are bad for us. The ‘mixed bag’ idea leads naturally to the second idea: the fact that something is part of our nature is, by itself, normatively inert. The Inert View claims that nothing normative follows from the mere fact that some trait is a part of our nature. If the Inert View is correct, then appeals to the value or importance of human nature in debates about enhancement are indeed misplaced. We argue that the Inert View is wrong, and that a certain concept of human nature – which we refer to as ‘human form’ – does have an important role to play in debates about enhancement.
Speaking for Oneself: Wittgenstein, Nabokov and Sartre on How (Not) to Be a Philistine
Authors: De Mesel Benjamin
Published: July 2015

The aim of this article is twofold. First, I want to offer an introduction of and a comparison between three accounts of philistinism. Secondly, I show how the phenomenon of philistinism, a failure to speak for oneself, helps to develop an original perspective on Wittgenstein's moral thought. It is often claimed that Wittgenstein's personal ethics were quite unorthodox because he repeatedly seems to have supported destruction, war and slavery. I argue that, in the light of my discussion of philistinism, the remarks upon which such conclusions are based should be read differently.
On patience: thinking with and beyond Karl Barth
Authors: Jones Paul Dafydd
Published: July 2015

This article has three goals: (1) to provide a careful analysis of Barth's treatment of divine patience inChurch DogmaticsII/1; (2) to show how Barth's thinking about divine patience helps to illumine his account of human being and human activity in later portions of theChurch Dogmatics; and (3) to offer a series of constructive suggestions which connect Barth's theology with liberationist visions of human existence.

With respect toChurch DogmaticsII/1, I argue that Barth breaks with a number of earlier thinkers and focuses attention onGod'sexercise of patience, treating it as a key dimension of God's creative and providential work. This exercise of patience means, specifically, that God accords creatures their own integrity and a capacity for free action, tempers God's punishment of sin and, in Christ, fulfils but does not temporally close the covenant. My analysis of divine patience in II/1 then serves as an interpretative key for reading later volumes of theDogmatics. It sets in vivid relief Barth's belief that Christ's fulfilment of the covenant, achieved through Christ's life, suffering, death and resurrection, is the condition of possibility for humans being able to act with genuine integrity and consequence in the created realm. I propose, too, that Barth develops his thinking about patience by emphasising the ‘pressure’ of the patient God's empowering command – a command which is a constant summons, directed towards each and every human being, to live freely into God's future through acts of gratitude, obedience and responsibility, and to play some part in bringing creation to its glorious end. Finally, I explore the convergence between certain aspects of theChurch Dogmaticsand anti-essentialist construals of the self in contemporary theology. I aim to identify points of connection between Barth and thinkers like Marcella Althaus-Reid, and I voice support for a style of scholarship which elides the distinction between ‘systematic’ and ‘liberationist’ modes of inquiry.
‘Offenbarung, Philosophie, und Theologie’: Karl Barth and Georges Florovsky in dialogue
Authors: Baker Matthew
Published: July 2015

Karl Barth and Georges Florovsky interacted in several contexts, beginning in 1931 and then later within the ecumenical movement. Although some have noted a ‘Barthian’ accent in Florovsky's Christocentric theology, in fact both theologians remained critical of the other. Making use of extensive historical sources, this article attempts to reconstruct the meeting between Barth and Florovsky, and to pinpoint the areas of fundamental reservation and disagreement between the two. As will be shown, at the heart of their disagreement lay the role of eschatology in its impact on ecclesiology, a difference finally Christological in foundation. This fundamental disagreement shows itself likewise in relation to the two theologians' ideas concerning history, the relationship of philosophy to theology and the place of Hellenism in Church tradition. The role of Florovsky's opposition to the sophiology of Bulgakov in his interpretation of Barth, and Florovsky's stance vis-à-vis the debate between Barth and Brunner on natural theology, will also be considered. Uniquely, Florovsky anticipated the contemporary debate concerning Barth's doctrine of election, and drew crucial connections between Barth and Bulgakov on this point – an issue which for him was related to the question of the role of German Idealism in modern theology. Notwithstanding these disagreements, this article concludes by highlighting crucial areas of convergence between Barth and Florovsky concerning Christocentrism, revelation and theology as an enterprise in fides quaerens intellectum. Florovsky's ideas on analogy, naming and realism in theology will also be illumined, in relation to Barth and with reference to Bulgakov and Torrance.
Christopher Beeley, The Unity of Christ
Authors: Gavrilyuk Paul L.
Published: July 2015

Professor Beeley has contributed a new chapter to the history of the doctrine of communicatio idiomatum. He has written a provocative book, whose argument is both revisionist and orthodox. Beeley proposes to revise the accepted christological narrative by questioning the significance and theological genius of Athanasius of Alexandria. In Beeley's judgement, Athanasius' contribution pales in comparison with such giants as Origen, Eusebius of Caesarea, Gregory Nazianzen and Maximus the Confessor. Beeley finds especially in Nazianzen's Christology the most profound and consistent rendering of the unity of Christ, a golden standard for expressing communicatio idiomatum. According to Beeley, Gregory's achievement was only partially matched by the Christologies of Cyril of Alexandria and Leo of Rome. Gregory's Christology is the apex of the Origenist tradition, its most complete and compelling expression. A permanent contribution of Beeley's work is the restoration of Gregory the Theologian to the diptychs of contemporary Western patristic scholarship, in which Nazianzen has been overshadowed by another Cappadocian, Gregory of Nyssa.
Editorial
Authors: Torrance Iain R.
Published: July 2015

Scottish Journal of Theology has avoided producing editorials as we have preferred to allow our authors to speak for themselves with minimal editorial intrusion.