Effect of individualized anesthesia and analgesia on postoperative pain in patients stratified for pain sensitivity: A study protocol for the PeriOPerative individualization trial randomized controlled trial.

BACKGROUND: Despite advancements in surgical and anesthesia techniques, acute and persistent postoperative pain are still a common challenge. Postoperative pain has direct effects on individual patient care and outcome, as well as putting strain on limited health care resources. Several prediction methods for postoperative pain have been described. One such method is the assessment of pain during peripheral venous cannulation (VCP). It is not known if different approaches to anesthesia and analgesia, depending on the evaluation of risk for postoperative pain, can improve outcome. The aim of this study is to evaluate if individualized anesthesia and analgesia can affect postoperative pain and recovery after surgery, in patients stratified by VCP. METHODS: Adult patients scheduled for laparoscopic surgery undergo pain-sensitivity stratification using VCP on the day of surgery. Patients scoring VCP ≥2.0 on the visual analogue scale (pain-sensitive) are randomized to multimodal anaesthesia and analgesia with opioids or standard of care. Patients scoring VCP ≤1.9 (pain-tolerant) are randomized to opioid-free anaesthesia or standard of care. The primary outcome is acute postoperative pain measured with numeric rating scale in the postoperative care unit. Secondary outcomes include analysis of pain after 24 h, persistent postoperative pain and quality of recovery. DISCUSSION: Individualized perioperative pain management has the potential to improve patient care. This study will examine the impact of different anesthesia and analgesia regimes, in patients with differing pain sensitivity, on postoperative pain. TRIAL REGISTRATION: Prospectively posted at ClinicalTrials.gov, identifier NCT04751812.

Pre-school hearing screening is necessary to detect childhood hearing loss after the newborn period: a study exploring risk factors, additional disabilities, and referral pathways.

OBJECTIVE: To explore strategies for detecting childhood hearing loss, aside from newborn hearing screening. DESIGN: A retrospective review of medical records on the modes of detection of hearing loss, risk factors for late-onset hearing loss, hearing loss degree, aetiology, additional disabilities, and timelines from referral to intervention. STUDY SAMPLE: Children, born 2006 to 2015, enrolled for intervention whose hearing loss was detected up to age 7 years but not from newborn hearing screening (n = 326). RESULTS: Universal pre-school hearing screening detected 38% of the cohort at 4-5 years of age. Risk factors for late-onset hearing loss were present in 36% of children, 80% of whom had a reported family history. Sixty-nine percent had mild bilateral or unilateral hearing loss. Children with additional disabilities faced significantly longer delays from referral to intervention. Children self-referred due to parent concern had more severe degree of hearing loss than those referred from screening. CONCLUSION: Most children with hearing loss detected after the newborn period do not have any known risk factors for late-onset hearing loss. Pre-school hearing screening is needed for comprehensive detection of hearing loss in early childhood. More work is needed towards improving timely diagnosis and intervention for children with additional disabilities.

Contrasting effects of tree origin and urbanization on invertebrate abundance and tree phenology.

The ongoing wide-scale introduction of nonnative plants across the world may negatively influence native invertebrate fauna, due to a lack of coevolved traits related to the novel plants, e.g., unique phytochemicals or shifted phenology. Nonnative plants, specifically trees, are common in urban environments, areas that already pose novel habitats to plants and wildlife through a wide array of anthropogenic factors. For example, impervious surfaces contribute to increased ambient temperatures, the so-called urban heat island effect (UHI), which can affect local plant phenology. Yet, few studies have simultaneously studied the effects of urbanization and tree species origin on urban invertebrate communities. We measured the city-level UHI and phenology of nine native and seven nonnative tree species in five city-center parks in southern Sweden, as well as four common native species in a rural control forest. We quantified the abundance of invertebrates on a subset of native and nonnative tree species through shake sampling, sticky traps, and frass collection. In the urban environment, nonnative trees hosted significantly fewer invertebrates compared to native trees. Furthermore, the nonnative trees had a delayed phenology compared to native species, while the peak of caterpillars associated with the subset of trees surveyed for this measure was significantly earlier compared to that of the native species studied. The effect of tree species origin on urban invertebrate abundance was of a greater magnitude (effect size) than the effect of urbanization on invertebrate abundance in native tree hosts. Hence, the results indicate that the impact of nonnative vegetation may be a stronger driver of invertebrate declines in urban areas than other factors. As the effect of species origin on tree phenology was at a level comparable to the urban effect, increasing prevalence of nonnative vegetation can potentially obscure effects of urbanization on phenology in large-scale studies, as well as induce mismatches to invertebrate populations. Since parks harbor a large proportion of urban biodiversity, native trees play a crucial role in such habitats and should not be considered replaceable by nonnative species in terms of conservation value.

Impact of auditory variables on consonant production in babbling and early speech in children with moderate hearing loss - a longitudinal study.

This longitudinal study aimed to investigate early consonant production and the impact of hearing aid (HA) use, and aided audibility in Swedish children with moderate hearing loss (CHL) who received amplification before 6 months of age. CHL (n = 11) and children with normal hearing (CNH) (n = 11) were followed-up at 10, 18, and 36 months of age. At 10 months of age, the CHL used significantly fewer oral stops (p < 0.01), dental/alveolar stops (p < 0.05) and had a significantly fewer number of different true consonants (p < 0.01). At 18 months, there were no significant differences between the groups regarding presence of oral stops, and dental/alveolar stops, but the significant difference in the number of different true consonants remained (p < 0.00). At 36 months of age, consonant proficiency did not differ between the groups. A higher number of hours of HA use was associated with the presence of consonant variables at 10 months. Aided audibility showed weak to moderate correlations with number of consonants produced and proficiency. This group of children presented with initial delays in their early consonant production but seemed to catch up as they aged. Consistency of HA use from initial fitting is an important factor that may decrease the possible delays in the development of early consonant production and proficiency in CHL by 36 months of age.

Expressive vocabulary development in children with moderate hearing loss - the impact of auditory variables and early consonant production.

In this study, the early expressive vocabulary development was investigated in a group of children with moderate hearing loss (HL). Size and development of expressive vocabulary from 18 30 months were analyzed and compared to a group of children with normal hearing (NH). For the children with HL, the impact of auditory variables on number of words were examined. The relationship of early consonant production to number of words produced of both groups were examined and the phonological complexity of reported words was compared between the groups. The results showed that children with HL (n = 8) produced a similar number of words as the NH (n = 8) at 18 months, but fewer at 24 and 30 months. Hours of HA use showed significant correlations to number of words. The number of different true consonants at 18 months for the whole group showed a significant relationship to number of words produced at 24 months. No significant differences were found between children with HL and NH children regarding phonological complexity of reported words. The findings indicate that the children born with moderate HL who were fitted with hearing aids (HAs) before 6 months of age are at risk in their development of expressive vocabulary. Full-time use of HAs and monitoring of early consonant use should be encouraged in the early intervention of this target group.

Reliability of the Addiction Severity Index self-report form (ASI-SR): a self-administered questionnaire based on the Addiction Severity Index composite score domains.

Objectives: The Addiction Severity Index (ASI) is a standardized interview used to assess problems associated with substance use. Although widely used, the time required for the interview remains an obstacle to its acceptance in many clinical settings. We examined if a self-administered questionnaire based on the composite score (CS) items, the ASI Self-Report form (ASI-SR), offers a reliable alternative to the ASI in assessing current substance use and related problems.Methods: Participants were 59 treatment seeking individuals entering outpatient programs at the Addiction Psychiatric Clinic at Uppsala University Hospital who were assessed with Swedish versions of the ASI and ASI-SR. Agreement between the ASI interview's CS and ASI-SR's CS was evaluated on the individual basis by intraclass correlation analysis (ICC) and on group level with the Wilcoxon signed rank test. Reliability and internal consistency were evaluated using Cronbach's alpha.Results: For 6 out of 7 CS domains, the ICC for the ASI interview and ASI-SR were good to excellent. Internal consistency was acceptable for 6 out of 7 CS domains on the ASI interview and for 5 out of 7 CS domains on the ASI-SR.Conclusions: The present study suggests that the ASI-SR is a reliable alternative to the ASI interview for assessing current patient functioning and evaluation of problems related to alcohol and drug use.

Validation of the Swedish version of the LittlEARS® Auditory Questionnaire in children with normal hearing - a longitudinal study.

Objective: To externally validate the Swedish version of the LittlEARS® Auditory Questionnaire (LEAQ) in children with normal hearing followed longitudinally, and to examine to what extent the LEAQ correlates to other measures of auditory and language development. Design: The Swedish version of the LEAQ was completed every other month over a 2-year period and correlated with the Parents' Evaluation of Aural/Oral Performance of Children (PEACH) and McArthur-Bates Communicative Development Inventory (CDI) to examine overlapping areas of development. Normative curve was derived through linear mixed models and the effect of time investigated with repeated measures ANOVA. Study sample: Parents of 25 typically developing children with normal hearing (13 girls, 12 boys). Results: The norm curve of the Swedish LEAQ showed a similar equation as the original German version and the effect of time was significant. Correlations between LEAQ and CDI were moderate to high, and between LEAQ and PEACH weak or non-existing. Conclusion: The Swedish version of the LEAQ is a reliable tool in accordance with the original version. However, results indicate that this questionnaire to a large extent measures language skill rather than audition specifically.

Prediction of Acute Postoperative Pain from Assessment of Pain Associated With Venous Cannulation.

BACKGROUND: It has previously been reported that venous cannulation-induced pain (VCP) can be used to predict acute postoperative pain after laparoscopic cholecystectomy. Patients rating VCP at ≥2.0 VAS units had 3.4 times higher risk for moderate or severe pain. The purpose of this study was to evaluate if VCP scores of ≥2.0 VAS units are associated with higher risk for acute postoperative pain after various common surgical procedures. METHODS: In a prospective clinical observational study, 600 male and female 18- to 80-year-old patients scheduled for elective surgery were included. The primary outcome measure was the difference in maximum postoperative pain intensity between low responders (VCP < 2.0) and high responders (VCP ≥ 2.0) to VCP. Secondary outcome measures were the difference in proportion of patients with moderate or severe postoperative pain between low and high responders, and potential influence of age, gender, and preoperative habitual pain. RESULTS: Patients scoring VCP ≥2.0 VAS units reported higher acute postoperative pain intensity levels than those scoring VCP <2.0 VAS units (median 3.0 [interquartile range 0.0 to 5.0] vs. 0.2 [interquartile range 0.0 to 4.0], P = 0.001), and also had 1.7 times higher risk for moderate or severe postoperative pain (P = 0.005). Moderate or severe postoperative pain was reported by 38% of patients with VCP scores of ≥2.0 VAS units and by 26% with VCP scores of <2.0 VAS units (P = 0.005). CONCLUSION: Scoring of VCP intensity before surgery, requiring no specific equipment or training, is useful to predict individual risks for moderate or severe postoperative pain, regardless of patient age or gender, in a setting involving different kinds of surgery.

FemtoMAX - an X-ray beamline for structural dynamics at the short-pulse facility of MAX IV.

The FemtoMAX beamline facilitates studies of the structural dynamics of materials. Such studies are of fundamental importance for key scientific problems related to programming materials using light, enabling new storage media and new manufacturing techniques, obtaining sustainable energy by mimicking photosynthesis, and gleaning insights into chemical and biological functional dynamics. The FemtoMAX beamline utilizes the MAX IV linear accelerator as an electron source. The photon bursts have a pulse length of 100 fs, which is on the timescale of molecular vibrations, and have wavelengths matching interatomic distances (Å). The uniqueness of the beamline has called for special beamline components. This paper presents the beamline design including ultrasensitive X-ray beam-position monitors based on thin Ce:YAG screens, efficient harmonic separators and novel timing tools.

Single Nucleotide Polymorphisms Associated with Pain Sensitivity After Laparoscopic Cholecystectomy.

Objective: To systematically evaluate variations in single-nucleotide polymorphisms within 13 candidate pain genes in patients differing in phenotype characteristics based on a composite measure of pain sensitivity. Methods: In a case-control study, 149 patients scheduled for laparoscopic cholecystectomy were individually categorized according to preoperative pain sensitivity and postoperative pain intensity. Cases (pain group) reported cannulation-induced pain intensity higher than 2.0, together with postoperative pain intensity of 7.0 or higher (visual analog scale [VAS] units), and controls (low-pain group) reported cannulation-induced pain intensity of 2.0 or lower, together with postoperative pain intensity lower than 4.0 (VAS units). Genotyping of exomes was performed in 32 case and 25 control patients compared with respect to variations within 13 candidate pain genes. Results: There were no statistically significant differences in single nucleotide polymorphisms (SNPs) within the candidate genes between the case and control groups, but minor allele SNPs in the ABCB1 and COMT genes were more common in patients with higher levels of pain sensitivity and intensity. Conclusion: In this candidate gene study, based on a composite measure of pain sensitivity, no variations reached statistical significance after correction for multiple testing, most likely due to the large number of markers analyzed and few patients. Nevertheless, the results suggest a possible genetic contribution of single-nucleotide polymorphisms within the ABCB1 and COMT genes in individuals with higher levels of pain sensitivity.

The development of a vocabulary for PEEPS-SE-profiles of early expressive phonological skills for Swedish.

This paper describes the development of a vocabulary for Profiles of Early Expressive Phonological Skills for Swedish (PEEPS-SE), a tool for assessment of expressive phonology in Swedish-learning children in the age range of 18-36 months. PEEPS-SE is the Swedish version of the original PEEPS, Profiles of Early Expressive Phonological Skills, which uses two age-adequate word lists-a basic word list (BWL) for the assessment of 18-24-month-old children, to which an expanded word list (EWL) is added for assessment of 24-36-month-old children, or children with more than 250 words in their expressive vocabulary. The selection of words in PEEPS-SE is based on two types of criteria: age of acquisition and phonological complexity. The words also need to be easy to elicit in a natural way in test situations. Vocabulary data previously collected with the Swedish Early Communicative Development Inventory are used for selection of age-adequate words, where the BWL contains words acquired earlier compared to the additional words in the EWL. The latter also contains words that are more phonologically complex compared to those in the BWL. Word complexity was determined by the Swedish version of word complexity measure. PEEPS-SE has made an attempt to match the original version of PEEPS in terms of both assessment method and word selection.

In vivo engineering of mobilized stem cell grafts with the immunomodulatory drug FTY720 for allogeneic transplantation.

The immunological attributes of stem cell grafts play an important role in the outcome of allogeneic stem cell transplants. Currently, ex vivo manipulation techniques such as bulk T-cell depletion or positive selection of CD34(+) cells are utilized to improve the immunological attributes of grafts and minimize the potential for graft-versus-host disease (GvHD). Here, we demonstrate a novel graft engineering technique, which utilizes the immunomodulatory drug FTY720 for in vivo depletion of naïve T (TN ) cells from donor G-CSF-mobilized grafts without ex vivo manipulation. We show that treatment of donor mice with FTY720 during mobilization depletes grafts of TN cells and prevents lethal GvHD following transplantation in a major mismatch setting. Importantly, both stem cells and NK cells are retained in the FTY720-treated grafts. FTY720 treatment does not negatively affect the engraftment potential of stem cells as demonstrated in our congenic transplants or the functionality of NK cells. In addition, potentially useful memory T cells may be retained in the graft. These findings suggest that FTY720 may be used to optimize the immunological attributes of G-CSF-mobilized grafts by removing potentially deleterious TN cells which can contribute to GvHD, and by retaining useful cells which can promote immunity in the recipient.

Preliminary study of two antiviral agents for hepatitis C genotype 1.

BACKGROUND: Patients with chronic hepatitis C virus (HCV) infection who have not had a response to therapy with peginterferon and ribavirin may benefit from the addition of multiple direct-acting antiviral agents to their treatment regimen. METHODS: This open-label, phase 2a study included an exploratory cohort of 21 patients with chronic HCV genotype 1 infection who had not had a response to previous therapy (i.e., had not had ≥2 log(10) decline in HCV RNA after ≥12 weeks of treatment with peginterferon and ribavirin). We randomly assigned patients to receive the NS5A replication complex inhibitor daclatasvir (60 mg once daily) and the NS3 protease inhibitor asunaprevir (600 mg twice daily) alone (group A, 11 patients) or in combination with peginterferon alfa-2a and ribavirin (group B, 10 patients) for 24 weeks. The primary end point was the percentage of patients with a sustained virologic response 12 weeks after the end of the treatment period. RESULTS: A total of 4 patients in group A (36%; 2 of 9 with HCV genotype 1a and 2 of 2 with genotype 1b) had a sustained virologic response at 12 weeks after treatment and also at 24 weeks after treatment.. Six patients (all with HCV genotype 1a) had viral breakthrough while receiving therapy, and resistance mutations to both antiviral agents were found in all cases; 1 patient had a viral response at the end of treatment but had a relapse after the treatment period. All 10 patients in group B had a sustained virologic response at 12 weeks after treatment, and 9 had a sustained virologic response at 24 weeks after treatment. Diarrhea was the most common adverse event in both groups. Six patients had transient elevations of alanine aminotransferase levels to more than 3 times the upper limit of the normal range. CONCLUSIONS: This preliminary study involving patients with HCV genotype 1 infection who had not had a response to prior therapy showed that a sustained virologic response can be achieved with two direct-acting antiviral agents only. In addition, a high rate of sustained virologic response was achieved when the two direct-acting antiviral agents were combined with peginterferon alfa-2a and ribavirin. (Funded by Bristol-Myers Squibb; ClinicalTrials.gov number, NCT01012895.).

Gain-of-function Nav1.8 mutations in painful neuropathy.

Painful peripheral neuropathy often occurs without apparent underlying cause. Gain-of-function variants of sodium channel Na(v)1.7 have recently been found in ∼30% of cases of idiopathic painful small-fiber neuropathy. Here, we describe mutations in Na(v)1.8, another sodium channel that is specifically expressed in dorsal root ganglion (DRG) neurons and peripheral nerve axons, in patients with painful neuropathy. Seven Na(v)1.8 mutations were identified in 9 subjects within a series of 104 patients with painful predominantly small-fiber neuropathy. Three mutations met criteria for potential pathogenicity based on predictive algorithms and were assessed by voltage and current clamp. Functional profiling showed that two of these three Na(v)1.8 mutations enhance the channel's response to depolarization and produce hyperexcitability in DRG neurons. These observations suggest that mutations of Na(v)1.8 contribute to painful peripheral neuropathy.

Sodium channels contribute to degeneration of dorsal root ganglion neurites induced by mitochondrial dysfunction in an in vitro model of axonal injury.

Axonal degeneration occurs in multiple neurodegenerative disorders of the central and peripheral nervous system. Although the underlying molecular pathways leading to axonal degeneration are incompletely understood, accumulating evidence suggests contributions of impaired mitochondrial function, disrupted axonal transport, and/or dysfunctional intracellular Ca(2+)-homeostasis in the injurious cascade associated with axonal degeneration. Utilizing an in vitro model of axonal degeneration, we studied a subset of mouse peripheral sensory neurons in which neurites were exposed selectively to conditions associated with the pathogenesis of axonal neuropathies in vivo. Rotenone-induced mitochondrial dysfunction resulted in neurite degeneration accompanied by reduced ATP levels and increased ROS levels in neurites. Blockade of voltage-gated sodium channels with TTX and reverse (Ca(2+)-importing) mode of the sodium-calcium exchanger (NCX) with KB-R7943 partially protected rotenone-treated neurites from degeneration, suggesting a contribution of sodium channels and reverse NCX activity to the degeneration of neurites resulting from impaired mitochondrial function. Pharmacological inhibition of the Na(+)/K(+)-ATPase with ouabain induced neurite degeneration, which was attenuated by TTX and KB-R7943, supporting a contribution of sodium channels in axonal degenerative pathways accompanying impaired Na(+)/K(+)-ATPase activity. Conversely, oxidant stress (H2O2)-induced neurite degeneration was not attenuated by TTX. Our results demonstrate that both energetic and oxidative stress targeted selectively to neurites induces neurite degeneration and that blockade of sodium channels and of reverse NCX activity blockade partially protects neurites from injury due to energetic stress, but not from oxidative stress induced by H2O2.

Contribution of sodium channels to lamellipodial protrusion and Rac1 and ERK1/2 activation in ATP-stimulated microglia.

Microglia are motile resident immune cells of the central nervous system (CNS) that continuously explore their territories for threats to tissue homeostasis. Following CNS insult (e.g., cellular injury, infection, or ischemia), microglia respond to signals such as ATP, transform into an activated state, and migrate towards the threat. Directed migration is a complex and highly-coordinated process involving multiple intersecting cellular pathways, including signal transduction, membrane adhesion and retraction, cellular polarization, and rearrangement of cytoskeletal elements. We previously demonstrated that the activity of sodium channels contributes to ATP-induced migration of microglia. Here we show that TTX-sensitive sodium channels, specifically NaV 1.6, participate in an initial event in the migratory process, i.e., the formation in ATP-stimulated microglia of polymerized actin-rich membrane protrusions, lamellipodia, containing accumulations of Rac1 and phosphorylated ERK1/2. We also examined Ca(2+) transients in microglia and found that blockade of sodium channels with TTX produced a downward shift in the level of [Ca(2+) ]i during the delayed, slower recovery of [Ca(2+) ]i following ATP stimulation. These observations demonstrate a modulatory role of sodium channels on Ca(2+) transients in microglia that are likely to affect down-stream signaling cascades. Consistent with these observations, we demonstrate that ATP-induced microglial migration is mediated via Rac1 and ERK1/2, but not p38α/ß and JNK, dependent pathways, and that activation of both Rac1 and ERK1/2 is modulated by sodium channel activity. Our results provide evidence for a direct link between sodium channel activity and modulation of Rac1 and ERK1/2 activation in ATP-stimulated microglia, possibly by regulating Ca(2+) transients.

Neuropathy-associated Nav1.7 variant I228M impairs integrity of dorsal root ganglion neuron axons.

Small-fiber neuropathy (SFN) is characterized by injury to small-diameter peripheral nerve axons and intraepidermal nerve fibers (IENF). Although mechanisms underlying loss of IENF in SFN are poorly understood, available data suggest that it results from axonal degeneration and reduced regenerative capacity. Gain-of-function variants in sodium channel Na(V)1.7 that increase firing frequency and spontaneous firing of dorsal root ganglion (DRG) neurons have recently been identified in ∼30% of patients with idiopathic SFN. In the present study, to determine whether these channel variants can impair axonal integrity, we developed an in vitro assay of DRG neurite length, and examined the effect of 3 SFN-associated variant Na(V)1.7 channels, I228M, M932L/V991L (ML/VL), and I720K, on DRG neurites in vitro. At 3 days after culturing, DRG neurons transfected with I228M channels exhibited ∼20% reduced neurite length compared to wild-type channels; DRG neurons transfected with ML/VL and I720K variants displayed a trend toward reduced neurite length. I228M-induced reduction in neurite length was ameliorated by the use-dependent sodium channel blocker carbamazepine and by a blocker of reverse Na-Ca exchange. These in vitro observations provide evidence supporting a contribution of the I228M variant Na(V)1.7 channel to impaired regeneration and/or degeneration of sensory axons in idiopathic SFN, and suggest that enhanced sodium channel activity and reverse Na-Ca exchange can contribute to a decrease in length of peripheral sensory axons.

Behavioral disturbances in adult mice following neonatal virus infection or kynurenine treatment--role of brain kynurenic acid.

Exposure to infections in early life is considered a risk-factor for developing schizophrenia. Recently we reported that a neonatal CNS infection with influenza A virus in mice resulted in a transient induction of the brain kynurenine pathway, and subsequent behavioral disturbances in immune-deficient adult mice. The aim of the present study was to investigate a potential role in this regard of kynurenic acid (KYNA), an endogenous antagonist at the glycine site of the N-methyl-D-aspartic acid (NMDA) receptor and at the cholinergic α7 nicotinic receptor. C57BL/6 mice were injected i.p. with neurotropic influenza A/WSN/33 virus (2400 plaque-forming units) at postnatal day (P) 3 or with L-kynurenine (2×200 mg/kg/day) at P7-16. In mice neonatally treated with L-kynurenine prepulse inhibition of the acoustic startle, anxiety, and learning and memory were also assessed. Neonatally infected mice showed enhanced sensitivity to D-amphetamine-induced (5 mg/kg i.p.) increase in locomotor activity as adults. Neonatally L-kynurenine treated mice showed enhanced sensitivity to D-amphetamine-induced (5 mg/kg i.p.) increase in locomotor activity as well as mild impairments in prepulse inhibition and memory. Also, D-amphetamine tended to potentiate dopamine release in the striatum in kynurenine-treated mice. These long-lasting behavioral and neurochemical alterations suggest that the kynurenine pathway can link early-life infection with the development of neuropsychiatric disturbances in adulthood.

A high intake of dietary fiber influences C-reactive protein and fibrinogen, but not glucose and lipid metabolism, in mildly hypercholesterolemic subjects.

PURPOSE: The aim of the study was to investigate how a diet high in dietary fiber, with several fiber sources included, modulates glucose and lipid metabolism and the inflammatory response in humans. METHODS: Subjects (n = 25) aged 58.6 (1.1) years (mean and SD) with a BMI of 26.6 (0.5) kg/m(2) and a total cholesterol (TC) of 5.8 (0.1) mmol/L (mean and SEM) were given a high fiber (HF) and low fiber (LF) diet, in a randomized controlled 5-week crossover intervention, separated by a 3-week washout. The HF diet consisted of oat bran, rye bran, and sugar beet fiber incorporated into test food products; one bread roll, one ready meal, and two beverages consumed daily. Equivalent food products, without added fibers, were provided in the LF diet. RESULTS: Total dietary fiber intake was 48.0 g and 30.2 g per day for the HF and LF diet, respectively. Significant reduction in C-reactive protein (CRP) was observed between the diets (P = 0.017) and a significant reduction in fibrinogen within the HF diet (P = 0.044). There were no significant effects in other measured circulating cytokines or in glucose, insulin, and lipid levels. CONCLUSIONS: Our study suggests that a 5-week high dietary fiber intake of oat bran, rye bran, and sugar beet fiber might reduce the low-grade inflammatory response measured as CRP which could, together with reduced fibrinogen, help to prevent the risk of cardiovascular disease.

Obstetric outcomes for nulliparous women who received routine individualized treatment for severe fear of childbirth - a retrospective case control study.

BACKGROUND: To study pregnancy and delivery outcomes in nulliparous women with severe FOC (fear of childbirth), all of whom had received routine treatment for their FOC and to make comparisons with a healthy reference group of nulliparous women.To study the possible relationship between the number of FOC-treatment sessions and the delivery method. METHODS: All nulliparous women with a diagnose FOC who received routine treatment for FOC (n = 181) and a reference group of nulliparous women without FOC (n = 431) at a university and a county hospital in the south east region of Sweden were analysed. Data from antenatal and delivery medical records were used to study outcome. RESULTS: The majority of women with severe FOC had a vaginal delivery. The incidence of elective CS was greater in the index group than in the reference group (p < 0.001). The total number of women with a planned CS in the index group was 35 (19.4%) and in the control group 14 (3.2%). Thus, on average five women per year received an elective CS during the study years due to severe FOC. The women in the index group who wished to have a CS were similar to the other women in the index group with reference to age, BMI, chronic disease but had been in in-patient care more often during their pregnancy than those who did not ask for CS (p = 0.009). CONCLUSION: In this study of women treated for severe FOC, the majority gave birth vaginally and no relationship was found between number of treatment sessions and mode of childbirth.