Active interoceptive inference and the emotional brain

We review a recent shift in conceptions of interoception and its relationship to hierarchical inference in the brain. The notion of interoceptive inference means that bodily states are regulated by autonomic reflexes that are enslaved by descending predictions from deep generative models of our internal and external milieu. This re-conceptualization illuminates several issues in cognitive and clinical neuroscience with implications for experiences of selfhood and emotion. We first contextualize interoception in terms of active (Bayesian) inference in the brain, highlighting its enactivist (embodied) aspects. We then consider the key role of uncertainty or precision and how this might translate into neuromodulation. We next examine the implications for understanding the functional anatomy of the emotional brain, surveying recent observations on agranular cortex. Finally, we turn to theoretical issues, namely, the role of interoception in shaping a sense of embodied self and feelings. We will draw links between physiological homoeostasis and allostasis, early cybernetic ideas of predictive control and hierarchical generative models in predictive processing. The explanatory scope of interoceptive inference ranges from explanations for autism and depression, through to consciousness. We offer a brief survey of these exciting developments

Factors associated with unintended pregnancy in Brazil: cross-sectional results from the Birth in Brazil National Survey, 2011/2012

Background Unintended pregnancy, a pregnancy that have been either unwanted or mistimed, is a serious public health issue in Brazil. It is reported for more than half of women who gave birth in the country, but the characteristics of women who conceive unintentionally are rarely documented. The aim of this study is to analyse the prevalence and the association between unintended pregnancy and a set of sociodemographic characteristics, individual-level variables and history of obstetric outcomes. Methods Birth in Brazil is a cross-sectional study with countrywide representation that interviewed 23,894 women after birth. The information about intendedness of pregnancy was obtained after birth at the hospital and classified into three categories: intended, mistimed or unwanted. Multinomial regression analysis was used to estimate the associations between intendedness of a pregnancy, and sociodemographic and obstetric variables, calculating odds ratios and 95 % confidence intervals. All significant variables in the bivariate analysis were included in the multinomial multivariate model and the final model retaining variables that remained significant at the 5 % level. Results Unintended pregnancy was reported by 55.4 % of postpartum women. The following variables maintained positive and significant statistical associations with mistimed pregnancy: maternal age < 20 years (OR = 1.89, 95 % CI: 1.68–2.14); brown (OR = 1.15, 95 % CI: 1.04–1.27) or yellow skin color (OR = 1.56, 95 % CI: 1.05–2.32); having no partner (OR = 2.32, 95 % CI: 1.99–2.71); having no paid job (OR = 1.15, 95 % CI: 1.04–1.27); alcohol abuse with risk of alcoholism (OR = 1.25, 95 % CI: 1.04–1.50) and having had three or more births (OR = 2.01, 95 % CI: 1.63–2.47). The same factors were associated with unwanted pregnancy, though the strength of the associations was generally stronger. Women with three or more births were 14 times more likely to have an unwanted pregnancy, and complication in the previous pregnancies and preterm birth were 40 % and 19 % higher, respectively. Previous neonatal death was a protective factor for both mistimed (OR = 0.61, 95 % CI: 0.44–0.85) and unwanted pregnancy (OR = 0.44, 95 % CI: 0.34–0.57). Conclusions This study confirms findings from previous research about the influence of socioeconomic and individual risk factors on unintended pregnancy. It takes a new approach to the problem by showing the importance of previous neonatal death, preterm birth and complication during pregnancy as risk factors for unintended pregnancy

A randomised trial into the effect of an isolated hip abductor strengthening programme and a functional motor control programme on knee kinematics and hip muscle strength

Background: Dynamic knee valgus and internal femoral rotation are proposed to be contributory risk factors for patellofemoral pain and anterior cruciate ligament injuries. Multimodal interventions including hip abductor strengthening or functional motor control programmes have a positive impact of pain, however their effect on knee kinematics and muscle strength is less clear. The aim of this study was to examine the effect of isolated hip abductor strengthening and a functional motor control exercise on knee kinematics and hip abductor strength. Methods: This prospective, randomised, repeated measures design included 29 asymptomatic volunteers presenting with increase knee valgus and femoral internal rotation. Participants completed either isolated hip abductor strengthening or a functional motor control exercise for 5 weeks. Knee kinematics were measured using inertial sensors during 2 functional activities and hip abductor strength measured using a load cell during isometric hip abduction. Results: There were no significant differences in dynamic knee valgus and internal rotation following the isolated hip abductor or functional motor control intervention, and no significant differences between the groups for knee angles. Despite this, the actual magnitude of reduction in valgus was 10° and 5° for the functional motor control group and strengthening group respectively. The actual magnitude of reduction in internal rotation was 9° and 18° for the functional motor control group and strengthening group respectively. Therefore there was a tendency towards clinically significant improvements in knee kinematics in both exercise groups. A statistically significant improvement in hip abductor strength was evident for the functional motor control group (27% increase; p = 0.008) and strengthening group (35% increase; p = 0.009) with no significant difference between the groups being identified (p = 0.475). Conclusions: Isolated hip strengthening and functional motor control exercises resulted in non-statistically significant changes in knee kinematics, however there was a clear trend towards clinically meaningful reductions in valgus and internal rotation. Both groups demonstrated similar significant gains in hip abductor strength suggesting\ud either approach could be used to strengthen the hip abductors

Determination of the prebiotic activity of wheat arabinogalactan peptide (AGP) using batch culture fermentation

Purpose To test the prebiotic activity of wheat arabinogalactan-peptide (AGP), which is a soluble dietary fibre composed of arabinogalactan polysaccharide linked to a 15-residue peptide, which accounts for up to 0.4% of the dry weight of wheat flour. Methods The prebiotic activity of AGP prepared from white wheat flour was tested using in-vitro fermentation by colonic bacteria in automated pH controlled anaerobic stirred batch cultures and compared to fructooligosaccharide (FOS) and wheat flour arabinoxylan (AX). Bacterial populations were measured using fluorescence in-situ hybridisation (flow-FISH) and short-chain fatty acid (SCFA) concentrations were measured using HPLC. Results Fermentation of AGP resulted in a significant bifidogenic activity and increased concentrations of SCFAs, mainly acetate after 24 h of fermentation. Conclusions These results were comparable to those obtained with AX and confirm the prebiotic potential of AGP. Furthermore, fermentation of a mixture of AGP and AX was faster compared to the single substrates and more similar to FOS, indicating that combinations of fermentable carbohydrates with different structures are potentially more effective as prebiotics than single substrates

Skeletal muscle and performance adaptations to high-intensity training in elite male soccer players: speed endurance runs versus small-sided game training.

PURPOSE: To examine the skeletal muscle and performance responses across two different exercise training modalities which are highly applied in soccer training. METHODS: Using an RCT design, 39 well-trained male soccer players were randomized into either a speed endurance training (SET; n = 21) or a small-sided game group (SSG; n = 18). Over 4 weeks, thrice weekly, SET performed 6-10 × 30-s all-out runs with 3-min recovery, while SSG completed 2 × 7-9-min small-sided games with 2-min recovery. Muscle biopsies were obtained from m. vastus lateralis pre and post intervention and were subsequently analysed for metabolic enzyme activity and muscle protein expression. Moreover, the Yo-Yo Intermittent Recovery level 2 test (Yo-Yo IR2) was performed. RESULTS: Muscle CS maximal activity increased (P < 0.05) by 18% in SET only, demonstrating larger (P < 0.05) improvement than SSG, while HAD activity increased (P < 0.05) by 24% in both groups. Na(+)-K(+) ATPase α1 subunit protein expression increased (P < 0.05) in SET and SSG (19 and 37%, respectively), while MCT4 protein expression rose (P < 0.05) by 30 and 61% in SET and SSG, respectively. SOD2 protein expression increased (P < 0.05) by 28 and 37% in SET and SSG, respectively, while GLUT-4 protein expression increased (P < 0.05) by 40% in SSG only. Finally, SET displayed 39% greater improvement (P < 0.05) in Yo-Yo IR2 performance than SSG. CONCLUSION: Speed endurance training improved muscle oxidative capacity and exercise performance more pronouncedly than small-sided game training, but comparable responses were in muscle ion transporters and antioxidative capacity in well-trained male soccer players

Outer membrane protein folding from an energy landscape perspective

The cell envelope is essential for the survival of Gram-negative bacteria. This specialised membrane is densely packed with outer membrane proteins (OMPs), which perform a variety of functions. How OMPs fold into this crowded environment remains an open question. Here, we review current knowledge about OFMP folding mechanisms in vitro and discuss how the need to fold to a stable native state has shaped their folding energy landscapes. We also highlight the role of chaperones and the β-barrel assembly machinery (BAM) in assisting OMP folding in vivo and discuss proposed mechanisms by which this fascinating machinery may catalyse OMP folding

Genetic variation and exercise-induced muscle damage: implications for athletic performance, injury and ageing.

Prolonged unaccustomed exercise involving muscle lengthening (eccentric) actions can result in ultrastructural muscle disruption, impaired excitation-contraction coupling, inflammation and muscle protein degradation. This process is associated with delayed onset muscle soreness and is referred to as exercise-induced muscle damage. Although a certain amount of muscle damage may be necessary for adaptation to occur, excessive damage or inadequate recovery from exercise-induced muscle damage can increase injury risk, particularly in older individuals, who experience more damage and require longer to recover from muscle damaging exercise than younger adults. Furthermore, it is apparent that inter-individual variation exists in the response to exercise-induced muscle damage, and there is evidence that genetic variability may play a key role. Although this area of research is in its infancy, certain gene variations, or polymorphisms have been associated with exercise-induced muscle damage (i.e. individuals with certain genotypes experience greater muscle damage, and require longer recovery, following strenuous exercise). These polymorphisms include ACTN3 (R577X, rs1815739), TNF (-308 G>A, rs1800629), IL6 (-174 G>C, rs1800795), and IGF2 (ApaI, 17200 G>A, rs680). Knowing how someone is likely to respond to a particular type of exercise could help coaches/practitioners individualise the exercise training of their athletes/patients, thus maximising recovery and adaptation, while reducing overload-associated injury risk. The purpose of this review is to provide a critical analysis of the literature concerning gene polymorphisms associated with exercise-induced muscle damage, both in young and older individuals, and to highlight the potential mechanisms underpinning these associations, thus providing a better understanding of exercise-induced muscle damage

Combined experimental and computational analysis of DNA damage signaling reveals context-dependent roles for Erk in apoptosis and G1/S arrest after genotoxic stress

Data-driven modeling was used to analyze the complex signaling dynamics that connect DNA repair with cell survival, cell-cycle arrest, or apoptosis. This analysis revealed an unexpected role for Erk in G1/S arrest and apoptotic cell death following doxorubicin-induced DNA damage

Feasibility of preoperative planning using anatomical facsimile models for mandibular reconstruction

BACKGROUND: Functional and aesthetic mandibular reconstruction after ablative tumor surgery continues to be a challenge even after the introduction of microvascular bone transfer. Complex microvascular reconstruction of the resection site requires accurate preoperative planning. In the recent past, bone graft and fixation plates had to be reshaped during the operation by trial and error, often a time-consuming procedure. This paper outlines the possibilities and advantages of the clinical application of anatomical facsimile models in the preoperative planning of complex mandibular reconstructions after tumor resections. METHODS: From 2003 to 2005, in the Department of Maxillofacial Surgery of the University of Udine, a protocol was applied with the preoperative realization of stereolithographic models for all the patients who underwent mandibular reconstruction with microvascular flaps. 24 stereolithographic models were realized prior to surgery before emimandibulectomy or segmental mandibulectomy. The titanium plates to be used for fixation were chosen and bent on the model preoperatively. The geometrical information of the virtual mandibular resections and of the stereolithographic models were used to choose the ideal flap and to contour the flap into an ideal neomandible when it was still pedicled before harvesting. RESULTS: Good functional and aesthetic results were achieved. The surgical time was decreased on average by about 1.5 hours compared to the same surgical kind of procedures performed, in the same institution by the same surgical team, without the aforesaid protocol of planning. CONCLUSION: Producing virtual and stereolithographic models, and using them for preoperative planning substantially reduces operative time and difficulty of the operation during microvascular reconstruction of the mandible

Evaluation of the efficacy and safety of olanzapine as an adjunctive treatment for anorexia nervosa in adolescent females: a randomized, double-blind, placebo-controlled trial

<p>Abstract</p> <p>Background</p> <p>Anorexia Nervosa (AN) is a serious, debilitating condition that causes significant physical, emotional, and functional impairment. The condition is characterized by destructive weight loss behaviours and a refusal to maintain body weight at or above a minimally normal weight for age and height. AN often develops in adolescence and is a predominantly female disorder. Treatment for AN typically involves medical, nutritional and psychological interventions. Pharmacotherapy is also often used; however, the literature on the effectiveness of these drugs in a pediatric population is very limited. Olanzapine, which is an 'atypical' antipsychotic, is becoming more widespread in the treatment of AN. Olanzapine is hypothesized to facilitate weight gain, while decreasing levels of agitation and decreasing resistance to treatment in young women with AN. This randomized, double-blind placebo-controlled trial seeks to examine the effectiveness and safety of olanzapine in female youth with AN.</p> <p>Methods/Design</p> <p>Adolescent females between the ages of 12 and 17 diagnosed with AN (either restricting or binge/purge type) or Eating Disorder Not Otherwise Specified with a Body Mass Index of less than or equal to 17.5, will be offered inclusion in the study. Patients will be randomly assigned to receive either olanzapine or placebo. Patients assigned to receive olanzapine will start at a low dose of 1.25 mg/day for three days, followed by 2.5 mg/day for four days, 5 mg/day for one week, then 7.5 mg/day (the target dose chosen) for 10 weeks. After 10 weeks at 7.5 mg the medication will be tapered and discontinued over a period of two weeks. The effectiveness of olanzapine versus placebo will be determined by investigating the change from baseline on measures of eating attitudes and behaviors, depression and anxiety, and change in Body Mass Index at week 12, and after a follow-up period at week 40. It is anticipated that 67 participants will be recruited over two years to complete enrollment.</p> <p>Discussion</p> <p>Randomized controlled trials designed to measure the safety and effectiveness of olanzapine in comparison to placebo are desperately needed, particularly in the adolescent population.</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN23032339</p