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Introduction Fatty acid desaturase 1 (FADS1) gene encodes for delta-5 desaturase enzyme which is needed in conversion of linoleic acid (LA) to arachidonic acid (AA). Recent studies have shown that response to dietary PUFAs differs between the genotypes in circulating fatty acids. However, interactions between the FADS1 genotype and dietary LA on overall metabolism have not been studied. Objectives We aimed to examine the interactions of FADS1 rs174550 genotypes (TT and CC) and high-LA diet to identify plasma metabolites that respond differentially to dietary LA according to the FADS1 genotype. Methods A total of 59 men (TT n = 26, CC n = 33) consumed a sunflower oil supplemented diet for 4 weeks. Daily dose of 30, 40, or 50 ml was calculated based on body mass index. It resulted in 17–28 g of LA on top of the usual daily intake. Fasting plasma samples at the beginning and at the end of the intervention were analyzed with LC–MS/MS non-targeted metabolomics method. Results At the baseline, the carriers of FADS1 rs174550-TT genotype had higher abundance of long-chain PUFA phospholipids compared to the FADS1 rs174550-CC one. In response to the high-LA diet, LA phospholipids and long-chain acylcarnitines increased and lysophospholipids decreased in fasting plasma similarly in both genotypes. LysoPE (20:4), LysoPC (20:4), and PC (16:0_20:4) decreased and cortisol increased in the carriers of rs174550-CC genotype; however, these genotype–diet interactions were not significant after correction for multiple testing. Conclusion Our findings show that both FADS1 rs174550 genotype and high-LA diet modify plasma phospholipid composition. Trial registration The study was registered to ClinicalTrials: NCT02543216, September 7, 2015 (retrospectively registered).

Objectives To investigate the safety and feasibility of magnetic resonance imaging (MRI)-guided transurethral ultrasound ablation (TULSA) for the treatment of benign prostatic obstruction (BPO). Patients and methods An investigator-initiated, prospective, registered (NCT03350529), phase I study enrolled men with lower urinary tract symptoms due to benign prostatic hyperplasia in need of surgical intervention. Patients were followed for 12 months after TULSA. Uroflowmetry, prostate-specific antigen (PSA) level, and a comprehensive set of functional questionnaires including the Expanded Prostate cancer Index Composite-26, International Prostate Symptom Score (IPSS) and five-item version of the International Index of Erectile Function were obtained at baseline and every 3 months afterwards. MRI was obtained at baseline, and at 3 and 12 months after TULSA. Medication use before and after TULSA were recorded. Adverse events (AEs) were reported using the Clavien-Dindo classification. Results A total of 10 men underwent TULSA with no severe AEs encountered. The baseline median (interquartile range [IQR]) age and prostate volume were 68 (63-72) years and 53 (45-66) mL, respectively. At baseline, six patients were moderately symptomatic and four patients severely symptomatic. Nine patients at baseline were on BPO medication. The median (IQR) improvement in the IPSS was 82%, from 17.5 (15.3-23.0) at baseline to 4.0 (2.3-6.3) at 12 months. Similarly, the median maximum urinary flow rate improved by 101%, from a median (IQR) of 12.4 (8.8-17.6) mL/s at baseline to 21.8 (17.6-26.5) mL/s at 12 months. Improvements were already seen at 3 months. The median prostate volume and PSA reduction at 12 months were 33% and 48%, respectively. There were no changes in continence, sexual, erectile or bowel functions. At 12 months, five out of six men with normal ejaculatory function before TULSA reported normal antegrade ejaculations. All patients taking BPO medication before TULSA discontinued medication after TULSA. Conclusion TULSA appears to be a safe and effective treatment for BPO, with promising 12-month follow-up outcomes. Further studies with larger cohorts are needed to confirm the observed results.

Artificial light at night, often referred to as 'light pollution', isa global environmental problem that threatens many nocturnal organisms. One such species is the European common glow-worm (Lampyris noctiluca), in which reproduc-tion relies on the ability of sedentary bioluminescent females to attract flying males to mate. Previous studies show that broad-spectrum white artificial light interferes with mate attraction in this beetle. However, much less is known about wavelength-specific effects. In this study, we experimentally investigate how the peak wavelength (color) of artificial light affects glow-worm mate attraction success in the field by using dummy females that trap males landing to mate. Each dummy was illuminated from above by either a blue (peak wavelength: 452 nm), white (449 nm), yellow (575 nm), or red (625 nm) LED lighting, or light switched off in the control. We estimated mate attraction success as both the probability of attracting at least one male and the number of males attracted. In both cases, mate attraction success depended on the peak wavelength of the artificial light, with short wavelengths (blue and white) decreasing it more than long wavelengths (yellow and red). Hence, adjusting the spectrum of artifi-cial light can be an effective measure for mitigating the negative effects of light pollution on glow-worm reproduction.

Background and purpose - Traditionally, overriding distal radius fractures in children have been reduced and immobilized with a cast or treated with percutaneous pin fixation. There is recent evidence that these fractures heal well if immobilized in the bayonet position without reduction. We evaluated the present treatment of these fractures. Methods - A questionnaire including AP and lateral radiographs of overriding distal radius fractures in 3 pre-pubertal children was answered by 213 surgeons from 28 countries. The surgeons were asked to choose their preferred method of treatment (no reduction, reduction, reduction and osteosynthesis), type and length of cast immobilization, and the number of clinical and radiographic follow-ups. Results - Of the 213 participating surgeons, 176 (83%) would have reduced all 3 presented fractures, whereas 4 (2%) would have treated all 3 children with cast immobilization without reduction. Most reductions (77%) would have been done under general anesthesia. Over half (54%) of the surgeons who preferred anesthesia would have fixed (pins 99%, plate 1%) the fractures. An above-elbow splint or circular cast was chosen in 84% of responses, and the most popular (44%) length of immobilization was 4 weeks. Surgeons from the Nordic countries were more eager to fix the fractures (54% vs. 31%, p

Background Eighteen patients underwent simultaneous bilateral stapes surgery in 2003-2006. Objectives We evaluated the long-term outcomes in this patient group, and assessed their hearing in noise and binaural hearing. Material and Methods Fifteen patients returned questionnaires concerning their hearing, taste function, and balance. Thirteen patients underwent pure-tone and speech audiogram, Finnish matrix sentence test, video head impulse test, and clinical examination on average 13 years after surgery. Results We found no significant difference in air- and bone conduction pure-tone average, speech audiometry, and the air-bone gap between the 1-year and the late postoperative visits. One patient had bilaterally a partial loss of the vestibulo-ocular reflex of unknown cause. Conclusions and Significance The hearing results 13 years after simultaneous bilateral stapes surgery remained good without any significant delayed complications. Simultaneous bilateral stapes surgery is a viable treatment option in selected patients with otosclerosis.

Natural environments are subject to a range of anthropogenic stressors, with pharmaceutical pollution being among the fastest-growing agents of global change. However, despite wild animals living in complex multi-stressor environments, interactions between pharmaceutical exposure and other stressors remain poorly understood. Accordingly, we investigated effects of long-term exposure to the pervasive pharmaceutical contaminant fluoxetine (Prozac) and acute temperature stress on reproductive behaviors and activity levels in the guppy (Poecilia reticulata). Fish were exposed to environmentally realistic fluoxetine concentrations (measured average: 38 or 312 ng/L) or a solvent control for 15 months using a mesocosm system. Additionally, fish were subjected to one of three acute (24 h) temperature treatments: cold stress (18 °C), heat stress (32 °C), or a control (24 °C). We found no evidence for interactive effects of fluoxetine exposure and temperature stress on guppy behavior. However, both stressors had independent impacts. Fluoxetine exposure resulted in increased male coercive copulatory behavior, while fish activity levels were unaffected. Under cold-temperature stress, both sexes were less active and males exhibited less frequent reproductive behaviors. Our results demonstrate that long-term exposure to a common pharmaceutical pollutant and acute temperature stress alter fundamental fitness-related behaviors in fish, potentially shifting population dynamics in contaminated ecosystems.

Background and purpose — Unnecessary radiographic and clinical follow-ups are common in treatment of pediatric fractures. We hypothesized that follow-up radiographs are unnecessary to monitor union of physeal fractures of the distal tibia. Patients and methods — All 224 (147 boys) children under 16 years old treated for a physeal fracture of the distal tibia during a 5-year period (2010–14) in Helsinki Children’s Hospital were included in this study. Peterson type II fractures comprised 55% and transitional fractures (Tillaux and Triplane) 20% of all injuries. Fracture displacement and alignment was measured. Type and place of treatment was recorded. Number of follow-up radiographs and outpatient visits was calculated and their clinical significance was assessed. Results — 109 children had fractures with < 2 mm displacement and no angulation. The other 115 children’s mean fracture displacement was 6 mm (2–28). 54% of all children were treated by casting in situ in the emergency room, 20% with manipulation under anesthesia and 26% with surgery (internal 57, external fixation 2). Median 3 (1–7) follow-up appointments and median 3 (0–6) radiographs were taken. Follow-up radiographs at or before cast removal did not alter treatment in any of the patients. 223 patients’ fractures healed within 4–9 weeks in good alignment (≤ 5° angulation). Interpretation — Routine radiographic follow-up is unnecessary to monitor alignment and union of physeal fractures of the distal tibia.

BACKGROUND The incidence of completely displaced overriding distal metaphyseal radial fractures in children is unknown, and the optimal treatment is controversial. METHODS All completely displaced distal metaphyseal radial fractures in patients

Professional and colloquial sleep hygiene guidelines advise against evening physical activity, despite meta-analyses of laboratory studies concluding that evening exercise does not impair sleep. This study is the first to investigate the association between objectively measured evening physical activity and sleep within a real-world big-data sample. A total of 153,154 nights from 12,638 individuals aged 18–60 years (M = 40.1 SD = 10.1; 44.5% female) were analyzed. Nighttime sleep and minutes of physical activity were assessed using Polar wearable devices for 14 consecutive days. Thirty minutes or more of moderate-to-near maximal physical activity during the 3 h before sleep onset were recorded in 12.4% of evenings, and were more frequent on weekdays than weekends (13.3 vs. 10.2% respectively, p < 0.001). Linear mixed modeling revealed that sleep efficiency was not significantly associated with evening physical activity, and that sleep duration was 3.4 min longer on average on nights following evenings in which participants engaged in 30 min or more of moderate-intense physical activity. Effects were found for sleep timing metrics, as evening physical activity was linked with earlier sleep onset and offset times (−13.7 and −9.3 min, respectively). Overall, these effects were greater– but still very small– on weekdays compared to weekends. The present study provides further evidence for the lack of meaningful links between sleep duration or quality and physical activity in the hours preceding sleep. Taken together with recent meta-analytic findings, these findings suggest that changes in public health recommendations are warranted regarding evening physical activity and its relation to sleep.

Background: Inflammatory bowel diseases (IBD), which include Crohn’s disease (CD) and ulcerative colitis (UC), are described as a chronic inflammation of the small intestine and colon, caused by a dysregulated immune response to host intestinal microbiota in genetically susceptible subjects. Objective: The aim of this study was to compare probiotic therapy versus placebo in Oxidative Stress Values and clinical features in patients affected by IBD. Method: Forty (40) patients previously diagnosed for IBD were recruited and randomized to receive probiotics (test group, n=20) or placebo (control group, n=20) administered for 90 days. Subjects in both the groups were assessed for overall oxidant ability (d-ROMs test) and for the antioxidant response (BAP test): data were reported at baseline, after 1 and 3 months. Additional data from anamnesis and haematological investigation were also reported during the study. Results: d-ROM assay clearly showed that the values observed in the test group were significantly improved, leading to oxidative stress values which are not pathological. The test group showed increasing BAP values, thus confirming the overall improvements of patients ‘health following administration of probiotics. Conclusion: Oral administration of the specific probiotics demonstrated its efficacy and safety on patients affected by IBD.

Funding Information: We thank all triathlon clubs and athletes for help and a positive attitude toward our study. This work was supported by the Helsinki University Hospital Research Fund and The Finnish ORL‐HNS Foundation under Grant 2020022. Publisher Copyright: © 2021 The Authors. Scandinavian Journal of Medicine & Science In Sports published by John Wiley & Sons Ltd. Dizziness during or after the swimming leg is a common complaint among triathletes. We hypothesized that the dizziness is caused by asymmetrical cooling of the vestibular organ. This caloric response is characterized by involuntary eye movements called nystagmus. Altogether, 125 triathletes completed an electronic questionnaire. Fifteen triathletes who had frequently experienced dizziness during the swimming leg agreed to take part in a cold water swimming test. The test comprised two cold water swimming legs, first without earplugs and then with earplugs to prevent a potential caloric response. Eye movements and possible nystagmus were recorded immediately after the swimming legs. A majority (87%, 109/125) of athletes had experienced dizziness during triathlon races or training. Of these, almost all (97%, 106/109) experienced it during or after swimming. Dizziness affected the triathlon performance in half of the athletes with dizziness (50%, 51/102). Fifteen athletes participated in a cold water swimming test. During the first leg (without earplugs), 11/15 athletes (73%) experienced dizziness. Of these, six had nystagmus (55%), four had uncertain nystagmus (36%), and one did not have nystagmus (9%). Only one of these athletes experienced dizziness during the second leg with earplugs. The prevalence of dizziness among triathletes is notable. A large part of the dizziness is likely to be caused by caloric reaction of the vestibular organ. We recommend earplug usage for triathletes suffering from dizziness during the swimming leg.

Background and Aims: The coronavirus outbreak significantly changed the need of healthcare services. We hypothesized that the COVID-19 pandemic decreased the frequency of pediatric fracture operations. We also hypothesized that the frequency of emergency pediatric surgical operations decreased as well, as a result of patient-related reasons, such as neglecting or underestimating the symptoms, to avoid hospital admission. Materials and Methods: Nationwide data were individually collected and analyzed in all five tertiary pediatric surgical/trauma centers in Finland. Operations related to fractures, appendicitis, and acute scrotum in children aged above 16 years between March 1 and May 31 from 2017 to 2020 were identified. The monthly frequencies of operations and type of traumas were compared between prepandemic 3 years and 2020. Results: Altogether, 1755 patients were identified in five tertiary hospitals who had an emergency operation during the investigation period. There was a significant decrease (31%, p = 0.03) in trauma operations. It was mostly due to reduction in lower limb trauma operations (32%, p = 0.006). Daycare, school, and organized sports–related injuries decreased significantly during the pandemic. These reductions were observed in March and in April. The frequencies of appendectomies and scrotal explorations remained constant. Conclusion: According to the postulation, a great decrease in the need of trauma operations was observed during the peak of COVID-19 pandemic. In the future, in case similar public restrictions are ordered, the spared resources could be deployed to other clinical areas. However, the need of pediatric surgical emergencies held stable during the COVID-19 restrictions.

Scope We investigated the FADS1 rs174550 genotype interaction with dietary intakes of high linoleic acid (LA) and high alpha-linolenic acid (ALA) on the response of fatty acid composition of plasma phospholipids (PLs), and markers of low-grade inflammation and glucose-insulin homeostasis. Methods and results One-hundred thirty homozygotes men for FADS1 rs174550 SNP (TT and CC genotypes) were randomized to an 8-week intervention with either LA- or ALA-enriched diet (13 E% PUFA). The source of LA and ALA were 30-50 ml of sunflower oil (SFO, 62-63 % LA) and Camelina sativa oil (CSO, 30-35 % ALA), respectively. In the SFO arm, there was a significant genotype x diet interaction for the proportion of arachidonic acid in plasma phospholipids (p 10 mg/l and users of statins or anti-inflammatory therapy. In the CSO arm, there were significant genotype x diet interactions for n-3 polyunsaturated fatty acids, but not for the clinical characteristics. Conclusions The FADS1 genotype modifies the response to high PUFA diets, especially to high-LA diet. These findings suggest that approaches considering FADS variation might be useful in personalized dietary counseling. This article is protected by copyright. All rights reserved.

Numerous studies in the literature confirm the importance of the use of probiotics in inflammatory states of the prostate in humans. Our pilot study aimed to test probiotics strains ability to improve urinary bacterial load in male subjects.Twenty healthy men aged 55-65 years, with recurrent urinatory infections were enrolled and randomized into 2 groups. Urine culturing to detect Enterobacteriaceae (Escherichia Coli and Enterococcus faecalis) was performed at baseline and at 12 weeks after the starting of the study.We found that taking the probiotic reduces the bacterial load of E. coli and E. faecalis in urine cultures. The use of the probiotic in these inflammatory states does not affect the change in weight in the tested subjects.Our data confirm and improve the main results reported in the scientific literature on the importance of taking probiotics in prostatitis.

Human colorectal cancer (CRC) is characterized by a sequence of biological events that determine its induction and progression. Gut microbiota has an important role in this multistep model of carcinogenesis, as well as constitutive activation of Signal Transducer and Activator Factors 3 (p-STAT3) and Protein Inhibitor of Activated STAT3 (PIAS3), which negatively controls STAT3. It has been reported that a liver growth factor, the Augmenter of Liver Regeneration (ALR), an anti-apoptotic, anti-metastatic factor, exerts protective/cell survival and anti-metastatic activities and has been detected highly expressed in neoplastic cells.To evaluate, by immunohistochemistry, p-STAT3, PIAS3 and ALR expression in neoplastic human tissues from CRC patients, grouping the data in accordance with the histological alterations (G1, G2 and G3) and metastasis presence. Western blot (WB) analysis of ALR was also determined in neoplastic and surrounding tissues. Finally, cell proliferation (Ki-67) and apoptosis (Bcl-2) were determined.Colon cancer tissue samples showed: (1) ALR and p-STAT3 strongly over-expression in 100% of G1 tissue samples, reducing in G2 and G3 tissue samples; (2) PIAS3 immunological determination was poorly expressed in G1 tissue samples and highly expressed in the 100% of colorectal tissues from group G2 and G3. Ki-67 progressively increases with the importance of the anatomic-pathological alterations and Bcl-2 resulted higher in G3 tissue samples compared to G1 neoplastic tissues. WB data evidenced, in neoplastic tissues, compared to the tumour-surrounding tissues, ALR over-expressed in G1 neoplastic tissues and down-expressed in G3 neoplastic tissues.Our data demonstrate a different dynamism of the investigated factors in relation to the severity of CRC histological findings. We hypothesize that the positive expression of ALR and p-STAT3 in the neoplastic tissue samples from CRC G1 group, associated to the absence of PIAS3, could be useful marker to identify an early stage of the disease. Based on these data and on our previous studies on gut microbiota in precancerous intestinal lesions, we are confident that, after microbial priming, a cascade of molecular events is started. So, the detectable molecules acting in these initial steps should be considered for the study of CRC progression and therapy.

BACKGROUND: Despite intense research, the prognosis for patients with advanced colorectal cancer (CRC) remains poor. The prostaglandin D(2) receptors DP1 and DP2 are explored here as potential therapeutic targets for advanced CRC. METHODS: A CRC cohort was analysed to determine whether DP1 and DP2 receptor expression correlates with patient survival. Four colon cancer cell lines and a zebrafish metastasis model were used to explore how DP1/DP2 receptor expression correlates with CRC progression. RESULTS: Analysis of the clinical CRC cohort revealed high DP2 expression in tumour tissue, whereas DP1 expression was low. High DP2 expression negatively correlated with overall survival. Other pathological indicators, such as TNM stage and metastasis, positively correlated with DP2 but not DP1 expression. In accordance, the in vitro results showed high DP2 expression in four CC-cell lines, but only one expressed DP1. DP2 stimulation resulted in increased proliferation, p-ERK1/2 and VEGF expression/secretion. DP2-stimulated cells exhibited increased migration in the zebrafish metastasis model. CONCLUSION: Our results support DP2 receptor expression and signalling as a therapeutic target in CRC progression based on its expression in CRC tissue correlating with poor patient survival and that it triggers proliferation, p-ERK1/2 and VEGF expression and release and increased metastatic activity in CC-cells.

Objective: To analyse the impact noise generated by prostate biopsy devices.Materials and methods: In a laboratory setting, repeated impact noise was recorded at distances of 50 cm and 100 cm using...

n-3 and n-6 polyunsaturated fatty acids (PUFAs) and their lipid mediator metabolites are associated with inflammation. We investigated the effect of dietary intake of plant- and animal-derived n-3 PUFAs and fish protein on the circulatory concentrations of lipid mediators. Seventy-nine subjects with impaired fasting glucose who completed the controlled dietary intervention after randomization to the fatty fish (FF, n=20), lean fish (LF, n=21), Camelina sativa oil (CSO, n=18) or control group (n=20) for 12 weeks were studied. Lipid mediator profiling from fasting plasma samples before and after the intervention was performed by liquid chromatography-mass spectrometry (LC-MS/MS). The FF diet increased concentrations of 18-hydroxyeicosapentaenoic acid (18-HEPE) and 4- and 17-hydroxydocosahexaenoic acid (4-, 17-HDoHE) derived from eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), respectively. Concentrations of lipid mediators derived from α-linolenic acid (ALA) increased and arachidonic acid (AA) derived 5-iso prostaglandin F

Background The oestrogen receptor beta (ERβ) is the predominant oestrogen receptor in the normal colon mucosa and has been reported to exert anti-proliferative and pro-apoptotic effects. However, the role of ERβ in colorectal cancer (CRC) progression remains unclear. Aim To investigate the role of ERβ and its association with hormone status and lifestyle indicators in a female cohort of patients with CRC. Methods Tissue microarrays of primary CRC tumour samples from 320 female patients were conducted with a monoclonal anti-ERβ antibody. The staining intensity was evaluated using immunohistochemistry. The association of ERβ expression with overall survival, disease-free survival, hormone status and lifestyle was evaluated, and effect estimators with 95% confidence intervals (CIs) were reported. Results Among the 314 samples with successfully detected ERβ, 182 (58%) had low expression and 132 (42%) had high expression. The Cox multivariate analysis indicated that patients with high ERβ expression had a decreased risk of overall mortality by 50% (hazard ratio [HR], 0.50; CI, 0.30–0.83) and of cancer recurrence by 76% (HR, 0.24; CI, 0.11–0.52) after adjusting for age, tumour-node-metastasis stage and tumour intravascular invasion. Furthermore, high ERβ expression was significantly correlated with shorter breastfeeding time and longer use of hormone replacement therapy. No association was found between ERβ expression and lifestyle indicators. Conclusion Elevated ERβ expression is independently associated with a better prognosis and hormone status but not lifestyle indicators in female CRC patients.

Recent advances in the translational research showed that dietary nutrients have critical importance to the microbioma balance in the gastrointestinal tract. Therefore, the alteration of the intestinal microbiota in order to achieve, restore, and maintain favorable balance in the ecosystem, and the activity of microorganisms present in the gastrointestinal tract is necessary for the improved health condition of the host. The objective of this translational study was to evaluate, in a pediatric population, the efficacy and safety of prophylactic probiotics for a better nutritional absorption capacity in the view to enhance their overall health and immunity.A total of 40 pediatric patients between the ages of 14 and 18 years were enrolled in the study and divided under two categories (treated/active group and placebo group). Three-time points clinical evaluations were performed: a baseline assessment (Time 0), a second evaluation at 5 weeks after the start of probiotic use (Time 1), and a final evaluation at the timeline after 10 weeks (Time 2). In the initial phase of the study, the recruited subjects underwent a panel of initial T0 clinical tests. For each of the patients, a blood sample was taken in order to evaluate the following biochemical measurements: Vitamin D, Vitamin A, Calcium, Zinc, and Iron. Moreover, an initial nutritional evaluation was carried out through which the nutritionist estimated the body composition of the subject (weight and body mass index), the caloric needs and dietary behaviour of each recruited patient.Eligible participants were randomized into placebo (n = 20) or treated/active (n = 20) treatment conditions by random allocation using a computerized random number generator, ensuring all investigators remained blind to the treatment distribution. The data were compared within and between groups using statistical methods. The results confirmed that the probiotic supplementation was effective in increasing the overall blood biomarkers levels of vitamins, calcium, and mineral absorption from baseline to 10 weeks of treatment, compared with the placebo.Probiotics may be suggested as supplements to improve biomarkers serum concentration if administered for a period of at least ≥ 5 weeks. However, further studies are required for optimal recommendations in patient treatment.

Mitochondrial disorders (MDs) are inherited multi-organ diseases with variable phenotypes. Inclusion body myositis (IBM), a sporadic inflammatory muscle disease, also shows mitochondrial dysfunction. We investigated whether primary and secondary MDs modify metabolism to reveal pathogenic pathways and biomarkers. We investigated metabolomes of 25 mitochondrial myopathy or ataxias patients, 16 unaffected carriers, six IBM and 15 non-mitochondrial neuromuscular disease (NMD) patients and 30 matched controls. MD and IBM metabolomes clustered separately from controls and NMDs. MDs and IBM showed transsulfuration pathway changes; creatine and niacinamide depletion marked NMDs, IBM and infantile-onset spinocerebellar ataxia (IOSCA). Low blood and muscle arginine was specific for patients with m.3243A>G mutation. A four-metabolite blood multi-biomarker (sorbitol, alanine, myoinositol, cystathionine) distinguished primary MDs from others (76% sensitivity, 95% specificity). Our omics approach identified pathways currently used to treat NMDs and mitochondrial stroke-like episodes and proposes nicotinamide riboside in MDs and IBM, and creatine in IOSCA and IBM as novel treatment targets. The disease-specific metabolic fingerprints are valuable "multi-biomarkers" for diagnosis and promising tools for follow-up of disease progression and treatment effect.

Primary central nervous system lymphoma (PCNSL) is a rare brain tumour with a dismal prognosis. Several phase II studies with high-dose methotrexate-based regimens have shown promising early results, but in all hospital-based data published so far, the disease outcome has been poor. Patients with relapsed or refractory disease have a dismal prognosis. We performed retrospective analysis to evaluate results and tolerabilities of BBBD therapy in combination with high-dose therapy supported by autologous stem cell transplantation. We analysed 25 patients (age range: 40-71 years) who were treated in first or second line with BBBD therapy. When we started BBBD treatment, patients had relapsed or refractory PCNSL or they did not tolerate Bonn-like therapy. In recent years, some of the patients were treated in first line. We found promising response rates. Altogether 19 (76 %) of the patients achieved a complete response (CR). Two-year progression-free survival (PFS) and overall survival (OS) rates were 61 and 57 % respectively and the five-year OS was 47 %. Patients who were treated with a five-drug therapy had a very promising prognosis. The CR rate was 100 % in first-line therapy and 60 % in relapsed cases. These findings suggest that BBBD is a promising therapy for PCNSL, especially for patients in first line, but also for patients with relapsed or refractory disease after conventional chemotherapy, who commonly have a very poor prognosis. Treatment-related toxicity was generally manageable. Thus, BBBD followed by ASCT could be a treatment of choice in transplant-eligible patients with PCNSL.

Inflammatory cells and inflammatory mediators play an important role in colorectal cancer (CRC). Previous studies have shown that CRC patients with increased expression of cysteinyl leukotriene receptor 1 (CysLTR1) have a poorer prognosis, and Cysltr1A tissue microarray from 72 CRC patients was stained with MC anti-tryptase and -chymase antibodies. Mouse colon tissue was stained with MC anti-tryptase antibody. Immunohistochemistry was used to identify MCs in patients and mice.Patient colon cancer tissue had in comparison with normal colon tissue a reduced number of MCs, predominantly of chymase-positive cells. Further analysis revealed that patients with a relative high MCD in their cancer tissues showed significantly longer overall survival compared to those with a low MCD [hazard ratio (HR) 0.539; 95% confidence interval (CI), 0.302-0.961]. Similar results were observed in subgroups of patients with either no distant metastasis (p = 0.004), or 75 years (p = 0.015) at time of diagnosis. Multivariate Cox analysis showed that MCD independently correlated with reduced risk of death in colon cancer patients (HR 0.380; 95% CI 0.202-0.713). Additionally, a negative correlation was found between cytoplasmic CysLTR1 expression and number of MCs. In agreement, in the CAC mouse model, Cysltr1A high MCD in cancer tissue correlated with longer patient survival independently from other risk factors for CRC. The concept that MCs have an anti-tumor effect in CRC is further supported by the findings of a negative correlation with CysLTR1 expression in patients and a high MCD in colon polyps/tumors from CysLTR1

Pharmaceutical pollutants constitute a major threat to wildlife because of their capacity to induce biological effects at low doses. One such pollutant is the antidepressant fluoxetine, which has been detected in surface waters globally at levels that recent studies suggest can alter physiology and behaviour in aquatic organisms. However, wildlife exposed to pharmaceutical contaminants are typically confronted with multiple stressors simultaneously, including predation risk, which is a particularly important natural stressor that can have direct (e.g. mortality) and indirect (e.g. changed prey behaviour) fitness effects. Accordingly, we investigated potential impacts of environmentally realistic fluoxetine exposure on reproductive behaviour in the guppy (Poecilia reticulata) under predation risk. Specifically, we tested whether fluoxetine exposure altered mating behaviour in male and female guppies in the presence of either a predatory spangled perch (Leiopotherapon unicolor) or a non-predatory rainbowfish (Melanotaenia splendida) control. We found that fluoxetine and the presence of a predatory spangled perch did not interact to affect reproductive behaviour. We also found that, independent of a predatory threat, fluoxetine exposure altered male mating strategy, with males in the high treatment conducting significantly more coercive ‘sneak’ copulations, whereas the number of courtship displays performed was not significantly affected. Moreover, while fluoxetine exposure did not significantly affect the amount of time that males and females spent following one another, we found that females, but not males, followed a potential partner less when in the presence of the predatory fish. Finally, both sexes reacted to the risk of predation by spending less time in close proximity to a predator than a non-predator. In combination, our findings highlight the capacity of fluoxetine to influence processes of sexual selection at field-realistic concentrations and emphasise the importance of considering multiple stressors when assessing impacts of pharmaceutical pollutants on the behaviour of wildlife.

Both between- and within-individual variation in behaviour can be important in determining mating opportunities and reproductive outcomes. Such behavioural variability can be induced by environmental conditions, especially if individuals vary in their tolerance levels or resource allocation patterns. We tested the effects of exposure to different salinity levels on male investment into two important components of mating success–intrasexual aggression and intersexual courtship–in a fish with a resource defence mating system, the desert goby, Chlamydogobius eremius. We found that males that were more aggressive to rivals also exhibited higher rates of courtship displays towards females. Contrary to predictions, this positive relationship, and the consistency of the two behaviours, were not affected by the salinity treatment, despite the physiological costs that high salinity imposes on the species. Moreover, over the entire data-set, there was only a marginally non-significant tendency for males to show higher levels of aggression and courtship in low, than high, salinity. The positive correlation between male aggression and courtship, independent of the physiological demands of the environment, suggests that males are not inclined to make contrasting resource investments into these two key reproductive behaviours. Instead, in this relatively euryhaline freshwater species, typical investment into current reproductive behaviours can occur under a range of different salinity conditions.

Background Surgical treatment of pediatric tibia shaft fractures has gained popularity despite closed reduction and cast-immobilization providing good long-term results. There is no consensus about optimal methods and satisfactory quality of treatment. Materials and Methods During 2010 to 2014, 226 pediatric patients were treated under anesthesia for tibia shaft fractures in Finland's five university hospitals. A total of 164 (73%) patients had closed fractures of the tibia or both tibia and fibula without other injuries (62 tibia only and 102 both tibia and fibula). Forty-one (18%) had open tibia fractures, 16 had additional fractures, and 5 (2%) had sustained a polytrauma (Injury Severity Score [ISS] > 15). Treatment methods, follow-up protocols, complications, and the outcome were analyzed. Results A total of 143 (63%) of the tibia fractures were treated surgically: 87 (53%) closed fractures, 36 (88%) open fractures, 15 (94%) with additional fractures, and 5 (2%) polytrauma patients. The rate of surgical treatment of closed tibia fractures was significantly higher in patients older than 10 and in patients with a concomitant fibula fracture. Fasciotomy was done in 33 (15%) patients. Reoperations were performed in 13 (6%) patients because of unsatisfactory treatment (inappropriate primary reduction 6, malunion 6, and non-union 1). There were no differences between the five university hospitals in treatment or follow-up protocols. Conclusion Internal fixation is used for the majority of tibia shaft fractures treated under anesthesia in university hospitals in Finland. Serious fracture or treatment related complications are very rare, but the percentage (6%) of re-operations because of unsatisfactory standard of treatment should be lower and could probably be improved by concentrating internal fixation to fewer hands. A prospective randomized controlled trial comparing non-operative treatment to intramedullary nailing in pediatric tibia fractures should be performed.

The aim of this study was to develop and cross-validate two models to estimate total energy expenditure (TEE) based on respiration variables in healthy subjects during daily physical activities. Ninety-nine male and female subjects systematically varying in age (18–60 years) and body mass index (BMI; 17–36 kg*m−2) completed eleven aerobic activities with a portable spirometer as the criterion measure. Two models were developed using linear regression analyses with the data from 67 randomly selected subjects (50.0% female, 39.9 ± 11.8 years, 25.1 ± 5.2 kg*m−2). The models were cross-validated with the other 32 subjects (49% female, 40.4 ± 10.7 years, 24.7 ± 4.6 kg*m−2) by applying equivalence testing and Bland-and-Altman analyses. Model 1, estimating TEE based solely on respiratory volume, respiratory rate, and age, was significantly equivalent to the measured TEE with a systematic bias of 0.06 kJ*min−1 (0.22%) and limits of agreement of ±6.83 kJ*min−1. Model 1 was as accurate in estimating TEE as Model 2, which incorporated further information on activity categories, heart rate, sex, and BMI. The results demonstrated that respiration variables and age can be used to accurately determine daily TEE for different types of aerobic activities in healthy adults across a broad range of ages and body sizes.

Fine-scaled genetic structuring, as seen for example in many lacustrine fish, typically relates to the patterns of migration, habitat use, mating system or other ecological factors. Because the same processes can also affect the propensity of population differentiation and divergence, assessments of species from rapidly speciating clades, or with particularly interesting ecological traits, can be especially insightful. For this study, we assessed the spatial genetic relationships, including the genetic evidence for sex-biased dispersal, in a colony-breeding cichlid fish, Amphilophus astorquii, endemic to Crater Lake Apoyo in Nicaragua, using 11 polymorphic microsatellite loci (n = 123 individuals from three colonies). We found no population structure in A. astorquii either within colonies (no spatial genetic autocorrelation, r ~0), or at the lake-wide level (pairwise population differentiation FST = 0-0.013 and no clustering), and there was no sex-bias (male and female AIc values bounded 0) to this lack of genetic structure. These patterns may be driven by the colony-breeding reproductive behaviour of A. astorquii. The results suggest that strong philopatry or spatial assortative mating are unlikely to explain the rapid speciation processes associated with the history of this species in Lake Apoyo. published

Chemotherapy aided by opening of the blood-brain barrier with intra-arterial infusion of hyperosmolar mannitol improves the outcome in primary central nervous system lymphoma. Proper opening of the blood-brain barrier is crucial for the treatment, yet there are no means available for its real-time monitoring. The intact blood-brain barrier maintains a mV-level electrical potential difference between blood and brain tissue, giving rise to a measurable electrical signal at the scalp. Therefore, we used direct-current electroencephalography ( DC-EEG) to characterize the spatiotemporal behavior of scalp-recorded slow electrical signals during blood-brain barrier opening. Nine anesthetized patients receiving chemotherapy were monitored continuously during 47 blood-brain barrier openings induced by carotid or vertebral artery mannitol infusion. Left or right carotid artery mannitol infusion generated a strongly lateralized DC-EEG response that began with a 2 min negative shift of up to 2000 mu V followed by a positive shift lasting up to 20 min above the infused carotid artery territory, whereas contralateral responses were of opposite polarity. Vertebral artery mannitol infusion gave rise to a minimally lateralized and more uniformly distributed slow negative response with a posterior-frontal gradient. Simultaneously performed near-infrared spectroscopy detected a multiphasic response beginning with mannitol-bolus induced dilution of blood and ending in a prolonged increase in the oxy/deoxyhemoglobin ratio. The pronounced DC-EEG shifts are readily accounted for by opening and sealing of the blood-brain barrier. These data show that DC-EEG is a promising real-time monitoring tool for bloodbrain barrier disruption augmented drug delivery.

We correlated liver and kidney manifestations in a national cohort of patients with autosomal recessive polycystic kidney disease (ARPKD).A total of 27 consecutive patients with ARPKD were included. Hepatobiliary disorders were comparatively evaluated in 2 groups: children in group 1 (n = 10) displayed renal failure as infants and those in group 2 (n = 17) had normal kidney function through the first year of life.Median follow-up time was 10.6 (range, 0.4-40) years. Portal hypertension was diagnosed in 13 patients (48%) at the median age 5.0 (1.5-27.9) years. Esophageal varices developed in 8 patients (30%) at age 8.0 (2.1-11.9) years; 4 patients (15%) had variceal bleeding, and hypersplenism/splenomegaly occurred in 52%, similarly in both groups. Biliary tract dilatation was detected at 2.8 years in group 1 and at 7.9 years in group 2, significantly more frequently in group 1 (60% vs 18%, P = 0.039), causing cholangitis in 2 (20%) versus none in group 2 (P = 0.055). A total of 10 patients (37%) underwent cadaveric liver transplantation (LT) at a median age of 6.6 (1.0-20.0) years. In 1 patient LT was performed because of hepatoblastoma. Nine of these were combined liver-kidney transplantations (CLKT). Patients in group 1 required LT earlier (4.1 years vs 18.2 years, P = 0.017) and more frequently (70% vs 18%, P = 0.01). Overall survival beyond neonatal period was 85%. Two patients died because of infectious complications after CLKT, and 1 patient because of recurrent hepatoblastoma.Although correlation of renal and liver manifestations was variable, biliary dilatation was associated with early renal failure. CLKT may be a treatment for patients with ARPKD with marked hepatobiliary complications.

Discrete colour morphs have provided important insights into the evolution of phenotypic diversity. One of the mechanisms that can help to explain coexistence of ecologically similar colour morphs and incipient species is (colour) biased aggression, which has the potential to promote continued existence of the morphs in a frequency-dependent manner. I addressed colour biases in territorial aggression in a field-based study on a Neotropical cichlid fish species, Amphilophus sagittae, which has two ecologically indistinguishable colour morphs that mate assortatively. I found that A. sagittae, in particular females, were more aggressive towards models of their own colour than those mimicking colours of the other morph. Such a behavioural pattern should result in a selection regime that benefits the rarer morph, and hence could help explain how novel, rare phenotypes may avoid competitive exclusion.

Background Social and environmental factors can profoundly impact an individual’s investment of resources into different components of reproduction. Such allocation trade-offs are expected to be amplified under challenging environmental conditions. To test these predictions, we used a desert-dwelling fish, the desert goby, Chlamydogobius eremius, to experimentally investigate the effects of prior social experience (with either a male or a female) on male investment in courtship and aggression under physiologically benign and challenging conditions (i.e., low versus high salinity). Results We found that males maintained a higher level of aggression towards a rival after a recent encounter with a female, compared to an encounter with a male, under low (but not high) salinity. In contrast, male investment in courtship behaviour was unaffected by either salinity or social experience. Conclusion Together, our results suggest that male investment in aggression and courtship displays can differ in their sensitivity to environmental conditions and that not all reproductive behaviours are similarly influenced by the same environmental context.

Background The internal jugular vein is routinely used as a graft for the Rex shunt. We analyzed results of mesoportal bypass using an alternative autologous graft. Methods Twenty-one children with extrahepatic portal vein obstruction were treated with a Rex shunt constructed using both greater saphenous veins. Follow-up included ultrasound and blood count screening at 3, 6, and 12 months and annually thereafter. Results Median age was 8.7 years (range, 3.6-14 years), and follow-up time, 5.3 years (range, 0.6-7.1 years). Occlusion or narrowing occurred in 6 patients after a median of 20 months (range, 2.6-52 months). In 2 cases, patency was restored, giving an overall success rate of 81%. During follow-up, no variceal bleeding occurred while hemoglobin, platelet count, and leukocyte levels increased ( P ≤ .02 for all) and spleen size decreased ( P = .001). Patients with occlusive shunt complications weighed less ( P = .01), had higher preoperative platelet levels ( P = .02), and tended to have a smaller spleen preoperatively ( P = .06) than patients without shunt complications. Cumulative graft patency at 6 months, 1 year, 3 years, and 5 years was 100%, 89%, 82%, and 74%, respectively. Conclusions Rex shunt constructed using the greater saphenous veins is a valuable alternative to the internal jugular vein graft, allowing long-term reversal of portal hypertension, splenomegaly, and hypersplenism. Low patient weight and high platelet count predicted shunt occlusion.

Utricular dysfunction has been indirectly measured with subjective visual horizontal or vertical testing. Video-oculography equipment with integrated head position sensor allows direct evaluation of head tilt. The aim was to assess head tilt after peripheral vestibular lesion by recording tilting of the head after excluding visual cues (static test condition), and after three lateral head tilts to both sides [subjective head vertical (SHV)]. Thirty patients with unilateral, peripheral vestibular loss were measured in the acute state, and 3 months later. Twenty healthy, age- and sex-matched subjects served as controls. Mean static tilt of 2.6 ± 1.1° in patients with acute vestibular loss differed significantly from that of 1.0 ± 0.4° in healthy subjects (p = 0.004), and from that of 1.1 ± 0.5° during the follow-up visit (p = 0.008). The mean SHV of 3.4 ± 0.7° in patients with acute vestibular loss was significantly more than that of 1.2 ± 0.5° in controls (p

Cichlid fishes are a textbook example of rapid speciation and exuberant diversity—this applies especially to haplochromines, a lineage with approximately 1800 species. Haplochromine males uniquely possess oval, bright spots on their anal fin, called ‘egg-spots’ or ‘egg-dummies’. These are presumed to be an evolutionary key innovation that contributed to the tribe's evolutionary success. Egg-spots have been proposed to mimic the ova of the mouthbrooding females of the corresponding species, contribute to fertilization success and even facilitate species recognition. Interestingly, egg-spot number varies extensively not only between species, but also within some populations. This high degree of intraspecific variation may appear to be counterintuitive since selection might be expected to act to stabilize traits that are correlated with fitness measures. We addressed this ‘paradox’ experimentally, and found that in the haplochromine cichlid Astatotilapia burtoni , the number of egg-spots was related to male age, body condition and dominance status. Intriguingly, the egg-spot number also had a high heritable component (narrow sense heritability of 0.5). These results suggest that the function of egg-spots might have less to do with fertilization success or species recognition, but rather relate to mate choice and/or male–male competition, helping to explain the high variability in this important trait.

Three-dimensional signal analysis can be applied to eye movements called nystagmus in order to study otoneurological patients suffering from vertigo and other balance problems. We developed an analysis and modeling algorithm for three-dimensional nystagmus measured by a video-oculography system. We were also interested in verifying an otoneurological hands-on convention called Ewald's first law in a strict physiological sense in vestibular patients. We recorded nystagmus from 42 patients all suffering from vertigo or dizziness. The underlying pathology was unilateral in 39 patients, bilateral in one patient, and central in two patients. Video-oculography was used to record three-dimensional nystagmus to separately produce horizontal, vertical, and torsional signals for each eye. On the basis of signal analysis techniques and straightforward vector calculus, we were able to recognize slow phases of nystagmus to compute their angular velocities to estimate from which part of the inner ear the disorder originated. We found that for all 42 patients the plane of one of the two horizontal semicircular canals was the closest. We were able to quantitatively estimate the influence of different semicircular canals, and, despite the pathology, horizontal canals seemed to be predominant in driving the nystagmus. The signal analysis and modeling algorithm developed is effective in studying otoneurological problems registered with nystagmus and opens new insights in three-dimensional nystagmography. Our results strongly support Ewald's first law.

The strength of brain responses to others' pain has been shown to depend on the intensity of the observed pain. To investigate the temporal profile of such modulation, we recorded neuromagnetic brain responses of healthy subjects to facial expressions of pain. The subjects observed grayscale photos of the faces of genuine chronic pain patients when the patients were suffering from their ordinary pain (Chronic) and when the patients' pain was transiently intensified (Provoked). The cortical activation sequence during observation of the facial expressions of pain advanced from occipital to temporo‐occipital areas, and it differed between Provoked and Chronic pain expressions in the right middle superior temporal sulcus (STS) at 300–500 ms: the responses were about a third stronger for Provoked than Chronic pain faces. Furthermore, the responses to Provoked pain faces were about 40% stronger in the right than the left STS, and they decreased from the first to the second measurement session by one‐fourth, whereas no similar decrease in responses was found for Chronic pain faces. Thus, the STS responses to the pain expressions were modulated by the intensity of the observed pain and by stimulus repetition; the location and latency of the responses suggest close similarities between processing of pain and other affective facial expressions. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.

BACKGROUND AND PURPOSE: Peripheral aneurysms of the posterior inferior cerebellar artery (PICA) are rare, and pre-existing literature concerning their endovascular treatment is limited. The purpose of this study was to assess the etiology and clinical characteristics of peripheral PICA aneurysms and to evaluate the angiographic and clinical results of the patients who underwent endovascular treatment for a peripheral PICA aneurysm in a single center. MATERIALS AND METHODS: Twelve consecutive patients with 12 peripheral PICA aneurysms (10 ruptured) included in an internal data base were retrospectively reviewed. Posttreatment and follow-up angiograms were analyzed, and the clinical outcome was recorded. RESULTS: The etiology was dissection in 7 (58%) and unknown in 5 cases (42%). Three dissecting aneurysms reruptured before endovascular treatment, and another 3 demonstrated angiographic progress. Four aneurysms were treated by endosaccular coiling, 6 (all dissecting) by parent artery occlusion, and in 2 cases endovascular treatment failed. Angiographic outcome was complete aneurysm and/or parent artery occlusion in 9 cases and neck remnant in 1 case. One aneurysm needed retreatment at follow-up. One lethal procedural complication occurred, and transient ischemic symptoms appeared in 2 patients. The clinical outcome was good in 7 patients, whereas 3 patients, all poor clinical grade, died (1 for unrelated reasons). No rebleedings have occurred during the follow-up. CONCLUSION: In this series, most peripheral PICA aneurysms were secondary to arterial dissection. They were unstable with a high risk of rebleeding and a high mortality if not treated without delay. Endovascular treatment was effective in preventing rehemorrhage.

Background Parental allocation and reproductive success are often strongly influenced by environmental factors. In this respect, salinity is a key factor influencing species distributions and community structure in aquatic animals. Nevertheless, the effects of salinity on reproductive behaviours are not well known. Here, we used the sand goby (Pomatoschistus minutus), a small fish inhabiting a range of different salinities, to experimentally assess the effects of changes in salinity on nesting behaviour, a key component of reproduction in sand gobies and many other taxa. Results We found that salinity levels influenced some aspects of male nesting behaviour (i.e. nest entrance size) but not others (i.e. latency to build a nest, choice of nest site, sand on top of nest) and that small and large individuals were differently affected. In particular, the importance of body size in adjustment of nest entrance depended on the salinity level. Conclusion The results support the prediction that geographically widespread aquatic species, such as sand gobies, are able to perform well under a range of salinity levels. The phenotype by environment interaction found between male size and behavioural responses to salinity can, in turn, help to explain the notable variation observed in nest-building (and other) behaviours closely linked to reproduction. Electronic supplementary material The online version of this article (doi:10.1186/s12898-016-0067-y) contains supplementary material, which is available to authorized users.

Background Aggressive behaviour can have significant evolutionary consequences–not only within species, but also in the context of heterospecific interactions. Here, we carried out an experimental field study to investigate the importance of phenotypic similarity on levels of aggression between species whilst controlling for familiarity effects using manipulated allopatric stimuli. Specifically, we investigated aggressive responses of territory holding males and females in two species of Neotropical cichlid fish, Amphilophus sagittae and Hypsophrys nicaraguensis, that differ in their phenotypic similarity to our allopatric stimulus species, Amphilophus astorquii. Results We found that, independent of phenotypic similarity (and correlated phylogenetic proximity) between the territory holders and intruder, territorial aggression was not adjusted in relation to allopatric intruder colour markings that are associated with different levels of threat and known to provoke different responses in a sympatric setting. We also found that males and females did not differ in their overall patterns of aggression adjustment towards intruder cues. Nevertheless, the two focal species, which share the same breeding grounds and external threats, exhibited different sex roles in breeding territory defence. Conclusion Together with earlier studies assessing hetrospecific aggression in sympatry, our current results highlight the importance of coevolution and learning in species interactions.

In order to characterize cortical responses to coherent motion we use magnetoencephalography (MEG) to measure human brain activity that is modulated by the degree of global coherence in a visual motion stimulus. Five subjects passively viewed two-phase motion sequences of sparse random dot fields. In the first (incoherent) phase the dots moved in random directions; in the second (coherent) phase a variable percentage of dots moved uniformly in one direction while the others moved randomly. We show that: (i) visual-motion-evoked magnetic fields, measured with a whole-scalp neuromagnetometer, reveal two transient events, within which we identify two significant peaks--the 'ON-M220' peak approximately 220 ms after the onset of incoherent motion and the 'TR-M230' peak, approximately 230 ms after the transition from incoherent to coherent motion; (ii) in lateral occipital channels, the TR-M230 peak amplitude varies with the percentage of motion coherence; (iii) two main sources are active in response to the transition from incoherent to coherent motion, the human medial temporal area complex/V3 accessory area (hMT+/V3A) and the superior temporal sulcus (STS), and (iv) these distinct areas show a similar, significant dependence of response strength and latency on motion coherence.

To find cortical correlates of face recognition, we manipulated the recognizability of face images in a parametric manner by masking them with narrow-band spatial noise. Face recognition performance was best at the lowest and highest noise spatial frequencies (NSFs, 2 and 45 c/image, respectively), and degraded gradually towards central NSFs (11-16 c/image). The strength of the 130-180 ms neuromagnetic response (M170) in the temporo-occipital cortex paralleled the recognition performance, whereas the mid-occipital response at 70-120 ms acted in the opposite manner, being strongest for the central NSFs. To noise stimuli without faces, M170 was small and rather insensitive to NSF, whereas the mid-occipital responses resembled closely the responses to the combined face and noise stimuli. These results suggest that the 100 ms mid-occipital response is sensitive to the central spatial frequencies that are critical for face recognition, whereas the M170 response is sensitive to the visibility of a face and closely related to face recognition.

Decreased horizontal vestibulo-ocular reflex (VOR) gain measured with the motorized head impulse rotator usually recovers at least partially within a few months after sudden unilateral vestibular loss. In addition to traditional evaluation of nystagmus, head impulse test responses provide valuable information on the severity and recovery of vestibular loss.To quantify recovery of vestibular function with the motorized head impulse test in patients with acute unilateral peripheral vestibular loss, and to compare these results with other signs and symptoms.We recorded prospectively the horizontal VOR with the motorized head impulse rotator in 30 patients with sudden unilateral vestibular deficit on average 3 days after the onset (early). Twenty patients were measured sequentially on average 3 months later (late). We calculated VOR gain and asymmetry (mean ± standard deviation).The early ipsilesional gain of 0.49 ± 0.21 improved highly significantly to the late gain of 0.79 ± 0.23 (p = 0.0000). The respective asymmetry improved highly significantly from 32 ± 18% to 12 ± 14% (p = 0.0002). Gain or asymmetry recovered at least partially in 80% of the patients. The late high symptom score correlated with low gain (p = 0.043) and high asymmetry (p = 0.018).

Body size, social setting, and the physical environment can all influence reproductive behaviours, but their interactions are not well understood. Here, we investigated how male body size, male–male competition, and water turbidity influence nest-building behaviour in the sand goby (Pomatoschistus minutus), a marine fish with exclusive paternal care. We found that environmental and social factors affected the nest characteristics of small and large males differently. In particular, association between male size and the level of nest elaboration (i.e. the amount of sand piled on top of the nest) was positive only under clear water conditions. Similarly, male size and nest entrance size were positively associated only in the absence of competition. Such interactions may, in turn, help to explain the persistence of variation in reproductive behaviours, which—due to their importance in offspring survival—are otherwise expected to be under strong balancing selection.

This article is a study of melodic expectancy in North Sami yoiks, a style of music quite distinct from Western tonal music. Three different approaches were taken. The first approach was a statistical style analysis of tones in a representative corpus of 18 yoiks. The analysis determined the relative frequencies of tone onsets and two- and three-tone transitions. It also identified style characteristics, such as pentatonic orientation, the presence of two reference pitches, the frequency of large consonant intervals, and a relatively large set of possible melodic continuations. The second approach was a behavioral experiment in which listeners made judgments about melodic continuations. Three groups of listeners participated. One group was from the Sami culture, the second group consisted of Finnish music students who had learned some yoiks, and the third group consisted of Western musicians unfamiliar with yoiks. Expertise was associated with stronger veridical expectations (for the correct next tone) than schematic expectations (based on general style characteristics). Familiarity with the particular yoiks was found to compensate for lack of experience with the musical culture. The third approach simulated melodic expectancy with neural network models of the self-organizing map (SOM) type (Kohonen, T. (1997). Self-organizing maps (2nd ed.). Berlin: Springer). One model was trained on the excerpts of yoiks used in the behavioral experiment including the correct continuation tone, while another was trained with a set of Finnish folk songs and Lutheran hymns. The convergence of the three approaches showed that both listeners and the SOM model are influenced by the statistical distributions of tones and tone sequences. The listeners and SOM models also provided evidence supporting a core set of psychological principles underlying melody formation whose relative weights appear to differ across musical styles.

Surgery of neck paragangliomas carries inherent risks of excessive blood loss and cranial nerve injury. Preoperative embolization has been used to lessen the morbidity of surgery. We sought to characterize our experience with preoperative embolization by evaluating safety, efficacy, and surgical data. During a period of 22 years (1974 to 1996), 19 consecutive patients with 27 histopathologically confirmed neck paragangliomas were surgically treated at the Oulu University Hospital. All patients underwent preoperative arteriography and 17 patients had cervical ultrasonography (US). Eleven patients with 15 tumors were operated on without embolization and nine patients with 12 tumors were preoperatively embolized with 150- to 250-microm polyvinyl alcohol (PVA) particles. The mean blood loss during surgery in the nonembolized group was 1374 mL (range, 100 to 4500 mL) and the mean operation time was 4 hours and 48 minutes (range, 1.5 to 9 hours). In the embolized group the mean blood loss was significantly less (588 mL; range, 100 to 1800 mL; P = 0.04) and the mean operation time shorter (3 hours 24 minutes; range, 2 to 5 hours; P = 0.05). No embolic complications were recorded after the embolization. We conclude that preoperative embolization of neck paragangliomas 3 cm or greater in diameter with PVA particles is safe. Embolization to minimize operative bleeding facilitates surgery, shortens the operation time, and lessens the surgical risks.

Thirty-eight patients with venous malformations of the face, neck, and tongue underwent percutaneous sclerotherapy with direct puncture and instillation of sodium tetradecyl sulphate (Sotradecol) (33-67% solution, mixed with contrast material) into the lesions. Each patient underwent from one to seven treatment sessions (mean 2.2), followed by reconstructive surgery in three cases. Of the 34 patients who responded to the follow-up questionnaire, the late results were excellent or good in 23 patients (68%), moderate in eight, unchanged in three, and were worse in one. Compared with our previous experience of embolisation of such malformations with ethanol, the results with Sotradecol were slightly worse. There was one serious complication, unilateral loss of vision in a patient with a large malformation that extended to the orbit. In conclusion, percutaneous sclerotherapy with Sotradecol is effective treatment for venous malformations of the head and neck. Careful planning is essential to reduce the risks of the treatment.

The study aimed to measure utricular function by directly quantifying head tilt in vestibular schwannoma (VS) patients using regular video-oculography (VOG) equipment with integrated head-position sensor, and to correlate the results with patients’ symptoms and signs. We recorded head tilting after exclusion of visual cues (static head tilt), and after returning to the centre following lateral head rolls towards each side [subjective head vertical (SHV)]. Head tilt in 43 patients was measured preoperatively and approximately 4 months postoperatively, and compared to that of 20 healthy subjects. Symptoms were assessed with a structured questionnaire. Static head tilt in patients was significantly greater than in controls (1.0° ± 0.9°) preoperatively (1.6° ± 1.5°, p = 0.04) and postoperatively (1.7° ± 1.5°, p = 0.01). Mean SHV in patients was significantly greater than in controls (1.2° ± 1.0°) preoperatively (2.0° ± 1.9°, p = 0.03) and postoperatively (2.5° ± 1.8°, p = 0.001), increasing non-significantly after surgery (p = 0.3). Side-specific SHV after ipsilateral head rolls was significantly greater than after contralateral head rolls preoperatively (2.8° ± 3.3° vs. −0.5° ± 3.0°, p = 0.001) and postoperatively (3.3° ± 3.0° vs. 0.6° ± 3.2°, p

Oncogenic transcription factor Myc deregulates the cell cycle and simultaneously reprograms cellular metabolism to meet the biosynthetic and bioenergetic needs of proliferation. Myc also sensitizes cells to mitochondria-dependent apoptosis. Although metabolic reprogramming has been circumstantially connected to vulnerability to apoptosis, the connecting molecular pathways have remained poorly defined. Here, we show that Myc-induced altered glutamine metabolism involves ATP depletion and activation of the energy sensor AMP-activated protein kinase (AMPK), which induces stabilizing phosphorylation of p53 at Ser15. Under influence of Myc, AMPK-stabilized tumor suppressor protein p53 accumulates in the mitochondria and interacts with the protein complex comprised of B-cell lymphoma 2 (Bcl-2) antagonist/killer (BAK) and Bcl2-like 1 (Bcl-xL). Mitochondrial p53 induces conformational activation of proapoptotic Bak without disrupting the Bak–Bcl-x L interaction. Further liberation of Bak specifically from the p53-activated Bak–Bcl-x L complex leads to spontaneous oligomerization of Bak and apoptosis. Thus, Myc-induced metabolic changes are coupled via AMPK and phospho-p53 to the mitochondrial apoptosis effector Bak, demonstrating a cell-intrinsic mechanism to counteract uncontrolled proliferation.