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In this installment of the Longevity & Aging Series, Dr. Jon Berner from the Woodinville Psychiatric Associates in Woodinville, WA, joined host Dr. Evgeniy Galimov to discuss a research paper he co-authored that was published in Volume 16, Issue 14 of Aging (Aging-US), entitled, “mTORC1 activation in presumed classical monocytes: observed correlation with human size variation and neuropsychiatric disease.” DOI - https://doi.org/10.18632/aging.206033 Corresponding author - Jon Berner - jonbernermd@gmail.com Video interview - https://www.youtube.com/watch?v=45L89MaJ7qA Abstract Background: Gain of function disturbances in nutrient sensing are likely the largest component in human age-related disease. Mammalian target of rapamycin complex 1 (mTORC1) activity affects health span and longevity. The drugs ketamine and rapamycin are effective against chronic pain and depression, and both affect mTORC1 activity. Our objective was to measure phosphorylated p70S6K, a marker for mTORC1 activity, in individuals with psychiatric disease to determine whether phosphorylated p70S6K could predict medication response. Methods: Twenty-seven females provided blood samples in which p70S6K and phosphorylated p70S6K were analyzed. Chart review gathered biometric measurements, clinical phenotypes, and medication response. Questionnaires assessed anxiety, depression, autism traits, and mitochondrial dysfunction, to determine neuropsychiatric disease profiles. Univariate and multivariate statistical analyses were used to identify predictors of medication response. Results: mTORC1 activity correlated highly with both classical biometrics (height, macrocephaly, pupil distance) and specific neuropsychiatric disease profiles (anxiety and autism). Across all cases, phosphorylated p70S6K was the best predictor for ketamine response, and also the best predictor for rapamycin response in a single instance. Conclusions: The data illustrate the importance of mTORC1 activity in both observable body structure and medication response. This report suggests that a simple assay may allow cost-effective prediction of medication response. Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206033 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, ketamine, lithium, monocyte, mTORC1, rapamycin About Aging-US The mission of the journal is to understand the mechanisms surrounding aging and age-related diseases, including cancer as the main cause of death in the modern aged population. The journal aims to promote 1) treatment of age-related diseases by slowing down aging, 2) validation of anti-aging drugs by treating age-related diseases, and 3) prevention of cancer by inhibiting aging. (Cancer and COVID-19 are age-related diseases.) Please visit our website at https://www.Aging-US.com​​ and connect with us: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.03.535439v1?rss=1 Authors: Riganello, F., Pearce, A., Lyons, K., Owen, A. M., Soddu, A. M., Stojanoski, B. Abstract: Objectives: Our aim is to better understand the relationship between prolonged aerobic and resistance exercise and cognitive abilities in sedentary young adults, and how this relationship is mediated by changes in cardiovascular fitness. Methods: Twenty-three volunteers were recruited and assigned to two groups to complete one hour of continuous daily workout sessions of aerobic (SPIN) and anaerobic (SCSW) exercises over a 30 day period. Each subject was provided with a Polar-10 wearable to record the heart rate (HR) activity during the workout sessions. The workout sessions were completed during five consecutive days over four consecutive weeks. Each week, HR data were collected from the last workout session. Volunteers also completed a neurocognitive test battery (Cambridge Brain Sciences, CBS) each exercise session, including an additional baseline measure before exercise regime began. Results: We found that memory, reasoning and verbal abilities improved throughout the aerobic, but not the resistance exercise program. We found a positive correlation between heart rate index (HRI) and memory and reasoning test scores. We also found a negative correlation between reasoning ability and HRM (heart rate mean), and heart rate skewness (SKW). The results of a regression model to predict memory and reasoning abiltiies revealed that memory was best predicted by HRI and HRM, while the reasoning ability was best predicted by only HRI. Conclusion: Regular aerobic exercises improved specific cognitive performance and it was possible to predict the performance by employing the HR parameters HRI and HRM. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.24.529927v1?rss=1 Authors: Desmet, D. M., Kazanski, M. E., Cusumano, J. P., Dingwell, J. B. Abstract: Background: Walking requires frequent maneuvers to navigate changing environments with shifting goals. Humans accomplish maneuvers and simultaneously maintain balance primarily by modulating their foot placement, but a direct trade-off between these two objectives has been proposed. As older adults rely more on foot placement to maintain lateral balance, they may be less able to adequately adapt stepping to perform lateral maneuvers. Research Question: How do older adults adapt stepping to enact lateral lane-change maneuvers, and how do physical and perceived ability influence their task performance. Methods: Twenty young (21.7 {+/-} 2.6 yrs) and 18 older (71.6 {+/-} 6.0 yrs) adults walked on a motorized treadmill in a virtual environment. Following an audible and visual cue, participants switched between two parallel paths, centered 0.6m apart, to continue walking on their new path. We quantified when participants initiated the maneuver following the cue, as well as their step width, lateral position, and stepping variability ellipses at each maneuver step. Results: Young and older adults did not differ in when they initiated the maneuver, but participants with lower perceived ability took longer to do so. Young and older adults also did not exhibit differences in step width or lateral positions at any maneuver step, but participants with greater physical ability reached their new path faster. While only older adults exhibited stepping adaptations prior to initiating the maneuver, both groups traded-off stability for maneuverability to enact the lateral maneuver. Significance: Physical and perceived balance ability, rather than age per se, differentially influenced maneuver task performance. Humans must make decisions related to the task of walking itself and do so based on both physical and perceived factors. Understanding and targeting these interactions may help improve walking performance among older adults. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.01.04.522698v1?rss=1 Authors: Naaman, T., Hayek, R., Gutman, I., Springer, S. Abstract: Background: The aim of this study was to investigate the effects of walking in reduced lighting with or without performing a secondary cognitive task on gait dynamics in middle-aged adults and to compare them with young and old adults. Methods: Twenty young (age 28.8{+/-}4.1), 20 middle-aged (age 50.2{+/-}4.4), and 19 elderly (age 70.7{+/-}4.2) subjects participated in the study. Subjects walked on an instrumented treadmill at a self-determined pace under four conditions in randomized order: (1) walking in usual lighting (1000 lumens); (2) walking in near-darkness (5 lumens); (3) walking in usual lighting with a serial-7 subtraction dual-task; and (4) walking in near-darkness with a serial-7 subtraction dual-task. Variability in stride time and variability in the trajectory of the center of pressure in the sagittal and frontal planes (anterior/posterior and lateral variability) were measured. Repeated measures ANOVA and post hoc analysis were used to determine the effects of age, lighting conditions, and cognitive task on each gait outcome. Results: Under usual lighting, stride time variability and anterior/posterior variability of the middle-aged subjects were similar to those of the young and lower than those of the old. The lateral variability of the middle-aged subjects was higher than that of young adults under both lighting conditions. Similar to the older adults, the middle-aged participants increased their stride time variability and anterior/posterior variability when walking in near-darkness, but they were the only ones to exhibit increased lateral variability in near-darkness. Young adult gait was not affected by lighting, and concurrent performance of a cognitive task while walking did not affect gait stability in all groups under any of the lighting conditions. Conclusions: Gait stability decreases in middle age when walking in the dark. Recognition of functional deficits in middle age could promote appropriate interventions to optimize aging and reduce fall risk. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.12.22.521564v1?rss=1 Authors: Christensen, I. B., Ribas, L., Buch-Larsen, K., Marina, D., Larsen, S., Schwarz, P., Dela, F., Gillberg, L. Abstract: Background: Adjuvant chemo- and radiotherapy cause cellular damage not only to cancerous but also to healthy dividing cells. Antineoplastic treatments have been shown to cause mitochondrial respiratory dysfunction in non-tumorous tissues, but the effects on circulating human peripheral blood mononuclear cells (PBMCs) remain unknown. Aim: We aimed to identify changes in mitochondrial respiration of PBMCs after adjuvant chemo- and radiotherapy in postmenopausal early breast cancer (EBC) patients and relate these to metabolic parameters of the patients. Methods: Twenty-three postmenopausal women diagnosed with EBC were examined before and shortly after chemotherapy treatment often administered in combination with radiotherapy (n=18). Respiration (O2 flux per million PBMCs) was assessed by high-resolution respirometry of intact and permeabilized PBMCs. Clinical metabolic characteristics were furthermore assessed. Results: Respiration of intact and permeabilized PBMCs from EBC patients was significantly increased after adjuvant chemo- and radiotherapy (p=6x10-5 and p=1x10-7, respectively). The oxygen flux attributed to specific mitochondrial complexes and respiratory states increased by 17-43% compared to before therapy commencement. Leukocyte counts (p=1x10-4), hemoglobin levels (p=0.0003), and HDL cholesterol (p=0.003) decreased while triglyceride (p=0.01) and LDL levels (p=0.02) increased after treatment suggesting a worsened metabolic state. None of the metabolic parameters correlated significantly with PBMC respiration. Conclusion: This study shows that mitochondrial respiration in circulating PBMCs is significantly increased after adjuvant chemo- and radiotherapy in postmenopausal EBC patients. The increase might be explained by a shift in PBMC subpopulation proportions towards cells relying on oxidative phosphorylation rather than glycolysis or a generally increased mitochondrial content in PBMCs. Both parameters might be influenced by therapy-induced changes to the bone marrow or vascular microenvironment wherein PBMCs differentiate and reside. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.10.374538v1?rss=1 Authors: Schomaker, J., Grouls, M. M. E., Rau, E., Hendriks, M., Colon, A., Meeter, M. Abstract: Objectives: The goal of the present study was to identify the role of the medial temporal lobe (MTL) in the detection and later processing of novelty stimuli. Methods: Twenty-one epilepsy patients with unilateral MTL resection (10 left-sided; 11 right-sided) performed an adapted visual novelty oddball task. In this task two streams of stimuli were presented on the left and right of fixation while the patients' electroencephalogram was measured. Patients responded to infrequent target stimuli, while ignoring frequent standard, and infrequent novel stimuli that could appear either contra- or ipsilateral to the resected side. Results: Novelty detection, as indexed by the N2 ERP component elicited by novels, was not affected by the MTL resections. Later processing of novels, however, as indexed by the novelty P3 ERP component, was reduced for novels presented contra- versus ipsilateral to the resected side. Target processing, as indexed by the P3b, was unaffected. Conclusions: The current results suggest that MTL structures play a role in novelty processing, but that the novelty signal may originate from a distinct neural source. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.14.297010v1?rss=1 Authors: Manoccio, F., Lowe, C., Hall, P. Abstract: Background: The beneficial effects of both single-session bouts of aerobic exercise and therapeutic exercise interventions on the cortical regions associated with executive functions (i.e., prefrontal cortex (PFC)) have been well documented. However, it remains unclear whether aerobic exercise can be used to offset temporary fluctuations in cortical activity. Objective: The current study sought to determine whether a single session of moderate intensity aerobic exercise can offset the attenuating effects of continuous theta burst stimulation (cTBS) targeting the dorsolateral prefrontal cortex (dlPFC). Methods: Twenty-two right-handed participants between 18-30 years completed a 20 minute session of light intensity (10% heart rate reserve (HRR)) and moderate intensity (50% HRR) exercise in a counterbalanced order. Following each exercise session, participants received active cTBS to the left dlPFC. Changes in executive functions were quantified using a flanker paradigm employed at baseline, post-exercise and post-cTBS time points. Additionally, EEG methodologies were used to measure changes in inhibitory control specific event-related potential components (i.e., P3 and N2) in response to the flanker task. Results: Behavioural results from the flanker task revealed a significant improvement in task performance following an acute bout of moderate intensity exercise. Furthermore, the effect of cTBS in both light and moderate intensity conditions were non significant. Similarly, EEG data from P3 and N2 ERP components revealed no changes to amplitude across time and condition. P3 latency data revealed a significant effect of time in the light intensity condition, such that latency was faster following cTBS. Similarly, latency data within the N2 ERP component revealed a significant effect of time on congruent trials in the light intensity condition; N2 latency was faster following cTBS. Conclusion: The current study revealed that light and moderate intensity exercise may provide a buffer to cTBS- induced attenuation of the dlPFC. This study provides empirical and theoretical implications on the potential for exercise to promote cognitive control. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.03.280685v1?rss=1 Authors: Ottesen, T., Davis, K. C., Hobbs, L. K., Muncy, N. M., Stevens, N. M., Anderson, M., Johnson, P., Doxey, C. R., Richter, K., Wang, H., Hartley, R., Kirwan, C. B., Wisco, J. J. Abstract: Introduction: Previous studies have shown that putative pheromones 4,16-androstadien-3-one (AND) and estra-1,3,5(10),16-tetraen-3-ol (EST) cause activation in the preoptic area/anterior hypothalamus in men and women. Sex differences in neural activation patterns have been demonstrated when participants are subject to pheromone stimulation; however, whether other compounds give rise to similar neural activity has not been completely investigated. Methods: Twenty-nine young adults [16 female (21.3+/-0.54; mean yrs+/-SE), 13 male (22.85+/- 0.42)] participated in a 3-block design, where participants were exposed to a scent (lavender), a synthetic male pheromone (4,16-androstadien-3b-ol; ALD), and a synthetic female pheromone (1,3,5(10),16-Estratetraen-3-ol; EST) via an automated olfactometer. Whole-brain, high-resolution (1.8mm 3 ) functional MRI data from a Siemens Trio 3T MRI scanner were collected during all blocks. Five adults were excluded due to excessive movement. MANOVA analysis, a 2 x 3 multivariate model and analysis of 2x2 effects between sex and subsets of stimuli was done for activation over the whole brain and small volumes involved in olfaction. Results: Exploratory analysis of 2x2 effects between sex and subsets of stimuli exhibited significant interactions when assessing activations over the whole brain, and small volumes involved in olfaction. The left and right frontal poles (LFP, RFP) shows significant interaction when assessing sex with lavender and EST for whole brain analysis. For small volume analysis, the right orbitofrontal cortex (ROFC) exhibited a sex with lavender and ALD interaction, and a sex with lavender and EST interaction was observed in the left inferior frontal gyrus (LIFG). Main effects of sex, stimulus, or interaction show no differences analyzed using a 2 x 3 multivariate model. Conclusion: The study shows there is a sexually dimorphic response in the olfactory system to pheromones not previously studied. Scents like lavender do not have this same response. These distinct functional differences in activation patterns may be a result of neural development and maturation differences between sexes. Future studies should expand this pilot study and involve a younger demographic to accurately determine the age at which the olfactory response differentiates between males and females. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.01.278259v1?rss=1 Authors: Oakley, J. D., Sodhi, S. K., Russakoff, D. B., Choudhry, N. Abstract: Purpose: To evaluate the performance of a deep learning-based, fully automated, multi-class, macular fluid segmentation algorithm relative to expert annotations in a heterogeneous population of confirmed wet age-related macular degeneration (wAMD) subjects. Methods: Twenty-two swept-source optical coherence tomography (SS-OCT) volumes of the macula from 22 from different individuals with wAMD were manually annotated by two expert graders. These results were compared using cross-validation (CV) to automated segmentations using a deep learning-based algorithm encoding spatial information about retinal tissue as an additional input to the network. The algorithm detects and delineates fluid regions in the OCT data, differentiating between intra- and sub-retinal fluid (IRF, SRF), as well as fluid resulting from in serous pigment epithelial detachments (PED). Standard metrics for fluid detection and quantification were used to evaluate performance. Results: The per slice receiver operating characteristic (ROC) area under the curves (AUCs) for each of these fluid types were 0.90, 0.94 and 0.94 for IRF, SRF and PED, respectively. Per volume results were 0.94 and 0.88 for IRF and PED (SRF being present in all cases). The correlation of fluid volume between the expert graders and the algorithm were 0.99 for IRF, 0.99 for SRF and 0.82 for PED. Conclusions: Automated, deep learning-based segmentation is able to accurately detect and quantify different macular fluid types in SS-OCT data on par with expert graders. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.13.199224v1?rss=1 Authors: Troisi Lopez, E., Minino, R., Sorrentino, P., Rucco, R., Carotenuto, A., Agosti, V., Tafuri, D., Manzo, V., Liparoti, M., Sorrentino, G. Abstract: BACKGROUND: Parkinson's disease (PD) is characterized by motor impairment, affecting quality of life and increasing fall risk, due to ineffective postural control. To this day, the diagnosis remains based on clinical approach. Similarly, motor evaluation is based on heterogeneous, operator-dependent observational criteria. A synthetic, replicable index to quantify motor impairment is still lacking. In this paper, we build upon the idea that the trunk is crucial in balance control. Hence, we have designed a new measure of postural stability which assess the trunk displacement in relation to the center of mass, that we named trunk displacement index (TDI). METHODS: Twenty-three PD patients and twenty-three healthy controls underwent clinical (UPDRS-III) and motor examination (3D gait analysis). The TDI was extracted from kinematic measurements using a stereophotogrammetric system. A correlation analysis was performed to assess the relationship of TDI with typical gait parameters, to verify its biomechanical value, and UPDRS-III, to observe its clinical relevance. Finally, its sensitivity was measured, comparing pre- and post- L-DOPA subclinical intake. RESULTS: The TDI showed significant correlations with many gait parameters, including both velocity and stability characteristics of gait, and with the UPDRS-III. Finally, the TDI resulted capable in discriminating between off and on state in PD, whereas typical gait parameters failed two show any difference between those two conditions. CONCLUSIONS: Our results suggest that the TDI may be considered a highly sensitive biomechanical index, reflecting the overall motor condition in PD, and provided of clinical relevance due to the correlation with the clinical evaluation. Copy rights belong to original authors. Visit the link for more info

S4P Radio, Sleep Science Audio Abstract 12: Sleep and Weight Cutting in Combat Sports Athletes In our latest S4P Radio, Audio Abstract we review a new article published in the Journal of Exercise and Nutrition, entitled “The Effect of Water Loading for Acute Weight Loss Following Fluid Restriction on Sleep Quality and Quantity in Combat Sports Athletes”. Combat sport athletes commonly engage in established and novel acute weight-loss strategies to achieve weight division targets. The effect of such practices on sleep is unknown. Methods: Twenty-two combat sports athletes wore wrist actigraphy devices for nine nights during a training camp and completed questionnaires assessing daytime sleepiness, insomnia, sleep apnoea and chronotype. Athletes were assigned to a control (CG) or water loading group (WLG). Both followed a low residue diet for 96h, and restricted fluid for 24h before weigh-in. Prior to restriction, the CG consumed 40ml/kg and WLG consumed 100ml/kg fluid daily.   You can check out the full paper at this link! Contact me at iandunican@sleep4performance.com.au or our editor/producer at ricky.krstic@meliusconsulting.com.au www.sleep4performance.com.au Twitter @sleep4perform You can also listen to S4P Radio on YouTube and Spotify

Objective: The effects of 4-aminopyridine (4-AP) on downbeat nystagmus (DBN) were analysed in terms of slow-phase velocity (SPV), stance, locomotion, visual acuity (VA), patient satisfaction and side effects using standardised questionnaires. Methods: Twenty-seven patients with DBN received 5 mg 4-AP four times a day or placebo for 3 days and 10 mg 4-AP four times a day or placebo for 4 days. Recordings were done before the first, 60 min after the first and 60 min after the last drug administration. Results: SPV decreased from 2.42 deg/s at baseline to 1.38 deg/s with 5 mg 4-AP and to 2.03 deg/s with 10 mg 4-AP (p

Background: Conjugated linoleic acids (CLA) in general, and in particular the trans-10, cis-12 (t10, c12-CLA) isomer are potent modulators of milk fat synthesis in dairy cows. Studies in rodents, such as mice, have revealed that t10, c12-CLA is responsible for hepatic lipodystrophy and decreased adipose tissue with subsequent changes in the fatty acid distribution. The present study aimed to investigate the fatty acid distribution of lipids in several body tissues compared to their distribution in milk fat in early lactating cows in response to CLA treatment. Effects in mammary gland are further analyzed at gene expression level. Methods: Twenty-five Holstein heifers were fed a diet supplemented with (CLA groups) or without (CON groups) a rumen-protected CLA supplement that provided 6 g/d of c9, t11-and t10, c12-CLA. Five groups of randomly assigned cows were analyzed according to experimental design based on feeding and time of slaughter. Cows in the first group received no CLA supplement and were slaughtered one day postpartum (CON0). Milk samples were taken from the remaining cows in CON and CLA groups until slaughter at 42 (period 1) and 105 (period 2) days in milk (DIM). Immediately after slaughter, tissue samples from liver, retroperitoneal fat, mammary gland and M. longissimus (13th rib) were obtained and analyzed for fatty acid distribution. Relevant genes involved in lipid metabolism of the mammary gland were analyzed using a custom-made microarray platform. Results: Both supplemented CLA isomers increased significantly in milk fat. Furthermore, preformed fatty acids increased at the expense of de novo-synthesized fatty acids. Total and single trans-octadecenoic acids (e. g., t10-18:1 and t11-18:1) also significantly increased. Fatty acid distribution of the mammary gland showed similar changes to those in milk fat, due mainly to residual milk but without affecting gene expression. Liver fatty acids were not altered except for trans-octadecenoic acids, which were increased. Adipose tissue and M. longissimus were only marginally affected by CLA supplementation. Conclusions: Daily supplementation with CLA led to typical alterations usually observed in milk fat depression (reduction of de novo-synthesized fatty acids) but only marginally affected tissue lipids. Gene expression of the mammary gland was not influenced by CLA supplementation.

Background: The current pilot study compares the impact of an intravenous infusion of Ringer's lactate to an acetate-based solution with regard to acid-base balance. The study design included the variables of the Stewart approach and focused on the effective strong ion difference. Because adverse hemodynamic effects have been reported when using acetate buffered solutions in hemodialysis, hemodynamics were also evaluated. Methods: Twenty-four women who had undergone abdominal gynecologic surgery and who had received either Ringer's lactate (Strong Ion Difference 28 mmol/L; n = 12) or an acetate-based solution (Strong Ion Difference 36.8 mmol/L; n = 12) according to an established clinical protocol and its precursor were included in the investigation. After induction of general anesthesia, a set of acid-base variables, hemodynamic values and serum electrolytes was measured three times during the next 120 minutes. Results: Patients received a mean dose of 4,054 +/- 450 ml of either one or the other of the solutions. In terms of mean arterial blood pressure and norepinephrine requirements there were no differences to observe between the study groups. pH and serum HCO3- concentration decreased slightly but significantly only with Ringer's lactate. In addition, the acetate-based solution kept the plasma effective strong ion difference more stable than Ringer's lactate. Conclusions: Both of the solutions provided hemodynamic stability. Concerning consistency of acid base parameters none of the solutions seemed to be inferior, either. Whether the slight advantages observed for the acetate-buffered solution in terms of stability of pH and plasma HCO3- are clinically relevant, needs to be investigated in a larger randomized controlled trial.

Background: Secondary sclerosing cholangitis is a severe disease of the biliary tract. Over the last decade, several cases of sclerosing cholangitis in critically ill patients (SC-CIP) were reported. Reports in the literature so far are characterized by a wide variety of underlying causes of critical illness, thereby hindering a risk-factor analysis. We report on a homogenous cohort of critically ill patients with influenza A (H1N1) pneumonia and severe acute respiratory distress syndrome (ARDS), of whom a subgroup developed sclerosing cholangitis, allowing for probing of risk factors associated with SC-CIP. Methods: Twenty-one patients (5 female, 16 male, 46.3 +/- 10.8 years) with severe ARDS due to H1N1 pneumonia were retrospectively divided into two groups, characterized by the presence (n = 5) and absence of SC-CIP (n = 16). A large array of clinical data, laboratory parameters, and multi-detector computed tomography-derived measures were compared. Results: Both patient groups showed severe pulmonary impairment. Severity of disease on admission day and during the first 14 days of treatment showed no difference. The patients developing SC-CIP had a higher body mass index (BMI) (37.4 +/- 6.0 kg/m(2) vs. 29.3 +/- 6.8 kg/m(2); P = 0.029) and a higher volume of intraperitoneal fat (8273 +/- 3659 cm(3) vs. 5131 +/- 2268 cm(3); P = 0.033) and spent a longer cumulative period in the prone position during the first 14 days (165 +/- 117 h vs. 78 +/- 61 h; P = 0.038). Conclusion: Our results suggest that obesity, intraperitoneal fat volume, and a longer cumulative duration spent in the prone position may put patients with ARDS at risk of developing SC-CIP. These results lead us to propose that the prone position should be carefully deployed, particularly in abdominally obese patients, and that frequent checks be made for early hepatic dysfunction.

Background: Demodex mites are involved in different skin diseases and are commonly detected by skin scrape tests or superficial biopsies. A new high-definition optical coherence tomography (HD-OCT) with high lateral and axial resolution in a horizontal (en-face) and vertical (slice) imaging mode might offer the possibility of noninvasive and fast in vivo examination of demodex mites. Methods: Twenty patients with demodex-related skin diseases and 20 age- and gender-matched healthy controls were examined by HD-OCT. Mites per follicle and follicles per field of view were counted and compared to skin scrape tests. Results: HD-OCT images depicted mites in the en-face mode as bright round dots in groups of 3-5 mites per hair follicle. In the patients with demodex-related disease, a mean number of 3.4 mites per follicle were detected with a mean number of 2.9 infested follicles per area of view compared to a mean of 0.6 mites in 0.4 infested follicles in the controls. The skin scrape tests were negative in 21% of the patients. Conclusion: The innovative HD-OCT enables fast and noninvasive in vivo recognition of demodex mites and might become a useful tool in the diagnosis and treatment monitoring of demodex-related skin diseases. Copyright (C) 2012 S. Karger AG, Basel

Background/Aims: Specific language impairment (SLI) is believed to be associated with nonverbal auditory (NVA) deficits. It remains unclear, however, whether children with SLI show deficits in auditory time processing, time processing in general, frequency discrimination (FD), or NVA processing in general. Patients and Methods: Twenty-seven children (aged 8-11) with SLI and 27 control children (CG), matched for age and gender, were retrospectively compared with regard to their performance on five NVA skills in terms of just noticeable differences (JND) and time order judgments (TOJ). JND was used for FD, intensity discrimination, and gap detection, while TOJ was used for FD and clicks. Results: Children with SLI performed significantly worse than the CG only on the FD tasks (JND and TOJ). The other nonverbal tasks showed no significant intergroup differences. Additionally, moderate associations were found between the FD tasks and phonological skills, as well as between FD tasks and language scores. Conclusion: Children with SLI appear to have restricted FD skills compared to controls, but there was no evidence for a common NVA deficit or reduced temporal auditory abilities. Copyright (C) 2009 S. Karger AG, Basel

Introduction Increased serum B-type natriuretic peptide (BNP) has been identified for diagnosis and prognosis of impaired cardiac function in patients suffering from congestive heart failure, ischemic heart disease, and sepsis. However, the prognostic value of BNP in multiple injured patients developing multiple organ dysfunction syndrome (MODS) remains undetermined. Therefore, the aims of this study were to assess N-terminal pro-BNP (NT-proBNP) in multiple injured patients and to correlate the results with invasively assessed cardiac output and clinical signs of MODS. Methods Twenty-six multiple injured patients presenting a New Injury Severity Score of greater than 16 points were included. The MODS score was calculated on admission as well as 24, 48, and 72 hours after injury. Patients were subdivided into groups: group A showed minor signs of organ dysfunction ( MODS score less than or equal to 4 points) and group B suffered from major organ dysfunction ( MODS score of greater than 4 points). Venous blood (5 mL) was collected after admission and 6, 12, 24, 48, and 72 hours after injury. NT-proBNP was determined using the Elecsys proBNP (R) assay. The hemodynamic monitoring of cardiac index (CI) was performed using transpulmonary thermodilution. Results Serum NT-proBNP levels were elevated in all 26 patients. At admission, the serum NT- proBNP values were 116 +/- 21 pg/mL in group A versus 209 +/- 93 pg/mL in group B. NT-proBNP was significantly lower at all subsequent time points in group A in comparison with group B (P < 0.001). In contrast, the CI in group A was significantly higher than in group B at all time points (P < 0.001). Concerning MODS score and CI at 24, 48, and 72 hours after injury, an inverse correlation was found (r = 0.664, P < 0.001). Furthermore, a correlation was found comparing MODS score and serum NT- proBNP levels (r = 0.75, P < 0.0001). Conclusions Serum NT-proBNP levels significantly correlate with clinical signs of MODS 24 hours after multiple injury. Furthermore, a distinct correlation of serum NT-proBNP and decreased CI was found. The data of this pilot study may indicate a potential value of NT-proBNP in the diagnosis of post-traumatic cardiac impairment. However, further studies are needed to elucidate this issue.

Background: Tissue inhibitor of metalloproteinases-1 (TIMP-1) in blood might be a helpful biomarker in various diseases. However, various authors report that TIMP-1 is dependent on preanalytical procedures. Our study was performed to determine how storage conditions and time to centrifugation influence TIMP-1. Materials and Methods: Twenty-six blood specimens were collected from each of 20 volunteers. Two specimens from each person were centrifuged/measured within 1 h after venipuncture and frozen at -80 degrees C. They were thawed once or twice within 72 h. Eight specimens were stored at 20 degrees C in daylight, 8 at 20 degrees C covered and 8 at 4 C in daylight. Four of each of these 8 specimens were mixed once a day until centrifugation. A mixed and an unmixed specimen of each group was centrifuged/measured after 3, 6, 24 and 72 h. Results: TIMP-1 increased after freeze/ thaw (p < 0.001). Mixing blood specimens more than once caused increased TIMP-1 (p < 0.001). TIMP-1 increased within 3 h of storage (p < 0.001). The increase was lower in specimens covered and refrigerated (p < 0.001). Conclusion: TIMP-1 is unstable and has to be evaluated carefully. Blood should be centrifuged directly after venipuncture. For routine application, specimen handling must be standardized and carefully followed. Research should be done on specimens handled identically. Copyright (C) 2008 S. Karger AG, Basel.

Objective: The aim of the present study was to investigate if somatoform disorders (SFD) are associated with changes in the normal serum levels of important interleukins, and further, to establish if these changes are related to the presence and severity of alexithymia in patients with SFD. Methods: Twenty-four unmedicated patients who met the International Classification of Diseases (ICD-10) diagnostic criteria for SFD completed the psychological questionnaire to assess alexithymia (Toronto Alexithymia Scale), symptom reporting (SCL-90-R) and diagnostic criteria for SFD (Screening for Somatoform Symptoms scale). Serum concentrations of soluble interleukin 2 receptor alpha(sIL-2R alpha), IL-4, IL-6, IL-10 and IL-12 were determined in patients with SFD and in 9 healthy subjects. Results: In patients with SFD, serum levels of IL-6 (p ! 0.001), IL-10 (p = 0.047) and immunoglobulin E (p = 0.045) were significantly increased in comparison with healthy controls. Additionally, a negative correlation was observed between the level of alexithymia ('total' Toronto Alexithymia Scale score) and the serum levels of sIL-2R alpha (r = -0.538) in SFD. Conclusions: Taken together, these results suggest that SFD, with clinically significant alexithymia, are associated with a reduction in Th1-mediated immune function and an increase in the activation of the Th2 immune function, indicated by the augmented serum levels of IL-6 and IL-10 and elevated immunoglobulin E. Copyright (c) 2007 S. Karger AG, Basel.

BACKGROUND: Intraoperative graft patency verification is of major clinical importance for quality control after coronary artery bypass grafting (CABG), especially if surgery is performed on the beating heart. This is one of the first reports of fluorescence coronary angiography (FCA) using the dye indocyanine green (ICG), a noninvasive technology for direct visualization of coronary arteries and myocardial perfusion. METHODS: Twenty-five domestic pigs underwent FCA of the left anterior descending coronary artery (LAD). In the first group (n = 6 pigs), FCA was used to visualize the native coronary vessels and myocardial perfusion. In the second group (n = 8 pigs), 14 stenoses of various degrees and 4 total vessel occlusions were created by snares on different segments of the LAD, and FCA was used to visualize the effects of these obstructions. In the third group (n = 11 pigs) defined stenoses (25%; 50%, 75%, 100% flow reduction) on the distal part of the LAD were created by a custom-made screw occluder and determined using TTFM (transit-time-flow measurement). ICG was intravenously applied, and the heart was illuminated with near-infrared light emitted by laser diodes. The fluorescence emission was detected by an adapted charge-coupled device camera system. The images were displayed in real time on a high-resolution monitor. Subsequently, images obtained with FCA were correlated with fluorescent microspheres data (n = 11 pigs). RESULTS: In all cases, high-quality FCA images of coronary arteries and myocardial perfusion were obtained. All stenoses resulted in an impairment of the myocardial perfusion visualized by FCA. Occlusion of the LAD or the diagonal branch resulted in a total perfusion defect of the corresponding anterior myocardial wall with immediate reperfusion after releasing the snare. Correlation between FCA and fluorescent microspheres in determination of myocardial perfusion was excellent. CONCLUSION: With the fluorescence technique using ICG, visualization of blood flow in coronary vessels and myocardial perfusion, is feasible. FCA is a highly sensitive and reproducible method and an excellent technique for intraoperative quality control in CABG.