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Sample records for abnormal autonomic function

  1. Abnormal autonomic cardiovascular control in ankylosing spondylitis

    PubMed Central

    Toussirot, E.; Bahjaoui-Bouhaddi, M.; Poncet, J.; Cappelle, S.; Henriet, M.; Wendling, D.; Regnard, J.

    1999-01-01

    OBJECTIVE—This study was aimed at assessing the contribution of the autonomic nervous system to adjustments of cardiovascular function in patients with ankylosing spondylitis (AS).
METHODS—In 18 AS patients (mean age: 34.9; mean disease duration: 6.4 years) and 13 healthy controls (mean age: 31.7) the changes of heart rate (HR) with deep breathing (E/I ratio) and standing up (30/15 ratio) were recorded. The slope of cardiac baroreflex, the times series of blood pressure and HR values upon lying and standing, and venous plasma concentrations of catecholamines were also analysed. Erythrocyte sedimentation rate (ESR), plasma C reactive protein (CRP) concentration and a clinical index (BASDAI score) were used to assess the degree of disease activity in patients.
RESULTS—In the standing patients, blood pressure was found to decrease progressively (p< 0.001). Furthermore, the patients with a BASDAI score > 5 had a higher heart rate than patients with a BASDAI score < 5 (p<0.02), and there was a trend for a similar difference when patients were classified according to their ESR and CRP. Plasma catecholamine concentrations and the E/I ratio were not different in patients from controls. The 30/15 ratio and the slope of the spontaneous baroreflex during standing were both lower in AS patients than controls (p< 0.01).
CONCLUSIONS—This study demonstrated a change in autonomic nervous system function of AS patients, with a decreased parasympathetic activity, as evidenced by higher HR and lower baroreflex slope. As these significant deviances were mainly observed in patients with more active (or more inflammatory) disease, the autonomic nervous system involvement could be related to the inflammatory process. This autonomic strain may be related to the cardiac involvement in AS patients.

 PMID:10419866

  2. Malicious Hubs: Detecting Abnormally Malicious Autonomous Systems

    SciTech Connect

    Kalafut, Andrew J.; Shue, Craig A; Gupta, Prof. Minaxi

    2010-01-01

    While many attacks are distributed across botnets, investigators and network operators have recently targeted malicious networks through high profile autonomous system (AS) de-peerings and network shut-downs. In this paper, we explore whether some ASes indeed are safe havens for malicious activity. We look for ISPs and ASes that exhibit disproportionately high malicious behavior using 12 popular blacklists. We find that some ASes have over 80% of their routable IP address space blacklisted and others account for large fractions of blacklisted IPs. Overall, we conclude that examining malicious activity at the AS granularity can unearth networks with lax security or those that harbor cybercrime.

  3. Evaluation of autonomic functions in subclinical hypothyroid and hypothyroid patients

    PubMed Central

    Mahajan, Aarti S.; Lal, Ram; Dhanwal, Dinesh K.; Jain, Ajay K.; Chowdhury, Veena

    2013-01-01

    Background: Autonomic dysfunction may contribute to cardiovascular morbidity in subclinical hypothyroid patients. It is controversial whether the abnormality exists in sympathetic or the parasympathetic function. It is also not known whether the severity of autonomic dysfunction is related to the degree of thyroid deficiency. Design of Study: Prospective case control. Materials and Methods: Autonomic functions based on heart rate (HR) and blood pressure (BP) responses to various maneuvers were evaluated and scored in twenty two subclinical hypothyroid patients, 30-50 years and compared with twenty hypothyroid patients. Biochemical estimation of TSH, fT3, fT4, TPO antibody was done. Result: Sympathetic function abnormalities were seen in 82% subclinical hypothyroid patients and 85%hypothyroid patients when one test was abnormal. Parasympathetic dysfunction was also recorded in eight patients in both groups. When two abnormal tests were used as the selection criteria sympathetic function abnormality was observed in about 41% subclinical hypothyroid and 65% hypothyroid patients. There were no intergroup differences in autonomic functions, score and TPO levels. The TSH levels were not related to type or degree of autonomic dysfunction. Systolic BP in both groups and diastolic BP in hypothyroid patients were higher with lower thyroxine levels but the patients were normotensive. Conclusion: Autonomic dysfunction of comparable degree was seen in subclinical hypothyroid and hypothyroid patients. Sympathetic function abnormality was more common although decreased parasympathetic function reactivity was also present. These abnormalities were unrelated to TSH levels. PMID:23869303

  4. Autonomic correlations with MRI are abnormal in the brainstem vasomotor centre in Chronic Fatigue Syndrome

    PubMed Central

    Barnden, Leighton R.; Kwiatek, Richard; Crouch, Benjamin; Burnet, Richard; Del Fante, Peter

    2016-01-01

    Autonomic changes are often associated with the chronic fatigue syndrome (CFS), but their pathogenetic role is unclear and brain imaging investigations are lacking. The vasomotor centre and, through it, nuclei in the midbrain and hypothalamus play a key role in autonomic nervous system regulation of steady state blood pressure (BP) and heart rate (HR). In this exploratory cross-sectional study, BP and HR, as indicators of autonomic function, were correlated with volumetric and T1- and T2-weighted spin-echo (T1w and T2w) brain MRI in 25 CFS subjects and 25 normal controls (NC). Steady state BP (systolic, diastolic and pulse pressure) and HR in two postures were extracted from 24 h blood pressure monitoring. We performed (1) MRI versus autonomic score interaction-with-group regressions to detect locations where regression slopes differed in the CFS and NC groups (collectively indicating abnormality in CFS), and (2) MRI regressions in the CFS and NC groups alone to detect additional locations with abnormal correlations in CFS. Significant CFS regressions were repeated controlling for anxiety and depression (A&D). Abnormal regressions were detected in nuclei of the brainstem vasomotor centre, midbrain reticular formation and hypothalamus, but also in limbic nuclei involved in stress responses and in prefrontal white matter. Group comparisons of CFS and NC did not find MRI differences in these locations. We propose therefore that these regulatory nuclei are functioning correctly, but that two-way communication between them is impaired in CFS and this affects signalling to/from peripheral effectors/sensors, culminating in inverted or magnified correlations. This single explanation for the diverse abnormal correlations detected here consolidates the conclusion for a brainstem/midbrain nerve conduction deficit inferred earlier (Barnden et al., 2015). Strong correlations were also detected in isolated NC regressions. PMID:27114901

  5. Autonomic and cognitive functions in Parkinson's disease (PD).

    PubMed

    Oh, Eung Seok; Lee, Ji Hee; Seo, Jin Gi; Sohn, Eun Hee; Lee, Ae Young

    2011-01-01

    We performed this study to evaluate the relationship between the stages of PD and autonomic dysfunction, and to find an association between the autonomic dysfunction and cognitive impairment in PD. Sixty-three patients who met the criteria of the United Kingdom PD Society Brain Bank were enrolled prospectively. Clinical stages were using the Hoehn and Yahr (H&Y) staging and unified PD rating scale motor scores. Cognitive functions were evaluated using the mini-mental state examination (MMSE) and the modified MMSE (3MS) test. The scale for outcome in PD-autonomic (SCOPA-AUT) was used to evaluate autonomic symptoms. Severities of autonomic dysfunction were classified using the composite autonomic scoring scale (CASS). Fifty-four of the 63 patients (86%) had shown abnormalities on CASS. H&Y stages correlated with SCOPA-AUT (p<0.05) and 3MS and MMSE scores (p<0.05). H&Y stages were positively related with autonomic dysfunction, heart rate ratios during deep breathing and the quantitative sudomotor axon reflex test (QSART) scores. Autonomic dysfunction may be present from disease onset, whereas the rate of cognitive decline increases with disease progression. We recommend that both qualitative and quantitative autonomic evaluation from the early stage of disease and regular cognitive screening with disease progression might be useful to facilitate optimal management in PD.

  6. Autonomic Function following Acute Organophosphorus Poisoning: A Cohort Study

    PubMed Central

    Jayasinghe, Sudheera S.; Pathirana, Kithsiri D.

    2012-01-01

    Autonomic dysfunction after chronic low level exposure to organophosphorus (OP) pesticides has been consistently reported in the literature, but not following a single acute overdose. In order to study autonomic function after an acute OP overdose, sixty-six overdose patients were compared to 70 matched controls. Assessment of autonomic function was done by heart rate response to standing, deep breathing (HR-DB) and Valsalva manoeuvre; blood pressure (BP) response to standing and sustained hand grip; amplitude and latency of sympathetic skin response (SSR); pupil size and post-void urine volume. The patients were assessed one and six weeks after the exposure. The number of patients who showed abnormal autonomic function compared to standard cut-off values did not show statistically significantly difference from that of controls by Chi-Square test. When compared to the controls at one week the only significant differences consistent with autonomic dysfunction were change of diastolic BP 3 min after standing, HR-DB, SSR-Amplitude, SSR-Latency, post-void urine volume and size of the pupil. At 6 weeks significant recovery of autonomic function was observed and only HR-DB was decreased to a minor degree, −5 beats/min [95%CI 2–8]. This study provides good evidence for the lack of long term autonomic dysfunction following acute exposure to OP pesticides. PMID:22655091

  7. Autonomic, locomotor and cardiac abnormalities in a mouse model of muscular dystrophy: targeting the renin-angiotensin system.

    PubMed

    Sabharwal, Rasna; Chapleau, Mark W

    2014-04-01

    New Findings What is the topic of this review? This symposium report summarizes autonomic, cardiac and skeletal muscle abnormalities in sarcoglycan-δ-deficient mice (Sgcd-/-), a mouse model of limb girdle muscular dystrophy, with emphasis on the roles of autonomic dysregulation and activation of the renin-angiotensin system at a young age. What advances does it highlight? The contributions of the autonomic nervous system and the renin-angiotensin system to the pathogenesis of muscular dystrophy are highlighted. Results demonstrate that autonomic dysregulation precedes and predicts later development of cardiac dysfunction in Sgcd-/- mice and that treatment of young Sgcd-/- mice with the angiotensin type 1 receptor antagonist losartan or with angiotensin-(1-7) abrogates the autonomic dysregulation, attenuates skeletal muscle pathology and increases spontaneous locomotor activity. Muscular dystrophies are a heterogeneous group of genetic muscle diseases characterized by muscle weakness and atrophy. Mutations in sarcoglycans and other subunits of the dystrophin-glycoprotein complex cause muscular dystrophy and dilated cardiomyopathy in animals and humans. Aberrant autonomic signalling is recognized in a variety of neuromuscular disorders. We hypothesized that activation of the renin-angiotensin system contributes to skeletal muscle and autonomic dysfunction in mice deficient in the sarcoglycan-δ (Sgcd) gene at a young age and that this early autonomic dysfunction contributes to the later development of left ventricular (LV) dysfunction and increased mortality. We demonstrated that young Sgcd-/- mice exhibit histopathological features of skeletal muscle dystrophy, decreased locomotor activity and severe autonomic dysregulation, but normal LV function. Autonomic regulation continued to deteriorate in Sgcd-/- mice with age and was accompanied by LV dysfunction and dilated cardiomyopathy at older ages. Autonomic dysregulation at a young age predicted later development of

  8. Abnormal autonomic and associated brain activities during rest in autism spectrum disorder

    PubMed Central

    Eilam-Stock, Tehila; Xu, Pengfei; Cao, Miao; Gu, Xiaosi; Van Dam, Nicholas T.; Anagnostou, Evdokia; Kolevzon, Alexander; Soorya, Latha; Park, Yunsoo; Siller, Michael; He, Yong; Hof, Patrick R.

    2014-01-01

    Autism spectrum disorders are associated with social and emotional deficits, the aetiology of which are not well understood. A growing consensus is that the autonomic nervous system serves a key role in emotional processes, by providing physiological signals essential to subjective states. We hypothesized that altered autonomic processing is related to the socio-emotional deficits in autism spectrum disorders. Here, we investigated the relationship between non-specific skin conductance response, an objective index of sympathetic neural activity, and brain fluctuations during rest in high-functioning adults with autism spectrum disorder relative to neurotypical controls. Compared with control participants, individuals with autism spectrum disorder showed less skin conductance responses overall. They also showed weaker correlations between skin conductance responses and frontal brain regions, including the anterior cingulate and anterior insular cortices. Additionally, skin conductance responses were found to have less contribution to default mode network connectivity in individuals with autism spectrum disorders relative to controls. These results suggest that autonomic processing is altered in autism spectrum disorders, which may be related to the abnormal socio-emotional behaviours that characterize this condition. PMID:24424916

  9. The Functioning of Autonomous Colleges

    ERIC Educational Resources Information Center

    Rao, V. Pala Prasada; Rao, Digumarti Bhaskara

    2012-01-01

    The college gets separated from the university, though not completely, when it is an autonomous college, which is practice in India. Academic package will become flexible and the decision-making is internalized, changes and updating could be easily carried out, depending on the need as reflected from the feedback taken from alumni, user sectors,…

  10. Sinus node function after autonomic blockade in normals and in sick sinus syndrome.

    PubMed

    Sethi, K K; Jaishankar, S; Balachander, J; Bahl, V K; Gupta, M P

    1984-06-01

    Electrophysiologic studies were performed in 10 normals and 33 patients with sick sinus syndrome before and after total autonomic blockade with propranolol and atropine. In normals both corrected sinus node recovery time (SNRT) and sinoatrial conduction time (SACT) decreased significantly after autonomic blockade. In patients with sick sinus syndrome the corrected SNRT was abnormal (greater than 450 msec) in 16 (48.5%) cases before and 25 (76%) cases (greater than 285 msec) after autonomic ablation (P less than 0.02). Thirteen of 21 patients (62%) with normal intrinsic heart rate and all 12 cases with abnormally low intrinsic rate after autonomic blockade had abnormal corrected SNRT (greater than 285 msec). Mean SACT measured in 19 patients also shortened significantly following pharmacologic denervation. During control it was prolonged (greater than 226 msec) in 8 patients (44%). After autonomic blockade 2 of 13 patients with normal intrinsic heart rate and 3 of 6 with low intrinsic rate showed abnormal SACT (greater than 151 msec). The data suggest that the majority (76%) of patients with sick sinus syndrome have intrinsic abnormality of sinus node automaticity while in a minority (24%) disturbed autonomic regulation is the pathogenetic mechanism. Patients with normal intrinsic heart rate usually have normal intrinsic SACT, while a significant proportion of those with low intrinsic rate have abnormal perinodal conduction. Subjects with abnormal intrinsic heart rate have more severe disturbances of sinus node function than those with normal intrinsic rate.

  11. Abnormally Malicious Autonomous Systems and their Internet Connectivity

    SciTech Connect

    Shue, Craig A; Kalafut, Prof. Andrew; Gupta, Prof. Minaxi

    2011-01-01

    While many attacks are distributed across botnets, investigators and network operators have recently targeted malicious networks through high profile autonomous system (AS) de-peerings and network shut-downs. In this paper, we explore whether some ASes indeed are safe havens for malicious activity. We look for ISPs and ASes that exhibit disproportionately high malicious behavior using ten popular blacklists, plus local spam data, and extensive DNS resolutions based on the contents of the blacklists. We find that some ASes have over 80% of their routable IP address space blacklisted. Yet others account for large fractions of blacklisted IP addresses. Several ASes regularly peer with ASes associated with significant malicious activity. We also find that malicious ASes as a whole differ from benign ones in other properties not obviously related to their malicious activities, such as more frequent connectivity changes with their BGP peers. Overall, we conclude that examining malicious activity at AS granularity can unearth networks with lax security or those that harbor cybercrime.

  12. Clinical and electrophysiologic attributes as predictors of results of autonomic function tests

    NASA Technical Reports Server (NTRS)

    Wu, C. L.; Denq, J. C.; Harper, C. M.; O'Brien, P. C.; Low, P. A.

    1998-01-01

    Autonomic dysfunction is a feature of some neuropathies and not others. It has been suggested that some clinical and electrophysiologic attributes are predictable of autonomic impairment detected using laboratory testing; however, dear guidelines are unavailable. We evaluated 138 relatively unselected patients with peripheral neuropathy who underwent neurologic evaluation, electromyography (EMG), nerve conduction studies, and autonomic function tests to determine which variables were predictive of laboratory findings of autonomic failure. The variables evaluated were 1) clinical somatic neuropathic findings, 2) clinical autonomic symptoms, and 3) electrophysiologic findings. Autonomic symptoms were strongly predictive (Rs = 0.40, p < 0.001) of autonomic failure. Among the non-autonomic indices, absent ankle reflexes were mildly predictive (Rs = 0.19, p = 0.022) of autonomic impairment, but all others were not (duration, clinical pattern, severity, weakness, sensory loss). Electrophysiologic changes of an axonal neuropathy predicted autonomic impairment while demyelinating neuropathy did not. We conclude that autonomic studies will most likely be abnormal in patients who have symptoms of autonomic involvement and those who have an axonal neuropathy.

  13. Autonomic Functions In Raja-yoga Meditators.

    PubMed

    Bharshankar, Jyotsana R; Mandape, Archana D; Phatak, Mrunal S; Bharshankar, Rajay N

    2015-01-01

    Stress, an inevitable and constant feature throughout the lifetime, induces autonomic dysfunctions, for which meditation is considered to be an antidote. So the case control study was planned including 50 Raja-yoga meditators practicing meditation for 5 years and 50 age matched non-meditators. Autonomic function tests were performed and results were compared using the Student-t test. Mean values of resting HR, SBP and DBP were less in meditators. Galvanic Skin Response in meditators was significantly more (p < 0.001). Mean increase BP response to Hand Grip Test and Cold Pressor Test was significantly less in meditators than non-meditators (p < 0.001). Standing: Lying ratio, Valsalva ratio, Inspiration: Expiration ratio and 30:15 ratios were significantly increased in meditators than non-meditators. From the results, there was shifting of the autonomic balance to parasympathetic side in Raja-yoga meditators, which suggests its utility to combat the ill effects of stress. PMID:27530006

  14. Autonomic nervous system functions in obese children.

    PubMed

    Yakinci, C; Mungen, B; Karabiber, H; Tayfun, M; Evereklioglu, C

    2000-05-01

    Childhood obesity is a complex syndrome, probably due to the multiplicity of contributing factors, contradictory literature information about etiology, prognosis, prevention and treatment. In the recent reports, autonomic nervous system (ANS) dysfunction has been documented in adult obesity. Autonomic nervous system functions in obese children are not clear. This study was planned to investigate autonomic nervous system function in childhood (7-13 years of age) obesity. Study and control groups consisted of 33 simple obese (23 boys and ten girls, mean age 9.5+/-1.4 years) and 30 healthy children (18 boys and 12 girls, mean age 10.1+/-1.8 years), respectively. Four non-invasive autonomic nervous system function tests (Orthostatic test, Valsalva ratio, 30/15 ratio, Heart rate responses to deep breathing) and general ophthalmic examination were performed on both groups. The difference between the obese and control groups was found statistically significant in Valsalva ratio, 30/15 ratio and Heart rate responses to deep breathing (P<0.025), and insignificant in Orthostatic test (P>0.05). Ophthalmic examinations were normal. The result of these tests suggested normal activity of sympathetic, and hypoactivity of parasympathetic nervous system, implying parasympathetic nervous system dysfunction as a risk factor or associated finding in childhood obesity. PMID:10814895

  15. Autonomic functions in acrocyanosis assessed by heart rate variability

    PubMed Central

    Yılmaz, Sedat; Yokuşoğlu, Mehmet; Çınar, Muhammet; Şimşek, İsmail; Baysan, Oben; Öz, Bilgehan Savaş; Erdem, Hakan; Pay, Salih; Dinç, Ayhan

    2014-01-01

    Objective To evaluate the autonomic activity of patients with acrocyanosis by using heart rate variability indices. Material and Methods The study group consisted of 24 patients with acrocyanosis and the control group contained 22 sex- and age-matched healthy subjects. All subjects underwent 24-hour Holter monitoring. Among the heart rate variability (HRV) parameters, time-domain and frequency-domain indices were analysed. Results The time-domain indices of HRV indicating global autonomic functions were found to be increased, and indices indicating parasympathetic activity showed a significant decrease in the patient group. Power-spectral analysis of HRV revealed that the low frequency and high frequency power were higher in the patient group than in controls. However, the ratio of Low Frequency/High Frequency was found to be lower in the patient group than in controls. Conclusion In acrocyanosis, both sympathetic and parasympathetic systems seem to be disrupted. Therefore, we may conclude that acrocyanosis may be resulted of systemic autonomic imbalance rather than pure sympathetic over-activation. Also, these results suggest that acrocyanosis is not a localised disorder; on the contrary, it is associated with various abnormalities of the systemic autonomic nervous system.

  16. Autonomic control of adrenal function.

    PubMed Central

    Edwards, A V; Jones, C T

    1993-01-01

    Recent studies of adrenal function in conscious calves are reviewed. These have involved collecting the whole of the adrenal effluent blood from the right adrenal gland at intervals and, where necessary, prior functional hypophysectomy by destruction of the pituitary stalk under general halothane anaesthesia 3 d previously. The adrenal medulla was found to release numerous neuropeptides, in addition to catecholamines, in response to stimulation of the peripheral end of the right splanchnic nerve, which was carried out below behavioural threshold. Many of these responses were enhanced by stimulating intermittently at a relatively high frequency. Intra-aortic infusions of a relatively low dose of acetylcholine (4.5 nmol min-1 kg-1) elicited similar responses. In the adrenal cortex, agonists which either potentiated the steroidogenic response to ACTH or exerted a direct steroidogenic action included VIP, CGRP, CRF and ACh acting via muscarinic receptors. Stimulation of the peripheral end of the right splanchnic nerve strongly potentiated the steroidogenic response to ACTH and there is compelling evidence that the innervation normally plays an important part in cortisol secretion. PMID:8300417

  17. Abnormalities of the QT interval in primary disorders of autonomic failure

    NASA Technical Reports Server (NTRS)

    Choy, A. M.; Lang, C. C.; Roden, D. M.; Robertson, D.; Wood, A. J.; Robertson, R. M.; Biaggioni, I.

    1998-01-01

    BACKGROUND: Experimental evidence shows that activation of the autonomic nervous system influences ventricular repolarization and, therefore, the QT interval on the ECG. To test the hypothesis that the QT interval is abnormal in autonomic dysfunction, we examined ECGs in patients with severe primary autonomic failure and in patients with congenital dopamine beta-hydroxylase (DbetaH) deficiency who are unable to synthesize norepinephrine and epinephrine. SUBJECTS AND METHODS: Maximal QT and rate-corrected QT (QTc) intervals and adjusted QTc dispersion [(maximal QTc - minimum QTc on 12 lead ECG)/square root of the number of leads measured] were determined in blinded fashion from ECGs of 67 patients with primary autonomic failure (36 patients with multiple system atrophy [MSA], and 31 patients with pure autonomic failure [PAF]) and 17 age- and sex-matched healthy controls. ECGs of 5 patients with congenital DbetaH deficiency and 6 age- and sex-matched controls were also analyzed. RESULTS: Patients with MSA and PAF had significantly prolonged maximum QTc intervals (492+/-58 ms(1/2) and 502+/-61 ms(1/2) [mean +/- SD]), respectively, compared with controls (450+/-18 ms(1/2), P < .05 and P < .01, respectively). A similar but not significant trend was observed for QT. QTc dispersion was also increased in MSA (40+/-20 ms(1/2), P < .05 vs controls) and PAF patients (32+/-19 ms(1/2), NS) compared with controls (21+/-5 ms(1/2)). In contrast, patients with congenital DbetaH deficiency did not have significantly different RR, QT, QTc intervals, or QTc dispersion when compared with controls. CONCLUSIONS: Patients with primary autonomic failure who have combined parasympathetic and sympathetic failure have abnormally prolonged QT interval and increased QT dispersion. However, QT interval in patients with congenital DbetaH deficiency was not significantly different from controls. It is possible, therefore, that QT abnormalities in patients with primary autonomic failure are not

  18. Normal and abnormal human vestibular ocular function

    NASA Technical Reports Server (NTRS)

    Peterka, R. J.; Black, F. O.

    1986-01-01

    The major motivation of this research is to understand the role the vestibular system plays in sensorimotor interactions which result in spatial disorientation and motion sickness. A second goal was to explore the range of abnormality as it is reflected in quantitative measures of vestibular reflex responses. The results of a study of vestibular reflex measurements in normal subjects and preliminary results in abnormal subjects are presented in this report. Statistical methods were used to define the range of normal responses, and determine age related changes in function.

  19. Age Related Changes in Autonomic Functions

    PubMed Central

    Amir, Mohammed; Pakhare, Abhijit; Rathi, Preeti; Chaudhary, Lalita

    2016-01-01

    Introduction Autonomic Nervous System (ANS) imbalance may trigger or enhance pathology in different organ systems that varies in different age groups hence objective of present study was to evaluate association of different Age-groups with autonomic functions. Materials and Methods A cross-sectional study was conducted in 62 healthy volunteers in Department of Physiology LLRM Medical College Meerut, India. Volunteers were divided into three groups as younger (15-45 years), middle (45-60) and elder age (above 60), Autonomic functions were tested in three domains viz. Cardio-vagal, adrenergic and sudomotor functions. Numerical data was summarized as mean and standard deviation and categorical data as count and percentage. ANOVA and Chi-square test were used to find difference among groups, p<0.05 was considered statistically significant. Results Mean ± standard deviation OHT(Orthostatic Hypotension Test) among of younger, middle and elder age groups were 8.80±2.28, 13.40±4.64 and 21.82±6.04 respectively which represent decrease in sympathetic functions with age (p<0.001). Cardio-vagal or parasympathetic responses indicated by DBT (Deep Breathing Test) Valsalva and 30:15 ratio of HR response to standing tests has shown statistically significant (p<0.001) decrease in mean response with increasing age. Sudomotor response appeared normal in younger and middle group but was interrupted in more than half of elderly people (p<0.001). Conclusion Sympathetic responses & para-sympathetic responses have shown the significant decline with increasing age group. Sudomotor responses were partially interrupted in elderly age group. PMID:27134865

  20. Cardiac Autonomic Function in Patients With Ankylosing Spondylitis

    PubMed Central

    Wei, Cheng-Yu; Kung, Woon-Man; Chou, Yi-Sheng; Wang, Yao-Chin; Tai, Hsu-Chih; Wei, James Cheng-Chung

    2016-01-01

    Abstract Ankylosing spondylitis (AS) is a chronic inflammatory disease involing spine and enthesis. The primary aim of this study is to investigate the autonomic nervous system (ANS) function and the association between ANS and the functional status or disease activity in AS. The study included 42 AS patients, all fulfilling the modified New York criteria. All the patients are totally symptom free for ANS involvement and had normal neurological findings. These AS patients and 230 healthy volunteers receive analysis of 5 minutes heart rate variability (HRV) in lying posture. In addition, disease activity and functional status of these AS patients are assessed by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), and Bath Ankylosing Spondylitis Global Score (BAS-G). Both groups were age and sex-matched. Although the HRV analysis indicates that the peaks of total power (TP, 0–0.5 Hz) and high-frequency power (HF, 0.15–0.40 Hz) are similar in both groups, the activities of low-frequency power (LF, 0.04–0.15 Hz), LF in normalized units (LF%), and the ratio of LF to HF (LF/HF) in AS patients are obviously lower than healthy controls. The erythrocyte sedimentation rate and C-reactive protein revealed negative relationship with HF. The AS patients without peripheral joint disease have higher LF, TP, variance, LF%, and HF than the patients with peripheral joint disease. The AS patients without uvetis have higher HF than the patients with uvetis. The total scores of BASDI, BASFI, and BAS-G do not show any association to HRV parameters. AS patients have significantly abnormal cardiac autonomic regulation. This is closely related with some inflammatory activities. Reduced autonomic function may be one of the factors of high cardiovascular risk in AS patients. PMID:27227940

  1. Small fibre function in primary autonomic failure.

    PubMed

    Baron, R; Feldmann, R; Lindner, V

    1993-12-01

    A case of primary autonomic failure (AF) with uncomplicated Parkinson's disease is presented with clinical and neurophysiological data. Special emphasis is placed on new methods of examining impairment of unmyelinated sympathetic and afferent C-fibres. Sympathetic vasoconstrictor responses in the skin induced by deep inspiration were examined quantitatively with laser Doppler flowmetry. The vasoconstriction was markedly depressed in primary AF compared with healthy controls and similar to secondary forms of AF. Peripheral nociceptive C-fibre function was quantitatively assessed by measurement of axon reflex vasodilatation induced by histamine iontophoresis. The axon reflex vasodilatation was completely intact in primary AF in contrast to patients with secondary peripheral small fibre neuropathy. The results indicate that sympathetic C-fibres are considerably affected by the degenerative disease, whereas the afferent C-fibres seem to be totally preserved. Modern neurophysiological methods of testing sympathetic and afferent small fibre function in combination with other neurophysiological tests, e.g. brain-stem auditory evoked potentials, might help to diagnose and differentiate primary AF in early stages and make it easier to distinguish between secondary autonomic neuropathies of unknown origin that often also involve unmyelinated afferent fibres. PMID:8138830

  2. Cognitive Function in Peripheral Autonomic Disorders

    PubMed Central

    Guaraldi, Pietro; Poda, Roberto; Calandra-Buonaura, Giovanna; Solieri, Laura; Sambati, Luisa; Gallassi, Roberto; Cortelli, Pietro

    2014-01-01

    Objective aims of the current study were 1) to evaluate global cognitive function in patients with autonomic failure (AF) of peripheral origin and 2) to investigate the effect of a documented fall in blood pressure (BP) fulfilling the criteria for orthostatic hypotension (OH) on cognitive performances. Methods we assessed 12 consecutive patients (10 males, 68±7 years old) with pure AF (PAF) or autoimmune autonomic neuropathy (AAN) and 12 age- and gender-matched controls. All patients had no clinical signs of central nervous system involvement and normal brain CT/MRI scan. Cognitive function was assessed on two consecutive days in 3 conditions: on day 1, while sitting, by means of a comprehensive battery of neuropsychological tests; on day 2, while tilted (HUT) and during supine rest (supine) in a randomized manner. BP and heart rate (HR) were continuously recorded non-invasively for the whole duration of the examination. Results patients with PAF or AAN displayed a preserved global cognitive function while sitting. However, compared to supine assessment, during HUT patients scored significantly worse during the Trail Making Test A and B, Barrage test, Analogies test, Immediate Visual Memory, Span Forward and Span Backward test. Pathological scores, with regard to Italian normative range values, were observed only during HUT in the Barrage test and in the Analogies test in 3 and 6 patients respectively. On the contrary, in healthy controls, results to neuropsychological tests were not significantly different, during HUT compared to supine rest. Conclusions these data demonstrate that patients with PAF and AAN present a normal sitting global cognitive evaluation. However, their executive functions worsen significantly during the orthostatic challenge, possibly because of transient frontal lobes hypoperfusion. PMID:24465471

  3. Sweat testing to evaluate autonomic function

    PubMed Central

    Illigens, Ben M.W.; Gibbons, Christopher H.

    2011-01-01

    Sudomotor dysfunction is one of the earliest detectable neurophysiologic abnormalities in distal small fiber neuropathy. Traditional neurophysiologic measurements of sudomotor function include thermoregulatory sweat testing (TST), quantitative sudomotor axon reflex testing (QSART), silicone impressions, the sympathetic skin response (SSR), and the recent addition of quantitative direct and indirect axon reflex testing (QDIRT). These testing techniques, when used in combination, can detect and localized pre- and postganglionic lesions, can provide early diagnosis of sudomotor dysfunction and can monitor disease progression or disease recovery. In this article, we review the common tests available for assessment of sudomotor function, detail the testing methodology, review the limitations and provide examples of test results. PMID:18989618

  4. Autonomic function in manganese alloy workers

    SciTech Connect

    Barrington, W.W.; Angle, C.R.; Willcockson, N.K.; Padula, M.A.; Korn, T.

    1998-07-01

    The observation of orthostatic hypotension in an index case of manganese toxicity lead to this prospective attempt to evaluate cardiovascular autonomic function and cognitive and emotional neurotoxicity in eight manganese alloy welders and machinists. The subjects consisted of a convenience sample consisting of an index case of manganese dementia, his four co-workers in a frog shop for gouging, welding, and grinding repair of high manganese railway track and a convenience sample of three mild steel welders with lesser manganese exposure also referred because of cognitive or autonomic symptoms. Frog shop air manganese samples 9.6--10 years before and 1.2--3.4 years after the diagnosis of the index case exceeded 1.0 mg/m{sup 3} in 29% and 0.2 mg/m{sup 3} in 62%. Twenty-four-hour electrocardiographic (Holter) monitoring was used to determine the temporal variability of the heartrate (RR{prime} interval) and the rates of change at low frequency and high frequency. MMPI and MCMI personality assessment and short-term memory, figure copy, controlled oral word association, and symbol digit tests were used.

  5. Cardiac autonomic function in healthy young smokers.

    PubMed

    Erdem, Alim; Ayhan, Suzi Selim; Öztürk, Serkan; Özlü, Mehmet Fatih; Alcelik, Aytekin; Sahin, Safak; Tosun, Mehmet; Erdem, Fatma Hizal; Gumustekin, Kenan; Yazici, Mehmet

    2015-01-01

    The present study examined the heart rate turbulence (HRT) and heart rate variability (HRV) parameters in healthy young smokers (<40 years) to assess the effects of smoking on cardiac autonomic function. The study included 75 smokers with a history of habitual smoking for at least 1 year (41 males and 34 females; mean age, 29.3 ± 7.3 years) and 30 nonsmokers (hospital staff; 16 males and 14 females; mean age, 29.0 ± 6.1 years). Addiction to smoking was evaluated using the modified Fagerström test for nicotine-dependence index (NDI). HRT, HRV, basic clinical and echocardiographic, and Holter test parameters were compared between groups. No significant differences between the two groups were found in the basic clinical and echocardiographic variables. Turbulence onset (TO) was significantly higher in the smoking group than in the controls, and turbulence slope was significantly lower in the smokers, than in the controls (p < 0.05). Standard deviation of all normal-to-normal (NN) interval index (SDNNI) was the only HRV parameter that was significantly different between the smoking and control groups (p < 0.05). The NDI was positively correlated with the TO (p < 0.05). Smoking impairs the baroregulatory function in healthy young smokers, particularly the HRT parameters and SDNNI. Our findings highlight the importance of complete smoking cessation.

  6. Functional Imaging of Autonomic Regulation: Methods and Key Findings

    PubMed Central

    Macey, Paul M.; Ogren, Jennifer A.; Kumar, Rajesh; Harper, Ronald M.

    2016-01-01

    Central nervous system processing of autonomic function involves a network of regions throughout the brain which can be visualized and measured with neuroimaging techniques, notably functional magnetic resonance imaging (fMRI). The development of fMRI procedures has both confirmed and extended earlier findings from animal models, and human stroke and lesion studies. Assessments with fMRI can elucidate interactions between different central sites in regulating normal autonomic patterning, and demonstrate how disturbed systems can interact to produce aberrant regulation during autonomic challenges. Understanding autonomic dysfunction in various illnesses reveals mechanisms that potentially lead to interventions in the impairments. The objectives here are to: (1) describe the fMRI neuroimaging methodology for assessment of autonomic neural control, (2) outline the widespread, lateralized distribution of function in autonomic sites in the normal brain which includes structures from the neocortex through the medulla and cerebellum, (3) illustrate the importance of the time course of neural changes when coordinating responses, and how those patterns are impacted in conditions of sleep-disordered breathing, and (4) highlight opportunities for future research studies with emerging methodologies. Methodological considerations specific to autonomic testing include timing of challenges relative to the underlying fMRI signal, spatial resolution sufficient to identify autonomic brainstem nuclei, blood pressure, and blood oxygenation influences on the fMRI signal, and the sustained timing, often measured in minutes of challenge periods and recovery. Key findings include the lateralized nature of autonomic organization, which is reminiscent of asymmetric motor, sensory, and language pathways. Testing brain function during autonomic challenges demonstrate closely-integrated timing of responses in connected brain areas during autonomic challenges, and the involvement with brain

  7. Squatting test: A posture to study and counteract cardiovascular abnormalities associated with autonomic dysfunction.

    PubMed

    Philips, Jean-Christophe; Scheen, André J

    2011-07-01

    The squatting test is an active posture manoeuvre that imposes one of the most potent orthostatic stresses. In normal subjects, the changes in blood pressure and heart rate are transient because of appropriate baroreflex homeostasis and do not provoke symptoms. However, in various pathological conditions, both the increase in blood pressure during squatting and the decrease in blood pressure during standing may be more important and sustained, potentially leading to complaints and adverse events. Squatting has been used to evaluate patients with tetralogy of Fallot, heart transplant, dysautonomia, including diabetic cardiovascular autonomic neuropathy, and individuals prone to vasovagal syncope. Careful analysis of changes in blood pressure and heart rate during the transition from standing to squatting and from squatting to standing allows the early detection of altered vagal and/or sympathetic function. Of note squatting position has been proposed as a therapeutic means to counteract the fall in blood pressure in patients suffering from dizziness due to dysautonomia and orthostatic hypotension or presenting pre-syncope symptoms, such as soon after exercise. The aims of the present review are to analyse the haemodynamic pattern during a squatting test in various pathological situations and to describe what may be the negative and positive haemodynamic changes associated with this posture. We were especially interested in using the squatting test for the assessment of cardiovascular autonomic neuropathy associated with diabetes mellitus.

  8. The Function of the Autonomic Nervous System during Spaceflight

    PubMed Central

    Mandsager, Kyle Timothy; Robertson, David; Diedrich, André

    2015-01-01

    Introduction Despite decades of study, a clear understanding of autonomic nervous system activity in space remains elusive. Differential interpretation of fundamental data have driven divergent theories of sympathetic activation and vasorelaxation. Methods This paper will review the available in-flight autonomic and hemodynamic data in an effort to resolve these discrepancies. The NASA NEUROLAB mission, the most comprehensive assessment of autonomic function in microgravity to date, will be highlighted. The mechanisms responsible for altered autonomic activity during spaceflight, which include the effects of hypovolemia, cardiovascular deconditioning, and altered central processing, will be presented. Results The NEUROLAB experiments demonstrated increased sympathetic activity and impairment of vagal baroreflex function during short-duration spaceflight. Subsequent non-invasive studies of autonomic function during spaceflight have largely reinforced these findings, and provide strong evidence that sympathetic activity is increased in space relative to the supine position on Earth. Others have suggested that microgravity induces a state of relative vasorelaxation and increased vagal activity when compared to upright posture on Earth. These ostensibly disparate theories are not mutually exclusive, but rather directly reflect different pre-flight postural controls. Conclusion When these results are taken together, they demonstrate that the effectual autonomic challenge of spaceflight is small, and represents an orthostatic stress less than that of upright posture on Earth. In-flight countermeasures, including aerobic and resistance exercise, as well as short-arm centrifugation have been successfully deployed to counteract these mechanisms. Despite subtle changes in autonomic activity during spaceflight, underlying neurohumoral mechanisms of the autonomic nervous system remain intact and cardiovascular function remains stable during long-duration flight. PMID:25820827

  9. Myelodysplastic syndromes: pathogenesis, functional abnormalities, and clinical implications.

    PubMed Central

    Jacobs, A

    1985-01-01

    The myelodysplastic syndromes represent a preleukaemic state in which a clonal abnormality of haemopoietic stem cell is characterised by a variety of phenotypic manifestations with varying degrees of ineffective haemopoiesis. This state probably develops as a sequence of events in which the earliest stages may be difficult to detect by conventional pathological techniques. The process is characterised by genetic changes leading to abnormal control of cell proliferation and differentiation. Expansion of an abnormal clone may be related to independence from normal growth factors, insensitivity to normal inhibitory factors, suppression of normal clonal growth, or changes in the immunological or nutritional condition of the host. The haematological picture is of peripheral blood cytopenias: a cellular bone marrow, and functional abnormalities of erythroid, myeloid, and megakaryocytic cells. In most cases marrow cells have an abnormal DNA content, often with disturbances of the cell cycle: an abnormal karyotype is common in premalignant clones. Growth abnormalities of erythroid or granulocyte-macrophage progenitors are common in marrow cultures, and lineage specific surface membrane markers indicate aberrations of differentiation. Progression of the disorder may occur through clonal expansion or through clonal evolution with a greater degree of malignancy. Current attempts to influence abnormal growth and differentiation have had only limited success. Clinical recognition of the syndrome depends on an acute awareness of the signs combined with the identification of clonal and functional abnormalities. PMID:2999194

  10. Post-weaning social isolation induces abnormal forms of aggression in conjunction with increased glucocorticoid and autonomic stress responses.

    PubMed

    Toth, Mate; Mikics, Eva; Tulogdi, Aron; Aliczki, Mano; Haller, Jozsef

    2011-06-01

    We showed earlier that social isolation from weaning (a paradigm frequently used to model social neglect in children) induces abnormal forms of attack in rats, and assumed that these are associated with hyperarousal. To investigate this hypothesis, we deprived rats of social contacts from weaning and studied their behavior, glucocorticoid and autonomic stress responses in the resident-intruder paradigm at the age of 82 days. Social isolation resulted in abnormal attack patterns characterized by attacks on vulnerable targets, deficient social communication and increased defensive behaviors (defensive upright, flight, freezing). During aggressive encounters, socially deprived rats rapidly switched from one behavior to another, i.e. showed an increased number of behavioral transitions as compared to controls. We tentatively term this behavioral feature "behavioral fragmentation" and considered it a form of behavioral arousal. Basal levels of plasma corticosterone regularly assessed by radioimmunoassay between 27 and 78 days of age were not affected. In contrast, aggression-induced glucocorticoid responses were approximately doubled by socially isolation. Diurnal oscillations in heart rate assessed by in vivo biotelemetry were not affected by social isolation. In contrast, the aggression-induced increase in heart rate was higher in socially isolated than in socially housed rats. Thus, post-weaning social isolation induced abnormal forms of aggression that developed on the background of increased behavioral, endocrine and autonomic arousal. We suggest that this paradigm may be used to model aggression-related psychopathologies associated with hyperarousal, particularly those that are triggered by adverse rearing conditions.

  11. Correlation functions of an autonomous stochastic system with time delays

    NASA Astrophysics Data System (ADS)

    Zhu, Ping; Mei, Dong Cheng

    2014-03-01

    The auto-correlation function and the cross-correlation function of an autonomous stochastic system with time delays are investigated. We obtain the distribution curves of the auto-correlation function Cx(s) and Cy(s), and the cross-correlation function C(s) and C(s) of the stochastic dynamic variables by the stochastic simulation method. The delay time changes prominently the behaviors of the dynamical variables of an autonomous stochastic system, which makes the auto-correlation and the cross-correlation of the autonomous stochastic system alternate oscillate periodically from positive to negative, or from negative to positive, decrease gradually, and finally tends to zero with the decay time. The delay time and the noise strength have important impacts for the auto-correlation and the cross-correlation of the autonomous stochastic delay system. The delay time enhances the auto-correlation and the cross-correlation, on the contrary, the noise strength lowers the auto-correlation and the cross-correlation. Under the time delay, by comparison we further show differences of the auto-correlation and the cross-correlation between the dynamical variables x and y.

  12. Diverticular Disease of the Colon: Neuromuscular Function Abnormalities.

    PubMed

    Bassotti, Gabrio; Villanacci, Vincenzo; Bernardini, Nunzia; Dore, Maria P

    2016-10-01

    Colonic diverticular disease is a frequent finding in daily clinical practice. However, its pathophysiological mechanisms are largely unknown. This condition is likely the result of several concomitant factors occurring together to cause anatomic and functional abnormalities, leading as a result to the outpouching of the colonic mucosa. A pivotal role seems to be played by an abnormal colonic neuromuscular function, as shown repeatedly in these patients, and by an altered visceral perception. There is recent evidence that these abnormalities might be related to the derangement of the enteric innervation, to an abnormal distribution of mucosal neuropeptides, and to low-grade mucosal inflammation. The latter might be responsible for the development of visceral hypersensitivity, often causing abdominal pain in a subset of these patients. PMID:27622368

  13. Neural circuits controlling behavior and autonomic functions in medicinal leeches.

    PubMed

    Lamb, Damon G; Calabrese, Ronald L

    2011-09-28

    In the study of the neural circuits underlying behavior and autonomic functions, the stereotyped and accessible nervous system of medicinal leeches, Hirudo sp., has been particularly informative. These leeches express well-defined behaviors and autonomic movements which are amenable to investigation at the circuit and neuronal levels. In this review, we discuss some of the best understood of these movements and the circuits which underlie them, focusing on swimming, crawling and heartbeat. We also discuss the rudiments of decision-making: the selection between generally mutually exclusive behaviors at the neuronal level.

  14. Effects of Deep Brain Stimulation on Autonomic Function.

    PubMed

    Basiago, Adam; Binder, Devin K

    2016-01-01

    Over the course of the development of deep brain stimulation (DBS) into a well-established therapy for Parkinson's disease, essential tremor, and dystonia, its utility as a potential treatment for autonomic dysfunction has emerged. Dysfunction of autonomic processes is common in neurological diseases. Depending on the specific target in the brain, DBS has been shown to raise or lower blood pressure, normalize the baroreflex, to alter the caliber of bronchioles, and eliminate hyperhidrosis, all through modulation of the sympathetic nervous system. It has also been shown to improve cortical control of the bladder, directly induce or inhibit the micturition reflex, and to improve deglutition and gastric emptying. In this review, we will attempt to summarize the relevant available studies describing these effects of DBS on autonomic function, which vary greatly in character and magnitude with respect to stimulation target. PMID:27537920

  15. Effects of Deep Brain Stimulation on Autonomic Function

    PubMed Central

    Basiago, Adam; Binder, Devin K.

    2016-01-01

    Over the course of the development of deep brain stimulation (DBS) into a well-established therapy for Parkinson’s disease, essential tremor, and dystonia, its utility as a potential treatment for autonomic dysfunction has emerged. Dysfunction of autonomic processes is common in neurological diseases. Depending on the specific target in the brain, DBS has been shown to raise or lower blood pressure, normalize the baroreflex, to alter the caliber of bronchioles, and eliminate hyperhidrosis, all through modulation of the sympathetic nervous system. It has also been shown to improve cortical control of the bladder, directly induce or inhibit the micturition reflex, and to improve deglutition and gastric emptying. In this review, we will attempt to summarize the relevant available studies describing these effects of DBS on autonomic function, which vary greatly in character and magnitude with respect to stimulation target. PMID:27537920

  16. Reconciling abnormalities of brain network structure and function in schizophrenia.

    PubMed

    Fornito, Alex; Bullmore, Edward T

    2015-02-01

    Schizophrenia is widely regarded as a disorder of abnormal brain connectivity. Magnetic resonance imaging (MRI) suggests that patients show robust reductions of structural connectivity. However, corresponding changes in functional connectivity do not always follow, with increased functional connectivity being reported in many cases. Here, we consider different methodological and mechanistic accounts that might reconcile these apparently contradictory findings and argue that increased functional connectivity in schizophrenia likely represents a pathophysiological dysregulation of brain activity arising from abnormal neurodevelopmental wiring of structural connections linking putative hub regions of association cortex to other brain areas. Elucidating the pathophysiological significance of connectivity abnormalities in schizophrenia will be contingent on better understanding how network structure shapes and constrains function.

  17. Abnormal Functional Connectivity in Autism Spectrum Disorders during Face Processing

    ERIC Educational Resources Information Center

    Kleinhans, Natalia M.; Richards, Todd; Sterling, Lindsey; Stegbauer, Keith C.; Mahurin, Roderick; Johnson, L. Clark; Greenson, Jessica; Dawson, Geraldine; Aylward, Elizabeth

    2008-01-01

    Abnormalities in the interactions between functionally linked brain regions have been suggested to be associated with the clinical impairments observed in autism spectrum disorders (ASD). We investigated functional connectivity within the limbic system during face identification; a primary component of social cognition, in 19 high-functioning…

  18. Brief Report: Brain Mechanisms in Autism: Functional and Structural Abnormalities.

    ERIC Educational Resources Information Center

    Minshew, Nancy J.

    1996-01-01

    This paper summarizes results of research on functional and structural abnormalities of the brain in autism. The current concept of causation is seen to involve multiple biologic levels. A consistent profile of brain function and dysfunction across methods has been found and specific neuropathologic findings have been found; but some research…

  19. Identifying functional thermodynamics in autonomous Maxwellian ratchets

    NASA Astrophysics Data System (ADS)

    Boyd, Alexander B.; Mandal, Dibyendu; Crutchfield, James P.

    2016-02-01

    We introduce a family of Maxwellian Demons for which correlations among information bearing degrees of freedom can be calculated exactly and in compact analytical form. This allows one to precisely determine Demon functional thermodynamic operating regimes, when previous methods either misclassify or simply fail due to approximations they invoke. This reveals that these Demons are more functional than previous candidates. They too behave either as engines, lifting a mass against gravity by extracting energy from a single heat reservoir, or as Landauer erasers, consuming external work to remove information from a sequence of binary symbols by decreasing their individual uncertainty. Going beyond these, our Demon exhibits a new functionality that erases bits not by simply decreasing individual-symbol uncertainty, but by increasing inter-bit correlations (that is, by adding temporal order) while increasing single-symbol uncertainty. In all cases, but especially in the new erasure regime, exactly accounting for informational correlations leads to tight bounds on Demon performance, expressed as a refined Second Law of thermodynamics that relies on the Kolmogorov-Sinai entropy for dynamical processes and not on changes purely in system configurational entropy, as previously employed. We rigorously derive the refined Second Law under minimal assumptions and so it applies quite broadly—for Demons with and without memory and input sequences that are correlated or not. We note that general Maxwellian Demons readily violate previously proposed, alternative such bounds, while the current bound still holds. As such, it broadly describes the minimal energetic cost of any computation by a thermodynamic system.

  20. Abnormal autonomic cardiac response to transient hypoxia in sickle cell anemia

    PubMed Central

    Sangkatumvong, S; Coates, T D; Khoo, M C K

    2010-01-01

    The objective of this study was to non-invasively assess cardiac autonomic control in subjects with sickle cell anemia (SCA) by tracking the changes in heart rate variability (HRV) that occur following brief exposure to a hypoxic stimulus. Five African–American SCA patients and seven healthy control subjects were recruited to participate in this study. Each subject was exposed to a controlled hypoxic stimulus consisting of five breaths of nitrogen. Time-varying spectral analysis of HRV was applied to estimate the cardiac autonomic response to the transient episode of hypoxia. The confounding effects of changes in respiration on the HRV spectral indices were reduced by using a computational model. A significant decrease in the parameters related to parasympathetic control was detected in the post-hypoxic responses of the SCA subjects relative to normal controls. The spectral index related to sympathetic activity, on the other hand, showed a tendency to increase the following hypoxic stimulation, but the change was not significant. This study suggests that there is some degree of cardiovascular autonomic dysfunction in SCA that is revealed by the response to transient hypoxia. PMID:18460753

  1. [The general practitioner and abnormal liver function tests].

    PubMed

    Hallez, R

    1997-09-01

    In case of abnormal liver function tests, it's necessary to distinguish different situations, starting from this first data. We will successively consider: the high and moderate acute increases of aminotransferase, the chronic increases of aminotransferase, the isolated cholestase picture and the isolated increases of gamma GT or of bilirubine. We will finish with a partial survey about drug-induced liver diseases.

  2. Association between Birth Characteristics and Cardiovascular Autonomic Function at Mid-Life

    PubMed Central

    Perkiömäki, Nelli; Auvinen, Juha; Tulppo, Mikko P.; Hautala, Arto J.; Perkiömäki, Juha; Karhunen, Ville; Keinänen-Kiukaanniemi, Sirkka; Puukka, Katri; Ruokonen, Aimo; Järvelin, Marjo-Riitta; Huikuri, Heikki V.

    2016-01-01

    Background Low birth weight is associated with an increased risk of cardiovascular diseases in adulthood. As abnormal cardiac autonomic function is a common feature in cardiovascular diseases, we tested the hypothesis that low birth weight may also be associated with poorer cardiac autonomic function in middle-aged subjects. Methods At the age of 46, the subjects of the Northern Finland Birth Cohort 1966 were invited to examinations including questionnaires about health status and life style and measurement of vagally-mediated heart rate variability (rMSSD) from R-R intervals (RRi) and spontaneous baroreflex sensitivity (BRS) in both seated and standing positions. Maternal parameters had been collected in 1965–1966 since the 16th gestational week and birth variables immediately after delivery. For rMSSD, 1,799 men and 2,279 women without cardiorespiratory diseases and diabetes were included and 902 men and 1,020 women for BRS. The analyses were adjusted for maternal (age, anthropometry, socioeconomics, parity, gestational smoking) and adult variables (life style, anthropometry, blood pressure, glycemic and lipid status) potentially confounding the relationship between birth weight and autonomic function. Results In men, birth weight correlated negatively with seated (r = -0.058, p = 0.014) and standing rMSSD (r = -0.090, p<0.001), as well as with standing BRS (r = -0.092, p = 0.006). These observations were verified using relevant birth weight categories (<2,500 g; 2,500–3,999 g; ≥4,000 g). In women, birth weight was positively correlated with seated BRS (r = 0.081, p = 0.010), but none of the other measures of cardiovascular autonomic function. These correlations remained significant after adjustment for potential confounders (p<0.05 for all). Conclusions In men, higher birth weight was independently associated with poorer cardiac autonomic function at mid-life. Same association was not observed in women. Our findings suggest that higher, not lower, birth

  3. A Controlled Study of Autonomic Nervous System Function in Adults with Attention-Deficit/Hyperactivity Disorder Treated with Stimulant Medications: Results of a Pilot Study

    ERIC Educational Resources Information Center

    Schubiner, Howard; Hassunizadeh, Bischan; Kaczynski, Richard

    2006-01-01

    Objective: Despite the fact that autonomic nervous system (ANS) abnormalities are commonly found in adults and predict increased cardiovascular mortality, no studies have assessed ANS function in adults with attention-deficit/hyperactivity disorder (ADHD) taking stimulants. Method: This pilot study evaluated ANS function in adults with ADHD in…

  4. Connectivity and functional profiling of abnormal brain structures in pedophilia

    PubMed Central

    Poeppl, Timm B.; Eickhoff, Simon B.; Fox, Peter T.; Laird, Angela R.; Rupprecht, Rainer; Langguth, Berthold; Bzdok, Danilo

    2015-01-01

    Despite its 0.5–1% lifetime prevalence in men and its general societal relevance, neuroimaging investigations in pedophilia are scarce. Preliminary findings indicate abnormal brain structure and function. However, no study has yet linked structural alterations in pedophiles to both connectional and functional properties of the aberrant hotspots. The relationship between morphological alterations and brain function in pedophilia as well as their contribution to its psychopathology thus remain unclear. First, we assessed bimodal connectivity of structurally altered candidate regions using meta-analytic connectivity modeling (MACM) and resting-state correlations employing openly accessible data. We compared the ensuing connectivity maps to the activation likelihood estimation (ALE) maps of a recent quantitative meta-analysis of brain activity during processing of sexual stimuli. Second, we functionally characterized the structurally altered regions employing meta-data of a large-scale neuroimaging database. Candidate regions were functionally connected to key areas for processing of sexual stimuli. Moreover, we found that the functional role of structurally altered brain regions in pedophilia relates to nonsexual emotional as well as neurocognitive and executive functions, previously reported to be impaired in pedophiles. Our results suggest that structural brain alterations affect neural networks for sexual processing by way of disrupted functional connectivity, which may entail abnormal sexual arousal patterns. The findings moreover indicate that structural alterations account for common affective and neurocognitive impairments in pedophilia. The present multi-modal integration of brain structure and function analyses links sexual and nonsexual psychopathology in pedophilia. PMID:25733379

  5. Abnormal thalamocortical structural and functional connectivity in juvenile myoclonic epilepsy

    PubMed Central

    O’Muircheartaigh, Jonathan; Vollmar, Christian; Barker, Gareth J.; Kumari, Veena; Symms, Mark R.; Thompson, Pam; Duncan, John S.; Koepp, Matthias J.

    2012-01-01

    Juvenile myoclonic epilepsy is the most common idiopathic generalized epilepsy, characterized by frequent myoclonic jerks, generalized tonic-clonic seizures and, less commonly, absences. Neuropsychological and, less consistently, anatomical studies have indicated frontal lobe dysfunction in the disease. Given its presumed thalamo–cortical basis, we investigated thalamo–cortical structural connectivity, as measured by diffusion tensor imaging, in a cohort of 28 participants with juvenile myoclonic epilepsy and detected changes in an anterior thalamo–cortical bundle compared with healthy control subjects. We then investigated task-modulated functional connectivity from the anterior thalamic region identified using functional magnetic resonance imaging in a task consistently shown to be impaired in this group, phonemic verbal fluency. We demonstrate an alteration in task-modulated connectivity in a region of frontal cortex directly connected to the thalamus via the same anatomical bundle, and overlapping with the supplementary motor area. Further, we show that the degree of abnormal connectivity is related to disease severity in those with active seizures. By integrating methods examining structural and effective interregional connectivity, these results provide convincing evidence for abnormalities in a specific thalamo–cortical circuit, with reduced structural and task-induced functional connectivity, which may underlie the functional abnormalities in this idiopathic epilepsy. PMID:23250883

  6. Cardiac Autonomic Function in Patients With Ankylosing Spondylitis: A Case-Control Study.

    PubMed

    Wei, Cheng-Yu; Kung, Woon-Man; Chou, Yi-Sheng; Wang, Yao-Chin; Tai, Hsu-Chih; Wei, James Cheng-Chung

    2016-05-01

    Ankylosing spondylitis (AS) is a chronic inflammatory disease involing spine and enthesis. The primary aim of this study is to investigate the autonomic nervous system (ANS) function and the association between ANS and the functional status or disease activity in AS.The study included 42 AS patients, all fulfilling the modified New York criteria. All the patients are totally symptom free for ANS involvement and had normal neurological findings. These AS patients and 230 healthy volunteers receive analysis of 5 minutes heart rate variability (HRV) in lying posture. In addition, disease activity and functional status of these AS patients are assessed by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), and Bath Ankylosing Spondylitis Global Score (BAS-G).Both groups were age and sex-matched. Although the HRV analysis indicates that the peaks of total power (TP, 0-0.5 Hz) and high-frequency power (HF, 0.15-0.40 Hz) are similar in both groups, the activities of low-frequency power (LF, 0.04-0.15 Hz), LF in normalized units (LF%), and the ratio of LF to HF (LF/HF) in AS patients are obviously lower than healthy controls. The erythrocyte sedimentation rate and C-reactive protein revealed negative relationship with HF. The AS patients without peripheral joint disease have higher LF, TP, variance, LF%, and HF than the patients with peripheral joint disease. The AS patients without uvetis have higher HF than the patients with uvetis. The total scores of BASDI, BASFI, and BAS-G do not show any association to HRV parameters.AS patients have significantly abnormal cardiac autonomic regulation. This is closely related with some inflammatory activities. Reduced autonomic function may be one of the factors of high cardiovascular risk in AS patients.

  7. Abnormal fronto-striatal functional connectivity in Parkinson's disease.

    PubMed

    Xu, Jinping; Zhang, Jiuquan; Wang, Jiaojian; Li, Guanglin; Hu, Qingmao; Zhang, Yuanchao

    2016-02-01

    Parkinson's disease (PD) is characterized by the relatively selective depletion of dopamine in the striatum, which consequently leads to dysfunctions in cortico-striatal-thalamic-cortical circuitries. It has been shown that the most common cognitive deficits in PD patients are related to the fronto-striatal circuits. In PD, most previous functional connectivity studies have been performed using seed-based methods to identify the brain regions that are abnormally connected to one or more seeds, but these cannot be used to quantify the interactions between one region and all other regions in a particular network. Functional connectivity degree, which is a measurement that can be used to quantify the functional or structural connectivity of a complex brain network, was adopted in this study to assess the interactions of the fronto-striatal network. Compared to healthy controls, PD patients had significantly decreased total functional connectivity degree for the left putamen and the right globus pallidum in fronto-striatal networks. Additionally, negative correlations between the fronto-pallial functional connectivity degree (i.e., the right globus pallidum with the left middle frontal gyrus, and with the right triangular part of inferior frontal gyrus) and disease duration were observed in PD patients. The results of this study demonstrate that fronto-striatal functional connectivity is abnormal in patients with PD and indicate that these deficits might be the result of motor and cognitive dysfunctions in PD patients. PMID:26724369

  8. Regular Football Practice Improves Autonomic Cardiac Function in Male Children

    PubMed Central

    Fernandes, Luis; Oliveira, Jose; Soares-Miranda, Luisa; Rebelo, Antonio; Brito, Joao

    2015-01-01

    Background: The role of the autonomic nervous system (ANS) in the cardiovascular regulation is of primal importance. Since it has been associated with adverse conditions such as cardiac arrhythmias, sudden death, sleep disorders, hypertension and obesity. Objectives: The present study aimed to investigate the impact of recreational football practice on the autonomic cardiac function of male children, as measured by heart rate variability. Patients and Methods: Forty-seven male children aged 9 - 12 years were selected according to their engagement with football oriented practice outside school context. The children were divided into a football group (FG; n = 22) and a control group (CG; n = 25). The FG had regular football practices, with 2 weekly training sessions and occasional weekend matches. The CG was not engaged with any physical activity other than complementary school-based physical education classes. Data from physical activity, physical fitness, and heart rate variability measured in time and frequency domains were obtained. Results: The anthropometric and body composition characteristics were similar in both groups (P > 0.05). The groups were also similar in time spent daily on moderate-to-vigorous physical activities (FG vs. CG: 114 ± 64 vs. 87 ± 55 minutes; P > 0.05). However, the FG performed better (P < 0.05) in Yo-Yo intermittent endurance test (1394 ± 558 vs. 778 ± 408 m) and 15-m sprint test (3.06 ± 0.17 vs. 3.20 ± 0.23 s). Also, the FG presented enhanced autonomic function. Significant differences were detected (P < 0.05) between groups for low frequency normalized units (38.0 ± 15.2 vs. 47.3 ± 14.2 n.u (normalized units)), high frequency normalized units (62.1 ± 15.2 vs. 52.8 ± 14.2 n.u.), and LF:HF ratio (0.7 ± 0.4 vs. 1.1 ± 0.6 ms2). Conclusions: Children engaged with regular football practice presented enhanced physical fitness and autonomic function, by increasing vagal tone at rest. PMID:26448848

  9. Effect of ramipril therapy on abnormal left atrial appendage function.

    PubMed

    Asker, M; Timucin, O B; Asker, S; Karadag, M F

    2011-01-01

    This study investigated whether ramipril treatment has a beneficial effect on left atrial appendage (LAA) function in patients with systemic hypertension in sinus rhythm. Patients with untreated systemic hypertension and normal left ventricular systolic function in sinus rhythm (n = 20; six males/14 females; age 35 - 69 years, mean ± SD 52.8 ± 8.9 years) were evaluated using transthoracic and transoesophageal echocardiography at baseline and after 6 months of treatment with 5 mg/day ramipril. Mean systolic and diastolic blood pressures decreased significantly after ramipril therapy. Baseline LAA emptying velocity was below the age-related reference value for this parameter, indicating abnormal LAA function. There were significant increases in the LAA filling and emptying velocities after ramipril treatment. It is concluded that the decrease in blood pressure and haemodynamic improvements brought about by ramipril therapy resulted in improved LAA function in hypertensive patients with normal left ventricular systolic function in sinus rhythm.

  10. Effects of epilepsy on autonomic nervous system and respiratory function tests.

    PubMed

    Berilgen, M Said; Sari, Tacim; Bulut, Serpil; Mungen, Bulent

    2004-08-01

    We have investigated autonomic nervous system function during the interictal period in epileptic patients and the possible effects of autonomic dysfunction on respiratory functions. A total of 32 epileptic patients (23 generalized, 9 partial epilepsy) and 32 healthy volunteers were involved. Sympathetic skin response (SSR), for evaluating the sympathetic nervous system, and RR interval variation (RRIV) were measured at the beginning and third month of antiepileptic treatment, and respiratory function tests (RFTs) were performed. In patients with partial epilepsy, SSR latency in the upper extremity (1.3+/-0.2 s) was longer than that of controls (1.2+/-0.3 s) at baseline (P=0.05), and was significantly reduced (1.1+/-0.3 s) after treatment (P<0.05). RRIV values of patients with generalized epilepsy were statistically significantly lower than those of controls (P<0.01). However, deep breathing RRIV values (32.6+/-15.3%) of patients were lower than those (43.0+/-18.2%) of controls (P<0.05). Sympathetic dysfunction was determined in patients with partial epilepsy and parasympathetic dysfunction in patients with generalized epilepsy. No abnormality was observed on RFTs for both patients with partial epilepsy and patients with generalized epilepsy.

  11. Diabetic autonomic neuropathy.

    PubMed

    Clarke, B F; Ewing, D J; Campbell, I W

    1979-10-01

    This review attempts to outline the present understanding of diabetic autonomic neuropathy. The clinical features have been increasinly recognised but knowledge of the localization and morphology of the lesions and their pathogenesis remains fragmentary. A metabolic causation as postulated in somatic nerves accords best with clinical observations. Most bodily systems, particularly the cardiovascular, gastrointestinal and urogenital, are involved with added disturbances of thermoregulatory function and pupillary reflexes. Possible effects on neuroendocrine and peptidergic secretion and respiratory control await definition. Current interest centres around the development of a new generation of tests of autonomic nerve function that are simple, non-invasive, reproducible and allow precision in diagnosis and accurate quantitation. Most are based on cardiovascular reflexes and abnormality in them is assumed to reflect autonomic damage elsewhere. Probably no single test suffices and a battery of tests reflecting both parasympathetic and sympathetic function is preferable. Little is known of the natural history. The prevalence may be greater than previously suspected and although symptoms are mild in the majority, a few develop florid features. The relation of control and duration of diabetes to the onset and progression of autonomic neuropathy is not clearly established. Once tests of autonomic function become abnormal they usually remain abnormal. Symptomatic autonomic neuropathy carries a greatly increased mortality rate possibly due to indirect mechanisms such as renal failure and direct mechanisms such as cardio-resiratory arrest. Improved treatment of some of the more disabling symptoms has been possible in recent years. PMID:387501

  12. Abnormalities of vascular structure and function in pediatric hypertension.

    PubMed

    Urbina, Elaine M

    2016-07-01

    Hypertension is associated with adverse cardiovascular (CV) events in adults. Measures of vascular structure and function, including increased carotid intima-media thickness (cIMT) and elevated arterial stiffness predict hard CV events in adulthood. Newer data suggest that abnormalities in target organ damage are occurring in adolescents and young adults with high blood pressure. In this review, we discuss the techniques for measuring vascular dysfunction in young people and the evidence linking blood pressure levels to this type of target organ damage.

  13. Association between respiratory mechanics and autonomic function in morbid obesity.

    PubMed

    Sant' Anna, M; Carvalhal, R F; Carneiro, J R I; Lapa, M S; Zin, W A; Lugon, J R; Guimarães, F S

    2014-01-01

    This study aimed to investigate the association between respiratory mechanics and autonomic modulation in morbidly obese patients. We evaluated 10 morbidly obese subjects (BMI=52.9±11.2kg/m(2)), aged 23-58 years. Assessment of respiratory mechanics was done by the forced oscillation technique (FOT), and cardiovascular autonomic function was recorded by heart rate variability analysis (HRV). The Pearson correlation coefficient was used to test the associations between respiratory mechanics and HRV variables. There were associations between the standard deviation of all RR intervals (SDNN) and airway resistance (Rm) (r=-0.82; p=0.004), SDNN and respiratory system resistance (R0) (r=-0.79; p=0.006), root mean square of successive differences between adjacent normal RR intervals (rMSSD) and respiratory system resistance (R5) (r=-0.643; p=0.0451), rMSSD and R0 (r=-0.64; p=0.047), and rMSSD and Rm (r=-0.658; p=0.039). We concluded that the airway and respiratory system resistances are negatively associated with parasympathetic activity in patients with morbid obesity.

  14. Autonomic nervous system function in young children with functional abdominal pain or irritable bowel syndrome

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Adults with irritable bowel syndrome (IBS) have been reported to have alterations in autonomic nervous system function as measured by vagal activity via heart rate variability. Whether the same is true for children is unknown. We compared young children 7 to 10 years of age with functional abdominal...

  15. Alterations in cardiovascular autonomic function tests in idiopathic hyperhidrosis.

    PubMed

    De Marinis, Milena; Colaizzo, Elisa; Petrelli, Rosa Anna Nives; Santilli, Valter

    2012-04-01

    We performed cardiovascular autonomic function tests to assess sympathetic and parasympathetic functions in patients with idiopathic hyperhidrosis. We studied 35 patients with idiopathic hyperhidrosis and 35 age- and sex-matched controls. A thermoregulatory sweat test (TST) was performed in all subjects. Sweating was qualitatively (Minor's test at 22°C) and quantitatively (skin conductance) evaluated. Orthostatism, tilt to 65°, cold pressor test, deep breathing, Valsalva maneuver and hyperventilation were performed in patients and controls. A greater fall in blood pressure values was observed in patients than in controls in the upright tests (p<0.05). In particular, postural hypotension was present in a subgroup of patients (34%), in whom changes in lying-to-standing blood pressure and heart rate were greater (p<0.001) than those of the remaining patients. The TST revealed that the total body sweat rate (ml/cm(2)/min) was more pronounced in patients with postural hypotension (p<0.001) than in the other patients and controls. The skin conductance values of patients with postural hypotension were higher (p<0.001) than those of the remaining patients. A positive correlation was found between skin conductance values and postural hypotension. Dehydration and poor water intake may play a role in postural hypotension in patients with severe hyperhidrosis and pronounced thermoregulatory sweating. A significantly marked increase in parasympathetic function was observed in patients. Responses to deep breathing, Valsalva maneuver and hyperventilation were significantly greater in patients (p<0.001) than in controls. Idiopathic hyperhidrosis seems to be a complex dysfunction that involves autonomic pathways other than those related to sweating.

  16. Human Skin Hypoxia Modulates Cerebrovascular and Autonomic Functions

    PubMed Central

    Pucci, Olivia; Qualls, Clifford; Battisti-Charbonney, Anne; Balaban, Dahlia Y.; Fisher, Joe A.; Duffin, Jim; Appenzeller, Otto

    2012-01-01

    Because the skin is an oxygen sensor in amphibians and mice, we thought to confirm this function also in humans. The human upright posture, however, introduces additional functional demands for the maintenance of oxygen homeostasis in which cerebral blood flow and autonomic nervous system (ANS) function may also be involved. We examined nine males and three females. While subjects were breathing ambient air, at sea level, we changed gases in a plastic body-bag during two conditions of the experiment such as to induce skin hypoxia (with pure nitrogen) or skin normoxia (with air). The subjects performed a test of hypoxic ventilatory drive during each condition of the experiment. We found no differences in the hypoxic ventilatory drive tests. However, ANS function and cerebral blood flow velocities were modulated by skin hypoxia and the effect was significantly greater on the left than right middle cerebral arteries. We conclude that skin hypoxia modulates ANS function and cerebral blood flow velocities and this might impact life styles and tolerance to ambient hypoxia at altitude. Thus the skin in normal humans, in addition to its numerous other functions, is also an oxygen sensor. PMID:23056597

  17. Abnormal Default System Functioning in Depression: Implications for Emotion Regulation.

    PubMed

    Messina, Irene; Bianco, Francesca; Cusinato, Maria; Calvo, Vincenzo; Sambin, Marco

    2016-01-01

    Depression is widely seen as the result of difficulties in regulating emotions. Based on neuroimaging studies on voluntary emotion regulation, neurobiological models have focused on the concept of cognitive control, considering emotion regulation as a shift toward involving controlled processes associated with activation of the prefrontal and parietal executive areas, instead of responding automatically to emotional stimuli. According to such models, the weaker executive area activation observed in depressed patients is attributable to a lack of cognitive control over negative emotions. Going beyond the concept of cognitive control, psychodynamic models describe the development of individuals' capacity to regulate their emotional states in mother-infant interactions during childhood, through the construction of the representation of the self, others, and relationships. In this mini-review, we link these psychodynamic models with recent findings regarding the abnormal functioning of the default system in depression. Consistently with psychodynamic models, psychological functions associated with the default system include self-related processing, semantic processes, and implicit forms of emotion regulation. The abnormal activation of the default system observed in depression may explain the dysfunctional aspects of emotion regulation typical of the condition, such as an exaggerated negative self-focus and rumination on self-esteem issues. We also discuss the clinical implications of these findings with reference to the therapeutic relationship as a key tool for revisiting impaired or distorted representations of the self and relational objects.

  18. Abnormal Default System Functioning in Depression: Implications for Emotion Regulation

    PubMed Central

    Messina, Irene; Bianco, Francesca; Cusinato, Maria; Calvo, Vincenzo; Sambin, Marco

    2016-01-01

    Depression is widely seen as the result of difficulties in regulating emotions. Based on neuroimaging studies on voluntary emotion regulation, neurobiological models have focused on the concept of cognitive control, considering emotion regulation as a shift toward involving controlled processes associated with activation of the prefrontal and parietal executive areas, instead of responding automatically to emotional stimuli. According to such models, the weaker executive area activation observed in depressed patients is attributable to a lack of cognitive control over negative emotions. Going beyond the concept of cognitive control, psychodynamic models describe the development of individuals’ capacity to regulate their emotional states in mother-infant interactions during childhood, through the construction of the representation of the self, others, and relationships. In this mini-review, we link these psychodynamic models with recent findings regarding the abnormal functioning of the default system in depression. Consistently with psychodynamic models, psychological functions associated with the default system include self-related processing, semantic processes, and implicit forms of emotion regulation. The abnormal activation of the default system observed in depression may explain the dysfunctional aspects of emotion regulation typical of the condition, such as an exaggerated negative self-focus and rumination on self-esteem issues. We also discuss the clinical implications of these findings with reference to the therapeutic relationship as a key tool for revisiting impaired or distorted representations of the self and relational objects. PMID:27375536

  19. Abnormal Default System Functioning in Depression: Implications for Emotion Regulation.

    PubMed

    Messina, Irene; Bianco, Francesca; Cusinato, Maria; Calvo, Vincenzo; Sambin, Marco

    2016-01-01

    Depression is widely seen as the result of difficulties in regulating emotions. Based on neuroimaging studies on voluntary emotion regulation, neurobiological models have focused on the concept of cognitive control, considering emotion regulation as a shift toward involving controlled processes associated with activation of the prefrontal and parietal executive areas, instead of responding automatically to emotional stimuli. According to such models, the weaker executive area activation observed in depressed patients is attributable to a lack of cognitive control over negative emotions. Going beyond the concept of cognitive control, psychodynamic models describe the development of individuals' capacity to regulate their emotional states in mother-infant interactions during childhood, through the construction of the representation of the self, others, and relationships. In this mini-review, we link these psychodynamic models with recent findings regarding the abnormal functioning of the default system in depression. Consistently with psychodynamic models, psychological functions associated with the default system include self-related processing, semantic processes, and implicit forms of emotion regulation. The abnormal activation of the default system observed in depression may explain the dysfunctional aspects of emotion regulation typical of the condition, such as an exaggerated negative self-focus and rumination on self-esteem issues. We also discuss the clinical implications of these findings with reference to the therapeutic relationship as a key tool for revisiting impaired or distorted representations of the self and relational objects. PMID:27375536

  20. Carotid body chemoreflex: a driver of autonomic abnormalities in sleep apnoea.

    PubMed

    Prabhakar, Nanduri R

    2016-08-01

    What is the topic of this review? This article presents emerging evidence for heightened carotid body chemoreflex activity as a major driver of sympathetic activation and hypertension in sleep apnoea patients. What advances does it heighlight? This article discusses the recent advances on cellular, molecular and epigenetic mechanisms underlying the exaggerated chemoreflex in experimental models of sleep apnoea. The carotid bodies are the principal peripheral chemoreceptors for detecting changes in arterial blood oxygen concentration, and the resulting chemoreflex is a potent regulator of the sympathetic tone, blood pressure and breathing. Sleep apnoea is a disease of the respiratory system that affects several million adult humans. Apnoeas occur during sleep, often as a result of obstruction of the upper airway (obstructive sleep apnoea) or because of defective respiratory rhythm generation by the CNS (central sleep apnoea). Patients with sleep apnoea exhibit several co-morbidities, with the most notable among them being heightened sympathetic nerve activity and hypertension. Emerging evidence suggests that intermittent hypoxia resulting from periodic apnoea stimulates the carotid body, and the ensuing chemoreflex mediates the increased sympathetic tone and hypertension in sleep apnoea patients. Rodent models of intermittent hypoxia that simulate the O2 saturation profiles encountered during sleep apnoea have provided important insights into the cellular and molecular mechanisms underlying the heightened carotid body chemoreflex. This article describes how intermittent hypoxia affects the carotid body function and discusses the cellular, molecular and epigenetic mechanisms underlying the exaggerated chemoreflex. PMID:27474260

  1. Abnormal Pulmonary Function in Adults with Sickle Cell Anemia

    PubMed Central

    Klings, Elizabeth S.; Wyszynski, Diego F.; Nolan, Vikki G.; Steinberg, Martin H.

    2006-01-01

    Rationale: Pulmonary complications of sickle cell anemia (Hb-SS) commonly cause morbidity, yet few large studies of pulmonary function tests (PFTs) in this population have been reported. Objectives: PFTs (spirometry, lung volumes, and diffusion capacity for carbon monoxide [DLCO]) from 310 adults with Hb-SS were analyzed to determine the pattern of pulmonary dysfunction and their association with other systemic complications of sickle cell disease. Methods: Raw PFT data were compared with predicted values. Each subject was subclassified into one of five groups: obstructive physiology, restrictive physiology, mixed obstructive/restrictive physiology, isolated low DLCO, or normal. The association between laboratory data of patients with decreased DLCO or restrictive physiology and those of normal subjects was assessed by multivariate linear regression. Measurements and Main Results: Normal PFTs were present in only 31 of 310 (10%) patients. Overall, adults with Hb-SS were characterized by decreased total lung capacities (70.2 ± 14.7% predicted) and DlCO (64.5 ± 19.9%). The most common PFT patterns were restrictive physiology (74%) and isolated low DlCO (13%). Decreased DLCO was associated with thrombocytosis (p = 0.05), with hepatic dysfunction (elevated alanine aminotransferase; p = 0.07), and a trend toward renal dysfunction (elevated blood urea nitrogen and creatinine; p = 0.05 and 0.07, respectively). Conclusions: Pulmonary function is abnormal in 90% of adult patients with Hb-SS. Common abnormalities include restrictive physiology and decreased DLCO. Decreased DLCO may indicate more severe sickle vasculopathy characterized by impaired hepatic and renal function. PMID:16556694

  2. Validation of a questionnaire measuring the regulation of autonomic function

    PubMed Central

    Kröz, M; Feder, G; von Laue, HB; Zerm, R; Reif, M; Girke, M; Matthes, H; Gutenbrunner, C; Heckmann, C

    2008-01-01

    Background To broaden the range of outcomes that we can measure for patients undergoing treatment for oncological and other chronic conditions, we aimed to validate a questionnaire measuring self-reported autonomic regulation (aR), i.e. to characterise a subject's autonomic functioning by questions on sleeping and waking, vertigo, morningness-eveningness, thermoregulation, perspiration, bowel movements and digestion. Methods We administered the questionnaire to 440 participants (♀: N = 316, ♂: N = 124): 95 patients with breast cancer, 49 with colorectal cancer, 60 with diabetes mellitus, 39 with coronary heart disease, 28 with rheumatological conditions, 32 with Hashimoto's disease, 22 with multiple morbidities and 115 healthy people. We administered the questionnaire a second time to 50.2% of the participants. External convergence criteria included the German version of the Hospital Anxiety and Depression Scale (HADS-D), a short questionnaire on morningness-eveningness, the Herdecke Quality of Life Questionnaire (HLQ) and a short version questionnaire on self-regulation. Results A principal component analysis yielded a three dimensional 18-item inventory of aR. The subscales orthostatic-circulatory, rest/activity and digestive regulation had internal consistency (Cronbach-α: rα = 0.65 – 0.75) and test-retest reliability (rrt = 0.70 – 85). AR was negatively associated with anxiety, depression, and dysmenorrhoea but positively correlated to HLQ, self-regulation and in part to morningness (except digestive aR) (0.49 – 0.13, all p < 0.05). Conclusion An internal validation of the long-version scale of aR yielded consistent relationships with health versus illness, quality of life and personality. Further studies are required to clarify the issues of external validity, clinical and physiological relevance. PMID:18533043

  3. Arterial Compliance and Autonomic Functions in Adult Male Smokers

    PubMed Central

    Saxena, Yogesh; Gupta, Rani

    2016-01-01

    Introduction Smoking is known to augment sympathetic activity and may lead to increased arterial stiffness. Several studies have reported association of increased sympathetic activity and arterial stiffness to cardiovascular risks among smokers. Pulse Wave Velocity (PWV) of peripheral arteries, instead of aorta can be used as a non-invasive indicator of arterial stiffness. Aim To measure non-invasively, the autonomic functions and peripheral arterial stiffness in smokers, and to find out whether the aforementioned factors are modified by the level of physical activity in these smokers. Materials and Methods This cross-sectional analytical study was conducted in the Department of Physiology, HIMS, Dehradun, over a period of 12 months (2013-2014) on 100 adult males (20-40 years); 50 smokers and 50 non-smokers. The parameters analysed include relevant anthropometric and cardiovascular parameters, Pulse Wave Velocity (PWV), sustained Hand Grip Test (HGT) and Heart Rate Variability (HRV) domains. Data interpretation and analysis was carried out using SPSS 17.0. Comparison of the above mentioned parameters amongst groups was done with unpaired t-test. The relationship of pack-years & physical activity with vascular functions was assessed by Pearson’s correlation. Interaction of various grades of smoking and physical activity with Cardiovascular System (CVS) parameters was assessed by one-way ANOVA. Results Smokers had higher values of PWV (5.7±0.5m/s) as compared to non-smokers (4.8±0.4m/s) (p<0.001). ΔDBP during HGT was lower (7±3.18mmHg) among smokers as compared to non-smokers (19.4±3.5mmHg) (p<0.001). Smoking (pack-years) was positively related to PWV (r= .03) but showed a weak negative relationship with change in Diastolic Blood Pressure (ΔDBP) (r= -0.084, p=0.56) showing that, more the frequency of smoking, the more was arterial stiffening and the lesser was the sympathetic response to the HGT. The smokers had significantly higher sympathetic activity; Low

  4. Functional interactions as a survival strategy against abnormal aggregation

    PubMed Central

    Laura, Masino; Giuseppe, Nicastro; Lesley, Calder; Michele, Vendruscolo; Annalisa, Pastore

    2011-01-01

    Protein aggregation is under intense scrutiny because of its role in human disease. Although increasing evidence indicates that protein native states are highly protected against aggregation, the specific protection mechanisms are poorly understood. Insight into such mechanisms can be gained through study of the relatively few proteins that aggregate under native conditions. Ataxin-3, the protein responsible for Spinocerebellar ataxia type 3, a polyglutamine expansion disease, represents one of such examples. Polyglutamine expansion is central for determining solubility and aggregation rates of ataxin-3, but these properties are profoundly modulated by its N-terminal Josephin domain. This work aims at identifying the regions that promote Josephin fibrillogenesis and rationalizing the mechanisms that protect Josephin and nonexpanded ataxin-3 from aberrant aggregation. Using different biophysical techniques, aggregation propensity predictions and rational design of amino acid substitutions, we show that Josephin has an intrinsic tendency to fibrillize under native conditions and that fibrillization is promoted by two solvent-exposed patches, which are also involved in recognition of natural substrates, such as ubiquitin. Indeed, designed mutations at these patches or substrate binding significantly reduce Josephin aggregation kinetics. Our results provide evidence that protein nonpathologic function can play an active role in preventing aberrant fibrillization and suggest the molecular mechanism whereby this occurs in ataxin-3.—Masino, L., Nicastro, G., Calder, L., Vendruscolo, M., Pastore, A. Functional interactions as a survival strategy against abnormal aggregation. PMID:20810784

  5. Neurotechnology for monitoring and restoring sensory, motor, and autonomic functions

    NASA Astrophysics Data System (ADS)

    Wu, Pae C.; Knaack, Gretchen; Weber, Douglas J.

    2016-05-01

    The rapid and exponential advances in micro- and nanotechnologies over the last decade have enabled devices that communicate directly with the nervous system to measure and influence neural activity. Many of the earliest implementations focused on restoration of sensory and motor function, but as knowledge of physiology advances and technology continues to improve in accuracy, precision, and safety, new modes of engaging with the autonomic system herald an era of health restoration that may augment or replace many conventional pharmacotherapies. DARPA's Biological Technologies Office is continuing to advance neurotechnology by investing in neural interface technologies that are effective, reliable, and safe for long-term use in humans. DARPA's Hand Proprioception and Touch Interfaces (HAPTIX) program is creating a fully implantable system that interfaces with peripheral nerves in amputees to enable natural control and sensation for prosthetic limbs. Beyond standard electrode implementations, the Electrical Prescriptions (ElectRx) program is investing in innovative approaches to minimally or non-invasively interface with the peripheral nervous system using novel magnetic, optogenetic, and ultrasound-based technologies. These new mechanisms of interrogating and stimulating the peripheral nervous system are driving towards unparalleled spatiotemporal resolution, specificity and targeting, and noninvasiveness to enable chronic, human-use applications in closed-loop neuromodulation for the treatment of disease.

  6. Autonomously functioning thyroid nodules in childhood and adolescence

    SciTech Connect

    Croom, R.D. III; Thomas, C.G. Jr.; Reddick, R.L.; Tawil, M.T.

    1987-12-01

    Autonomously functioning thyroid nodules (AFTNs) in children and adolescents (under age 18) are unusual but are not as rare as earlier reports suggested. These lesions have a significantly different biologic potential than similar lesions in older patients. In the younger age group there is a more rapid progression toward toxicity and a higher incidence of thyroid carcinoma. Our experience with 12 patients is combined with those previously reported for identification of a total of 61 children and adolescents with AFTNs, of whom 53 have undergone operation. Hyperthyroidism was present in 15 patients (24.6%), and in six patients (11.3%) the AFTN was due to a well-differentiated thyroid carcinoma. Surgical treatment is advisable for all children and adolescents with AFTNs because of the risks of hyperthyroidism and thyroid carcinoma. Surgical excision (lobectomy is preferred) results in rapid restoration of a euthyroid state for the toxic AFTN and allows histopathologic diagnosis. Therapy with radioiodine is not advisable for treatment of AFTNs in this age group. Thyroid-stimulating hormone suppression should be used for all patients with a diagnosis of thyroid carcinoma.

  7. Targeting the autonomic nervous system: measuring autonomic function and novel devices for heart failure management.

    PubMed

    Patel, Hitesh C; Rosen, Stuart D; Lindsay, Alistair; Hayward, Carl; Lyon, Alexander R; di Mario, Carlo

    2013-12-10

    Neurohumoral activation, in which enhanced activity of the autonomic nervous system (ANS) is a key component, plays a pivotal role in heart failure. The neurohumoral system affects several organs and currently our knowledge of the molecular and systemic pathways involved in the neurohumoral activation is incomplete. All the methods of assessing the degree of activation of the autonomic system have limitations and they are not interchangeable. The methods considered include noradrenaline spillover, microneurography, radiotracer imaging and analysis of heart rate and blood pressure (heart rate variability, baroreceptor sensitivity, heart rate turbulence). Despite the difficulties, medications that affect the ANS have been shown to improve mortality in heart failure and the mechanism is related to attenuation of the sympathetic nervous system (SNS) and stimulation of the parasympathetic nervous system. However, limitations of compliance with medication, side effects and inadequate SNS attenuation are issues of concern with the pharmacological approach. The newer device based therapies for sympathetic modulation are showing encouraging results. As they directly influence the autonomic nervous system, more mechanistic information can be gleaned if appropriate investigations are performed at the time of the outcome trials. However, clinicians should be reminded that the ANS is an evolutionary survival mechanism and therefore there is a need to proceed with caution when trying to completely attenuate its effects. So our enthusiasm for the application of these devices in heart failure should be controlled, especially as none of the devices have trial data powered to assess effects on mortality or cardiovascular events.

  8. Cytoarchitectural and Functional Abnormalities of the Inferior Colliculus in Sudden Unexplained Perinatal Death

    PubMed Central

    Lavezzi, Anna M.; Pusiol, Teresa; Matturri, Luigi

    2015-01-01

    Abstract The inferior colliculus is a mesencephalic structure endowed with serotonergic fibers that plays an important role in the processing of acoustic information. The implication of the neuromodulator serotonin also in the aetiology of sudden unexplained fetal and infant death syndromes and the demonstration in these pathologies of developmental alterations of the superior olivary complex (SOC), a group of pontine nuclei likewise involved in hearing, prompted us to investigate whether the inferior colliculus may somehow contribute to the pathogenetic mechanism of unexplained perinatal death. Therefore, we performed in a wide set of fetuses and infants, aged from 33 gestational weeks to 7 postnatal months and died of both known and unknown cause, an in-depth anatomopathological analysis of the brainstem, particularly of the midbrain. Peculiar neuroanatomical and functional abnormalities of the inferior colliculus, such as hypoplasia/structural disarrangement and immunonegativity or poor positivity of serotonin, were exclusively found in sudden death victims, and not in controls. In addition, these alterations were frequently related to dysgenesis of connected structures, precisely the raphé nuclei and the superior olivary complex, and to nicotine absorption in pregnancy. We propose, on the basis of these results, the involvement of the inferior colliculus in more important functions than those related to hearing, as breathing and, more extensively, all the vital activities, and then in pathological conditions underlying a sudden death in vulnerable periods of the autonomic nervous system development, particularly associated to harmful risk factors as cigarette smoking. PMID:25674737

  9. Biochemical and functional abnormalities in hypercholesterolemic rabbit platelets

    SciTech Connect

    Dalal, K.B.; Ebbe, S.; Mazoyer, E.; Carpenter, D.; Yee, T. )

    1990-02-01

    This study was designed to elucidate changes in rabbit platelet lipids induced by a cholesterol rich diet and to explore the possible correlation of these lipid changes with platelet abnormalities. Pronounced biochemical alterations were observed when serum cholesterol levels of 700-1000 mg% were reached. Hypercholesterolemic (HC) platelets contained 37% more neutral lipids and 16% less phospholipids than the controls. Lysolecithin, cholesterol esters and phosphatidylinositol (PI) levels were increased in HC platelets, and the levels of phosphatidylcholine (PC) were decreased. The cholesterol/phospholipid molar ratio of lipidemic platelets increased from 0.55 +/- 0.011 to 0.89 +/- 0.016 (P less than 0.01) in eight weeks. HC platelets had 90% more arachidonic acid (AA) in the PI than normal platelets. No significant changes in AA of PC were observed. Platelet function was monitored by the uptake and release of (14C)serotonin in platelet rich plasma (PRP), using varying concentrations of collagen as an aggregating agent. The uptake of (14C)serotonin in HC and normal platelets ranged from 78-94%. The percent of (14C)serotonin released from normal and HC platelets was proportional to the concentration of collagen. However, lipidemic platelets were hyperreactive to low concentrations of collagen. Incorporation of 50 microM acetylsalicylic acid into the aggregating medium suppressed the release of (14C)serotonin in normal PRP by more than 90%, but had only a partial effect on lipidemic PRP.

  10. Autonomous Control of Space Reactor Systems

    SciTech Connect

    Belle R. Upadhyaya; K. Zhao; S.R.P. Perillo; Xiaojia Xu; M.G. Na

    2007-11-30

    Autonomous and semi-autonomous control is a key element of space reactor design in order to meet the mission requirements of safety, reliability, survivability, and life expectancy. Interrestrial nuclear power plants, human operators are avilable to perform intelligent control functions that are necessary for both normal and abnormal operational conditions.

  11. CAROTID CHEMORECEPTOR ABLATION IMPROVES SURVIVAL IN HEART FAILURE: RESCUING AUTONOMIC CONTROL OF CARDIORESPIRATORY FUNCTION

    PubMed Central

    Del Rio, Rodrigo; Marcus, Noah J.; Schultz, Harold D.

    2013-01-01

    Objectives We investigated whether selective ablation of the carotid body (CB) chemoreceptors improves cardiorespiratory control and survival during heart failure. Background Chronic heart failure (CHF) is a recognized health problem worldwide, and novel treatments are needed to better improve life quality and decrease mortality. Enhanced carotid chemoreflex drive from the CB is thought to contribute significantly to autonomic dysfunction, abnormal breathing patterns, and increased mortality in heart failure. Methods CHF was induced by coronary ligation in rats. Selective CB denervation (CBD) was performed to remove carotid chemoreflex drive in the CHF state (16 weeks post MI). Indices of autonomic and respiratory function were assessed in CB intact and CBD animals. CBD at 2 weeks post-MI was performed to evaluate whether early targeted CB ablation decreases the progression of left ventricular dysfunction, cardiac remodeling and arrhythmic episodes and improves survival. Results CHF rats developed increased CB chemoreflex drive and chronic central pre-sympathetic neuronal activation, increased indices of elevated sympathetic outflow, increased breathing variability and apnea incidence, and desensitization of the baroreflex. Selective CB ablation reduced the central pre-sympathetic neuronal activation by 40%, normalized indices of sympathetic outflow and baroreflex sensitivity, and reduced the incidence of apneas in CHF animals from 16.8 ± 1.8 events/h to 8.0 ± 1.4 events/h. Remarkably, when CB ablation was performed early, cardiac remodeling, deterioration of left ventricle ejection fraction, and cardiac arrhythmias were reduced. Most importantly, the rats that underwent early CB ablation exhibited an 85% survival rate compared to 45% survival in CHF rats without the intervention. Conclusion Carotid chemoreceptors play a seminal role in the pathogenesis of heart failure and their targeted ablation might be of therapeutic value to reduce cardiorespiratory

  12. Cardiovascular control, autonomic function, and elite endurance performance in spinal cord injury.

    PubMed

    West, C R; Gee, C M; Voss, C; Hubli, M; Currie, K D; Schmid, J; Krassioukov, A V

    2015-08-01

    We aimed to determine the relationship between level of injury, completeness of injury, resting as well as exercise hemodynamics, and endurance performance in athletes with spinal cord injury (SCI). Twenty-three elite male paracycling athletes (C3-T8) were assessed for neurological level/completeness of injury, autonomic completeness of injury, resting cardiovascular function, and time to complete a 17.3-km World Championship time-trial test. A subset were also fitted with heart rate (HR) monitors and their cycles were fitted with a global positioning systems device (n = 15). Thoracic SCI exhibited higher seated systolic blood pressure along with superior time-trial performance compared with cervical SCI (all P < 0.01). When further stratified by autonomic completeness of injury, the four athletes with cervical autonomic incomplete SCI exhibited a faster time-trial time and a higher average speed compared with cervical autonomic complete SCI (all P < 0.042). Maximum and average HR also tended to be higher in cervical autonomic incomplete vs autonomic complete. There were no differences in time-trial time, HR, or speed between thoracic autonomic complete vs incomplete SCI. In conclusion, autonomic completeness of injury and the consequent ability of the cardiovascular system to respond to exercise appear to be a critical determinant of endurance performance in elite athletes with cervical SCI.

  13. The Therapeutic Function of the Instructor in Abnormal Psychology.

    ERIC Educational Resources Information Center

    Halgin, Richard P.

    1982-01-01

    Describes three main types of therapeutic problems which college instructors of abnormal psychology courses may encounter with their students. Students may seek the instructor's assistance in helping a relative or acquaintance or for self-help. Often a student may not seek help but may display pathological behavior. (AM)

  14. Dominant, toxic gain-of-function mutations in gars lead to non-cell autonomous neuropathology.

    PubMed

    Grice, Stuart J; Sleigh, James N; Motley, William W; Liu, Ji-Long; Burgess, Robert W; Talbot, Kevin; Cader, M Zameel

    2015-08-01

    Charcot-Marie-Tooth (CMT) neuropathies are collectively the most common hereditary neurological condition and a major health burden for society. Dominant mutations in the gene GARS, encoding the ubiquitous enzyme, glycyl-tRNA synthetase (GlyRS), cause peripheral nerve degeneration and lead to CMT disease type 2D. This genetic disorder exemplifies a recurring motif in neurodegeneration, whereby mutations in essential, widely expressed genes have selective deleterious consequences for the nervous system. Here, using novel Drosophila models, we show a potential solution to this phenomenon. Ubiquitous expression of mutant GlyRS leads to motor deficits, progressive neuromuscular junction (NMJ) denervation and pre-synaptic build-up of mutant GlyRS. Intriguingly, neuronal toxicity is, at least in part, non-cell autonomous, as expression of mutant GlyRS in mesoderm or muscle alone results in similar pathology. This mutant GlyRS toxic gain-of-function, which is WHEP domain-dependent, coincides with abnormal NMJ assembly, leading to synaptic degeneration, and, ultimately, reduced viability. Our findings suggest that mutant GlyRS gains access to ectopic sub-compartments of the motor neuron, providing a possible explanation for the selective neuropathology caused by mutations in a widely expressed gene.

  15. Dominant, toxic gain-of-function mutations in gars lead to non-cell autonomous neuropathology

    PubMed Central

    Grice, Stuart J.; Sleigh, James N.; Motley, William W.; Liu, Ji-Long; Burgess, Robert W.; Talbot, Kevin; Cader, M. Zameel

    2015-01-01

    Charcot–Marie–Tooth (CMT) neuropathies are collectively the most common hereditary neurological condition and a major health burden for society. Dominant mutations in the gene GARS, encoding the ubiquitous enzyme, glycyl-tRNA synthetase (GlyRS), cause peripheral nerve degeneration and lead to CMT disease type 2D. This genetic disorder exemplifies a recurring motif in neurodegeneration, whereby mutations in essential, widely expressed genes have selective deleterious consequences for the nervous system. Here, using novel Drosophila models, we show a potential solution to this phenomenon. Ubiquitous expression of mutant GlyRS leads to motor deficits, progressive neuromuscular junction (NMJ) denervation and pre-synaptic build-up of mutant GlyRS. Intriguingly, neuronal toxicity is, at least in part, non-cell autonomous, as expression of mutant GlyRS in mesoderm or muscle alone results in similar pathology. This mutant GlyRS toxic gain-of-function, which is WHEP domain-dependent, coincides with abnormal NMJ assembly, leading to synaptic degeneration, and, ultimately, reduced viability. Our findings suggest that mutant GlyRS gains access to ectopic sub-compartments of the motor neuron, providing a possible explanation for the selective neuropathology caused by mutations in a widely expressed gene. PMID:25972375

  16. Filaggrin genotype in ichthyosis vulgaris predicts abnormalities in epidermal structure and function.

    PubMed

    Gruber, Robert; Elias, Peter M; Crumrine, Debra; Lin, Tzu-Kai; Brandner, Johanna M; Hachem, Jean-Pierre; Presland, Richard B; Fleckman, Philip; Janecke, Andreas R; Sandilands, Aileen; McLean, W H Irwin; Fritsch, Peter O; Mildner, Michael; Tschachler, Erwin; Schmuth, Matthias

    2011-05-01

    Although it is widely accepted that filaggrin (FLG) deficiency contributes to an abnormal barrier function in ichthyosis vulgaris and atopic dermatitis, the pathomechanism of how FLG deficiency provokes a barrier abnormality in humans is unknown. We report here that the presence of FLG mutations in Caucasians predicts dose-dependent alterations in epidermal permeability barrier function. Although FLG is an intracellular protein, the barrier abnormality occurred solely via a paracellular route in affected stratum corneum. Abnormal barrier function correlated with alterations in keratin filament organization (perinuclear retraction), impaired loading of lamellar body contents, followed by nonuniform extracellular distribution of secreted organelle contents, and abnormalities in lamellar bilayer architecture. In addition, we observed reductions in corneodesmosome density and tight junction protein expression. Thus, FLG deficiency provokes alterations in keratinocyte architecture that influence epidermal functions localizing to the extracellular matrix. These results clarify how FLG mutations impair epidermal permeability barrier function.

  17. Abnormal ventilation scans in middle-aged smokers. Comparison with tests of overall lung function

    SciTech Connect

    Barter, S.J.; Cunningham, D.A.; Lavender, J.P.; Gibellino, F.; Connellan, S.J.; Pride, N.B.

    1985-07-01

    The uniformity of regional ventilation during tidal breathing has been assessed using continuous inhalation of krypton-81m in 43 male, lifelong nonsmokers and 46 male, current cigarette smokers (mean daily consumption 24.1 cigarettes/day) between 44 and 61 yr of age and with mild or no respiratory symptoms. All subjects had normal chest radiographs. The results of the ventilation scans were compared with tests of overall lung function (spirometry, maximal expiratory flow-volume curves, and single-breath N2 test). Diffuse abnormalities of the ventilation scan were found in 19 (41%) of the 46 smokers but in none of the nonsmokers. Focal abnormalities were found in 7 smokers and 3 nonsmokers. Smokers showed the expected abnormalities in overall lung function (reduced FEV1 and VC, increased single-breath N2 slope, and closing volume), but in individual smokers there was only a weak relation between the severity of abnormality of overall lung function and an abnormal ventilation scan. Abnormal scans could be found when overall lung function was normal and were not invariably found when significant abnormalities in FEV1/VC or N2 slope were present. There was no relation between the presence of chronic expectoration and an abnormal scan. The prognostic significance of an abnormal ventilation scan in such smokers remains to be established.

  18. Situational reactivity of autonomic functions in schizophrenic patients.

    PubMed

    Albus, M; Ackenheil, M; Engel, R R; Müller, F

    1982-06-01

    In a study designed to evaluate the state of arousal and the autonomic reactivity to experimental conditions in schizophrenic patients, 12 acute, unmedicated schizophrenic patients with paranoid hallucinatory symptomatology and 63 healthy normal control subjects were administered four standardized tasks: cold pressor test, noise, mental arithmetic, and active relaxation. Biochemical (norepinephrine and cortisol) and physiological (electromyogram, electroencephalogram, skin and conductance response, skin conductance level, finger pulse amplitude, finger temperature, heart rate, respiratory volume, pulse wave velocity, and electrogastrogram) parameters were measured simultaneously. Schizophrenic patients showed elevated levels of cortisol and norepinephrine, as well as heightened responsivity on measures of electromyographic activity, skin conductance level, and heart rate, throughout the trial, and reduced responsivity to conditions of stress. It is concluded that schizophrenic patients show higher nonspecific activation and reduced ability to react to external stimulation, perhaps induced by lack of inhibition of the reticular formation by the limbic system.

  19. Abnormal Liver Function Tests in an Anorexia Nervosa Patient and an Atypical Manifestation of Refeeding Syndrome

    PubMed Central

    Vootla, Vamshidhar R.; Daniel, Myrta

    2015-01-01

    Refeeding syndrome is defined as electrolyte and fluid abnormalities that occur in significantly malnourished patients when they are refed orally, enterally, or parenterally. The principal manifestations include hypophosphatemia, hypokalemia, vitamin deficiencies, volume overload and edema. This can affect multiple organ systems, such as the cardiovascular, pulmonary, or neurological systems, secondary to the above-mentioned abnormalities. Rarely, patients may develop gastrointestinal symptoms and show abnormal liver function test results. We report the case of a 52-year-old woman with anorexia nervosa who developed refeeding syndrome and simultaneous elevations of liver function test results, which normalized upon the resolution of the refeeding syndrome. PMID:26351414

  20. Abnormal Liver Function Tests in an Anorexia Nervosa Patient and an Atypical Manifestation of Refeeding Syndrome.

    PubMed

    Vootla, Vamshidhar R; Daniel, Myrta

    2015-01-01

    Refeeding syndrome is defined as electrolyte and fluid abnormalities that occur in significantly malnourished patients when they are refed orally, enterally, or parenterally. The principal manifestations include hypophosphatemia, hypokalemia, vitamin deficiencies, volume overload and edema. This can affect multiple organ systems, such as the cardiovascular, pulmonary, or neurological systems, secondary to the above-mentioned abnormalities. Rarely, patients may develop gastrointestinal symptoms and show abnormal liver function test results. We report the case of a 52-year-old woman with anorexia nervosa who developed refeeding syndrome and simultaneous elevations of liver function test results, which normalized upon the resolution of the refeeding syndrome.

  1. Implicit function theorem as a realization of the Lagrange principle. Abnormal points

    SciTech Connect

    Arutyunov, A V

    2000-02-28

    A smooth non-linear map is studied in a neighbourhood of an abnormal (degenerate) point. Inverse function and implicit function theorems are proved. The proof is based on the examination of a family of constrained extremal problems; second-order necessary conditions, which make sense also in the abnormal case, are used in the process. If the point under consideration is normal, then these conditions turn into the classical ones.

  2. Olfactory Influences on Mood and Autonomic, Endocrine, and Immune Function

    PubMed Central

    Kiecolt-Glaser, Janice K.; Graham, Jennifer E.; Malarkey, William B.; Porter, Kyle; Lemeshow, Stanley; Glaser, Ronald

    2008-01-01

    Despite aromatherapy’s popularity, efficacy data are scant, and potential mechanisms are controversial. This randomized controlled trial examined the psychological, autonomic, endocrine, and immune consequences of one purported relaxant odor (lavender), one stimulant odor (lemon), and a no-odor control (water), before and after a stressor (cold pressor); 56 healthy men and women were exposed to each of the odors during three separate visits. To assess the effects of expectancies, participants randomized to the “blind” condition were given no information about the odors they would smell; “primed” individuals were told what odors they would smell during the session, and what changes to expect. Experimenters were blind. Self-report and unobtrusive mood measures provided robust evidence that lemon oil reliably enhances positive mood compared to water and lavender regardless of expectancies or previous use of aromatherapy. Moreover, norepinephrine levels following the cold pressor remained elevated when subjects smelled lemon, compared to water or lavender. DTH responses to Candida were larger following inhalation of water than lemon or lavender. Odors did not reliably alter IL-6 and IL-10 production, salivary cortisol, heart rate or blood pressure, skin barrier repair following tape stripping, or pain ratings following the cold pressor. PMID:18178322

  3. Influence of cigarette smoking on human autonomic function

    NASA Technical Reports Server (NTRS)

    Niedermaier, O. N.; Smith, M. L.; Beightol, L. A.; Zukowska-Grojec, Z.; Goldstein, D. S.; Eckberg, D. L.

    1993-01-01

    BACKGROUND. Although cigarette smoking is known to lead to widespread augmentation of sympathetic nervous system activity, little is known about the effects of smoking on directly measured human sympathetic activity and its reflex control. METHODS AND RESULTS. We studied the acute effects of smoking two research-grade cigarettes on muscle sympathetic nerve activity and on arterial baroreflex-mediated changes of sympathetic and vagal neural cardiovascular outflows in eight healthy habitual smokers. Measurements were made during frequency-controlled breathing, graded Valsalva maneuvers, and carotid baroreceptor stimulation with ramped sequences of neck pressure and suction. Smoking provoked the following changes: Arterial pressure increased significantly, and RR intervals, RR interval spectral power at the respiratory frequency, and muscle sympathetic nerve activity decreased. Plasma nicotine levels increased significantly, but plasma epinephrine, norepinephrine, and neuropeptide Y levels did not change. Peak sympathetic nerve activity during and systolic pressure overshoots after Valsalva straining increased significantly in proportion to increases of plasma nicotine levels. The average carotid baroreceptor-cardiac reflex relation shifted rightward and downward on arterial pressure and RR interval axes; average gain, operational point, and response range did not change. CONCLUSIONS. In habitual smokers, smoking acutely reduces baseline levels of vagal-cardiac nerve activity and completely resets vagally mediated arterial baroreceptor-cardiac reflex responses. Smoking also reduces muscle sympathetic nerve activity but augments increases of sympathetic activity triggered by brief arterial pressure reductions. This pattern of autonomic changes is likely to influence smokers' responses to acute arterial pressure reductions importantly.

  4. Insulin resistance and autonomic function in traumatic lower limb amputees.

    PubMed

    Peles, E; Akselrod, S; Goldstein, D S; Nitzan, H; Azaria, M; Almog, S; Dolphin, D; Halkin, H; Modan, M

    1995-10-01

    This study examined plasma insulin response to oral glucose load and autonomic nervous system activity in male lower limb amputees (n = 52) aged 50-65 years, compared to matched controls (n = 53). The groups had similar body mass index, blood pressure and plasma lipid levels. The amputees had higher mean fasting plasma insulin levels (18.4 +/- 9.7 (SD) versus 13.7 +/- 5.1 mU/l, p = 0.005) and during an oral glucose tolerance test (OGTT) (1 h levels 88.1 +/- 45.3 versus 62.1 +/- 42.7, p = 0.016) with similar plasma glucose levels, indicating insulin resistance. At baseline with the subjects supine, there were no group differences in low- or high-frequency power of heart rate variability or in plasma levels of norepinephrine (NE) or epinephrine (EPI). In response to orthostasis, the groups had similarly increased plasma NE levels. During the OGTT, amputees had significantly larger increments in low-frequency power than did controls (2.2 +/- 1.3 versus 1.6 +/- 0.9 (beats/min)2 respectively, p < 0.01) and plasma NE levels increased significantly in amputees (1595 +/- 849 versus 1941 +/- 986 pM, p = 0.0008) but not in controls. At 1 h after glucose administration, plasma EPI levels were decreased significantly from baseline in both groups; at both 1 and 2 h after glucose administration, plasma EPI levels were higher in the amputees than controls. Amputees appear to have a combination of enhanced sympathoneural responsiveness and attenuated suppression of adrenomedullary secretion during glucose challenge. As catecholamines antagonize insulin effects, one possible explanation for insulin resistance in amputees is hyperglycaemia-induced sympathoneural activation and a failure of hyperglycaemia to decrease adrenomedullary secretion.

  5. A Double-Blind Atropine Trial for Active Learning of Autonomic Function

    ERIC Educational Resources Information Center

    Fry, Jeffrey R.; Burr, Steven A.

    2011-01-01

    Here, we describe a human physiology laboratory class measuring changes in autonomic function over time in response to atropine. Students use themselves as subjects, generating ownership and self-interest in the learning as well as directly experiencing the active link between physiology and pharmacology in people. The class is designed to…

  6. Cardiac Autonomic Function during Submaximal Treadmill Exercise in Adults with Down Syndrome

    ERIC Educational Resources Information Center

    Mendonca, Goncalo V.; Pereira, Fernando D.; Fernhall, Bo

    2011-01-01

    This study determined whether the cardiac autonomic function of adults with Down syndrome (DS) differs from that of nondisabled persons during submaximal dynamic exercise. Thirteen participants with DS and 12 nondisabled individuals performed maximal and submaximal treadmill tests with metabolic and heart rate (HR) measurements. Spectral analysis…

  7. Changes of Pain Perception, Autonomic Function, and Endocrine Parameters during Treatment of Anorectic Adolescents

    ERIC Educational Resources Information Center

    Bar, Karl-Jurgen; Boettger, Silke; Wagner, Gerd; Wilsdorf, Christine; Gerhard, Uwe Jens; Boettger, Michael K.; Blanz, Bernhard; Sauer, Heinrich

    2006-01-01

    Objectives: The underlying mechanisms of reduced pain perception in anorexia nervosa (AN) are unknown. To gain more insight into the pathology, the authors investigated pain perception, autonomic function, and endocrine parameters before and during successful treatment of adolescent AN patients. Method: Heat pain perception was assessed in 15…

  8. Teaching Cardiac Autonomic Function Dynamics Employing the Valsalva (Valsalva-Weber) Maneuver

    ERIC Educational Resources Information Center

    Junqueira, Luiz Fernando, Jr.

    2008-01-01

    In this report, a brief history of the Valsalva (Valsalva-Weber) maneuver is outlined, followed by an explanation on the use of this approach for the evaluation of cardiac autonomic function based on underlying heart rate changes. The most important methodological and interpretative aspects of the Valsalva-Weber maneuver are critically updated,…

  9. [Sleep and autonomic function: sleep related breathing disorders in Parkinson's disease and related disorders].

    PubMed

    Suzuki, Keisuke; Miyamoto, Masayuki; Miyamoto, Tomoyuki; Hirata, Koichi

    2014-01-01

    In patients with multiple system atrophy (MSA), sleep related breathing disorders (SRBD), including obstructive and central sleep apnea, vocal cord abductor paralysis and dysrhythmic breathing pattern, are frequently observed. SRBD may have a considerable impact on variation of autonomic nervous activity during sleep. The previous studies correlated upper airway muscle dysfunction related parkinsonism with increased prevalence of SRBD in patients with Parkinson's disease (PD). However, recently, the clinical significance of SRBD and its impact on sleepiness and disease severity have been debated. In this review, we discuss sleep and autonomic function, especially, SRBD in PD and related disorders, including the previous studies from our department.

  10. [Sleep and autonomic function: sleep related breathing disorders in Parkinson's disease and related disorders].

    PubMed

    Suzuki, Keisuke; Miyamoto, Masayuki; Miyamoto, Tomoyuki; Hirata, Koichi

    2014-01-01

    In patients with multiple system atrophy (MSA), sleep related breathing disorders (SRBD), including obstructive and central sleep apnea, vocal cord abductor paralysis and dysrhythmic breathing pattern, are frequently observed. SRBD may have a considerable impact on variation of autonomic nervous activity during sleep. The previous studies correlated upper airway muscle dysfunction related parkinsonism with increased prevalence of SRBD in patients with Parkinson's disease (PD). However, recently, the clinical significance of SRBD and its impact on sleepiness and disease severity have been debated. In this review, we discuss sleep and autonomic function, especially, SRBD in PD and related disorders, including the previous studies from our department. PMID:25672703

  11. Exploring the Relationship of Autonomic and Endocrine Activity with Social Functioning in Adults with Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Smeekens, I.; Didden, R.; Verhoeven, E. W. M.

    2015-01-01

    Several studies indicate that autonomic and endocrine activity may be related to social functioning in individuals with autism spectrum disorder (ASD), although the number of studies in adults is limited. The present study explored the relationship of autonomic and endocrine activity with social functioning in young adult males with ASD compared…

  12. Abnormal Red Cell Structure and Function in Neuroacanthocytosis

    PubMed Central

    Cluitmans, Judith C. A.; Tomelleri, Carlo; Yapici, Zuhal; Dinkla, Sip; Bovee-Geurts, Petra; Chokkalingam, Venkatachalam; De Franceschi, Lucia; Brock, Roland; Bosman, Giel J. G. C. M.

    2015-01-01

    Background Panthothenate kinase-associated neurodegeneration (PKAN) belongs to a group of hereditary neurodegenerative disorders known as neuroacanthocytosis (NA). This genetically heterogeneous group of diseases is characterized by degeneration of neurons in the basal ganglia and by the presence of deformed red blood cells with thorny protrusions, acanthocytes, in the circulation. Objective The goal of our study is to elucidate the molecular mechanisms underlying this aberrant red cell morphology and the corresponding functional consequences. This could shed light on the etiology of the neurodegeneration. Methods We performed a qualitative and semi-quantitative morphological, immunofluorescent, biochemical and functional analysis of the red cells of several patients with PKAN and, for the first time, of the red cells of their family members. Results We show that the blood of patients with PKAN contains not only variable numbers of acanthocytes, but also a wide range of other misshapen red cells. Immunofluorescent and immunoblot analyses suggest an altered membrane organization, rather than quantitative changes in protein expression. Strikingly, these changes are not limited to the red blood cells of PKAN patients, but are also present in the red cells of heterozygous carriers without neurological problems. Furthermore, changes are not only present in acanthocytes, but also in other red cells, including discocytes. The patients’ cells, however, are more fragile, as observed in a spleen-mimicking device. Conclusion These morphological, molecular and functional characteristics of red cells in patients with PKAN and their family members offer new tools for diagnosis and present a window into the pathophysiology of neuroacanthocytosis. PMID:25933379

  13. Functional abnormalities of experimental autogenous vein graft neoendothelium.

    PubMed Central

    Cross, K S; el-Sanadiki, M N; Murray, J J; Mikat, E M; McCann, R L; Hagen, P O

    1988-01-01

    When a vein is grafted into the arterial circulation, the endothelium of the graft is damaged. Regeneration of an intact neoendothelium occurs, but the functional properties of this surface have not been clarified. In this study, the functional integrity of the neoendothelium of veins grafted into the carotid artery of the rabbit was assessed through the use of acetylcholine and histamine to stimulate the production of the important endothelium-derived relaxing factor (EDRF). Control veins, precontracted with norepinephrine [10(-5) M], relaxed after exposure to acetylcholine [( 10(-7) M], 42.4% +/- 6.4%, p = 0.008) and histamine [( 10(-6) M], 30.6% +/- 4.3%, p = 0.03). This relaxation response was abolished after mechanical removal of the endothelium. By contrast, neither acetylcholine nor histamine caused an endothelium-dependent relaxation in the vein grafts, even though scanning electron microscopy demonstrated the presence of a morphologically intact endothelium. However, addition of stabilized EDRF purified from cultured endothelial cells induced relaxation of the vein grafts (35.8% +/- 3.6%, p = 0.002). These data indicate that vein graft endothelium is unable to produce EDRF in response to exposure to acetylcholine or histamine. The inability to produce this potent smooth muscle cell relaxing factor and anti-aggregatory substance may be a predisposition to vein graft failure. Images Figs. 4A-C. Fig. 4. (Continued) Fig. 4. (Continued) Figs. 5A-C. Fig. 5. (Continued) Fig. 5. (Continued) Fig. 6. PMID:3263843

  14. Impaired neural structure and function contributing to autonomic symptoms in congenital central hypoventilation syndrome

    PubMed Central

    Harper, Ronald M.; Kumar, Rajesh; Macey, Paul M.; Harper, Rebecca K.; Ogren, Jennifer A.

    2015-01-01

    Congenital central hypoventilation syndrome (CCHS) patients show major autonomic alterations in addition to their better-known breathing deficiencies. The processes underlying CCHS, mutations in the PHOX2B gene, target autonomic neuronal development, with frame shift extent contributing to symptom severity. Many autonomic characteristics, such as impaired pupillary constriction and poor temperature regulation, reflect parasympathetic alterations, and can include disturbed alimentary processes, with malabsorption and intestinal motility dyscontrol. The sympathetic nervous system changes can exert life-threatening outcomes, with dysregulation of sympathetic outflow leading to high blood pressure, time-altered and dampened heart rate and breathing responses to challenges, cardiac arrhythmia, profuse sweating, and poor fluid regulation. The central mechanisms contributing to failed autonomic processes are readily apparent from structural and functional magnetic resonance imaging studies, which reveal substantial cortical thinning, tissue injury, and disrupted functional responses in hypothalamic, hippocampal, posterior thalamic, and basal ganglia sites and their descending projections, as well as insular, cingulate, and medial frontal cortices, which influence subcortical autonomic structures. Midbrain structures are also compromised, including the raphe system and its projections to cerebellar and medullary sites, the locus coeruleus, and medullary reflex integrating sites, including the dorsal and ventrolateral medullary nuclei. The damage to rostral autonomic sites overlaps metabolic, affective and cognitive regulatory regions, leading to hormonal disruption, anxiety, depression, behavioral control, and sudden death concerns. The injuries suggest that interventions for mitigating hypoxic exposure and nutrient loss may provide cellular protection, in the same fashion as interventions in other conditions with similar malabsorption, fluid turnover, or hypoxic exposure

  15. Evidence for vestibular regulation of autonomic functions in a mouse genetic model

    NASA Technical Reports Server (NTRS)

    Murakami, Dean M.; Erkman, Linda; Hermanson, Ola; Rosenfeld, Michael G.; Fuller, Charles A.

    2002-01-01

    Physiological responses to changes in the gravitational field and body position, as well as symptoms of patients with anxiety-related disorders, have indicated an interrelationship between vestibular function and stress responses. However, the relative significance of cochlear and vestibular information in autonomic regulation remains unresolved because of the difficulties in distinguishing the relative contributions of other proprioceptive and interoceptive inputs, including vagal and somatic information. To investigate the role of cochlear and vestibular function in central and physiological responses, we have examined the effects of increased gravity in wild-type mice and mice lacking the POU homeodomain transcription factor Brn-3.1 (Brn-3bPou4f3). The only known phenotype of the Brn-3.1(-/-) mouse is related to hearing and balance functions, owing to the failure of cochlear and vestibular hair cells to differentiate properly. Here, we show that normal physiological responses to increased gravity (2G exposure), such as a dramatic drop in body temperature and concomitant circadian adjustment, were completely absent in Brn-3.1(-/-) mice. In line with the lack of autonomic responses, the massive increase in neuronal activity after 2G exposure normally detected in wild-type mice was virtually abolished in Brn-3.1(-/-) mice. Our results suggest that cochlear and vestibular hair cells are the primary regulators of autonomic responses to altered gravity and provide genetic evidence that these cells are sufficient to alter neural activity in regions involved in autonomic and neuroendocrine control.

  16. Viewing nature scenes positively affects recovery of autonomic function following acute-mental stress.

    PubMed

    Brown, Daniel K; Barton, Jo L; Gladwell, Valerie F

    2013-06-01

    A randomized crossover study explored whether viewing different scenes prior to a stressor altered autonomic function during the recovery from the stressor. The two scenes were (a) nature (composed of trees, grass, fields) or (b) built (composed of man-made, urban scenes lacking natural characteristics) environments. Autonomic function was assessed using noninvasive techniques of heart rate variability; in particular, time domain analyses evaluated parasympathetic activity, using root-mean-square of successive differences (RMSSD). During stress, secondary cardiovascular markers (heart rate, systolic and diastolic blood pressure) showed significant increases from baseline which did not differ between the two viewing conditions. Parasympathetic activity, however, was significantly higher in recovery following the stressor in the viewing scenes of nature condition compared to viewing scenes depicting built environments (RMSSD; 50.0 ± 31.3 vs 34.8 ± 14.8 ms). Thus, viewing nature scenes prior to a stressor alters autonomic activity in the recovery period. The secondary aim was to examine autonomic function during viewing of the two scenes. Standard deviation of R-R intervals (SDRR), as change from baseline, during the first 5 min of viewing nature scenes was greater than during built scenes. Overall, this suggests that nature can elicit improvements in the recovery process following a stressor.

  17. HFE gene: Structure, function, mutations, and associated iron abnormalities.

    PubMed

    Barton, James C; Edwards, Corwin Q; Acton, Ronald T

    2015-12-15

    The hemochromatosis gene HFE was discovered in 1996, more than a century after clinical and pathologic manifestations of hemochromatosis were reported. Linked to the major histocompatibility complex (MHC) on chromosome 6p, HFE encodes the MHC class I-like protein HFE that binds beta-2 microglobulin. HFE influences iron absorption by modulating the expression of hepcidin, the main controller of iron metabolism. Common HFE mutations account for ~90% of hemochromatosis phenotypes in whites of western European descent. We review HFE mapping and cloning, structure, promoters and controllers, and coding region mutations, HFE protein structure, cell and tissue expression and function, mouse Hfe knockouts and knockins, and HFE mutations in other mammals with iron overload. We describe the pertinence of HFE and HFE to mechanisms of iron homeostasis, the origin and fixation of HFE polymorphisms in European and other populations, and the genetic and biochemical basis of HFE hemochromatosis and iron overload.

  18. Local behavior of autonomous neutral functional differential equations.

    NASA Technical Reports Server (NTRS)

    Hale, J. K.

    1972-01-01

    Basic problems for a special class of neutral functional differential equations (NFDE) are formulated, and some contributions to a general qualitative theory in the neighborhood of an equilibrium point are indicated. The properties of a NFDE (G,f) are examined to determine in what sense these properties are insensitive to small changes in (G,f) in the topology G x F. The special class of equations that is introduced includes retarded functional differential equations and difference equations.

  19. Abnormal tracheal smooth muscle function in the CF mouse

    PubMed Central

    Wallace, Helen L; Southern, Kevin W; Connell, Marilyn G; Wray, Susan; Burdyga, Theodor

    2013-01-01

    Increased airway smooth muscle (ASM) contractility is thought to underlie symptoms of airway hyperresponsiveness (AHR). In the cystic fibrosis (CF) airway, ASM anomalies have been reported, but have not been fully characterized and the underlying mechanisms are largely unknown. We examined ASM in an adult CF mouse tracheal ring preparation, and determined whether changes in contractility were associated with altered ASM morphology. We looked for inherent changes in the cellular pathways involved in contractility, and characterized trachea morphology in the adult trachea and in an embryonic lung culture model during development. Results showed that that there was a reduction in tracheal caliber in CF mice as indicated by a reduction in the number of cartilage rings; proximal cross-sectional areas of cftr−/− tracheas and luminal areas were significantly smaller, but there was no difference in the area or distribution of smooth muscle. Morphological differences observed in adult trachea were not evident in the embryonic lung at 11.5 days gestation or after 72 h in culture. Functional data showed a significant reduction in the amplitude and duration of contraction in response to carbachol (CCh) in Ca-free conditions. The reduction in contraction was agonist specific, and occurred throughout the length of the trachea. These data show that there is a loss in the contractile capacity of the CF mouse trachea due to downregulation of the pathway specific to acetylcholine (ACh) activation. This reduction in contraction is not associated with changes in the area or distribution of ASM. PMID:24400140

  20. Effect of Sustained Human Centrifugation on Autonomic Cardiovascular and Vestibular Function

    NASA Technical Reports Server (NTRS)

    Schlegel, Todd T.; Wood, Scott J.; Brown, Troy E.; Benavides, Edgar W.; Harm, Deborah L.; Rupert, A. H.

    2002-01-01

    Repeated exposure to +Gz enhances human baroreflex responsiveness and improves tolerance to cardiovascular stress. However, both sustained exposure to +Gx and changes in otolith function resulting from the gravitational changes of space flight and parabolic flight may adversely affect autonomic cardiovascular function and orthostatic tolerance. HYPOTHESES: Baroreflex function and orthostatic tolerance are acutely improved by a single sustained (30 min) exposure to +3Gz but not +3Gx. Moreover, after 30 min of +3Gx, any changes that occur in autonomic cardiovascular function will relate commensurately to changes in otolith function. METHODS: Twenty-two healthy human subjects were first exposed to 5 min of +3 Gz centrifugation and then subsequently up to a total of30 min of either +3Gz (n = 15) or +3Gx (n = 7) centrifugation. Tests of autonomic cardiovascular function both before and after both types of centrifugation included: (a) power spectral determinations of beat-to-beat R-R intervals and arterial pressures; (b) carotid-cardiac baroreflex tests; ( c) Valsalva tests; and (d) 30-min head-up tilt (HUT) tests. Otolith function was assessed during centrifugation by the linear vestibulo-ocular reflex and both before and after centrifugation by measurements of ocular counter-rolling and dynamic posturography. RESULTS: All four +3Gz subjects who were intolerant to HUT before centrifugation became tolerant to HUT after centrifugation. The operational point of the carotid-cardiac baroreflex and the Valsalva-related baroreflex were also enhanced in the +3Gz group but not in the +3Gx group. No significant vestibular-autonomic relationships were detected, other than a significant vestibular-cerebrovascular interaction reported previously. CONCLUSIONS: A single, sustained exposure to +3 Gz centrifugation acutely improves baroreflex function and orthostatic tolerance whereas a similar exposure to +3 Gx centrifugation appears to have less effect.

  1. Autonomic response to approachability characteristics, approach behavior, and social functioning in Williams syndrome.

    PubMed

    Järvinen, Anna; Ng, Rowena; Bellugi, Ursula

    2015-11-01

    Williams syndrome (WS) is a neurogenetic disorder that is saliently characterized by a unique social phenotype, most notably associated with a dramatically increased affinity and approachability toward unfamiliar people. Despite a recent proliferation of studies into the social profile of WS, the underpinnings of the pro-social predisposition are poorly understood. To this end, the present study was aimed at elucidating approach behavior of individuals with WS contrasted with typical development (TD) by employing a multidimensional design combining measures of autonomic arousal, social functioning, and two levels of approach evaluations. Given previous evidence suggesting that approach behaviors of individuals with WS are driven by a desire for social closeness, approachability tendencies were probed across two levels of social interaction: talking versus befriending. The main results indicated that while overall level of approachability did not differ between groups, an important qualitative between-group difference emerged across the two social interaction contexts: whereas individuals with WS demonstrated a similar willingness to approach strangers across both experimental conditions, TD individuals were significantly more willing to talk to than to befriend strangers. In WS, high approachability to positive faces across both social interaction levels was further associated with more normal social functioning. A novel finding linked autonomic responses with willingness to befriend negative faces in the WS group: elevated autonomic responsivity was associated with increased affiliation to negative face stimuli, which may represent an autonomic correlate of approach behavior in WS. Implications for underlying organization of the social brain are discussed. PMID:26459097

  2. Autonomic response to approachability characteristics, approach behavior, and social functioning in Williams syndrome.

    PubMed

    Järvinen, Anna; Ng, Rowena; Bellugi, Ursula

    2015-11-01

    Williams syndrome (WS) is a neurogenetic disorder that is saliently characterized by a unique social phenotype, most notably associated with a dramatically increased affinity and approachability toward unfamiliar people. Despite a recent proliferation of studies into the social profile of WS, the underpinnings of the pro-social predisposition are poorly understood. To this end, the present study was aimed at elucidating approach behavior of individuals with WS contrasted with typical development (TD) by employing a multidimensional design combining measures of autonomic arousal, social functioning, and two levels of approach evaluations. Given previous evidence suggesting that approach behaviors of individuals with WS are driven by a desire for social closeness, approachability tendencies were probed across two levels of social interaction: talking versus befriending. The main results indicated that while overall level of approachability did not differ between groups, an important qualitative between-group difference emerged across the two social interaction contexts: whereas individuals with WS demonstrated a similar willingness to approach strangers across both experimental conditions, TD individuals were significantly more willing to talk to than to befriend strangers. In WS, high approachability to positive faces across both social interaction levels was further associated with more normal social functioning. A novel finding linked autonomic responses with willingness to befriend negative faces in the WS group: elevated autonomic responsivity was associated with increased affiliation to negative face stimuli, which may represent an autonomic correlate of approach behavior in WS. Implications for underlying organization of the social brain are discussed.

  3. Early-stage visual processing abnormalities in high-functioning autism spectrum disorder (ASD).

    PubMed

    Baruth, Joshua M; Casanova, Manuel F; Sears, Lonnie; Sokhadze, Estate

    2010-06-01

    It has been reported that individuals with autism spectrum disorder (ASD) have abnormal responses to the sensory environment. For these individuals sensory overload can impair functioning, raise physiological stress, and adversely affect social interaction. Early-stage (i.e. within 200ms of stimulus onset) auditory processing abnormalities have been widely examined in ASD using event-related potentials (ERP), while ERP studies investigating early-stage visual processing in ASD are less frequent. We wanted to test the hypothesis of early-stage visual processing abnormalities in ASD by investigating ERPs elicited in a visual oddball task using illusory figures. Our results indicate that individuals with ASD have abnormally large cortical responses to task irrelevant stimuli over both parieto-occipital and frontal regions-of-interest (ROI) during early stages of visual processing compared to the control group. Furthermore, ASD patients showed signs of an overall disruption in stimulus discrimination, and had a significantly higher rate of motor response errors.

  4. Functional neuroimaging of emotional learning and autonomic reactions.

    PubMed

    Peper, Martin; Herpers, Martin; Spreer, Joachim; Hennig, Jürgen; Zentner, Josef

    2006-06-01

    This article provides a selective overview of the functional neuroimaging literature with an emphasis on emotional activation processes. Emotions are fast and flexible response systems that provide basic tendencies for adaptive action. From the range of involved component functions, we first discuss selected automatic mechanisms that control basic adaptational changes. Second, we illustrate how neuroimaging work has contributed to the mapping of the network components associated with basic emotion families (fear, anger, disgust, happiness), and secondary dimensional concepts that organise the meaning space for subjective experience and verbal labels (emotional valence, activity/intensity, approach/withdrawal, etc.). Third, results and methodological difficulties are discussed in view of own neuroimaging experiments that investigated the component functions involved in emotional learning. The amygdala, prefrontal cortex, and striatum form a network of reciprocal connections that show topographically distinct patterns of activity as a correlate of up and down regulation processes during an emotional episode. Emotional modulations of other brain systems have attracted recent research interests. Emotional neuroimaging calls for more representative designs that highlight the modulatory influences of regulation strategies and socio-cultural factors responsible for inhibitory control and extinction. We conclude by emphasising the relevance of the temporal process dynamics of emotional activations that may provide improved prediction of individual differences in emotionality.

  5. [Alteration of neurobehavioral and autonomic nervous function in aluminum electrolytic workers].

    PubMed

    He, Shuchang; Zhang, Aimin; Niu, Qiao; Wang, Sheng; Chen, Yilan

    2003-05-01

    In order to explore the impairment of Aluminum on the neurobehavioral, autonomic nervous function. Neurobehavioral test battery (NCTB) recommended by WHO and autonomic nervous system (ANS) function test recommended by Ewing DJ were conducted in 32 Al electrolytic workers and 34 controls. Results showed that the scores of confusion-bewilderment and tension-anxious in Al exposed workers were higher than that of control group, while the scores of POMSA, POMSD, POMSF and POMSV in Al-exposed group had no obvious change. The scores of DSY, PA and PAC were lower than that of control group. The scores of DSPF, DDSPB, DSP, SANN, SANP and BVR had no significant alteration. R-R interval variability of maximin ratio of immediate standing up, which reflects parasympathetic nervous modification ability in aluminum electrolytic workers, was lower than that of the control group. This implied that Al exposure had adverse impact on workers' mood state, neurobehavioral and parasympathetic nervous function.

  6. [Emotion Disorders and Abnormal Perspiration].

    PubMed

    Umeda, Satoshi

    2016-08-01

    This article reviewed the relationship between emotional disorders and abnormal perspiration. First, I focused on local brain areas related to emotional processing, and summarized the functions of the emotional network involving those local areas. Functional disorders followed by the damage in the amygdala, orbitofrontal cortex, and insular cortex were reviewed, including related abnormal perspiration. I then addressed the mechanisms of how autonomic disorders influence emotional processing. Finally, possible future directions for integrated understanding of the connection between neural activities and bodily reactions were discussed. PMID:27503817

  7. [Emotion Disorders and Abnormal Perspiration].

    PubMed

    Umeda, Satoshi

    2016-08-01

    This article reviewed the relationship between emotional disorders and abnormal perspiration. First, I focused on local brain areas related to emotional processing, and summarized the functions of the emotional network involving those local areas. Functional disorders followed by the damage in the amygdala, orbitofrontal cortex, and insular cortex were reviewed, including related abnormal perspiration. I then addressed the mechanisms of how autonomic disorders influence emotional processing. Finally, possible future directions for integrated understanding of the connection between neural activities and bodily reactions were discussed.

  8. Cross correlation of heart rate and respiration versus deep breathing. Assessment of new test of cardiac autonomic function in diabetes.

    PubMed

    Bernardi, L; Rossi, M; Soffiantino, F; Marti, G; Ricordi, L; Finardi, G; Fratino, P

    1989-05-01

    Cross correlation is a mathematical function whereby spectral analysis is used to describe the relationship between heart-rate fluctuations (256 R-R intervals) and respiration (simultaneously obtained by pneumotacograph). To assess its usefulness for testing autonomic integrity, cross correlation and deep breathing were compared in 141 diabetic subjects (aged 39 +/- 14 yr) and in 77 control subjects (aged 33 +/- 13 yr). To characterize patients, Valsalva maneuver, 30:15 ratio, tilt, and handgrip tests were performed in 96 of these patients; 23 had two or more abnormal tests (group A), 28 had one (group B), and 45 had none (group C). Sensitivity to parasympathetic withdrawal was compared in 9 control subjects (aged 26 +/- 4 yr) by four sequential 0.01-mg/kg i.v. atropine administrations. Reproducibility was compared in 11 control subjects (aged 25 +/- 2 yr) by repeating the tests four times for 2 consecutive days. Considering all 141 patients, cross correlation and deep breathing were less than 2SD of the mean of control subjects in 64 and 36 subjects, respectively. Considering patients who also performed other tests of autonomic function, cross correlation and deep breathing were less than 2SD of the mean of controls in 42 and 30 subjects, respectively (group A, 20 and 15; group B, 12 and 9; group C, 10 and 6). Cross correlation had better reproducibility than deep breathing (C.V. 10.3 vs. 30.6% at 6 breaths/min) and greater sensitivity to atropine (after the 1st injection, cross correlation and deep breathing decreased to 34.6 and 48.2% of baseline values, respectively; P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

  9. Motion planning for autonomous vehicle based on radial basis function neural network in unstructured environment.

    PubMed

    Chen, Jiajia; Zhao, Pan; Liang, Huawei; Mei, Tao

    2014-09-18

    The autonomous vehicle is an automated system equipped with features like environment perception, decision-making, motion planning, and control and execution technology. Navigating in an unstructured and complex environment is a huge challenge for autonomous vehicles, due to the irregular shape of road, the requirement of real-time planning, and the nonholonomic constraints of vehicle. This paper presents a motion planning method, based on the Radial Basis Function (RBF) neural network, to guide the autonomous vehicle in unstructured environments. The proposed algorithm extracts the drivable region from the perception grid map based on the global path, which is available in the road network. The sample points are randomly selected in the drivable region, and a gradient descent method is used to train the RBF network. The parameters of the motion-planning algorithm are verified through the simulation and experiment. It is observed that the proposed approach produces a flexible, smooth, and safe path that can fit any road shape. The method is implemented on autonomous vehicle and verified against many outdoor scenes; furthermore, a comparison of proposed method with the existing well-known Rapidly-exploring Random Tree (RRT) method is presented. The experimental results show that the proposed method is highly effective in planning the vehicle path and offers better motion quality.

  10. Motion Planning for Autonomous Vehicle Based on Radial Basis Function Neural Network in Unstructured Environment

    PubMed Central

    Chen, Jiajia; Zhao, Pan; Liang, Huawei; Mei, Tao

    2014-01-01

    The autonomous vehicle is an automated system equipped with features like environment perception, decision-making, motion planning, and control and execution technology. Navigating in an unstructured and complex environment is a huge challenge for autonomous vehicles, due to the irregular shape of road, the requirement of real-time planning, and the nonholonomic constraints of vehicle. This paper presents a motion planning method, based on the Radial Basis Function (RBF) neural network, to guide the autonomous vehicle in unstructured environments. The proposed algorithm extracts the drivable region from the perception grid map based on the global path, which is available in the road network. The sample points are randomly selected in the drivable region, and a gradient descent method is used to train the RBF network. The parameters of the motion-planning algorithm are verified through the simulation and experiment. It is observed that the proposed approach produces a flexible, smooth, and safe path that can fit any road shape. The method is implemented on autonomous vehicle and verified against many outdoor scenes; furthermore, a comparison of proposed method with the existing well-known Rapidly-exploring Random Tree (RRT) method is presented. The experimental results show that the proposed method is highly effective in planning the vehicle path and offers better motion quality. PMID:25237902

  11. Motion planning for autonomous vehicle based on radial basis function neural network in unstructured environment.

    PubMed

    Chen, Jiajia; Zhao, Pan; Liang, Huawei; Mei, Tao

    2014-01-01

    The autonomous vehicle is an automated system equipped with features like environment perception, decision-making, motion planning, and control and execution technology. Navigating in an unstructured and complex environment is a huge challenge for autonomous vehicles, due to the irregular shape of road, the requirement of real-time planning, and the nonholonomic constraints of vehicle. This paper presents a motion planning method, based on the Radial Basis Function (RBF) neural network, to guide the autonomous vehicle in unstructured environments. The proposed algorithm extracts the drivable region from the perception grid map based on the global path, which is available in the road network. The sample points are randomly selected in the drivable region, and a gradient descent method is used to train the RBF network. The parameters of the motion-planning algorithm are verified through the simulation and experiment. It is observed that the proposed approach produces a flexible, smooth, and safe path that can fit any road shape. The method is implemented on autonomous vehicle and verified against many outdoor scenes; furthermore, a comparison of proposed method with the existing well-known Rapidly-exploring Random Tree (RRT) method is presented. The experimental results show that the proposed method is highly effective in planning the vehicle path and offers better motion quality. PMID:25237902

  12. Effects of metabolic and myocardial microcirculatory abnormalities on the pathogenesis of cardiac autonomic neuropathy in type 2 diabetes mellitus: A prospective study in Japanese patients*

    PubMed Central

    Komori, Hiromi

    2005-01-01

    Background: In diabetic patients, cardiac autonomic neuropathy is an important factor affecting prognosis. Whether this condition in diabetic patients is caused directly by neurovisceral metabolic disorder and/or indirectly by micro circulation remains to be clarified. Objective: The aim of this study was to determine whether cardiac sympathetic nerve dysfunction can be detected using adenosine triphosphate (ATP) testing, while also investigating the effects of metabolic and/or myocardial microcirculatory abnormalities on the pathogenesis of cardiac autonomic nerve dysfunction in patients with type 2 diabetes mellitus (DM-2) in Japan. Methods: This prospective study was performed at the Division of Diabetology Department of Internal Medicine, Toho University, Ohashi Hospital, Tokyo, Japan. Patients aged ≥ 18 years with DM-2 with no abnormalities on electrocardiography (ECG) or echocardiography were enrolled. An ATP thallium (Tl)-201 myocardial scintigraphy test (ATP test) and iodine (I)-123 metaiodobenzylguanidine (MIBG) scintigraphy were performed. ATP was administered by continuous IV infusion over 6 minutes at 0.16 mg/kg · min. Five minutes after the ATP infusion was started, T1-201 111 MBq IV was administered. Single-photon emission computed tomography (SPECT) imaging was begun immediately after the end of ATP infusion and was completed 3 hours after stress to show washout from stress to rest. I-123 MIBG 111 MBq IV was administered. A planar image from the front side and a SPECT image (early phase) was obtained 15 to 30 minutes later. After 3 hours, a planar image from the front side and a SPECT image (late phase) were obtained to show washout from stress to rest. The mean TI washout rate (ATP-WR) and heart-to-mediastinum (H/M) ratio in the late-phase scintigraphic images and the washout rate of MIBG (MIBG-WR) in the left ventricle was determined. The correlations of these measurements with the mean values of glycosylated hemoglobin (HbA1c) and fasting

  13. Liver Function Test Abnormalities in Patients with Inflammatory Bowel Diseases: A Hospital-based Survey

    PubMed Central

    Cappello, Maria; Randazzo, Claudia; Bravatà, Ivana; Licata, Anna; Peralta, Sergio; Craxì, Antonio; Almasio, Piero Luigi

    2014-01-01

    BACKGROUND AND AIMS Inflammatory bowel diseases (IBD) are frequently associated with altered liver function tests (LFTs). The causal relationship between abnormal LFTs and IBD is unclear. The aim of our study was to evaluate the prevalence and etiology of LFTs abnormalities and their association with clinical variables in a cohort of IBD patients followed up in a single center. MATERIALS AND METHODS A retrospective review was undertaken of all consecutive IBD in- and outpatients routinely followed up at a single referral center. Clinical and demographic parameters were recorded. Subjects were excluded if they had a previous diagnosis of chronic liver disease. LFT abnormality was defined as an increase in aspartate aminotransferase, (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), or total bilirubin. RESULTS A cohort of 335 patients (179 males, mean age 46.0 ± 15.6 years) was analyzed. Abnormal LFTs were detected in 70 patients (20.9%). In most cases, the alterations were mild and spontaneously returned to normal values in about 60% of patients. Patients with abnormal LFTs were less frequently on treatment with aminosalicylates (22.8 vs. 36.6%, P = 0.04). The most frequent cause for transient abnormal LFTs was drug-induced cholestasis (34.1%), whereas fatty liver was the most frequent cause of persistent liver damage (65.4%). A cholestatic pattern was found in 60.0% of patients and was mainly related to older age, longer duration of disease, and hypertension. CONCLUSIONS The prevalence of LFT abnormalities is relatively high in IBD patients, but the development of severe liver injury is exceptional. Moreover, most alterations of LFTs are mild and spontaneously return to normal values. Drug-induced hepatotoxicity and fatty liver are the most relevant causes of abnormal LFTs in patients with IBD. PMID:24966712

  14. Executive Cognitive Functioning and Cardiovascular Autonomic Regulation in a Population-Based Sample of Working Adults

    PubMed Central

    Stenfors, Cecilia U. D.; Hanson, Linda M.; Theorell, Töres; Osika, Walter S.

    2016-01-01

    Objective: Executive cognitive functioning is essential in private and working life and is sensitive to stress and aging. Cardiovascular (CV) health factors are related to cognitive decline and dementia, but there is relatively few studies of the role of CV autonomic regulation, a key component in stress responses and risk factor for cardiovascular disease (CVD), and executive processes. An emerging pattern of results from previous studies suggest that different executive processes may be differentially associated with CV autonomic regulation. The aim was thus to study the associations between multiple measures of CV autonomic regulation and measures of different executive cognitive processes. Method: Participants were 119 healthy working adults (79% women), from the Swedish Longitudinal Occupational Survey of Health. Electrocardiogram was sampled for analysis of heart rate variability (HRV) measures, including the Standard Deviation of NN, here heart beats (SDNN), root of the mean squares of successive differences (RMSSD), high frequency (HF) power band from spectral analyses, and QT variability index (QTVI), a measure of myocardial repolarization patterns. Executive cognitive functioning was measured by seven neuropsychological tests. The relationships between CV autonomic regulation measures and executive cognitive measures were tested with bivariate and partial correlational analyses, controlling for demographic variables, and mental health symptoms. Results: Higher SDNN and RMSSD and lower QTVI were significantly associated with better performance on cognitive tests tapping inhibition, updating, shifting, and psychomotor speed. After adjustments for demographic factors however (age being the greatest confounder), only QTVI was clearly associated with these executive tests. No such associations were seen for working memory capacity. Conclusion: Poorer CV autonomic regulation in terms of lower SDNN and RMSSD and higher QTVI was associated with poorer executive

  15. Gas House Autonomous System Monitoring

    NASA Technical Reports Server (NTRS)

    Miller, Luke; Edsall, Ashley

    2015-01-01

    Gas House Autonomous System Monitoring (GHASM) will employ Integrated System Health Monitoring (ISHM) of cryogenic fluids in the High Pressure Gas Facility at Stennis Space Center. The preliminary focus of development incorporates the passive monitoring and eventual commanding of the Nitrogen System. ISHM offers generic system awareness, adept at using concepts rather than specific error cases. As an enabler for autonomy, ISHM provides capabilities inclusive of anomaly detection, diagnosis, and abnormality prediction. Advancing ISHM and Autonomous Operation functional capabilities enhances quality of data, optimizes safety, improves cost effectiveness, and has direct benefits to a wide spectrum of aerospace applications.

  16. Autonomic arousal explains social cognitive abilities in high-functioning adults with autism spectrum disorder.

    PubMed

    Mathersul, Danielle; McDonald, Skye; Rushby, Jacqueline A

    2013-09-01

    Empirical research into behavioural profiles and autonomic responsivity in individuals with autism spectrum disorders (ASDs) is highly variable and inconsistent. Two preliminary studies of children with ASDs suggest that there may be subgroups of ASDs depending on their resting arousal levels, and that these subgroups show different profiles of autonomic responsivity. The aim of the present study was to determine whether (i) adults with high-functioning ASDs may be separated into subgroups according to variation in resting arousal; and (ii) these ASD arousal subgroups differ in their behavioural profiles for basic emotion recognition, judgements of trustworthiness, and cognitive and affective empathy. Thirty high-functioning adults with ASDs and 34 non-clinical controls participated. Resting arousal was determined as the average skin conductance (SCL) across a 2 min resting period. There was a subgroup of ASD adults with significantly lower resting SCL. These individuals demonstrated poorer emotion recognition, tended to judge faces more negatively, and had atypical relationships between SCL and affective empathy. In contrast, low cognitive empathy was a feature of all ASD adults. These findings have important implications for clinical interventions and future studies investigating autonomic functioning in ASDs.

  17. Functional Brain Network Abnormalities during Verbal Working Memory Performance in Adolescents and Young Adults with Dyslexia

    ERIC Educational Resources Information Center

    Wolf, Robert Christian; Sambataro, Fabio; Lohr, Christina; Steinbrink, Claudia; Martin, Claudia; Vasic, Nenad

    2010-01-01

    Behavioral and functional neuroimaging studies indicate deficits in verbal working memory (WM) and frontoparietal dysfunction in individuals with dyslexia. Additionally, structural brain abnormalities in dyslexics suggest a dysconnectivity of brain regions associated with phonological processing. However, little is known about the functional…

  18. Low yield of unselected testing in patients with acutely abnormal liver function tests

    PubMed Central

    Chadwick, Andrew

    2015-01-01

    Objectives To audit the diagnostic yield and cost implications of the use of a ‘liver screen’ for inpatients with abnormal liver function tests. Design We performed a retrospective audit of inpatients with abnormal liver function tests. We analysed all investigations ordered including biochemistry, immunology, virology and radiology. The final diagnosis was ascertained in each case, and the diagnostic yield and cost per positive diagnosis for each investigation were calculated. Setting St Thomas’ NHS Trust. Participants All inpatients investigated for abnormal liver function tests over a 12-month period. Main outcome measures We calculated the percentage of courses due to each diagnosis, the yield of each investigation and the cost per positive diagnosis for each investigation. Results A total of 308 patients were included, and a final diagnosis was made in 224 patients (73%) on the basis of both clinical data and investigations. There was considerable heterogeneity in the tests included in an acute liver screen. History and ultrasound yielded the most diagnoses (40% and 30%, respectively). The yield of autoimmune and metabolic screens was minimal. Conclusions Our results demonstrate the low yield of unselected testing in patients with abnormal liver function tests. A thorough history, ultrasound and testing for blood-borne viruses are the cornerstones of diagnosis. Specialist input should be sought before further testing. Prospective studies to evaluate the yield and cost-effectiveness of different testing strategies are needed. PMID:26770816

  19. Effect of integrated approach of yoga therapy on autonomic functions in patients with type 2 diabetes

    PubMed Central

    Vinutha, H. T.; Raghavendra, B. R.; Manjunath, N. K.

    2015-01-01

    Background and Objectives: Integrated approach of yoga therapy (IAYT) had shown beneficial effects in the management of type 2 diabetes mellitus (DM). Autonomic dysfunction is one of the major complications of type 2 DM. Research studies have demonstrated that yoga can modulate autonomic functions. Hence, the current study was designed to assess the effect of IAYT on autonomic functions in type 2 diabetics. Materials and Methods: 15 patients of type 2 DM with ages ranging from 35 to 60 years were recruited for the study. They were diagnosed with type 2 diabetes from 1-year to 15 years. Assessments were made on day 1 (before yoga) and day 7 (after 1-week of yoga practice). Heart rate variability (HRV), blood pressure (BP) response to the isometric handgrip and heart rate response to deep breathing were assessed before and after 1-week of IAYT. Results: There was a significant reduction in fasting plasma glucose from 154.67–130.27 mg/dL (Wilcoxon signed rank test, P = 0.029) following 1-week of IAYT. BP response to isometric hand grip improved significantly (Wilcoxon signed rank test, P = 0.01). There was no statistical significant change in HRV components and heart rate response to deep breathing test. However, there was a trend of increase in the low frequency power (41.07%), high frequency power (6.29%), total power (5.38%), and standard deviation of all NN intervals (SDNN) (6.29%). Conclusion: These findings suggest that, IAYT improved autonomic functions in type 2 diabetes patients. PMID:26425477

  20. Effects of cacao liquor polyphenols on cardiovascular and autonomic nervous functions in hypercholesterolaemic rabbits.

    PubMed

    Akita, Megumi; Kuwahara, Masayoshi; Itoh, Fumi; Nakano, Yoshihisa; Osakabe, Naomi; Kurosawa, Tohru; Tsubone, Hirokazu

    2008-12-01

    Many epidemiological studies have shown that polyphenols can reduce the risk of mortality from cardiovascular diseases. This study tested the hypothesis that cacao liquor polyphenols have the properties to restore the cardiovascular and autonomic nervous function in an animal model of familial hypercholesterolaemia. Male Kurosawa and Kusanagi-hypercholesterolaemic rabbits were housed in individual cages in a room where a 12-hr light:dark cycle (lights-on at 8:00 and lights-off at 20:00) was maintained. At 3 months of age, they were divided into two groups (standard diet and cacao liquor polyphenol) and the animals received 100 g of the respective diets per day and were provided with tap water ad libitum. Heart rate and blood pressure were measured by a telemetry system. To clarify the autonomic nervous function, power spectral analysis of heart rate variability, baroreflex sensitivity and autonomic nervous tone were measured. After 6 months of dietary administration of cacao liquor polyphenols, heart rate and blood pressure were lowered but plasma lipid concentrations were unchanged. The area of atherosclerotic lesions in the aorta in the cacao liquor polyphenol group was significantly smaller than that in the standard diet group. The high-frequency power of heart rate variability in the rabbits in the standard diet group was significantly decreased with ageing, but that in the cacao liquor polyphenol group was not different between short-term and long-term treatment. Moreover, cacao liquor polyphenols preserved parasympathetic nervous tone, although that in the standard diet group was significantly decreased with ageing. We conclude that cacao liquor polyphenols may play an important role to protect cardiovascular and autonomic nervous functions.

  1. Somatosensory cortex functional connectivity abnormalities in autism show opposite trends, depending on direction and spatial scale

    PubMed Central

    Khan, Sheraz; Michmizos, Konstantinos; Tommerdahl, Mark; Ganesan, Santosh; Kitzbichler, Manfred G.; Zetino, Manuel; Garel, Keri-Lee A.; Herbert, Martha R.; Hämäläinen, Matti S.

    2015-01-01

    Functional connectivity is abnormal in autism, but the nature of these abnormalities remains elusive. Different studies, mostly using functional magnetic resonance imaging, have found increased, decreased, or even mixed pattern functional connectivity abnormalities in autism, but no unifying framework has emerged to date. We measured functional connectivity in individuals with autism and in controls using magnetoencephalography, which allowed us to resolve both the directionality (feedforward versus feedback) and spatial scale (local or long-range) of functional connectivity. Specifically, we measured the cortical response and functional connectivity during a passive 25-Hz vibrotactile stimulation in the somatosensory cortex of 20 typically developing individuals and 15 individuals with autism, all males and right-handed, aged 8–18, and the mu-rhythm during resting state in a subset of these participants (12 per group, same age range). Two major significant group differences emerged in the response to the vibrotactile stimulus. First, the 50-Hz phase locking component of the cortical response, generated locally in the primary (S1) and secondary (S2) somatosensory cortex, was reduced in the autism group (P < 0.003, corrected). Second, feedforward functional connectivity between S1 and S2 was increased in the autism group (P < 0.004, corrected). During resting state, there was no group difference in the mu-α rhythm. In contrast, the mu-β rhythm, which has been associated with feedback connectivity, was significantly reduced in the autism group (P < 0.04, corrected). Furthermore, the strength of the mu-β was correlated to the relative strength of 50 Hz component of the response to the vibrotactile stimulus (r = 0.78, P < 0.00005), indicating a shared aetiology for these seemingly unrelated abnormalities. These magnetoencephalography-derived measures were correlated with two different behavioural sensory processing scores (P < 0.01 and P < 0.02 for the autism

  2. Docetaxel does not impair cardiac autonomic function in breast cancer patients previously treated with anthracyclines.

    PubMed

    Ekholm, Eeva; Rantanen, Virpi; Syvänen, Kari; Jalonen, Jarmo; Antila, Kari; Salminen, Eeva

    2002-04-01

    The effects of docetaxel treatment on autonomic cardiac function was studied with 24-h ECG recordings in breast cancer patients pretreated with anthracyclines. Twenty-four women were evaluated before docetaxel treatment and after 3-4 courses of docetaxel 100 mg/m(2). The heart rate, cardiac extrasystoles and heart rate variability (HRV) in both the time and frequency domain were assessed from 24-h ECG recordings. The acute effects of docetaxel were calculated from 1-h recordings immediately prior to, during and after infusion. Long-term effects were evaluated from 24-h recordings performed before treatment and after 3-4 courses of docetaxel. There was no increase in the number of cardiac extrasystoles during docetaxel infusion. The number of ventricular extrasystoles decreased from 14 (23) to 7 (14) during and 5 (10) after the first infusion (p=0.02). The heart rate, HRV and extrasystoles were similar before and after 3-4 courses of docetaxel. The treatment did not abolish circadian variability of the heart rate. Docetaxel did not deteriorate autonomic cardiac function. In conclusion, our findings suggest that docetaxel does not have harmful cumulative effects on autonomic control of the heart and is therefore unlikely to be cardiotoxic.

  3. Myocardial 123I-MIBG Uptake and Cardiovascular Autonomic Function in Parkinson's Disease

    PubMed Central

    Katagiri, Akira; Asahina, Masato; Araki, Nobuyuki; Poudel, Anupama; Fujinuma, Yoshikatsu; Yamanaka, Yoshitaka; Kuwabara, Satoshi

    2015-01-01

    Introduction. Patients with Parkinson's disease (PD) showed reduced myocardial 123I-MIBG uptake, which may affect autonomic regulation. We investigated correlation between MIBC accumulation and cardiovascular autonomic function in PD. Methods. We performed myocardial MIBG scintigraphy, heart rate variability (HRV) analysis, and the head-up tilt test (HUT) in 50 PD patients (66.4 ± 7.8 years; duration 5.5 ± 5.9 years). Autonomic function tests were also performed in 50 healthy controls (66.5 ± 8.9 years). As HRV parameters, a high-frequency power (HF, 0.15–0.4 Hz), a low-frequency power (LF, 0.04–0.15 Hz), and LF/HF ratio were used. Results. Our PD patients had a significant reduction in LF and HF compared with the controls (P = 0.005 and P = 0.01). In HUT, systolic and diastolic blood pressure falls in the PD group were significantly greater than those in the controls (P = 0.02 and P = 0.02). The washout rate of MIBG was negatively correlated with blood pressure changes during HUT. Conclusion. Our PD patients showed reduced HRV, blood pressure dysregulation, and reduced MIBG accumulation, which was correlated with blood pressure dysregulation. Orthostatic hypotension in PD may be mainly caused by sympathetic postganglionic degeneration. PMID:26649224

  4. Effect of Yoga on migraine: A comprehensive study using clinical profile and cardiac autonomic functions

    PubMed Central

    Kisan, Ravikiran; Sujan, MU; Adoor, Meghana; Rao, Raghavendra; Nalini, A; Kutty, Bindu M; Chindanda Murthy, BT; Raju, TR; Sathyaprabha, TN

    2014-01-01

    Context and Aims: Migraine is an episodic disabling headache requiring long-term management. Migraine management through Yoga therapy would reduce the medication cost with positive health benefits. Yoga has shown to improve the quality of life, reduce the episode of headache and medication. The aim of the present study was to evaluate the efficacy of Yoga as an adjuvant therapy in migraine patients by assessing clinical outcome and autonomic functions tests. Subjects and Methods: Migraine patients were randomly given either conventional care (n = 30) or Yoga with conventional care (n = 30). Yoga group received Yoga practice session for 5 days a week for 6 weeks along with conventional care. Clinical assessment (frequency, intensity of headache and headache impact) and autonomic function test were done at baseline and at the end of the intervention. Results: Yoga with conventional care and convention care groups showed significant improvement in clinical variables, but it was better with Yoga therapy. Improvement in the vagal tone along with reduced sympathetic activity was observed in patients with migraine receiving Yoga as adjuvant therapy. Conclusions: Intervention showed significant clinical improvement in both groups. Headache frequency and intensity were reduced more in Yoga with conventional care than the conventional care group alone. Furthermore, Yoga therapy enhanced the vagal tone and decreased the sympathetic drive, hence improving the cardiac autonomic balance. Thus, Yoga therapy can be effectively incorporated as an adjuvant therapy in migraine patients. PMID:25035622

  5. Teaching cardiac autonomic function dynamics employing the Valsalva (Valsalva-Weber) maneuver.

    PubMed

    Junqueira, Luiz Fernando

    2008-03-01

    In this report, a brief history of the Valsalva (Valsalva-Weber) maneuver is outlined, followed by an explanation on the use of this approach for the evaluation of cardiac autonomic function based on underlying heart rate changes. The most important methodological and interpretative aspects of the Valsalva-Weber maneuver are critically updated, and some guidelines are established for simple application of the maneuver in a teaching or research laboratory setting. These include the hemodynamic and cardiac autonomic mechanisms involved, technical aspects such as the intensity and duration of the expiratory straining, frequency of maneuver sessions, training and posture of the individuals tested, different time- and grade change-dependent indexes of heart interval variation, and clinical application of the maneuver.

  6. Abnormal hippocampal structure and function in clinical anxiety and comorbid depression.

    PubMed

    Cha, Jiook; Greenberg, Tsafrir; Song, Inkyung; Blair Simpson, Helen; Posner, Jonathan; Mujica-Parodi, Lilianne R

    2016-05-01

    Given the high prevalence rates of comorbidity of anxiety and depressive disorders, identifying a common neural pathway to both disorders is important not only for better diagnosis and treatment, but also for a more complete conceptualization of each disease. Hippocampal abnormalities have been implicated in anxiety and depression, separately; however, it remains unknown whether these abnormalities are also implicated in their comorbidity. Here we address this question by testing 32 adults with generalized anxiety disorder (15 GAD only and 17 comorbid MDD) and 25 healthy controls (HC) using multimodal MRI (structure, diffusion and functional) and automated hippocampal segmentation. We demonstrate that (i) abnormal microstructure of the CA1 and CA2-3 is associated with GAD/MDD comorbidity and (ii) decreased anterior hippocampal reactivity in response to repetition of the threat cue is associated with GAD (with or without MDD comorbidity). In addition, mediation-structural equation modeling (SEM) reveals that our hippocampal and dimensional symptom data are best explained by a model describing a significant influence of abnormal hippocampal microstructure on both anxiety and depression-mediated through its impact on abnormal hippocampal threat processing. Collectively, our findings show a strong association between changes in hippocampal microstructure and threat processing, which together may present a common neural pathway to comorbidity of anxiety and depression.

  7. Effect of 30-min +3 Gz centrifugation on vestibular and autonomic cardiovascular function

    NASA Technical Reports Server (NTRS)

    Schlegel, Todd T.; Wood, Scott J.; Brown, Troy E.; Harm, Deborah L.; Rupert, A. H.

    2003-01-01

    INTRODUCTION: Repeated exposure to increased +Gz enhances human baroreflex responsiveness and improves tolerance to cardiovascular stress. However, it is not known whether such enhancements might also result from a single, more prolonged exposure to increased +Gz. Our study was designed to investigate whether baroreflex function and orthostatic tolerance are acutely improved by a single prolonged exposure to +3 Gz, and moreover, whether changes in autonomic cardiovascular function resulting from exposure to increased +Gz are correlated with changes in otolith function. METHODS: We exposed 15 healthy human subjects to +3 Gz centrifugation for up to 30 min or until symptoms of incipient G-induced loss of consciousness (G-LOC) ensued. Tests of autonomic cardiovascular function both before and after centrifugation included: 1) power spectral determinations of beat-to-beat R-R intervals and arterial pressures; 2) carotid-cardiac baroreflex tests; 3) Valsalva tests; and 4) 30-min head-up tilt tests. Otolith function was assessed during centrifugation by the linear vestibulo-ocular reflex and both before and after centrifugation by measurements of ocular counter-rolling and dynamic posturography. RESULTS: Of the 15 subjects who underwent prolonged +3 Gz, 4 were intolerant to 30 min of head-up tilt before centrifugation but became tolerant to such tilt after centrifugation. The Valsalva-related baroreflex as well as a measure of the carotid-cardiac baroreflex were also enhanced after centrifugation. No significant vestibular-autonomic relationships were detected beyond a vestibular-cerebrovascular interaction reported earlier in a subset of seven participants. CONCLUSIONS: A single prolonged exposure to +3 Gz centrifugation acutely improves baroreflex function and orthostatic tolerance.

  8. Abnormal Vascular Function and Hypertension in Mice Deficient in Estrogen Receptor β

    NASA Astrophysics Data System (ADS)

    Zhu, Yan; Bian, Zhao; Lu, Ping; Karas, Richard H.; Bao, Lin; Cox, Daniel; Hodgin, Jeffrey; Shaul, Philip W.; Thorén, Peter; Smithies, Oliver; Gustafsson, Jan-Åke; Mendelsohn, Michael E.

    2002-01-01

    Blood vessels express estrogen receptors, but their role in cardiovascular physiology is not well understood. We show that vascular smooth muscle cells and blood vessels from estrogen receptor β (ERβ)-deficient mice exhibit multiple functional abnormalities. In wild-type mouse blood vessels, estrogen attenuates vasoconstriction by an ERβ-mediated increase in inducible nitric oxide synthase expression. In contrast, estrogen augments vasoconstriction in blood vessels from ERβ-deficient mice. Vascular smooth muscle cells isolated from ERβ-deficient mice show multiple abnormalities of ion channel function. Furthermore, ERβ-deficient mice develop sustained systolic and diastolic hypertension as they age. These data support an essential role for ERβ in the regulation of vascular function and blood pressure.

  9. Assessment of Autonomic Function by Phase Rectification of RRInterval Histogram Analysis in Chagas Disease

    PubMed Central

    Nasari-Junior, Olivassé; Benchimol-Barbosa, Paulo Roberto; Pedrosa, Roberto Coury; Nadal, Jurandir

    2015-01-01

    Background In chronic Chagas disease (ChD), impairment of cardiac autonomic function bears prognostic implications. Phase‑rectification of RR-interval series isolates the sympathetic, acceleration phase (AC) and parasympathetic, deceleration phase (DC) influences on cardiac autonomic modulation. Objective This study investigated heart rate variability (HRV) as a function of RR-interval to assess autonomic function in healthy and ChD subjects. Methods Control (n = 20) and ChD (n = 20) groups were studied. All underwent 60-min head-up tilt table test under ECG recording. Histogram of RR-interval series was calculated, with 100 ms class, ranging from 600–1100 ms. In each class, mean RR-intervals (MNN) and root-mean-squared difference (RMSNN) of consecutive normal RR-intervals that suited a particular class were calculated. Average of all RMSNN values in each class was analyzed as function of MNN, in the whole series (RMSNNT), and in AC (RMSNNAC) and DC (RMSNNDC) phases. Slopes of linear regression lines were compared between groups using Student t-test. Correlation coefficients were tested before comparisons. RMSNN was log-transformed. (α < 0.05). Results Correlation coefficient was significant in all regressions (p < 0.05). In the control group, RMSNNT, RMSNNAC, and RMSNNDC significantly increased linearly with MNN (p < 0.05). In ChD, only RMSNNAC showed significant increase as a function of MNN, whereas RMSNNT and RMSNNDC did not. Conclusion HRV increases in proportion with the RR-interval in healthy subjects. This behavior is lost in ChD, particularly in the DC phase, indicating cardiac vagal incompetence. PMID:26131700

  10. Abnormal interhemispheric resting state functional connectivity of the insula in heroin users under methadone maintenance treatment.

    PubMed

    Wang, Peng-Wei; Lin, Huang-Chi; Liu, Gin-Chung; Yang, Yi-Hsin Connie; Ko, Chih-Hung; Yen, Cheng-Fang

    2016-09-30

    Abnormal interhemispheric functional connectivity is attracting more and more attention in the field of substance use. This study aimed to examine 1) the differences in interhemispheric functional connections of the insula with the contralateral insula and other brain regions between heroin users under methadone maintenance treatment (MMT) and healthy controls, and 2) the association between heroin users' interhemispheric insular functional connectivity using resting functional magnetic resonance imaging (fMRI) and the results of urine heroin analysis. Sixty male right-handed persons, including 30 with heroin dependence under MMT and 30 healthy controls, were recruited to this study. Resting fMRI experiments and urine heroin analysis were performed. Compared with the controls, the heroin users had a significantly lower interhemispheric insular functional connectivity. They also exhibited lower functional connectivity between insula and contralateral inferior orbital frontal lobe. After controlling for age, educational level and methadone dosage, less deviation of the interhemispheric insula functional connectivity was significantly associated with a lower risk of a positive urine heroin analysis result. Our findings demonstrated that the heroin users under MMT had abnormal long-range and interhemispheric resting functional connections. Those with a less dysfunctional interhemispheric insula functional connectivity had a lower risk of a positive urine heroin test. PMID:27497215

  11. Functional programming of the autonomic nervous system by early life immune exposure: implications for anxiety.

    PubMed

    Sominsky, Luba; Fuller, Erin A; Bondarenko, Evgeny; Ong, Lin Kooi; Averell, Lee; Nalivaiko, Eugene; Dunkley, Peter R; Dickson, Phillip W; Hodgson, Deborah M

    2013-01-01

    Neonatal exposure of rodents to an immune challenge alters a variety of behavioural and physiological parameters in adulthood. In particular, neonatal lipopolysaccharide (LPS; 0.05 mg/kg, i.p.) exposure produces robust increases in anxiety-like behaviour, accompanied by persistent changes in hypothalamic-pituitary-adrenal (HPA) axis functioning. Altered autonomic nervous system (ANS) activity is an important physiological contributor to the generation of anxiety. Here we examined the long term effects of neonatal LPS exposure on ANS function and the associated changes in neuroendocrine and behavioural indices. ANS function in Wistar rats, neonatally treated with LPS, was assessed via analysis of tyrosine hydroxylase (TH) in the adrenal glands on postnatal days (PNDs) 50 and 85, and via plethysmographic assessment of adult respiratory rate in response to mild stress (acoustic and light stimuli). Expression of genes implicated in regulation of autonomic and endocrine activity in the relevant brain areas was also examined. Neonatal LPS exposure produced an increase in TH phosphorylation and activity at both PNDs 50 and 85. In adulthood, LPS-treated rats responded with increased respiratory rates to the lower intensities of stimuli, indicative of increased autonomic arousal. These changes were associated with increases in anxiety-like behaviours and HPA axis activity, alongside altered expression of the GABA-A receptor α2 subunit, CRH receptor type 1, CRH binding protein, and glucocorticoid receptor mRNA levels in the prefrontal cortex, hippocampus and hypothalamus. The current findings suggest that in addition to the commonly reported alterations in HPA axis functioning, neonatal LPS challenge is associated with a persistent change in ANS activity, associated with, and potentially contributing to, the anxiety-like phenotype. The findings of this study reflect the importance of changes in the perinatal microbial environment on the ontogeny of physiological processes.

  12. Neurobehavioral, autonomic nervous function and lymphocyte subsets among aluminum electrolytic workers.

    PubMed

    He, S C; Qiao, N; Sheng, W

    2003-01-01

    The purpose of our study is to determine the alteration of neurobehavioral parameters, autonomic nervous function and lymphocyte subsets in aluminum electrolytic workers of long-term aluminum exposure. 33 men who were 35.16 +/- 2.95 (mean +/- S.D) years old occupationally exposed to aluminum for 14.91 +/- 6.31 (mean +/- S.D) years. Air Al level and urinary aluminum concentration was measured by means of graphite furnace atomic absorption spectrophotometer. Normal reference group were selected from a flour plant. Neurobehavioral core test battery (NCTB) recommended by WHO was utilized. Autonomic nervous function test battery recommended by Ewing DJ was conducted on subjects. FAC SCAN was used to measure the lymphocyte subsets of peripheral blood. The mean air aluminum level in the workshop was 6.36 mg/m3, ranged from 2.90 to 11.38 mg/m3. Urinary aluminum of the Al electrolytic workers (40.08 +/- 9.36 microgram/mg.cre) was obviously higher than that of control group (26.84 +/- 8.93 m/mg.cre). Neurobehavioral results showed that the scores of DSY, PAC and PA in Al electrolytic workers were significantly lower than those of control group, The score of POMSC, POMSF and SRT among Al exposed workers were significantly augmented in relation to those of control group. Autonomic nervous function test results showed that R-R interval variability of maximum ratio of immediately standing up in Al electrolytic workers were decreased compare with the control group, while the BP-IS, HR-V, HR-DB, R30:15 had no significant change. Peripheral blood lymphocyte subsets test showed that CD4-CD8+ T lymphocyte in Al electrolytic workers increased. This study suggests that Al exposure exerts adverse effects on neurobehavioral performance, especially movement coordination and negative mood, and parasympathetic nervous function; moreover it increase CD4-CD8+ T lymphocyte subsets.

  13. Genetic autonomic disorders.

    PubMed

    Axelrod, Felicia B

    2013-03-01

    Genetic disorders affecting the autonomic nervous system can result in abnormal development of the nervous system or they can be caused by neurotransmitter imbalance, an ion-channel disturbance or by storage of deleterious material. The symptoms indicating autonomic dysfunction, however, will depend upon whether the genetic lesion has disrupted peripheral or central autonomic centers or both. Because the autonomic nervous system is pervasive and affects every organ system in the body, autonomic dysfunction will result in impaired homeostasis and symptoms will vary. The possibility of genetic confirmation by molecular testing for specific diagnosis is increasing but treatments tend to remain only supportive and directed toward particular symptoms. PMID:23465768

  14. [Respiratory function impairment in patients with Parkinson's disease--a consideration on the possible pathogenetic relation to autonomic dysfunction].

    PubMed

    Yamada, H; Murahashi, M; Takahashi, H; Kai, K; Shibuya, S; Jimi, T; Wakayama, Y; Yamada, M

    2000-02-01

    To investigate the characteristics and clinical significance of respiratory function in patients with Parkinson's disease (PD), we studied 38 patients (male, 19; female, 19: mean age, 65.5 years: mean duration of disease, 6.7 years) who had no history of respiratory disease and smoking. Fifty three non-respiratory disease subjects (male, 26; female, 27: mean age, 67.6 years) were served as age-matched control. We measured spirometry and maximal expiratory flow-volume curve in all patients, and analyzed the relations between respiratory function variables and clinical profiles. The clinical disability of PD was indicated by Hoehn-Yahr (H-Y) scale. The number of PD patients was 15 in H-Y 2, 18 in H-Y 3 and 5 in H-Y 4, respectively. The values of % VC, %FEV 1, FEV 1/FVC, %PEFR, % V50 in H-Y 4 group were significantly smaller than those in H-Y 2 and 3 groups. Small airway dysfunction (SAD) was represented by abnormality of % V25, % V50/V25. The prevalence of impairment in % V25 and % V50/V25 was detected in 13 patients (34.2%) and 15 patients (39.5%), respectively, this was significantly higher than age-matched controls. However, the mean value and prevalence of impairment in % V25, % V50/V25 were not affected by H-Y scale and duration of disease or ideal body weight (%predicted value). Twenty seven patients showed normal ventilatory function based on % VC over 80% and FEV 1/FVC over 70%. The prevalence of impairment in % V25, % V50/V25 was detected in 8 patients (29.6%), 9 patients (33.3%), respectively, among 27 patients with normal ventilatory function. These results suggest that ventilatory dysfunction is concerned with clinical disability but SAD which is independent of clinical disability seen prevalently in patients with PD. It is widely accepted that patients with PD frequently have cardiac or bowel dysfunction based on the visceral autonomic dysfunction. We hypothesize that SAD may also be caused by possible autonomic dysfunction in patients with PD.

  15. [Respiratory function impairment in patients with Parkinson's disease--a consideration on the possible pathogenetic relation to autonomic dysfunction].

    PubMed

    Yamada, H; Murahashi, M; Takahashi, H; Kai, K; Shibuya, S; Jimi, T; Wakayama, Y; Yamada, M

    2000-02-01

    To investigate the characteristics and clinical significance of respiratory function in patients with Parkinson's disease (PD), we studied 38 patients (male, 19; female, 19: mean age, 65.5 years: mean duration of disease, 6.7 years) who had no history of respiratory disease and smoking. Fifty three non-respiratory disease subjects (male, 26; female, 27: mean age, 67.6 years) were served as age-matched control. We measured spirometry and maximal expiratory flow-volume curve in all patients, and analyzed the relations between respiratory function variables and clinical profiles. The clinical disability of PD was indicated by Hoehn-Yahr (H-Y) scale. The number of PD patients was 15 in H-Y 2, 18 in H-Y 3 and 5 in H-Y 4, respectively. The values of % VC, %FEV 1, FEV 1/FVC, %PEFR, % V50 in H-Y 4 group were significantly smaller than those in H-Y 2 and 3 groups. Small airway dysfunction (SAD) was represented by abnormality of % V25, % V50/V25. The prevalence of impairment in % V25 and % V50/V25 was detected in 13 patients (34.2%) and 15 patients (39.5%), respectively, this was significantly higher than age-matched controls. However, the mean value and prevalence of impairment in % V25, % V50/V25 were not affected by H-Y scale and duration of disease or ideal body weight (%predicted value). Twenty seven patients showed normal ventilatory function based on % VC over 80% and FEV 1/FVC over 70%. The prevalence of impairment in % V25, % V50/V25 was detected in 8 patients (29.6%), 9 patients (33.3%), respectively, among 27 patients with normal ventilatory function. These results suggest that ventilatory dysfunction is concerned with clinical disability but SAD which is independent of clinical disability seen prevalently in patients with PD. It is widely accepted that patients with PD frequently have cardiac or bowel dysfunction based on the visceral autonomic dysfunction. We hypothesize that SAD may also be caused by possible autonomic dysfunction in patients with PD. PMID

  16. Autonomic dysreflexia

    MedlinePlus

    Autonomic hyperreflexia; Spinal cord injury - autonomic dysreflexia; SCI - autonomic dysreflexia ... most common cause of autonomic dysreflexia (AD) is spinal cord injury. The nervous system of people with AD ...

  17. Prevalence and Determinants of True Thyroid Dysfunction Among Pediatric Referrals for Abnormal Thyroid Function Tests

    PubMed Central

    Lahoti, Amit; Klein, Jason; Schumaker, Tiffany; Vuguin, Patricia; Frank, Graeme

    2016-01-01

    Background/Aims. Abnormalities in thyroid function tests (TFTs) are a common referral reason for pediatric endocrine evaluation. However, a sizable proportion of these laboratory abnormalities do not warrant therapy or endocrine follow-up. The objectives of this study were (a) to evaluate the prevalence of true thyroid dysfunction among pediatric endocrinology referrals for abnormal TFTs; (b) to identify the historical, clinical, and laboratory characteristics that predict decision to treat. Methods. This was a retrospective chart review of patients evaluated in pediatric endocrinology office during a weekly clinic designated for new referrals for abnormal TFTs in 2010. Results. A total of 230 patients were included in the study. Median age at referral was 12 years (range = 2-18); 56% were females. Routine screening was cited as the reason for performing TFTs by 33% patients. Majority was evaluated for hypothyroidism (n = 206). Elevated thyroid-stimulating hormone was the most common referral reason (n = 140). A total of 41 out of 206 patients were treated for hypothyroidism. Conclusions. Prevalence of hypothyroidism was 20%. Thyroid follow-up was not recommended for nearly one third of the patients. Among all the factors analyzed, an elevated thyroid-stimulating hormone level and antithyroglobulin antibodies strongly correlated with the decision to treat (P < .005). PMID:27336020

  18. Early-stage visual processing abnormalities in high-functioning autism spectrum disorder (ASD)

    PubMed Central

    Baruth, Joshua M.; Casanova, Manuel F.; Sears, Lonnie; Sokhadze, Estate

    2012-01-01

    It has been reported that individuals with autism spectrum disorder (ASD) have abnormal responses to the sensory environment. For these individuals sensory overload can impair functioning, raise physiological stress, and adversely affect social interaction. Early-stage (i.e. within 200ms of stimulus onset) auditory processing abnormalities have been widely examined in ASD using event-related potentials (ERP), while ERP studies investigating early-stage visual processing in ASD are less frequent. We wanted to test the hypothesis of early-stage visual processing abnormalities in ASD by investigating ERPs elicited in a visual oddball task using illusory figures. Our results indicate that individuals with ASD have abnormally large cortical responses to task irrelevant stimuli over both parieto-occipital and frontal regions-of-interest (ROI) during early stages of visual processing compared to the control group. Furthermore, ASD patients showed signs of an overall disruption in stimulus discrimination, and had a significantly higher rate of motor response errors. PMID:22563527

  19. Abnormal functional brain asymmetry in depression: evidence of biologic commonality between major depression and dysthymia.

    PubMed

    Bruder, Gerard E; Stewart, Jonathan W; Hellerstein, David; Alvarenga, Jorge E; Alschuler, Daniel; McGrath, Patrick J

    2012-04-30

    Prior studies have found abnormalities of functional brain asymmetry in patients having a major depressive disorder (MDD). This study aimed to replicate findings of reduced right hemisphere advantage for perceiving dichotic complex tones in depressed patients, and to determine whether patients having "pure" dysthymia show the same abnormality of perceptual asymmetry as MDD. It also examined gender differences in lateralization, and the extent to which abnormalities of perceptual asymmetry in depressed patients are dependent on gender. Unmedicated patients having either a MDD (n=96) or "pure" dysthymic disorder (n=42) and healthy controls (n=114) were tested on dichotic fused-words and complex-tone tests. Patient and control groups differed in right hemisphere advantage for complex tones, but not left hemisphere advantage for words. Reduced right hemisphere advantage for tones was equally present in MDD and dysthymia, but was more evident among depressed men than depressed women. Also, healthy men had greater hemispheric asymmetry than healthy women for both words and tones, whereas this gender difference was not seen for depressed patients. Dysthymia and MDD share a common abnormality of hemispheric asymmetry for dichotic listening.

  20. Prevalence and Determinants of True Thyroid Dysfunction Among Pediatric Referrals for Abnormal Thyroid Function Tests.

    PubMed

    Lahoti, Amit; Klein, Jason; Schumaker, Tiffany; Vuguin, Patricia; Frank, Graeme

    2016-01-01

    Background/Aims. Abnormalities in thyroid function tests (TFTs) are a common referral reason for pediatric endocrine evaluation. However, a sizable proportion of these laboratory abnormalities do not warrant therapy or endocrine follow-up. The objectives of this study were (a) to evaluate the prevalence of true thyroid dysfunction among pediatric endocrinology referrals for abnormal TFTs; (b) to identify the historical, clinical, and laboratory characteristics that predict decision to treat. Methods. This was a retrospective chart review of patients evaluated in pediatric endocrinology office during a weekly clinic designated for new referrals for abnormal TFTs in 2010. Results. A total of 230 patients were included in the study. Median age at referral was 12 years (range = 2-18); 56% were females. Routine screening was cited as the reason for performing TFTs by 33% patients. Majority was evaluated for hypothyroidism (n = 206). Elevated thyroid-stimulating hormone was the most common referral reason (n = 140). A total of 41 out of 206 patients were treated for hypothyroidism. Conclusions. Prevalence of hypothyroidism was 20%. Thyroid follow-up was not recommended for nearly one third of the patients. Among all the factors analyzed, an elevated thyroid-stimulating hormone level and antithyroglobulin antibodies strongly correlated with the decision to treat (P < .005).

  1. Functional Based Adaptive and Fuzzy Sliding Controller for Non-Autonomous Active Suspension System

    NASA Astrophysics Data System (ADS)

    Huang, Shiuh-Jer; Chen, Hung-Yi

    In this paper, an adaptive sliding controller is developed for controlling a vehicle active suspension system. The functional approximation technique is employed to substitute the unknown non-autonomous functions of the suspension system and release the model-based requirement of sliding mode control algorithm. In order to improve the control performance and reduce the implementation problem, a fuzzy strategy with online learning ability is added to compensate the functional approximation error. The update laws of the functional approximation coefficients and the fuzzy tuning parameters are derived from the Lyapunov theorem to guarantee the system stability. The proposed controller is implemented on a quarter-car hydraulic actuating active suspension system test-rig. The experimental results show that the proposed controller suppresses the oscillation amplitude of the suspension system effectively.

  2. Autonomic control of cardiac function and myocardial oxygen consumption during hypoxic hypoxia.

    NASA Technical Reports Server (NTRS)

    Erickson, H. H.; Stone, H. L.

    1972-01-01

    Investigation in 19 conscious dogs of the importance of the sympathetic nervous system in the coronary and cardiac response to altitude (hypoxic) hypoxia. Beta-adrenergic blockade was used to minimize the cardiac effect associated with sympathetic receptors. It is shown that the autonomic nervous system, and particularly the sympathetic nervous system, is responsible for the increase in ventricular function and myocardial oxygen consumption that occurs during hypoxia. Minimizing this response through appropriate conditioning and training may improve the operating efficiency of the heart and reduce the hazard of hypoxia and other environmental stresses, such as acceleration, which are encountered in advanced aircraft systems.

  3. Microheterogeneity of antithrombin III: effect of single amino acid substitutions and relationship with functional abnormalities.

    PubMed

    De Stefano, V; Leone, G; Mastrangelo, S; Lane, D A; Girolami, A; de Moerloose, P; Sas, G; Abildgaard, U; Blajchman, M; Rodeghiero, F

    1994-02-01

    Microheterogeneity of antithrombin III (AT-III) was investigated by crossed immunoelectrofocusing (CIEF) on eleven molecular variants. A normal pattern was found in five variants while two different abnormal CIEF patterns were found in the other four and two variants, respectively. Point mutations causing a major pI change (exceeding 4.0) of the amino acid substituted lead to alterations in the overall microheterogeneity. The variants thus substituted share a first type of abnormal CIEF pattern with alterations throughout the pH range, regardless of the location of the mutation (reactive site and adjacent regions or heparin binding region). Minor amino acid pI changes in these regions do not alter the AT-III overall microheterogeneity, whatever the resulting functional defect. However, if the mutation is placed in the region around positions 404 or 429, then even minor changes of the amino acid pI seem able to alter the overall charge, leading to a second type of abnormal CIEF pattern with the main alteration at pH 4.8-4.6. Neuraminidase treatment leads to disappearance of microheterogeneity except for the variants with the Arg393 to Cys substitution. Addition of thrombin induces CIEF modifications specifically related to the functional defect. A normal formation of thrombin-antithrombin complexes induces a shift towards the more acid pH range, whereas in the variants substituted at the reactive site the CIEF pattern is substantially unaffected by thrombin; variants substituted at positions 382-384 show a maximal thrombin-induced increase of the isoforms at pI 4.8-4.6. Therefore mutant antithrombins with different functional abnormalities but sharing a common CIEF pattern were well distinguished.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8180341

  4. Effect of exercise on cardiac autonomic function in females with rheumatoid arthritis.

    PubMed

    Janse van Rensburg, Dina C; Ker, James A; Grant, Catharina C; Fletcher, Lizelle

    2012-08-01

    The objective of this study is to evaluate the effect of exercise on cardiac autonomic function as measured by short-term heart rate variability (HRV) in females suffering from rheumatoid arthritis (RA). Females with confirmed RA were randomly assigned to an exercise group (RAE) and a sedentary group (RAC). RAE was required to train under supervision two to three times per week, for 3 months. Three techniques (time domain, frequency domain and Poincaré plot analyses) were used to measure HRV at baseline and study completion. At baseline, RAC (n = 18) had a significantly higher variability compared to RAE (n = 19) for most HRV indicators. At study completion, the variables showing significant changes (p = 0.01 to 0.05) favoured RAE in all instances. Wilcoxon signed rank tests were performed to assess changes within groups from start to end. RAE showed significant improvement for most of the standing variables, including measurements of combined autonomic influence, e.g. SDRR (p = 0.002) and variables indicating only vagal influence, e.g. pNN50 (p = 0.014). RAC mostly deteriorated with emphasis on variables measuring vagal influence (RMSSD, pNN50, SD1 and HF (ms(2)). Study results indicated that 12 weeks of exercise intervention had a positive effect on cardiac autonomic function as measured by short-term HRV, in females with RA. Several of the standing variables indicated improved vagal influence on the heart rate. Exercise can thus potentially be used as an instrument to improve cardiac health in a patient group known for increased cardiac morbidity.

  5. Assessment of Cardiac Autonomic Functions in Medical Students With Type D Personality

    PubMed Central

    Panwar, R. Abhilasha Singh

    2016-01-01

    Introduction Type D personality experiences joint occurrence of Negative Affectivity and Social Inhibition. It is an emerging risk factor for cardiovascular disease, with prevalence being 18-53% among cardiac patients. Type D personality people have exaggerated cardiovascular activity mediated by increased sympathetic drive and decreased vagal control of the heart which leads to enhanced risk of hypertension and is an independent risk factor for coronary heart disease. Aim To compare the cardiac autonomic function of Type D and non-Type D students. To compare cardiac autonomic functions among male and female students and students with and without family history of hypertension and coronary artery disease among Type D. To find the most affected test among Type D students. Materials and Methods Thirty Type D and 30 non- Type D medical students were identified by DS14. The Parasympathetic cardiac autonomic tests done assessed Heart Rate response to valsalva manoeuvre, immediate heart rate response to standing and heart rate variation during deep breathing. Sympathetic tests assessed BP response to standing and Sustained Hand Grip. The heart rate and R-R interval measurement were got from lead II of ECG recordings on Polyrite D. Statistical analysis was done using SPSS software. Unpaired student’s t-test was used and p-value <0.05 was considered to be statistically significant. Results Type D students showed slightly decreased parasympathetic activity and increased sympathetic activity when compared to non-Type D students even though there was no statistically significant difference between them. There is a statistically significant decrease in valsalva ratio among females (p<0.01) when compared to males. There is a statistically significant decrease in 30:15 ratio and BP response to handgrip (p<0.05) among students with family history of hypertension and coronary artery disease when compared with students with no family history of coronary artery disease. Valsalva

  6. Abnormalities in personal space and parietal-frontal function in schizophrenia.

    PubMed

    Holt, Daphne J; Boeke, Emily A; Coombs, Garth; DeCross, Stephanie N; Cassidy, Brittany S; Stufflebeam, Steven; Rauch, Scott L; Tootell, Roger B H

    2015-01-01

    Schizophrenia is associated with subtle abnormalities in day-to-day social behaviors, including a tendency in some patients to "keep their distance" from others in physical space. The neural basis of this abnormality, and related changes in social functioning, is unknown. Here we examined, in schizophrenic patients and healthy control subjects, the functioning of a parietal-frontal network involved in monitoring the space immediately surrounding the body ("personal space"). Using fMRI, we found that one region of this network, the dorsal intraparietal sulcus (DIPS), was hyper-responsive in schizophrenic patients to face stimuli appearing to move towards the subjects, intruding into personal space. This hyper-responsivity was predicted both by the size of personal space (which was abnormally elevated in the schizophrenia group) and the severity of negative symptoms. In contrast, in a second study, the activity of two lower-level visual areas that send information to DIPS (the fusiform face area and middle temporal area) was normal in schizophrenia. Together, these findings suggest that changes in parietal-frontal networks that support the sensory-guided initiation of behavior, including actions occurring in the space surrounding the body, contribute to social dysfunction and negative symptoms in schizophrenia. PMID:26484048

  7. Abnormalities in personal space and parietal-frontal function in schizophrenia.

    PubMed

    Holt, Daphne J; Boeke, Emily A; Coombs, Garth; DeCross, Stephanie N; Cassidy, Brittany S; Stufflebeam, Steven; Rauch, Scott L; Tootell, Roger B H

    2015-01-01

    Schizophrenia is associated with subtle abnormalities in day-to-day social behaviors, including a tendency in some patients to "keep their distance" from others in physical space. The neural basis of this abnormality, and related changes in social functioning, is unknown. Here we examined, in schizophrenic patients and healthy control subjects, the functioning of a parietal-frontal network involved in monitoring the space immediately surrounding the body ("personal space"). Using fMRI, we found that one region of this network, the dorsal intraparietal sulcus (DIPS), was hyper-responsive in schizophrenic patients to face stimuli appearing to move towards the subjects, intruding into personal space. This hyper-responsivity was predicted both by the size of personal space (which was abnormally elevated in the schizophrenia group) and the severity of negative symptoms. In contrast, in a second study, the activity of two lower-level visual areas that send information to DIPS (the fusiform face area and middle temporal area) was normal in schizophrenia. Together, these findings suggest that changes in parietal-frontal networks that support the sensory-guided initiation of behavior, including actions occurring in the space surrounding the body, contribute to social dysfunction and negative symptoms in schizophrenia.

  8. Abnormalities in personal space and parietal–frontal function in schizophrenia

    PubMed Central

    Holt, Daphne J.; Boeke, Emily A.; Coombs, Garth; DeCross, Stephanie N.; Cassidy, Brittany S.; Stufflebeam, Steven; Rauch, Scott L.; Tootell, Roger B.H.

    2015-01-01

    Schizophrenia is associated with subtle abnormalities in day-to-day social behaviors, including a tendency in some patients to “keep their distance” from others in physical space. The neural basis of this abnormality, and related changes in social functioning, is unknown. Here we examined, in schizophrenic patients and healthy control subjects, the functioning of a parietal–frontal network involved in monitoring the space immediately surrounding the body (“personal space”). Using fMRI, we found that one region of this network, the dorsal intraparietal sulcus (DIPS), was hyper-responsive in schizophrenic patients to face stimuli appearing to move towards the subjects, intruding into personal space. This hyper-responsivity was predicted both by the size of personal space (which was abnormally elevated in the schizophrenia group) and the severity of negative symptoms. In contrast, in a second study, the activity of two lower-level visual areas that send information to DIPS (the fusiform face area and middle temporal area) was normal in schizophrenia. Together, these findings suggest that changes in parietal–frontal networks that support the sensory-guided initiation of behavior, including actions occurring in the space surrounding the body, contribute to social dysfunction and negative symptoms in schizophrenia. PMID:26484048

  9. Effects of long-term vegetarian diets on cardiovascular autonomic functions in healthy postmenopausal women.

    PubMed

    Fu, Chin-Hua; Yang, Cheryl C H; Lin, Chin-Lon; Kuo, Terry B J

    2006-02-01

    The incidence of cardiovascular disease is higher in postmenopausal women than in premenopausal women. We hypothesized that long-term vegetarian diets might modulate cardiovascular autonomic functions measured by frequency-domain techniques in healthy postmenopausal women. A total of 35 healthy vegetarians (mean age +/- SEM 55.0 +/- 1.3 years) who had been vegetarians for > or =2 years and 35 omnivores (55.1 +/- 1.4 years) participated in this study. These subjects were all postmenopausal without hormone replacement therapy. Fluctuations in arterial blood pressure and heart rate variability were diffracted into low-frequency (0.04 to 0.15 Hz) and high-frequency (0.15 to 0.4 Hz) segments. Cardiovascular autonomic functions and baroreflex sensitivity were evaluated by specific frequency-domain measures. The vegetarians had statistically lower systolic and diastolic blood pressure, and lower serum total cholesterol, low-density lipoprotein cholesterol, triglycerides, fasting blood sugar, and hemoglobin levels compared with the nonvegetarians. They also exhibited a significantly higher high-frequency power of heart rate variability and increased baroreflex sensitivity than did omnivores. No statistical differences were found in the low-frequency/high-frequency ratio or percentage of low frequency of heart rate variability between the 2 groups. In conclusion, in addition to the lower blood pressure and lipid concentrations in vegetarians, long-term vegetarian diets may facilitate vagal regulation of the heart and increase baroreflex sensitivity in healthy postmenopausal women, without increasing the sympathetic modulations of the cardiovascular system.

  10. Abnormalities in large scale functional networks in unmedicated patients with schizophrenia and effects of risperidone

    PubMed Central

    Kraguljac, Nina Vanessa; White, David Matthew; Hadley, Jennifer Ann; Visscher, Kristina; Knight, David; ver Hoef, Lawrence; Falola, Blessing; Lahti, Adrienne Carol

    2015-01-01

    Objective To describe abnormalities in large scale functional networks in unmedicated patients with schizophrenia and to examine effects of risperidone on networks. Material and methods 34 unmedicated patients with schizophrenia and 34 matched healthy controls were enrolled in this longitudinal study. We collected resting state functional MRI data with a 3T scanner at baseline and six weeks after they were started on risperidone. In addition, a group of 19 healthy controls were scanned twice six weeks apart. Four large scale networks, the dorsal attention network, executive control network, salience network, and default mode network were identified with seed based functional connectivity analyses. Group differences in connectivity, as well as changes in connectivity over time, were assessed on the group's participant level functional connectivity maps. Results In unmedicated patients with schizophrenia we found resting state connectivity to be increased in the dorsal attention network, executive control network, and salience network relative to control participants, but not the default mode network. Dysconnectivity was attenuated after six weeks of treatment only in the dorsal attention network. Baseline connectivity in this network was also related to clinical response at six weeks of treatment with risperidone. Conclusions Our results demonstrate abnormalities in large scale functional networks in patients with schizophrenia that are modulated by risperidone only to a certain extent, underscoring the dire need for development of novel antipsychotic medications that have the ability to alleviate symptoms through attenuation of dysconnectivity. PMID:26793436

  11. Gene expression, autonomic function and chronic hypoxia:lessons from the Andes.

    PubMed

    Appenzeller, Otto; Minko, Tamara; Qualls, Clifford; Pozharov, Vitaly; Gamboa, Jorge; Gamboa, Alfredo; Wang, Yang

    2006-06-01

    Autonomic function is altered by altitude in sojourners and natives. We hypothesized that these physiologic responses are modulated by changes in gene expression. We compared gene product levels in 20 natives of Cerro de Pasco (CP), (4338 m), 10 of which had chronic mountain sickness (CMS) established by a CMS-scoring system, with gene products in the same men after 1 h at sea level. We further compared the results with those obtained from 10 US men residing at 1500 m. We measured gene products in white cells by reverse transcription polymerase chain reaction (RT-PCR). We focused on genes important in vascular autonomic physiology, and/or activated by hypoxia; hypoxia inducible factor 1-alpha (HIF 1-alpha), 2 splicing variants of vascular endothelial growth factor (VEGF); VEGF-121, VEGF-165, and phosphoglycerate kinase 1 (PGK 1). Normal CP natives showed high expression of all genes in CP, compared to US controls. Within 1 h of arrival at sea level, they had comparable levels to US residents. In CMS, the gene products were higher in CP. Although gene products decreased in Lima in this group, they never reached US values. VEGF 121 and 165 were correlated (P<0.001). VEGF 165 was higher in CMS in CP (P=0.006), and was positively correlated with CMS-score (R=0.86, P<0.001), and negatively correlated with arterial saturation (R=-0.79, P<0.001). Our findings underscore the changes in gene expression levels in intact humans in response to environmental stress. These changes may support the physiologic alterations induced by the ambient hypoxia at altitude and impact organism survival. They also suggest therapeutic strategies for autonomic and neurodegenerative diseases at sea level.

  12. Influence of hydrotherapy on clinical and cardiac autonomic function in migraine patients

    PubMed Central

    Sujan, M. U.; Rao, M. Raghavendra; Kisan, Ravikiran; Abhishekh, Hulegar A.; Nalini, Atchayaram; Raju, Trichur R.; Sathyaprabha, T. N.

    2016-01-01

    Background: Migraine is associated with autonomic symptoms. The growing body of literature suggests that the dysfunctional autonomic nervous system might play a pivotal role in the pathogenesis of migraine. Thermal therapies have been hypothesized to modulate these changes and alleviate pain. However, data regarding the efficacy of hydrotherapy in migraine remain scant. We evaluated the effect of add on hydrotherapy procedure (a hot arm and foot bath with ice massage to head) in migraine patients. Methods: Forty chronic migraine patients fulfilling the International Classification of Headache Disorders II criteria were recruited from the neurology outpatient clinic. Patients were randomized to receive either hydrotherapy plus conventional pharmacological care (n = 20) or conventional medication only (n = 20). Hydrotherapy group received treatment with hot arm and foot bath (103°F to 110°F) and ice massage to head daily for 20 min for 45 days. Patients were assessed using headache impact test (HIT), visual analog scale for pain and cardiac autonomic function by heart rate variability (HRV) before and after intervention period. Results: There was a significant decrease in HIT score, frequency, and intensity of headaches following treatment in both the groups. However, it was more evident in add on hydrotherapy group compared to pharmacological treatment alone group. There was also significant improvement in the HRV parameters. In particular, there was a significant decrease in heart rate (P = 0.017), increase in high frequency (HF) (P = 0.014) and decrease in low frequency/HF ratio (P = 0.004) in add on hydrotherapy group. Conclusion: Our study shows that add on hydrotherapy enhanced the vagal tone in addition to reducing the frequency and intensity of headaches in migraine patients. PMID:26933356

  13. The relationship between white matter abnormalities and cognitive functions in new-onset juvenile myoclonic epilepsy.

    PubMed

    Ekmekci, Burcu; Bulut, Hacı Taner; Gümüştaş, Funda; Yıldırım, Adem; Kuştepe, Ali

    2016-09-01

    Diffusion tensor imaging (DTI) has revealed evidence of subcortical white matter abnormalities in the frontal area in juvenile myoclonic epilepsy (JME). Decreased fractional anisotropy (FA) and increased mean diffusivity (MD) in the corticothalamic pathway have been detected in adult patients with JME. It has been demonstrated that, in adult patients with JME, frontal dysfunction is related to subcortical white matter damage and decreased volume in frontal cortical gray matter and the thalamus. Many studies have focused on adult patients. Twenty-four patients and 28 controls were evaluated. The group with JME had significantly worse results for the word fluency, trail-B, and Stroop tests that assessed executive functions. A significant decrease in FA values in the dorsolateral prefrontal cortex (DLPFC), the supplementary motor area (SMA), the right thalamus, the posterior cingulate, the corpus callosum anterior, the corona radiata, and the middle frontal white matter (MFWM) and an increase in ADC values in patients with JME were detected. The correlation between FA values in DLPFC and the letter fluency test results was positive, and the correlation with the Stroop and trail-B test results was negative. We found a negative correlation between SMA, anterior thalamus, and MFWM FA values and the trail-B test results and a positive correlation between the SMA, anterior thalamus, and MFWM FA values and the letter fluency test results. We detected white matter and gray matter abnormalities in patients with new-onset JME using DTI. In addition, we determined the relationship between cognitive deficit and microstructural abnormalities by evaluating the correlation between the neuropsychological test battery results and DTI parameters. We evaluated newly diagnosed patients with JME in our study. That leads us to believe that microstructural abnormalities exist from the very beginning of the disease and that they result from the genetic basis of the disease.

  14. Abnormal function of the corpus luteum in some ewes with phyto-oestrogenic infertility.

    PubMed

    Adams, N R; Hearnshaw, H; Oldham, C M

    1981-01-01

    Ewes with permanent phyto-estrogenic infertility show oestrus less regularly than normal ewes, and the present study examines the extent to which this results from abnormal ovarian function. Forty-nine affected ewes and 53 controls were run with rams fitted with marking crayons and harnesses, and crayon marks were recorded and laparoscopy performed at weekly intervals for 3 weeks. Fewer affected ewes showed oestrus accompanied by ovulation (28 v. 49, P less than 0.001), and four of these affected ewes had a second ovulation during the experiment. More of the ovulations observed in affected ewes were unaccompanied by behavioural oestrus than in controls (8 out of 38 v. 2 out of 50; P less than 0.05). Six affected ewes had no corpus luteum or oestrus, and five of these had adhesions over the genitalia. Hydrops uteri in five other affected ewes was accompanied by prolonged maintenance of the corpus luteum. Some other abnormalities were also observed. In a second study, plasma progesterone concentrations were measured twice daily in 12 affected ewes which were run with rams. Five ewes had oestrous cycles of abnormal duration (two of more than 23 days, two of 21 days, and one of 11 days), and these were accompanied by plasma progesterone patterns different from those of the ewes with an oestrous cycle duration of 16-18 days. It is concluded that the irregular oestrous cycles in affected ewes are due mainly to abnormal life span and progesterone secretion by the corpus luteum, which in turn largely result from changes in the uterus. PMID:7196218

  15. [Axon-reflex based nerve fiber function assessment in the detection of autonomic neuropathy].

    PubMed

    Siepmann, T; Illigens, B M-W; Reichmann, H; Ziemssen, T

    2014-10-01

    Axon-reflex-based tests of peripheral small nerve fiber function including techniques to quantify vasomotor and sudomotor responses following acetylcholine iontophoresis are used in the assessment of autonomic neuropathy. However, the established axon-reflex-based techniques, laser Doppler flowmetry (LDF) to assess vasomotor function and quantitative sudomotor axon-reflex test (QSART) to measure sudomotor function, are limited by technically demanding settings as well as interindividual variability and are therefore restricted to specialized clinical centers. New axon-reflex tests are characterized by quantification of axon responses with both temporal and spatial resolution and include "laser Doppler imaging (LDI) axon-reflex flare area test" to assess vasomotor function, the quantitative direct and indirect test of sudomotor function (QDIRT) to quantify sudomotor function, as well as the quantitative pilomotor axon-reflex test (QPART), a technique to measure pilomotor nerve fiber function using adrenergic cutaneous stimulation through phenylephrine iontophoresis. The effectiveness of new axon-reflex tests in the assessment of neuropathy is currently being investigated in clinical studies.

  16. Assessment of the peripheral, central, and autonomic nervous system function in styrene workers

    SciTech Connect

    Murata, K.; Araki, S.; Yokoyama, K. )

    1991-01-01

    To investigate the effects of styrene exposure on peripheral, central, and autonomic nervous system functions in man, we measured the distribution of nerve conduction velocities (DCV), short-latency somatosensory evoked potentials (SSEP), and variability in electrocardiographic R-R interval (CVRR) as well as conventional sensory and motor median nerve conduction velocities (SCV and MCV) in eleven styrene-exposed workers. The styrene workers' urinary phenylglyoxylic acid levels ranged from 31 to 419 (mean 169) mg/g creatinine at the end of the work shift on the examination day (estimated exposure to styrene of 22 ppm in air). Control subjects, matched to each styrene worker by sex and age, were selected from healthy adults without cardiovascular, neurologic and other potentially confounding disorders. In the styrene workers, we found that the V80 velocity of the DCV, below which 80% of active nerve fibers lie, and the SCV were both significantly slowed; the CVRR was also significantly reduced. There were no significant differences in SSEP latencies, MCV, or heart rate between the exposed workers and controls. These data, despite the small sample size, suggest that styrene affects the faster myelinated fibers of the peripheral sensory nerves, and that it also affects autonomic nervous activity.

  17. Functional changes are associated with tracheal structural abnormalities in patients with acromegaly

    PubMed Central

    Camilo, Gustavo Bittencourt; Guimarães, Fernando Silva; Mogami, Roberto; Faria, Alvaro Camilo Dias; Melo, Pedro Lopes

    2016-01-01

    Introduction Although impaired pulmonary function and respiratory sleep disorders are described as responsible for increased mortality in acromegalic patients, little is known about the tracheal abnormalities in this group of patients. Thus, the objectives of this study were to describe the tracheal structural abnormalities and correlate these changes with the respiratory function and clinical data of acromegalic patients. Material and methods This is a cross-sectional study that was carried out at two university hospitals. Twenty acromegalic patients underwent spirometry, forced oscillation technique, and computed tomography (CT) assessments. Dyspnea and daytime sleepiness were assessed using the Modified Medical Research Council (MMRC) scale and the Epworth Sleepiness Scale (ESS), respectively. Forty matched subjects served as controls. Results The acromegalic patients exhibited larger median ratios between forced expiratory flow and forced inspiratory flow at 50% of the forced vital capacity (FEF50%/FIF50%) (2.05 vs. 1.06, p = 0.0001) compared with healthy volunteers. In the CT analysis, acromegalic patients exhibited larger median differences between their cervical and thoracic tracheal diameters (Δ tracheal diameters) (3 vs. 1 mm; p = 0.003). An association was found between FEF50%/FIF50% and the following variables: mean resistance (Rm), cervical tracheal diameter, and Δ tracheal diameters. Rm also exhibited a negative correlation with cervical tracheal diameter. Neither the MMRC scale nor the ESS exhibited any significant correlation with large airway obstruction (LAO) indices or with the measured tracheal diameters. Conclusions Acromegalic patients have tracheal structural abnormalities which are associated with functional indicators of LAO but not with clinical data. PMID:26925121

  18. Abnormal functional architecture of amygdala-centered networks in adolescent posttraumatic stress disorder.

    PubMed

    Aghajani, Moji; Veer, Ilya M; van Hoof, Marie-José; Rombouts, Serge A R B; van der Wee, Nic J; Vermeiren, Robert R J M

    2016-03-01

    Posttraumatic stress disorder (PTSD) is a prevalent, debilitating, and difficult to treat psychiatric disorder. Very little is known of how PTSD affects neuroplasticity in the developing adolescent brain. Whereas multiple lines of research implicate amygdala-centered network dysfunction in the pathophysiology of adult PTSD, no study has yet examined the functional architecture of amygdala subregional networks in adolescent PTSD. Using intrinsic functional connectivity analysis, we investigated functional connectivity of the basolateral (BLA) and centromedial (CMA) amygdala in 19 sexually abused adolescents with PTSD relative to 23 matched controls. Additionally, we examined whether altered amygdala subregional connectivity coincides with abnormal grey matter volume of the amygdaloid complex. Our analysis revealed abnormal amygdalar connectivity and morphology in adolescent PTSD patients. More specifically, PTSD patients showed diminished right BLA connectivity with a cluster including dorsal and ventral portions of the anterior cingulate and medial prefrontal cortices (p < 0.05, corrected). In contrast, PTSD patients showed increased left CMA connectivity with a cluster including the orbitofrontal and subcallosal cortices (p < 0.05, corrected). Critically, these connectivity changes coincided with diminished grey matter volume within BLA and CMA subnuclei (p < 0.05, corrected), with CMA connectivity shifts additionally relating to more severe symptoms of PTSD. These findings provide unique insights into how perturbations in major amygdalar circuits could hamper fear regulation and drive excessive acquisition and expression of fear in PTSD. As such, they represent an important step toward characterizing the neurocircuitry of adolescent PTSD, thereby informing the development of reliable biomarkers and potential therapeutic targets.

  19. Selective functional connectivity abnormality of the transition zone of the inferior parietal lobule in schizophrenia.

    PubMed

    Liu, Xingyun; Zhuo, Chuanjun; Qin, Wen; Zhu, Jiajia; Xu, Lixue; Xu, Yongjie; Yu, Chunshui

    2016-01-01

    Structural and functional alterations in the inferior parietal lobule (IPL) in schizophrenia have been frequently reported; however, the IPL connectivity changes in schizophrenia remain largely unknown. Based on heterogeneity of the IPL in structure, connection and function, we hypothesize that the resting-state functional connectivities (rsFCs) of the IPL subregions are differentially affected in schizophrenia. This study included 95 schizophrenia patients and 104 healthy controls. The IPL subregions were defined according to a previous in vivo connection-based parcellation study. We calculated the rsFC of each IPL subregion and compared them between the two groups while controlling for the effects of age, gender, and grey matter volume. Among the six subregions of the left IPL and the five subregions of the right IPL, only the bilateral PFm (a transition zone of the IPL) subregions exhibited abnormal rsFC in schizophrenia. Specifically, the left PFm showed increased rsFC with the bilateral lingual gyri in schizophrenia patients than in healthy controls. The right PFm exhibited increased rsFC with the right lingual gyrus and inferior occipital gyrus, and bilateral mid-cingulate and sensorimotor cortices in schizophrenia patients. These findings suggest a selective rsFC abnormality in the IPL subregions in schizophrenia, characterized by the increased rsFC between the PFm subregion of the IPL and the visual and sensorimotor areas. PMID:27354957

  20. Abnormalities of functional brain networks in pathological gambling: a graph-theoretical approach

    PubMed Central

    Tschernegg, Melanie; Crone, Julia S.; Eigenberger, Tina; Schwartenbeck, Philipp; Fauth-Bühler, Mira; Lemènager, Tagrid; Mann, Karl; Thon, Natasha; Wurst, Friedrich M.; Kronbichler, Martin

    2013-01-01

    Functional neuroimaging studies of pathological gambling (PG) demonstrate alterations in frontal and subcortical regions of the mesolimbic reward system. However, most investigations were performed using tasks involving reward processing or executive functions. Little is known about brain network abnormalities during task-free resting state in PG. In the present study, graph-theoretical methods were used to investigate network properties of resting state functional magnetic resonance imaging data in PG. We compared 19 patients with PG to 19 healthy controls (HCs) using the Graph Analysis Toolbox (GAT). None of the examined global metrics differed between groups. At the nodal level, pathological gambler showed a reduced clustering coefficient in the left paracingulate cortex and the left juxtapositional lobe (supplementary motor area, SMA), reduced local efficiency in the left SMA, as well as an increased node betweenness for the left and right paracingulate cortex and the left SMA. At an uncorrected threshold level, the node betweenness in the left inferior frontal gyrus was decreased and increased in the caudate. Additionally, increased functional connectivity between fronto-striatal regions and within frontal regions has also been found for the gambling patients. These findings suggest that regions associated with the reward system demonstrate reduced segregation but enhanced integration while regions associated with executive functions demonstrate reduced integration. The present study makes evident that PG is also associated with abnormalities in the topological network structure of the brain during rest. Since alterations in PG cannot be explained by direct effects of abused substances on the brain, these findings will be of relevance for understanding functional connectivity in other addictive disorders. PMID:24098282

  1. Cell-Autonomous and Non-cell-autonomous Function of Hox Genes Specify Segmental Neuroblast Identity in the Gnathal Region of the Embryonic CNS in Drosophila

    PubMed Central

    Becker, Henrike; Renner, Simone; Technau, Gerhard M.; Berger, Christian

    2016-01-01

    During central nervous system (CNS) development neural stem cells (Neuroblasts, NBs) have to acquire an identity appropriate to their location. In thoracic and abdominal segments of Drosophila, the expression pattern of Bithorax-Complex Hox genes is known to specify the segmental identity of NBs prior to their delamination from the neuroectoderm. Compared to the thoracic, ground state segmental units in the head region are derived to different degrees, and the precise mechanism of segmental specification of NBs in this region is still unclear. We identified and characterized a set of serially homologous NB-lineages in the gnathal segments and used one of them (NB6-4 lineage) as a model to investigate the mechanism conferring segment-specific identities to gnathal NBs. We show that NB6-4 is primarily determined by the cell-autonomous function of the Hox gene Deformed (Dfd). Interestingly, however, it also requires a non-cell-autonomous function of labial and Antennapedia that are expressed in adjacent anterior or posterior compartments. We identify the secreted molecule Amalgam (Ama) as a downstream target of the Antennapedia-Complex Hox genes labial, Dfd, Sex combs reduced and Antennapedia. In conjunction with its receptor Neurotactin (Nrt) and the effector kinase Abelson tyrosine kinase (Abl), Ama is necessary in parallel to the cell-autonomous Dfd pathway for the correct specification of the maxillary identity of NB6-4. Both pathways repress CyclinE (CycE) and loss of function of either of these pathways leads to a partial transformation (40%), whereas simultaneous mutation of both pathways leads to a complete transformation (100%) of NB6-4 segmental identity. Finally, we provide genetic evidences, that the Ama-Nrt-Abl-pathway regulates CycE expression by altering the function of the Hippo effector Yorkie in embryonic NBs. The disclosure of a non-cell-autonomous influence of Hox genes on neural stem cells provides new insight into the process of segmental

  2. Cell-Autonomous and Non-cell-autonomous Function of Hox Genes Specify Segmental Neuroblast Identity in the Gnathal Region of the Embryonic CNS in Drosophila.

    PubMed

    Becker, Henrike; Renner, Simone; Technau, Gerhard M; Berger, Christian

    2016-03-01

    During central nervous system (CNS) development neural stem cells (Neuroblasts, NBs) have to acquire an identity appropriate to their location. In thoracic and abdominal segments of Drosophila, the expression pattern of Bithorax-Complex Hox genes is known to specify the segmental identity of NBs prior to their delamination from the neuroectoderm. Compared to the thoracic, ground state segmental units in the head region are derived to different degrees, and the precise mechanism of segmental specification of NBs in this region is still unclear. We identified and characterized a set of serially homologous NB-lineages in the gnathal segments and used one of them (NB6-4 lineage) as a model to investigate the mechanism conferring segment-specific identities to gnathal NBs. We show that NB6-4 is primarily determined by the cell-autonomous function of the Hox gene Deformed (Dfd). Interestingly, however, it also requires a non-cell-autonomous function of labial and Antennapedia that are expressed in adjacent anterior or posterior compartments. We identify the secreted molecule Amalgam (Ama) as a downstream target of the Antennapedia-Complex Hox genes labial, Dfd, Sex combs reduced and Antennapedia. In conjunction with its receptor Neurotactin (Nrt) and the effector kinase Abelson tyrosine kinase (Abl), Ama is necessary in parallel to the cell-autonomous Dfd pathway for the correct specification of the maxillary identity of NB6-4. Both pathways repress CyclinE (CycE) and loss of function of either of these pathways leads to a partial transformation (40%), whereas simultaneous mutation of both pathways leads to a complete transformation (100%) of NB6-4 segmental identity. Finally, we provide genetic evidences, that the Ama-Nrt-Abl-pathway regulates CycE expression by altering the function of the Hippo effector Yorkie in embryonic NBs. The disclosure of a non-cell-autonomous influence of Hox genes on neural stem cells provides new insight into the process of segmental

  3. Vagus nerve stimulation: state of the art of stimulation and recording strategies to address autonomic function neuromodulation

    NASA Astrophysics Data System (ADS)

    Guiraud, David; Andreu, David; Bonnet, Stéphane; Carrault, Guy; Couderc, Pascal; Hagège, Albert; Henry, Christine; Hernandez, Alfredo; Karam, Nicole; Le Rolle, Virginie; Mabo, Philippe; Maciejasz, Paweł; Malbert, Charles-Henri; Marijon, Eloi; Maubert, Sandrine; Picq, Chloé; Rossel, Olivier; Bonnet, Jean-Luc

    2016-08-01

    Objective. Neural signals along the vagus nerve (VN) drive many somatic and autonomic functions. The clinical interest of VN stimulation (VNS) is thus potentially huge and has already been demonstrated in epilepsy. However, side effects are often elicited, in addition to the targeted neuromodulation. Approach. This review examines the state of the art of VNS applied to two emerging modulations of autonomic function: heart failure and obesity, especially morbid obesity. Main results. We report that VNS may benefit from improved stimulation delivery using very advanced technologies. However, most of the results from fundamental animal studies still need to be demonstrated in humans.

  4. Structural and functional brain abnormalities place phenocopy frontotemporal dementia (FTD) in the FTD spectrum

    PubMed Central

    Steketee, Rebecca M.E.; Meijboom, Rozanna; Bron, Esther E.; Osse, Robert Jan; de Koning, Inge; Jiskoot, Lize C.; Klein, Stefan; de Jong, Frank Jan; van der Lugt, Aad; van Swieten, John C.; Smits, Marion

    2016-01-01

    Purpose ‘Phenocopy’ frontotemporal dementia (phFTD) patients may clinically mimic the behavioral variant of FTD (bvFTD), but do not show functional decline or abnormalities upon visual inspection of routine neuroimaging. We aimed to identify abnormalities in gray matter (GM) volume and perfusion in phFTD and to assess whether phFTD belongs to the FTD spectrum. We compared phFTD patients with both healthy controls and bvFTD patients. Materials & methods Seven phFTD and 11 bvFTD patients, and 20 age-matched controls underwent structural T1-weighted magnetic resonance imaging (MRI) and 3D pseudo-continuous arterial spin labeling (pCASL) at 3T. Normalized GM (nGM) volumes and perfusion, corrected for partial volume effects, were quantified regionally as well as in the entire supratentorial cortex, and compared between groups taking into account potential confounding effects of gender and scanner. Results PhFTD patients showed cortical atrophy, most prominently in the right temporal lobe. Apart from this regional atrophy, GM volume was generally not different from either controls or from bvFTD. BvFTD however showed extensive frontotemporal atrophy. Perfusion was increased in the left prefrontal cortex compared to bvFTD and to a lesser extent to controls. Conclusion PhFTD and bvFTD show overlapping cortical structural abnormalities indicating a continuum of changes especially in the frontotemporal regions. Together with functional changes suggestive of a compensatory response to incipient pathology in the left prefrontal regions, these findings are the first to support a possible neuropathological etiology of phFTD and suggest that phFTD may be a neurodegenerative disease on the FTD spectrum. PMID:27222795

  5. Perception system and functions for autonomous navigation in a natural environment

    NASA Technical Reports Server (NTRS)

    Chatila, Raja; Devy, Michel; Lacroix, Simon; Herrb, Matthieu

    1994-01-01

    This paper presents the approach, algorithms, and processes we developed for the perception system of a cross-country autonomous robot. After a presentation of the tele-programming context we favor for intervention robots, we introduce an adaptive navigation approach, well suited for the characteristics of complex natural environments. This approach lead us to develop a heterogeneous perception system that manages several different terrain representatives. The perception functionalities required during navigation are listed, along with the corresponding representations we consider. The main perception processes we developed are presented. They are integrated within an on-board control architecture we developed. First results of an ambitious experiment currently underway at LAAS are then presented.

  6. Autonomic Functioning Moderates the Relations between Contextual Factors and Externalizing Behaviors among Inner-city Children

    PubMed Central

    Bubier, Jennifer L.; Drabick, Deborah A. G.; Breiner, Tyler

    2009-01-01

    Although previous research has identified various child-specific and contextual risk factors associated with externalizing behaviors, there is a dearth of literature examining child × context interactions in the prospective prediction of externalizing behaviors. To address this gap, we examined autonomic functioning as a moderator of the relation between contextual factors (i.e., neighborhood cohesion and harsh parental behaviors) and externalizing behaviors. Participants were an ethnic minority, inner-city sample of first through fourth grade children (N = 57, 50% male) and their primary caregivers who participated in two assessments approximately 1 year apart. Results indicated that baseline sympathetic functioning moderated the relation between (a) neighborhood cohesion and externalizing behaviors and (b) harsh parental behaviors and externalizing behaviors. Post-hoc probing of these interactions revealed that higher levels of neighborhood cohesion prospectively predicted (a) higher levels of externalizing behaviors among children with heightened baseline sympathetic functioning, and (b) lower levels of externalizing behaviors among children with attenuated baseline sympathetic functioning. In addition, among children with heightened baseline sympathetic functioning, higher levels of harsh parental behaviors prospectively predicted higher levels of externalizing behaviors. PMID:19685985

  7. Abnormal pulmonary function and associated risk factors in children and adolescents with sickle cell anemia.

    PubMed

    Arteta, Manuel; Campbell, Andrew; Nouraie, Mehdi; Rana, Sohail; Onyekwere, Onyinye C; Ensing, Gregory; Sable, Craig; Dham, Niti; Darbari, Deepika; Luchtman-Jones, Lori; Kato, Gregory J; Gladwin, Mark T; Castro, Oswaldo L; Minniti, Caterina P; Gordeuk, Victor R

    2014-04-01

    Obstructive and restrictive pulmonary changes develop in children with sickle cell disease, but reports conflict as to the type of change that predominates. We prospectively performed spirometry, plethysmography, and lung diffusing capacity in 146 children aged 7 to 20 years with hemoglobin SS or Sβ(0)-thalassemia. Nineteen percent of the patients had obstructive physiology as defined according to guidelines of the American Thoracic Society. In addition, 9% had restrictive physiology and 11% had abnormal but not categorized physiology. Increasing age, patient-reported or family-reported history of asthma or wheezing, and higher lactate dehydrogenase concentration were independent predictors of obstruction as reflected in lower forced expiratory volume in the first second/forced vital capacity. In conclusion, abnormal pulmonary function, most often obstructive, is common in children with hemoglobin SS and Sβ(0)-thalassemia. Full pulmonary function testing should be performed in children with hemoglobin SS or Sβ(0)-thalassemia, especially with history of asthma or wheezing and accentuated elevations in hemolytic markers.

  8. Abnormalities of brain function during a nonverbal theory of mind task in schizophrenia.

    PubMed

    Brunet, Eric; Sarfati, Yves; Hardy-Baylé, Marie-Christine; Decety, Jean

    2003-01-01

    Theory of mind (ToM), the specific ability to attribute thoughts and feelings to oneself and others is generally impaired in schizophrenia. Previous studies demonstrated a deficit of the attribution of intentions to others among patients having formal thought disorder. During nonverbal tasks, such a function requires both the visual perception of human figures and the understanding of their intentions. These processes are considered to involve the superior temporal sulcus and the medial prefrontal cortex, respectively. Are the functional patterns of activation associated with those processes abnormal in schizophrenia? Seven schizophrenic patients on medication performed a nonverbal attribution of intentions task as well as two matched physical logic tasks, with and without human figures, while H2O15 PET-scanning was performed. Data from the patients were compared to those of eight healthy controls matched for verbal IQ and sex. The experimental design allowed dissociating the effect of the perception of human figures from that of the attribution of intentions. During attribution of intentions, significant activations in the right prefrontal cortex were detected in the control subjects. Those activations were not found in the schizophrenic group. However, in both groups, the perception of human figure elicited bilateral activation of the occipitotemporal regions and of the posterior part of the superior temporal sulcus. Schizophrenic patients performing a nonverbal attribution of intentions task have an abnormal cerebral activity. PMID:12887982

  9. Cell Autonomous and Nonautonomous Function of CUL4B in Mouse Spermatogenesis.

    PubMed

    Yin, Yan; Liu, Liren; Yang, Chenyi; Lin, Congxing; Veith, George Michael; Wang, Caihong; Sutovsky, Peter; Zhou, Pengbo; Ma, Liang

    2016-03-25

    CUL4B ubiquitin ligase belongs to the cullin-RING ubiquitin ligase family. Although sharing many sequence and structural similarities, CUL4B plays distinct roles in spermatogenesis from its homologous protein CUL4A. We previously reported that genetic ablation ofCul4ain mice led to male infertility because of aberrant meiotic progression. In the present study, we generated Cul4bgerm cell-specific conditional knock-out (Cul4b(Vasa)),as well asCul4bglobal knock-out (Cul4b(Sox2)) mouse, to investigate its roles in spermatogenesis. Germ cell-specific deletion of Cul4bled to male infertility, despite normal testicular morphology and comparable numbers of spermatozoa. Notably, significantly impaired sperm mobility caused by reduced mitochondrial activity and glycolysis level were observed in the majority of the mutant spermatozoa, manifested by low, if any, sperm ATP production. Furthermore,Cul4b(Vasa)spermatozoa exhibited defective arrangement of axonemal microtubules and flagella outer dense fibers. Our mass spectrometry analysis identified INSL6 as a novel CUL4B substrate in male germ cells, evidenced by its direct polyubiquination and degradation by CUL4B E3 ligase. Nevertheless,Cul4bglobal knock-out males lost their germ cells in an age-dependent manner, implying failure of maintaining the spermatogonial stem cell niche in somatic cells. Taken together, our results show that CUL4B is indispensable to spermatogenesis, and it functions cell autonomously in male germ cells to ensure spermatozoa motility, whereas it functions non-cell-autonomously in somatic cells to maintain spermatogonial stemness. Thus, CUL4B links two distinct spermatogenetic processes to a single E3 ligase, highlighting the significance of ubiquitin modification during spermatogenesis. PMID:26846852

  10. Effect of Mindfulness Meditation on Perceived Stress Scores and Autonomic Function Tests of Pregnant Indian Women

    PubMed Central

    Jain, Reena; Kohli, Sangeeta; Batra, Swaraj

    2016-01-01

    Introduction Various pregnancy complications like hypertension, preeclampsia have been strongly correlated with maternal stress. One of the connecting links between pregnancy complications and maternal stress is mind-body intervention which can be part of Complementary and Alternative Medicine (CAM). Biologic measures of stress during pregnancy may get reduced by such interventions. Aim To evaluate the effect of Mindfulness meditation on perceived stress scores and autonomic function tests of pregnant Indian women. Materials and Methods Pregnant Indian women of 12 weeks gestation were randomised to two treatment groups: Test group with Mindfulness meditation and control group with their usual obstetric care. The effect of Mindfulness meditation on perceived stress scores and cardiac sympathetic functions and parasympathetic functions (Heart rate variation with respiration, lying to standing ratio, standing to lying ratio and respiratory rate) were evaluated on pregnant Indian women. Results There was a significant decrease in perceived stress scores, a significant decrease of blood pressure response to cold pressor test and a significant increase in heart rate variability in the test group (p< 0.05, significant) which indicates that mindfulness meditation is a powerful modulator of the sympathetic nervous system and can thereby reduce the day-to-day perceived stress in pregnant women. Conclusion The results of this study suggest that mindfulness meditation improves parasympathetic functions in pregnant women and is a powerful modulator of the sympathetic nervous system during pregnancy. PMID:27190795

  11. Visually induced nausea causes characteristic changes in cerebral, autonomic and endocrine function in humans

    PubMed Central

    Farmer, Adam D; Ban, Vin F; Coen, Steven J; Sanger, Gareth J; Barker, Gareth J; Gresty, Michael A; Giampietro, Vincent P; Williams, Steven C; Webb, Dominic L; Hellström, Per M; Andrews, Paul L R; Aziz, Qasim

    2015-01-01

    Abstract An integrated understanding of the physiological mechanisms involved in the genesis of nausea remains lacking. We aimed to describe the psychophysiological changes accompanying visually induced motion sickness, using a motion video, hypothesizing that differences would be evident between subjects who developed nausea in comparison to those who did not. A motion, or a control, stimulus was presented to 98 healthy subjects in a randomized crossover design. Validated questionnaires and a visual analogue scale (VAS) were used for the assessment of anxiety and nausea. Autonomic and electrogastrographic activity were measured at baseline and continuously thereafter. Plasma vasopressin and ghrelin were measured in response to the motion video. Subjects were stratified into quartiles based on VAS nausea scores, with the upper and lower quartiles considered to be nausea sensitive and resistant, respectively. Twenty-eight subjects were exposed to the motion video during functional neuroimaging. During the motion video, nausea-sensitive subjects had lower normogastria/tachygastria ratio and cardiac vagal tone but higher cardiac sympathetic index in comparison to the control video. Furthermore, nausea-sensitive subjects had decreased plasma ghrelin and demonstrated increased activity of the left anterior cingulate cortex. Nausea VAS scores correlated positively with plasma vasopressin and left inferior frontal and middle occipital gyri activity and correlated negatively with plasma ghrelin and brain activity in the right cerebellar tonsil, declive, culmen, lingual gyrus and cuneus. This study demonstrates that the subjective sensation of nausea is associated with objective changes in autonomic, endocrine and brain networks, and thus identifies potential objective biomarkers and targets for therapeutic interventions. Key points Nausea is a highly individual and variable experience. The reasons for this variability are incompletely understood although

  12. Pupillary signs in diabetic autonomic neuropathy.

    PubMed Central

    Smith, S E; Smith, S A; Brown, P M; Fox, C; Sönksen, P H

    1978-01-01

    Pupillary function was investigated in 36 insulin-dependent diabetics and 36 controls matched for age and sex. About half of the diabetics had evidence of peripheral somatic or autonomic neuropathy, or both. The diabetic patients had abnormally small pupil diameters in the dark and less fluctuation in pupil size (hippus) during continuous illumination than the controls. They also had reduced reflex responses to light flashes of an intensity adjusted for individual retinal sensitivities. The pupillary findings were compared with results of five tests of cardiovascular function and five tests of peripheral sensory and motor nerve function. Almost all the patients with autonomic neuropathy had pupillary signs, which we therefore conclude are a common manifestation of diabetic autonomic neuropathy. PMID:709128

  13. Cardiovascular Autonomic Nervous System Function and Aerobic Capacity in Type 1 Diabetes

    PubMed Central

    Hägglund, Harriet; Uusitalo, Arja; Peltonen, Juha E.; Koponen, Anne S.; Aho, Jyrki; Tiinanen, Suvi; Seppänen, Tapio; Tulppo, Mikko; Tikkanen, Heikki O.

    2012-01-01

    Impaired cardiovascular autonomic nervous system (ANS) function has been reported in type 1 diabetes (T1D) patients. ANS function, evaluated by heart rate variability (HRV), systolic blood pressure variability (SBPV), and baroreflex sensitivity (BRS), has been linked to aerobic capacity (VO2peak) in healthy subjects, but this relationship is unknown in T1D. We examined cardiovascular ANS function at rest and during function tests, and its relations to VO2peak in T1D individuals. Ten T1D patients (34 ± 7 years) and 11 healthy control (CON; 31 ± 6 years) age and leisure-time physical activity-matched men were studied. ANS function was recorded at rest and during active standing and handgrip. Determination of VO2peak was obtained with a graded cycle ergometer test. During ANS recordings SBPV, BRS, and resting HRV did not differ between groups, but alpha1 responses to maneuvers in detrended fluctuation analyses were smaller in T1D (active standing; 32%, handgrip; 20%, medians) than in CON (active standing; 71%, handgrip; 54%, p < 0.05). VO2peak was lower in T1D (36 ± 4 ml kg−1 min−1) than in CON (45 ± 9 ml kg−1 min−1, p < 0.05). Resting HRV measures, RMSSD, HF, and SD1 correlated with VO2peak in CON (p < 0.05) and when analyzing groups together. These results suggest that T1D had lower VO2peak, weaker HRV response to maneuvers, but not impaired cardiovascular ANS function at rest compared with CON. Resting parasympathetic cardiac activity correlated with VO2peak in CON but not in T1D. Detrended fluctuation analysis could be a sensitive detector of changes in cardiac ANS function in T1D. PMID:22973238

  14. Forebrain neural patterns associated with sex differences in autonomic and cardiovascular function during baroreceptor unloading.

    PubMed

    Kimmerly, D S; Wong, S; Menon, R; Shoemaker, J K

    2007-02-01

    Generally, women demonstrate smaller autonomic and cardiovascular reactions to stress, compared with men. The mechanism of this sex-dependent difference is unknown, although reduced baroreflex sensitivity may be involved. Recently, we identified a cortical network associated with autonomic cardiovascular responses to baroreceptor unloading in men. The current investigation examined whether differences in the neural activity patterns within this network were related to sex-related physiological responses to lower body negative pressure (LBNP, 5, 15, and 35 mmHg). Forebrain activity in healthy men and women (n = 8 each) was measured using functional magnetic resonance imaging with blood oxygen level-dependent (BOLD) contrast. Stroke volume (SV), heart rate (HR), and muscle sympathetic nerve activity (MSNA) were collected on a separate day. Men had larger decreases in SV than women (P < 0.01) during 35 mmHg LBNP only. At 35 mmHg LBNP, HR increased more in males then females (9 +/- 1 beats/min vs. 4 +/- 1 beats/min, P < 0.05). Compared with women, increases in total MSNA were similar at 15 mmHg LBNP but greater during 35 mmHg LBNP in men [1,067 +/- 123 vs. 658 +/- 103 arbitrary units (au), P < 0.05]. BOLD signal changes (P < 0.005, uncorrected) were identified within discrete forebrain regions associated with these sex-specific HR and MSNA responses. Men had larger increases in BOLD signal within the right insula and dorsal anterior cingulate cortex than women. Furthermore, men demonstrated greater BOLD signal reductions in the right amygdala, left insula, ventral anterior cingulate, and ventral medial prefrontal cortex vs. women. The greater changes in forebrain activity in men vs. women may have contributed to the elevated HR and sympathetic responses observed in men during 35 mmHg LBNP. PMID:17272671

  15. Visually induced nausea causes characteristic changes in cerebral, autonomic and endocrine function in humans.

    PubMed

    Farmer, Adam D; Ban, Vin F; Coen, Steven J; Sanger, Gareth J; Barker, Gareth J; Gresty, Michael A; Giampietro, Vincent P; Williams, Steven C; Webb, Dominic L; Hellström, Per M; Andrews, Paul L R; Aziz, Qasim

    2015-03-01

    An integrated understanding of the physiological mechanisms involved in the genesis of nausea remains lacking. We aimed to describe the psychophysiological changes accompanying visually induced motion sickness, using a motion video, hypothesizing that differences would be evident between subjects who developed nausea in comparison to those who did not. A motion, or a control, stimulus was presented to 98 healthy subjects in a randomized crossover design. Validated questionnaires and a visual analogue scale (VAS) were used for the assessment of anxiety and nausea. Autonomic and electrogastrographic activity were measured at baseline and continuously thereafter. Plasma vasopressin and ghrelin were measured in response to the motion video. Subjects were stratified into quartiles based on VAS nausea scores, with the upper and lower quartiles considered to be nausea sensitive and resistant, respectively. Twenty-eight subjects were exposed to the motion video during functional neuroimaging. During the motion video, nausea-sensitive subjects had lower normogastria/tachygastria ratio and cardiac vagal tone but higher cardiac sympathetic index in comparison to the control video. Furthermore, nausea-sensitive subjects had decreased plasma ghrelin and demonstrated increased activity of the left anterior cingulate cortex. Nausea VAS scores correlated positively with plasma vasopressin and left inferior frontal and middle occipital gyri activity and correlated negatively with plasma ghrelin and brain activity in the right cerebellar tonsil, declive, culmen, lingual gyrus and cuneus. This study demonstrates that the subjective sensation of nausea is associated with objective changes in autonomic, endocrine and brain networks, and thus identifies potential objective biomarkers and targets for therapeutic interventions.

  16. Abnormal functional connectivity in focal hand dystonia: Mutual information analysis in EEG

    PubMed Central

    Jin, Seung-Hyun; Lin, Peter; Auh, Sungyoung; Hallett, Mark

    2011-01-01

    The aim of the present study was to investigate functional connectivity (FC) in focal hand dystonia (FHD) patients to understand the pathophysiology underlying their abnormality in movement. We recorded EEG from 58 electrodes in 15 FHD patients and 15 healthy volunteers during rest and a simple finger-tapping task that did not induce any dystonic symptoms. We investigated the mutual information (MI), which provides a quantitative measure of linear and nonlinear coupling, in the alpha, beta and gamma bands. Mean MI of all 58 channels and mean of the channels of interest (COIs) representative of regional FC over sensorimotor areas (C3, CP3, C4, CP4, FCz and Cz) were evaluated. For both groups, we found enhanced MI during the task compared to the rest condition specifically in the beta and gamma bands for mean MI of all channels, and in all bands for mean MI of COIs. Comparing the FHD patients to the healthy volunteers, for both rest and task, there was reduced MI in the beta band for both mean MI of all channels and mean MI of COIs. Regarding the properties of the connectivity in the beta band, we found that the majority of the MI differences were from linear connectivity. The abnormal beta band FC in FHD patients suggests deficient brain connectivity. PMID:21506166

  17. Calorie Restriction Prevents Metabolic Aging Caused by Abnormal SIRT1 Function in Adipose Tissues.

    PubMed

    Xu, Cheng; Cai, Yu; Fan, Pengcheng; Bai, Bo; Chen, Jie; Deng, Han-Bing; Che, Chi-Ming; Xu, Aimin; Vanhoutte, Paul M; Wang, Yu

    2015-05-01

    Adipose tissue is a pivotal organ determining longevity, due largely to its role in maintaining whole-body energy homeostasis and insulin sensitivity. SIRT1 is a NAD-dependent protein deacetylase possessing antiaging activities in a wide range of organisms. The current study demonstrates that mice with adipose tissue-selective overexpression of hSIRT1(H363Y), a dominant-negative mutant that disrupts endogenous SIRT1 activity, show accelerated development of metabolic aging. These mice, referred to as Adipo-H363Y, exhibit hyperglycemia, dyslipidemia, ectopic lipid deposition, insulin resistance, and glucose intolerance at a much younger age than their wild-type littermates. The metabolic defects of Adipo-H363Y are associated with abnormal epigenetic modifications and chromatin remodeling in their adipose tissues, as a result of excess accumulation of biotin, which inhibits endogenous SIRT1 activity, leading to increased inflammation, cellularity, and collagen deposition. The enzyme acetyl-CoA carboxylase 2 plays an important role in biotin accumulation within adipose tissues of Adipo-H363Y. Calorie restriction prevents biotin accumulation, abolishes abnormal histone biotinylation, and completely restores the metabolic and adipose functions of Adipo-H363Y. The effects are mimicked by short-term restriction of biotin intake, an approach potentially translatable to humans for maintaining the epigenetic and chromatin remodeling capacity of adipose tissues and preventing aging-associated metabolic disorders.

  18. Functional and Structural Abnormalities in Deferoxamine Retinopathy: A Review of the Literature

    PubMed Central

    Di Nicola, Maura; Barteselli, Giulio; Dell'Arti, Laura; Ratiglia, Roberto; Viola, Francesco

    2015-01-01

    Deferoxamine mesylate (DFO) is the most commonly used iron-chelating agent to treat transfusion-related hemosiderosis. Despite the clear advantages for the use of DFO, numerous DFO-related systemic toxicities have been reported in the literature, as well as sight-threatening ocular toxicity involving the retinal pigment epithelium (RPE). The damage to the RPE can lead to visual field defects, color-vision defects, abnormal electrophysiological tests, and permanent visual deterioration. The purpose of this review is to provide an updated summary of the ocular findings, including both functional and structural abnormalities, in DFO-treated patients. In particular, we pay particular attention to analyzing results of multimodal technologies for retinal imaging, which help ophthalmologists in the early diagnosis and correct management of DFO retinopathy. Fundus autofluorescence, for example, is not only useful for screening patients at high-risk of DFO retinopathy, but is also a prerequisite for identify specific high-risk patterns of RPE changes that are relevant for the prognosis of the disease. In addition, optical coherence tomography may have a clinical usefulness in detecting extent and location of different retinal changes in DFO retinopathy. Finally, this review wants to underline the need for universally approved guidelines for screening and followup of this particular disease. PMID:26167477

  19. Positron Emission Tomography Reveals Abnormal Topological Organization in Functional Brain Network in Diabetic Patients

    PubMed Central

    Qiu, Xiangzhe; Zhang, Yanjun; Feng, Hongbo; Jiang, Donglang

    2016-01-01

    Recent studies have demonstrated alterations in the topological organization of structural brain networks in diabetes mellitus (DM). However, the DM-related changes in the topological properties in functional brain networks are unexplored so far. We therefore used fluoro-D-glucose positron emission tomography (FDG-PET) data to construct functional brain networks of 73 DM patients and 91 sex- and age-matched normal controls (NCs), followed by a graph theoretical analysis. We found that both DM patients and NCs had a small-world topology in functional brain network. In comparison to the NC group, the DM group was found to have significantly lower small-world index, lower normalized clustering coefficients and higher normalized characteristic path length. Moreover, for diabetic patients, the nodal centrality was significantly reduced in the right rectus, the right cuneus, the left middle occipital gyrus, and the left postcentral gyrus, and it was significantly increased in the orbitofrontal region of the left middle frontal gyrus, the left olfactory region, and the right paracentral lobule. Our results demonstrated that the diabetic brain was associated with disrupted topological organization in the functional PET network, thus providing functional evidence for the abnormalities of brain networks in DM. PMID:27303259

  20. Cognitive, neurophysiological, and functional correlates of proverb interpretation abnormalities in schizophrenia.

    PubMed

    Kiang, Michael; Light, Gregory A; Prugh, Jocelyn; Coulson, Seana; Braff, David L; Kutas, Marta

    2007-07-01

    A hallmark of schizophrenia is impaired proverb interpretation, which could be due to: (1) aberrant activation of disorganized semantic associations, or (2) working memory (WM) deficits. We assessed 18 schizophrenia patients and 18 normal control participants on proverb interpretation, and evaluated these two hypotheses by examining within patients the correlations of proverb interpretation with disorganized symptoms and auditory WM, respectively. Secondarily, we also explored the relationships between proverb interpretation and a spectrum of cognitive functions including auditory sensory-memory encoding (as indexed by the mismatch negativity (MMN) event-related brain potential (ERP)); executive function; and social/occupational function. As expected, schizophrenia patients produced less accurate and less abstract descriptions of proverbs than did controls. These proverb interpretation difficulties in patients were not significantly correlated with disorganization or other symptom factors, but were significantly correlated (p < .05) with WM impairment, as well as with impairments in sensory-memory encoding, executive function, and social/occupational function. These results offer no support for disorganized associations in abnormal proverb interpretation in schizophrenia, but implicate WM deficits, perhaps as a part of a syndrome related to generalized frontal cortical dysfunction. PMID:17521483

  1. Positron Emission Tomography Reveals Abnormal Topological Organization in Functional Brain Network in Diabetic Patients.

    PubMed

    Qiu, Xiangzhe; Zhang, Yanjun; Feng, Hongbo; Jiang, Donglang

    2016-01-01

    Recent studies have demonstrated alterations in the topological organization of structural brain networks in diabetes mellitus (DM). However, the DM-related changes in the topological properties in functional brain networks are unexplored so far. We therefore used fluoro-D-glucose positron emission tomography (FDG-PET) data to construct functional brain networks of 73 DM patients and 91 sex- and age-matched normal controls (NCs), followed by a graph theoretical analysis. We found that both DM patients and NCs had a small-world topology in functional brain network. In comparison to the NC group, the DM group was found to have significantly lower small-world index, lower normalized clustering coefficients and higher normalized characteristic path length. Moreover, for diabetic patients, the nodal centrality was significantly reduced in the right rectus, the right cuneus, the left middle occipital gyrus, and the left postcentral gyrus, and it was significantly increased in the orbitofrontal region of the left middle frontal gyrus, the left olfactory region, and the right paracentral lobule. Our results demonstrated that the diabetic brain was associated with disrupted topological organization in the functional PET network, thus providing functional evidence for the abnormalities of brain networks in DM. PMID:27303259

  2. Abnormal GABAergic Function and Face Processing in Schizophrenia: A Pharmacologic-fMRI Study

    PubMed Central

    Tso, Ivy F.; Fang, Yu; Phan, K. Luan; Welsh, Robert C.; Taylor, Stephan F.

    2015-01-01

    The involvement of the gamma-aminobutyric acid (GABA) system in schizophrenia is suggested by postmortem studies and the common use of GABA receptor-potentiating agents in treatment. In a recent study, we used a benzodiazepine challenge to demonstrate abnormal GABAergic function during processing of negative visual stimuli in schizophrenia. This study extended this investigation by mapping GABAergic mechanisms associated with face processing and social appraisal in schizophrenia using a benzodiazepine challenge. Fourteen stable, medicated schizophrenia/schizoaffective patients (SZ) and 13 healthy controls (HC) underwent functional MRI using the blood oxygenation level-dependent (BOLD) technique while they performed the Socio-emotional Preference Task (SePT) on emotional face stimuli (“Do you like this face?”). Participants received single-blinded intravenous saline and lorazepam (LRZ) in two separate sessions separated by 1-3 weeks. Both SZ and HC recruited medial prefrontal cortex/anterior cingulate during the SePT, relative to gender identification. A significant drug by group interaction was observed in the medial occipital cortex, such that SZ showed increased BOLD signal to LRZ challenge, while HC showed an expected decrease of signal; the interaction did not vary by task. The altered BOLD response to LRZ challenge in SZ was significantly correlated with increased negative affect across multiple measures. The altered response to LRZ challenge suggests that abnormal face processing and negative affect in SZ are associated with altered GABAergic function in the visual cortex, underscoring the role of impaired visual processing in socio-emotional deficits in schizophrenia. PMID:26363970

  3. Abnormal GABAergic function and face processing in schizophrenia: A pharmacologic-fMRI study.

    PubMed

    Tso, Ivy F; Fang, Yu; Phan, K Luan; Welsh, Robert C; Taylor, Stephan F

    2015-10-01

    The involvement of the gamma-aminobutyric acid (GABA) system in schizophrenia is suggested by postmortem studies and the common use of GABA receptor-potentiating agents in treatment. In a recent study, we used a benzodiazepine challenge to demonstrate abnormal GABAergic function during processing of negative visual stimuli in schizophrenia. This study extended this investigation by mapping GABAergic mechanisms associated with face processing and social appraisal in schizophrenia using a benzodiazepine challenge. Fourteen stable, medicated schizophrenia/schizoaffective patients (SZ) and 13 healthy controls (HC) underwent functional MRI using the blood oxygenation level-dependent (BOLD) technique while they performed the Socio-emotional Preference Task (SePT) on emotional face stimuli ("Do you like this face?"). Participants received single-blinded intravenous saline and lorazepam (LRZ) in two separate sessions separated by 1-3weeks. Both SZ and HC recruited medial prefrontal cortex/anterior cingulate during the SePT, relative to gender identification. A significant drug by group interaction was observed in the medial occipital cortex, such that SZ showed increased BOLD signal to LRZ challenge, while HC showed an expected decrease of signal; the interaction did not vary by task. The altered BOLD response to LRZ challenge in SZ was significantly correlated with increased negative affect across multiple measures. The altered response to LRZ challenge suggests that abnormal face processing and negative affect in SZ are associated with altered GABAergic function in the visual cortex, underscoring the role of impaired visual processing in socio-emotional deficits in schizophrenia. PMID:26363970

  4. Abnormal Functional Connectivity of Amygdala in Late-Onset Depression Was Associated with Cognitive Deficits

    PubMed Central

    Yue, Yingying; Yuan, Yonggui; Hou, Zhenghua; Jiang, Wenhao; Bai, Feng; Zhang, Zhijun

    2013-01-01

    Background Major depressive disorder (MDD) is associated with decreased function of cortico-limbic circuits, which play important roles in the pathogenesis of MDD. Abnormal functional connectivity (FC) with the amygdala, which is involved in cortico-limbic circuits, has also been observed in MDD. However, little is known about connectivity alterations in late-onset depression (LOD) or whether disrupted connectivity is correlated with cognitive impairment in LOD. Methods and Results A total of twenty-two LOD patients and twenty-two matched healthy controls (HC) underwent neuropsychological tests and resting state functional magnetic resonance imaging (rs-fMRI). Regional homogeneity (ReHo) and FC with bilateral amygdala seeds were used to analyze blood oxygen level-dependent fMRI data between two groups. Compared with HC, LOD patients showed decreased ReHo in the right middle frontal gyrus and left superior frontal gyrus. In the LOD group, the left amygdala had decreased FC with the right middle frontal gyrus and the left superior frontal gyrus in the amygdala positive network, and it had increased FC with the right post-central gyrus in the amygdala negative network. However, significantly reduced FC with the right amygdala was observed in the right middle occipital gyrus in the amygdala negative network. Further correlative analyses revealed that decreased FC between the amygdala and the right middle occipital gyrus was negatively correlated with the verbal fluency test (VFT, r = −0.485, P = 0.022) and the digit span test (DST, r = −0.561, P = 0.007). Conclusions Our findings of reduced activity of the prefrontal gyrus and abnormal FC with the bilateral amygdala may be key markers of cognitive dysfunction in LOD patients. PMID:24040385

  5. Emotional Responses to Odors in Children with High-Functioning Autism: Autonomic Arousal, Facial Behavior and Self-Report

    ERIC Educational Resources Information Center

    Legisa, Jasna; Messinger, Daniel S.; Kermol, Enzo; Marlier, Luc

    2013-01-01

    Although emotional functioning is impaired in children with autism, it is unclear if this impairment is due to difficulties with facial expression, autonomic responsiveness, or the verbal description of emotional states. To shed light on this issue, we examined responses to pleasant and unpleasant odors in eight children (8-14 years) with…

  6. Novel heart rate parameters for the assessment of autonomic nervous system function in premature infants.

    PubMed

    Lucchini, M; Fifer, W P; Sahni, R; Signorini, M G

    2016-09-01

    Autonomic nervous system (ANS) balance is a key factor in homeostatic control of cardiac activity, breathing and certain reflex reactions such as coughing, sneezing and swallowing and thus plays a crucial role for survival. ANS impairment has been related to many neonatal pathologies, including sudden infant death syndrome (SIDS). Moreover, some conditions have been identified as risk factors for SIDS, such as prone sleep position. There is an urgent need for timely and non-invasive assessment of ANS function in at-risk infants. Systematic measurement of heart rate variability (HRV) offers an optimal approach to access indirectly both sympathetic and parasympathetic influences on ANS functioning. In this paper, data from premature infants collected in a sleep physiology laboratory in the NICU are presented: traditional and novel approaches to HRV analyses are applied and compared in order to evaluate their relative merits in the assessment of ANS activity and the influence of sleep position. Indices from time domain and nonlinear approaches contributed as markers of physiological development in premature infants. Moreover, significant differences were observed as a function of sleep position. PMID:27480495

  7. Autonomous gathering of livestock using a multi-functional sensor network platform

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In this paper we develop algorithms and hardware for the autonomous gathering of cattle. We present a comparison of three different autonomous gathering algorithms that employ sound and/or electric stimuli to guide the cattle. We evaluate these algorithms in simulation by extending previous behavior...

  8. Abnormalities of Reproductive Function in Male Obesity Before and After Bariatric Surgery-A Comprehensive Review.

    PubMed

    Rosenblatt, Alberto; Faintuch, Joel; Cecconello, Ivan

    2015-07-01

    Young males represent one of the populations with the steepest increases in the incidence of obesity. They are also prone to significant derangements in sexual health and fertility. Despite a growing number of reports about female reproductive health, in the setting of bariatric surgery, males have received much less attention. In the current review of reproductive abnormalities in severe obese males before and after bariatric surgery, erectile function, hypothalamic-pituitary-gonadal axis status, sex hormones, semen quality, fertility and assisted reproductive techniques, along with analysis of adipokines, gut hormones, and environmental factors are addressed. Available evidence about weight loss benefits, both medical and surgical, are highlighted, along with perspectives for future investigations, which may be relevant for the patient, for the couple, and for the community alike.

  9. Structural and Functional Coronary Artery Abnormalities in Patients With Vasospastic Angina Pectoris.

    PubMed

    Ong, Peter; Aziz, Ahmed; Hansen, Henrik Steen; Prescott, Eva; Athanasiadis, Anastasios; Sechtem, Udo

    2015-01-01

    Coronary spasm is involved in many clinical scenarios, such as stable angina, acute coronary syndrome, sudden cardiac death, non-ischemic cardiomyopathy, arrhythmia and syncope. In recent years, imaging tools such as computerized tomographic angiography, intravascular ultrasound or optical coherence tomography have been applied to study the coronary pathology in patients with vasospastic angina. Patients with vasospastic angina represent a heterogeneous cohort of patients with regard to the extent of concomitant coronary atherosclerosis. They share the common pathophysiological phenomenon of vascular smooth muscle hyperreactivity leading to spasm caused by various factors that may also overlap. Focal coronary spasm is related to epicardial atherosclerosis and in the presence of obstructive coronary artery disease it may be useful to treat the lesion to prevent further spasm. The aim of this article is to review structural and functional coronary artery abnormalities in patients with vasospastic angina.

  10. Functional Connectivity Abnormalities of Brain Regions with Structural Deficits in Young Adult Male Smokers

    PubMed Central

    Bu, Limei; Yu, Dahua; Su, Shaoping; Ma, Yao; von Deneen, Karen M.; Luo, Lin; Zhai, Jinquan; Liu, Bo; Cheng, Jiadong; Guan, Yanyan; Li, Yangding; Bi, Yanzhi; Xue, Ting; Lu, Xiaoqi; Yuan, Kai

    2016-01-01

    Smoking is one of the most prevalent dependence disorders. Previous studies have detected structural and functional deficits in smokers. However, few studies focused on the changes of resting state functional connectivity (RSFC) of the brain regions with structural deficits in young adult smokers. Twenty-six young adult smokers and 26 well-matched healthy non-smokers participated in our study. Voxel-based morphometry (VBM) and RSFC were employed to investigate the structural and functional changes in young adult smokers. Compared with healthy non-smokers, young smokers showed increased gray matter (GM) volume in the left putamen and decreased GM volume in the left anterior cingulate cortex (ACC). Moreover, GM volume in the left ACC has a negative correlation trend with pack-years and GM volume in the left putamen was positively correlated with pack-years. The left ACC and putamen with abnormal volumes were chosen as the regions of interest (ROIs) for the RSFC analysis. We found that smokers showed increased RSFC between the left ACC and right amygdala and between the left putamen and right anterior insula. We revealed structural and functional deficits within the frontostriatal circuits in young smokers, which may shed new insights into the neural mechanisms of smoking. PMID:27757078

  11. Abnormalities in Parentally Rated Executive Function in Methamphetamine/Polysubstance Exposed Children

    PubMed Central

    Piper, Brian J.; Acevedo, Summer F.; Kolchugina, Galena K.; Butler, Robert W.; Corbett, Selena M.; Honeycutt, Elizabeth B.; Craytor, Michael J.; Raber, Jacob

    2011-01-01

    Methamphetamine/polysubstance abuse in women of childbearing age is a major concern because of the potential long-term detrimental effects on the brain function of the fetus following in utero exposure. A battery of established tests, including the Wechsler Abbreviated Scale of Intelligence, Conners’ Continuous Performance Test II, Behavioral Rating Inventory of Executive Function, the CMS Family Pictures and Dot Location tests, the Spatial Span test from the WISC-IV-Integrated, and a recently developed spatial learning and memory measure (Memory Island), was used to assess the effects of prenatal drug exposure on neurobehavioral performance. Participants were 7 to 9 year old children from similar socioeconomic backgrounds who either had (N = 31) or had not (N = 35) been exposed to methamphetamine/polysubstance during pregnancy. Compared to unexposed children, exposed children showed pronounced elevations (i.e. more problems) in parental ratings of executive function, including behavioral regulation and metacognition. Exposed children also exhibited subtle reductions in spatial performance in the Memory Island test. In contrast, IQ, Spatial Span, Family Pictures, Dot Location, and vigilance performance was unaffected by prenatal drug exposure history. Thus, children of women who reported using methamphetamine and other recreational drugs during pregnancy showed a selective profile of abnormalities in parentally rated executive function. PMID:21334365

  12. Abnormalities in parentally rated executive function in methamphetamine/polysubstance exposed children.

    PubMed

    Piper, Brian J; Acevedo, Summer F; Kolchugina, Galena K; Butler, Robert W; Corbett, Selena M; Honeycutt, Elizabeth B; Craytor, Michael J; Raber, Jacob

    2011-05-01

    Methamphetamine/polysubstance abuse in women of childbearing age is a major concern because of the potential long-term detrimental effects on the brain function of the fetus following in utero exposure. A battery of established tests, including the Wechsler Abbreviated Scale of Intelligence, Conners' Continuous Performance Test II, Behavioral Rating Inventory of Executive Function, the CMS Family Pictures and Dot Location tests, the Spatial Span test from the WISC-IV-Integrated, and a recently developed spatial learning and memory measure (Memory Island), was used to assess the effects of prenatal drug exposure on neurobehavioral performance. Participants were 7 to 9 year old children from similar socioeconomic backgrounds who either had (N=31) or had not (N=35) been exposed to methamphetamine/polysubstance during pregnancy. Compared to unexposed children, exposed children showed pronounced elevations (i.e. more problems) in parental ratings of executive function, including behavioral regulation and metacognition. Exposed children also exhibited subtle reductions in spatial performance in the Memory Island test. In contrast, IQ, Spatial Span, Family Pictures, Dot Location, and vigilance performance were unaffected by prenatal drug exposure history. Thus, children of women who reported using methamphetamine and other recreational drugs during pregnancy showed a selective profile of abnormalities in parentally rated executive function.

  13. Abnormal functional connectivity of the medial cortex in euthymic bipolar II disorder.

    PubMed

    Marchand, William R; Lee, James N; Johnson, Susanna; Gale, Phillip; Thatcher, John

    2014-06-01

    This project utilized functional MRI (fMRI) and a motor activation paradigm to investigate neural circuitry in euthymic bipolar II disorder. We hypothesized that circuitry involving the cortical midline structures (CMS) would demonstrate abnormal functional connectivity. Nineteen subjects with recurrent bipolar disorder and 18 controls were studied using fMRI and a motor activation paradigm. We used functional connectivity analyses to identify circuits with aberrant connectivity. We found increased functional connectivity among bipolar subjects compared to healthy controls in two CMS circuits. One circuit included the medial aspect of the left superior frontal gyrus and the dorsolateral region of the left superior frontal gyrus. The other included the medial aspect of the right superior frontal gyrus, the dorsolateral region of the left superior frontal gyrus and the right medial frontal gyrus and surrounding region. Our results indicate that CMS circuit dysfunction persists in the euthymic state and thus may represent trait pathology. Future studies should address whether these circuits contribute to relapse of illness. Our results also suggest the possibility that aberrations of superior frontal circuitry may impact default mode network and cognitive processes.

  14. Abnormal striatal resting-state functional connectivity in adolescents with obsessive-compulsive disorder.

    PubMed

    Bernstein, Gail A; Mueller, Bryon A; Schreiner, Melinda Westlund; Campbell, Sarah M; Regan, Emily K; Nelson, Peter M; Houri, Alaa K; Lee, Susanne S; Zagoloff, Alexandra D; Lim, Kelvin O; Yacoub, Essa S; Cullen, Kathryn R

    2016-01-30

    Neuroimaging research has implicated abnormalities in cortico-striatal-thalamic-cortical (CSTC) circuitry in pediatric obsessive-compulsive disorder (OCD). In this study, resting-state functional magnetic resonance imaging (R-fMRI) was used to investigate functional connectivity in the CSTC circuitry in adolescents with OCD. Imaging was obtained with the Human Connectome Project (HCP) scanner using newly developed pulse sequences which allow for higher spatial and temporal resolution. Fifteen adolescents with OCD and 13 age- and gender-matched healthy controls (ages 12-19) underwent R-fMRI on the 3T HCP scanner. Twenty-four minutes of resting-state scans (two consecutive 12-min scans) were acquired. We investigated functional connectivity of the striatum using a seed-based, whole brain approach with anatomically-defined seeds placed in the bilateral caudate, putamen, and nucleus accumbens. Adolescents with OCD compared with controls exhibited significantly lower functional connectivity between the left putamen and a single cluster of right-sided cortical areas including parts of the orbitofrontal cortex, inferior frontal gyrus, insula, and operculum. Preliminary findings suggest that impaired striatal connectivity in adolescents with OCD in part falls within the predicted CSTC network, and also involves impaired connections between a key CSTC network region (i.e., putamen) and key regions in the salience network (i.e., insula/operculum). The relevance of impaired putamen-insula/operculum connectivity in OCD is discussed. PMID:26674413

  15. Functional brain abnormalities in psychiatric disorders: neural mechanisms to detect and resolve cognitive conflict and interference.

    PubMed

    Melcher, Tobias; Falkai, Peter; Gruber, Oliver

    2008-11-01

    In the present article, we review functional neuroimaging studies on interference processing and performance monitoring in three groups of psychiatric disorders, (1) mood disorders, (2) schizophrenia, and (3) obsessive-compulsive disorder (OCD). Ad (1) Behavioral performance measures suggest an impaired interference resolution capability in symptomatic bipolar disorder patients. A series of neuroimaging analyses found alterations in the ACC-DLPFC system in mood disorder (unipolar depressed and bipolar) patients, putatively reflective of an abnormal interplay of monitoring and executive neurocognitive functions. Other studies of euthymic bipolar patients showed relatively decreased interference-related activation in rostroventral PFC which conceivably underlies defective inhibitory control. Ad (2) Behavioral Stroop studies revealed a specific performance pattern of schizophrenia patients (normal RT interference but increased error interference and RT facilitation) suggestive of a deficit in ignoring irrelevant (word) information. Moreover, reduced/absent behavioral post-error and post-conflict adaptation effects suggest alterations in performance monitoring and/or adjustment capability in these patients. Neuroimaging findings converge to suggest a disorder-related abnormal neurophysiology in ACC which consistently showed conflict- and error-related hypoactivation that, however, appeared to be modulated by different factors. Moreover, studies suggest a specific deficit in context processing in schizophrenia, evidently related to activation reduction in DLPFC. Ad (3) Behavioral findings provide evidence for impaired interference resolution in OCD. Neuroimaging results consistently showed conflict- and error-related ACC hyperactivation which--conforming OCD pathogenesis models--can be conclusively interpreted as reflecting overactive performance monitoring. Taken together, interference resolution and performance monitoring appeared to be fruitful concepts in the

  16. Abnormal activation of the motor cortical network in idiopathic scoliosis demonstrated by functional MRI.

    PubMed

    Domenech, Julio; García-Martí, G; Martí-Bonmatí, L; Barrios, C; Tormos, J M; Pascual-Leone, A

    2011-07-01

    The aetiology of idiopathic scoliosis (IS) remains unknown, but there is growing support for the possibility of an underlying neurological disorder. Functional magnetic resonance imaging (fMRI) can characterize the abnormal activation of the sensorimotor brain network in movement disorders and could provide further insights into the neuropathogenesis of IS. Twenty subjects were included in the study; 10 adolescents with IS (mean age of 15.2, 8 girls and 2 boys) and 10 age-matched healthy controls. The average Cobb angle of the primary curve in the IS patients was 35° (range 27°-55°). All participants underwent a block-design fMRI experiment in a 1.5-Tesla MRI scanner to explore cortical activation following a simple motor task. Rest periods alternated with activation periods during which participants were required to open and close their hand at an internally paced rate of approximately 1 Hz. Data were analyzed with Statistical Parametric Mapping (SPM5) including age, sex and laterality as nuisance variables to minimise the presence of bias in the results. Compared to controls, IS patients showed significant increases in blood oxygenation level dependent (BOLD) activity in contralateral supplementary motor area when performing the motor task with either hand. No significant differences were observed when testing between groups in the functional activation in the primary motor cortex, premotor cortex and somatosensory cortex. Additionally, the IS group showed a greater interhemispheric asymmetry index than the control group (0.30 vs. 0.13, p < 0.001). This study demonstrates an abnormal pattern of brain activation in secondary motor areas during movement execution in patients with IS. These findings support the hypothesis that a sensorimotor integration disorder underlies the pathogenesis of IS.

  17. A study of autonomic nervous system status in children of asthmatic parents.

    PubMed

    Kumar, Seema; Babbar, Rashmi; Varshney, Ved Prakash; Daga, Mradul Kumar; Dalvi, Vrinda Shirish

    2012-01-01

    Asthmatic patients are known to have autonomic abnormalities. This study evaluated the status of autonomic nervous system in children of asthmatic parents for any occurrences of autonomic abnormalities that are known to occur in asthma. In this study autonomic function tests were conducted in children (5 to 10 years of age) divided into two groups: Group A had children from non-asthmatic parents as Control Group and Group B had children from asthmatic parents as Test Group. Both the groups had healthy children showing no clinical signs and symptoms of asthma, allergy or any illness known to affect autonomic nervous system. In response to various parasympathetic function tests (S/L ratio, 30:15 ratio, valsalva ratio and tachycardia ratio) and sympathetic function tests (handgrip test and cold pressor test) done, the two groups did not show any statistically significant dissimilarity for any of the parameters. The results of our study showed that there were no autonomic abnormalities found in the children of asthmatic parents. Thus this study indicates that the autonomic defects seen in asthmatics could be secondary to asthma and not because of autonomic aberrations inheritance in asthmatics as shown by earlier few studies supporting the possible role of inherited automatic reactivity in the pathogenesis and progression of asthma. PMID:23029968

  18. Designing Dual-functionalized Gels for Self-reconfiguration and Autonomous Motion

    NASA Astrophysics Data System (ADS)

    Kuksenok, Olga; Balazs, Anna C.

    2015-04-01

    Human motion is enabled by the concerted expansion and contraction of interconnected muscles that are powered by inherent biochemical reactions. One of the challenges in the field of biomimicry is eliciting this form of motion from purely synthetic materials, which typically do not generate internalized reactions to drive mechanical action. Moreover, for practical applications, this bio-inspired motion must be readily controllable. Herein, we develop a computational model to design a new class of polymer gels where structural reconfigurations and internalized reactions are intimately linked to produce autonomous motion, which can be directed with light. These gels contain both spirobenzopyran (SP) chromophores and the ruthenium catalysts that drive the oscillatory Belousov-Zhabotinsky (BZ) reaction. Importantly, both the SP moieties and the BZ reaction are photosensitive. When these dual-functionalized gels are exposed to non-uniform illumination, the localized contraction of the gel (due to the SP moieties) in the presence of traveling chemical waves (due to the BZ reaction) leads to new forms of spontaneous, self-sustained movement, which cannot be achieved by either of the mono-functionalized networks.

  19. Designing Dual-functionalized Gels for Self-reconfiguration and Autonomous Motion

    SciTech Connect

    Kuksenok, Olga; Balazs, Anna C.

    2015-04-30

    Human motion is enabled by the concerted expansion and contraction of interconnected muscles that are powered by inherent biochemical reactions. One of the challenges in the field of biomimicry is eliciting this form of motion from purely synthetic materials, which typically do not generate internalized reactions to drive mechanical action. Moreover, for practical applications, this bio-inspired motion must be readily controllable. Herein, we develop a computational model to design a new class of polymer gels where structural reconfigurations and internalized reactions are intimately linked to produce autonomous motion, which can be directed with light. These gels contain both spirobenzopyran (SP) chromophores and the ruthenium catalysts that drive the oscillatory Belousov-Zhabotinsky (BZ) reaction. Importantly, both the SP moieties and the BZ reaction are photosensitive. When these dual-functionalized gels are exposed to non-uniform illumination, the localized contraction of the gel (due to the SP moieties) in the presence of traveling chemical waves (due to the BZ reaction) leads to new forms of spontaneous, self-sustained movement, which cannot be achieved by either of the mono-functionalized networks.

  20. Designing Dual-functionalized Gels for Self-reconfiguration and Autonomous Motion

    DOE PAGES

    Kuksenok, Olga; Balazs, Anna C.

    2015-04-30

    Human motion is enabled by the concerted expansion and contraction of interconnected muscles that are powered by inherent biochemical reactions. One of the challenges in the field of biomimicry is eliciting this form of motion from purely synthetic materials, which typically do not generate internalized reactions to drive mechanical action. Moreover, for practical applications, this bio-inspired motion must be readily controllable. Herein, we develop a computational model to design a new class of polymer gels where structural reconfigurations and internalized reactions are intimately linked to produce autonomous motion, which can be directed with light. These gels contain both spirobenzopyran (SP)more » chromophores and the ruthenium catalysts that drive the oscillatory Belousov-Zhabotinsky (BZ) reaction. Importantly, both the SP moieties and the BZ reaction are photosensitive. When these dual-functionalized gels are exposed to non-uniform illumination, the localized contraction of the gel (due to the SP moieties) in the presence of traveling chemical waves (due to the BZ reaction) leads to new forms of spontaneous, self-sustained movement, which cannot be achieved by either of the mono-functionalized networks.« less

  1. A Rare Presentation of Autonomously Functioning Papillary Thyroid Cancer: Malignancy in Marine-Lenhart Syndrome Nodule

    PubMed Central

    Uludag, Mehmet; Aygun, Nurcihan; Ozel, Alper; Yener Ozturk, Feyza; Karasu, Rabia; Ozguven, Banu Yilmaz; Citgez, Bulent; Mihmanli, Mehmet; Isgor, Adnan

    2016-01-01

    Objective. Marine-Lenhart Syndrome (MLS) is defined as concomitant occurrence of autonomously functioning thyroid nodule (AFTN) with Graves' disease (GD). Malignancy in a functional nodule is rare. We aimed to present an extremely rare case of papillary thyroid cancer in a MLS nodule with lateral lymph node metastases. Case. A 43-year-old male presented with hyperthyroidism and Graves' ophthalmopathy. On Tc99m pertechnetate scintigraphy, a hyperactive nodule in the left upper thyroid pole was detected and the remaining tissue showed a mildly increased uptake. The ultrasonography demonstrated 15.5 × 13.5 × 12 mm sized hypoechoic nodule in the left upper pole of the thyroid and round lymph nodes on the left side of the neck. Fine needle aspiration biopsy (FNAB) of the nodule and lymph node revealed cytological findings consistent with papillary cancer. Total thyroidectomy with central and left modified radical neck dissection was performed. On pathologic examination, two foci of micropapillary cancer were detected. The skip metastases were present in three lymph nodes on the neck. Conclusion. AFTN can be seen rarely in association with GD. It is not possible to exclude malignancy due to the clinical and imaging findings. In the presence of suspicious clinical and sonographic features, FNAB should be performed. PMID:27110424

  2. Designing Dual-functionalized Gels for Self-reconfiguration and Autonomous Motion.

    PubMed

    Kuksenok, Olga; Balazs, Anna C

    2015-01-01

    Human motion is enabled by the concerted expansion and contraction of interconnected muscles that are powered by inherent biochemical reactions. One of the challenges in the field of biomimicry is eliciting this form of motion from purely synthetic materials, which typically do not generate internalized reactions to drive mechanical action. Moreover, for practical applications, this bio-inspired motion must be readily controllable. Herein, we develop a computational model to design a new class of polymer gels where structural reconfigurations and internalized reactions are intimately linked to produce autonomous motion, which can be directed with light. These gels contain both spirobenzopyran (SP) chromophores and the ruthenium catalysts that drive the oscillatory Belousov-Zhabotinsky (BZ) reaction. Importantly, both the SP moieties and the BZ reaction are photosensitive. When these dual-functionalized gels are exposed to non-uniform illumination, the localized contraction of the gel (due to the SP moieties) in the presence of traveling chemical waves (due to the BZ reaction) leads to new forms of spontaneous, self-sustained movement, which cannot be achieved by either of the mono-functionalized networks. PMID:25924823

  3. Gray Matter Abnormalities in Temporal Lobe Epilepsy: Relationships with Resting-State Functional Connectivity and Episodic Memory Performance

    PubMed Central

    Doucet, Gaelle E.; He, Xiaosong; Sperling, Michael; Sharan, Ashwini; Tracy, Joseph I.

    2016-01-01

    Temporal lobe epilepsy (TLE) affects multiple brain regions through evidence from both structural (gray matter; GM) and functional connectivity (FC) studies. We tested whether these structural abnormalities were associated with FC abnormalities, and assessed the ability of these measures to explain episodic memory impairments in this population. A resting-state and T1 sequences were acquired on 94 (45 with mesial temporal pathology) TLE patients and 50 controls, using magnetic resonance imaging (MRI) technique. A voxel-based morphometry analysis was computed to determine the GM volume differences between groups (right, left TLE, controls). Resting-state FC between the abnormal GM volume regions was computed, and compared between groups. Finally, we investigated the relation between EM, GM and FC findings. Patients with and without temporal pathology were analyzed separately. The results revealed reduced GM volume in multiple regions in the patients relative to the controls. Using FC, we found the abnormal GM regions did not display abnormal functional connectivity. Lastly, we found in left TLE patients, verbal episodic memory was associated with abnormal left posterior hippocampus volume, while in right TLE, non-verbal episodic memory was better predicted by resting-state FC measures. This study investigated TLE abnormalities using a multi-modal approach combining GM, FC and neurocognitive measures. We did not find that the GM abnormalities were functionally or abnormally connected during an inter-ictal resting state, which may reflect a weak sensitivity of functional connectivity to the epileptic network. We provided evidence that verbal and non-verbal episodic memory in left and right TLE patients may have distinct relationships with structural and functional measures. Lastly, we provide data suggesting that in the setting of occult, non-lesional right TLE pathology, a coupling of structural and functional abnormalities in extra-temporal/non-ictal regions is

  4. Neurological abnormalities and neurocognitive functions in healthy elder people: A structural equation modeling analysis

    PubMed Central

    2011-01-01

    Background/Aims Neurological abnormalities have been reported in normal aging population. However, most of them were limited to extrapyramidal signs and soft signs such as motor coordination and sensory integration have received much less attention. Very little is known about the relationship between neurological soft signs and neurocognitive function in healthy elder people. The current study aimed to examine the underlying relationships between neurological soft signs and neurocognition in a group of healthy elderly. Methods One hundred and eighty healthy elderly participated in the current study. Neurological soft signs were evaluated with the subscales of Cambridge Neurological Inventory. A set of neurocognitive tests was also administered to all the participants. Structural equation modeling was adopted to examine the underlying relationship between neurological soft signs and neurocognition. Results No significant differences were found between the male and female elder people in neurocognitive function performances and neurological soft signs. The model fitted well in the elderly and indicated the moderate associations between neurological soft signs and neurocognition, specifically verbal memory, visual memory and working memory. Conclusions The neurological soft signs are more or less statistically equivalent to capture the similar information done by conventional neurocognitive function tests in the elderly. The implication of these findings may serve as a potential neurological marker for the early detection of pathological aging diseases or related mental status such as mild cognitive impairment and Alzheimer's disease. PMID:21827719

  5. The autonomic laboratory

    NASA Technical Reports Server (NTRS)

    Low, P. A.; Opfer-Gehrking, T. L.

    1999-01-01

    The autonomic nervous system can now be studied quantitatively, noninvasively, and reproducibly in a clinical autonomic laboratory. The approach at the Mayo Clinic is to study the postganglionic sympathetic nerve fibers of peripheral nerve (using the quantitative sudomotor axon reflex test [QSART]), the parasympathetic nerves to the heart (cardiovagal tests), and the regulation of blood pressure by the baroreflexes (adrenergic tests). Patient preparation is extremely important, since the state of the patient influences the results of autonomic function tests. The autonomic technologist in this evolving field needs to have a solid core of knowledge of autonomic physiology and autonomic function tests, followed by training in the performance of these tests in a standardized fashion. The range and utilization of tests of autonomic function will likely continue to evolve.

  6. Effects of sleep deprivation on autonomic and endocrine functions throughout the day and on exercise tolerance in the evening.

    PubMed

    Konishi, Masayuki; Takahashi, Masaki; Endo, Naoya; Numao, Shigeharu; Takagi, Shun; Miyashita, Masashi; Midorikawa, Taishi; Suzuki, Katsuhiko; Sakamoto, Shizuo

    2013-01-01

    The aim of this study was to investigate the effects of sleep deprivation on autonomic and endocrine functions during the day and on exercise tolerance in the evening. Ten healthy young males completed two, 2-day control and sleep deprivation trials. For the control trial, participants were allowed normal sleep from 23:00 to 07:00 h. For the sleep deprivation trial, participants did not sleep for 34 h. Autonomic activity was measured from 19:00 h on day 1 to 16:00 h on day 2 by frequency-domain measures of heart rate variability. Endocrine function was examined by measuring adrenocorticotropic hormone and cortisol from venous blood samples collected on day 2 at 09:00, 13:00, and 17:00 h and immediately after an exercise tolerance testing. Autonomic regulation, particularly parasympathetic regulation estimated from the high-frequency component of heart rate variability analysis, was significantly higher in the sleep deprivation trial than in the control trial in the morning and afternoon of day 2. Plasma adrenocorticotropic hormone concentrations were significantly higher at 09:00 and 13:00 h of day 2 under sleep deprivation. Heart rate during exercise was significantly lower following sleep deprivation. Therefore, the effects of sleep deprivation on autonomic regulation depend on the time of the day.

  7. Alteration of cardiac autonomic function in patients with newly diagnosed epilepsy.

    PubMed

    Goit, Rajesh K; Jha, Santosh K; Pant, Bhawana N

    2016-06-01

    The aim of the study was to determine if heart rate variability (HRV) showed any changes in patients with newly diagnosed epilepsy in comparison with controls. Sixty-five patients with epilepsy (38 males and 27 females), aged 30-50 years, who had never previously received treatment with antiepileptic drugs were eligible for inclusion in this study. Resting electrocardiogram (ECG) at spontaneous respiration was recorded for 5 min in supine position. Time-domain analysis, frequency-domain analysis, and Poincare plot of HRV were recorded from ECG In time-domain measures, the square root of the mean of the sum of the squares of differences between adjacent RR intervals (RMSSD) and percentage of consecutive RR intervals that differ by more than 50 msec (pNN50) were significantly less in patients with epilepsy. In frequency-domain measures, high frequency [(HF) msec(2)], HF (nu), and low frequency [LF (msec(2))] were significantly less in patients with epilepsy while LF (nu) and LF/HF were significantly high in patients with epilepsy. In Poincare plot, standard deviation perpendicular to line of Poincare plot (SD1) and standard deviation along the line of entity in Poincare plot (SD2) were significantly less in patients with epilepsy. Our results suggest that epileptic patients have an impact on the cardiac autonomic function as measured by HRV.

  8. Olfactory stimulatory with grapefruit and lavender oils change autonomic nerve activity and physiological function.

    PubMed

    Nagai, Katsuya; Niijima, Akira; Horii, Yuko; Shen, Jiao; Tanida, Mamoru

    2014-10-01

    This review summarizes the effects of olfactory stimulation with grapefruit and lavender oils on autonomic nerve activity and physiological function. Olfactory stimulation with the scent of grapefruit oil (GFO) increases the activity of sympathetic nerves that innervate white and brown adipose tissues, the adrenal glands, and the kidneys, decreases the activity of the gastric vagal nerve in rats and mice. This results in an increase in lipolysis, thermogenesis, and blood pressure, and a decrease in food intake. Olfactory stimulation with the scent of lavender oil (LVO) elicits the opposite changes in nerve activity and physiological variables. Olfactory stimulation with scent of limonene, a component of GFO, and linalool, a component of LVO, has similar effects to stimulation with GFO and LVO, respectively. The histamine H1-receptor antagonist, diphenhydramine, abolishes all GFO-induced changes in nerve activity and physiological variables, and the hitstamine H3-receptor antagonist, thioperamide, eliminates all LVO-induced changes. Lesions to the hypothalamic suprachiasmatic nucleus and anosmic treatment with ZnSO4 also abolish all GFO- and LVO-induced changes. These findings indicate that limonene and linalool might be the active substances in GFO and LVO, and suggest that the suprachiasmatic nucleus and histamine are involved in mediating the GFO- and LVO-induced changes in nerve activity and physiological variables. PMID:25002406

  9. Race Differences in Age-Trends of Autonomic Nervous System Functioning

    PubMed Central

    Fuller-Rowell, Thomas E.; Williams, David R.; Love, Gayle D.; McKinley, Paula S.; Sloan, Richard P.; Ryff, Carol D.

    2013-01-01

    Objective The objective of this study was to consider race differences in age-trends of autonomic nervous system functioning, using a national dataset with a broad age range. Methods Measures of baseline heart rate variability (HRV) and HRV reactivity were derived from electrocardiograph (ECG) recordings taken at rest and during cognitive stress tasks. Age-trends in HRV and HRV reactivity were compared among 204 African Americans and 833 Whites ages 34 to 83 years (M=53.7, SD=11.4), before and after controlling for socioeconomic status (SES). Results For HRV-reactivity, age-trends were steeper among African Americans and lower-SES participants than Whites and higher-SES participants. For baseline HRV, age-trends varied by SES but not race. Discussion Results relating to HRV-reactivity (but not baseline HRV) were consistent with hypotheses suggesting that African Americans are exposed to higher levels of stress and experience accelerated declines in health across the life span. The relevance of the findings to research on social stress and health disparities is discussed. PMID:23781017

  10. Olfactory stimulatory with grapefruit and lavender oils change autonomic nerve activity and physiological function.

    PubMed

    Nagai, Katsuya; Niijima, Akira; Horii, Yuko; Shen, Jiao; Tanida, Mamoru

    2014-10-01

    This review summarizes the effects of olfactory stimulation with grapefruit and lavender oils on autonomic nerve activity and physiological function. Olfactory stimulation with the scent of grapefruit oil (GFO) increases the activity of sympathetic nerves that innervate white and brown adipose tissues, the adrenal glands, and the kidneys, decreases the activity of the gastric vagal nerve in rats and mice. This results in an increase in lipolysis, thermogenesis, and blood pressure, and a decrease in food intake. Olfactory stimulation with the scent of lavender oil (LVO) elicits the opposite changes in nerve activity and physiological variables. Olfactory stimulation with scent of limonene, a component of GFO, and linalool, a component of LVO, has similar effects to stimulation with GFO and LVO, respectively. The histamine H1-receptor antagonist, diphenhydramine, abolishes all GFO-induced changes in nerve activity and physiological variables, and the hitstamine H3-receptor antagonist, thioperamide, eliminates all LVO-induced changes. Lesions to the hypothalamic suprachiasmatic nucleus and anosmic treatment with ZnSO4 also abolish all GFO- and LVO-induced changes. These findings indicate that limonene and linalool might be the active substances in GFO and LVO, and suggest that the suprachiasmatic nucleus and histamine are involved in mediating the GFO- and LVO-induced changes in nerve activity and physiological variables.

  11. The Autonomic System Functional State Predicts Responsiveness in Disorder of Consciousness.

    PubMed

    Riganello, Francesco; Cortese, Maria D; Dolce, Giuliano; Lucca, Lucia F; Sannita, Walter G

    2015-07-15

    Diagnosis and early prognosis of the vegetative state/unresponsive wakefulness syndrome (VS/UWS) and its differentiation from the minimally-conscious state still rest on the clinical observation of responsiveness. The incidence of established clinical indicators of responsiveness also has proven variable in the single subject and is correlated to measures of heart rate variability (HRV) describing the sympathetic/parasympathetic balance. We tested responsiveness when the HRV descriptors nuLF and peakLF were or were not in the ranges with highest incidence of response based on findings from previous studies (10.0-70.0 and 0.05-0.11 Hz, respectively). Testing was blind by The Coma Recovery Scale-revised in the two conditions and in two experimental sessions with a one-week interval. The incidence of responses was not randomly distributed in the "response" and "no-response" conditions (McNemar test; p < 0.0001). The observed incidence in the "response" condition (visual: 55.1%; auditory: 51.5%) was higher than predicted statistically (32.1%) or described in previous clinical studies; responses were only occasional in the "no-response" condition (visual, 15.9%; auditory, 13.4%). Models validated the predictability with high accuracy. The current clinical criteria for diagnosis and prognosis based on neurological signs should be reconsidered, including variability over time and the autonomic system functional state, which could also qualify per se as an independent indicator for diagnosis and prognosis.

  12. A double-blind atropine trial for active learning of autonomic function.

    PubMed

    Fry, Jeffrey R; Burr, Steven A

    2011-12-01

    Here, we describe a human physiology laboratory class measuring changes in autonomic function over time in response to atropine. Students use themselves as subjects, generating ownership and self-interest in the learning as well as directly experiencing the active link between physiology and pharmacology in people. The class is designed to concomitantly convey the importance of bias in experimentation by adopting a double-blind placebo-controlled approach. We have used this class effectively in various forms with ∼600 students receiving atropine over the last 16 yr. This class has received favorable feedback from staff and students of medicine, pharmacy, and neuroscience, and we recommend it for such undergraduates. The learning objectives that students are expected to achieve are to be able to 1) know the ethical, safety, and hygiene requirements for using human volunteers as subjects; 2) implement and explain a double-blind placebo-controlled trial; 3) design, agree, and execute a protocol for making (and accurately recording) precise reproducible measurements of pulse rate, pupil diameter, and salivary flow; 4) evaluate the importance of predose periods and measurement consistency to detect effects (including any reversibility) after an intervention; 5) experience direct cause-and-effect relationships integrating physiology with pharmacology in people; 6) calculate appropriate summary statistics to describe the data and determine the data's statistical significance; 7) recognize normal variability both within and between subjects in baseline physiological parameters and also recognize normal variability in response to pharmacological treatment; 8) infer the distribution and role of muscarinic receptors in the autonomic nervous system with respect to the heart, eye, and mouth; 9) identify and explain the clinical significance of differences in effect due to the route and formulation of atropine; 10) produce and deliver a concise oral presentation of

  13. Diastolic abnormalities in systemic sclerosis: evidence for associated defective cardiac functional reserve.

    PubMed Central

    Valentini, G; Vitale, D F; Giunta, A; Maione, S; Gerundo, G; Arnese, M; Tirri, E; Pelaggi, N; Giacummo, A; Tirri, G; Condorelli, M

    1996-01-01

    OBJECTIVE: To investigate the pattern of diastolic abnormalities in patients with systemic sclerosis (SSc) and the relationship between impaired ventricular filling and systolic function. METHODS: Twenty four patients with SSc underwent M-mode and two dimensional echocardiography using echo-Doppler and gated blood pool cardiac angiography, both at rest and after exercise. RESULTS: An impaired diastolic relaxation of the left ventricle was detected in 10 of the 24 patients with SSc. Left ventricular ejection fraction at rest in these 10 patients with impaired ventricular filling did not differ from that in the remaining 14 patients, but eight of the 10 failed to increase their ejection fraction during exercise, compared with two of the 14 with normal ventricular filling (p = 0.003). CONCLUSION: Impaired relaxation of the left ventricle is a recently described feature of scleroderma heart disease. Diastolic dysfunction in SSc could depend on myocardial fibrosis or myocardial ischaemia, or both. It was found to be associated with a defective cardiac functional reserve. However, its prognostic significance remains to be clarified. PMID:8774164

  14. Reward Abnormalities Among Women with Full and Subthreshold Bulimia Nervosa: A Functional Magnetic Resonance Imaging Study

    PubMed Central

    Bohon, Cara; Stice, Eric

    2010-01-01

    Objective To test the hypothesis that women with full and subthreshold bulimia nervosa show abnormal neural activation in response to food intake and anticipated food intake relative to healthy control women. Method Females with and without full/subthreshold bulimia nervosa recruited from the community (N = 26) underwent functional magnetic resonance imaging (fMRI) during receipt and anticipated receipt of chocolate milkshake and a tasteless control solution. Results Women with bulimia nervosa showed trends for less activation than healthy controls in the right anterior insula in response to anticipated receipt of chocolate milkshake (versus tasteless solution) and in the left middle frontal gyrus, right posterior insula, right precentral gyrus, and right mid dorsal insula in response to consumptions of milkshake (versus tasteless solution). Discussion Bulimia nervosa may be related to potential hypo-functioning of the brain reward system, which may lead these individuals to binge eat to compensate for this reward deficit, though the hypo-responsivity might be a result of a history of binge eating highly palatable foods. PMID:21997421

  15. Kinesin family 17 (osmotic avoidance abnormal-3) is dispensable for photoreceptor morphology and function.

    PubMed

    Jiang, Li; Tam, Beatrice M; Ying, Guoxing; Wu, Sen; Hauswirth, William W; Frederick, Jeanne M; Moritz, Orson L; Baehr, Wolfgang

    2015-12-01

    In Caenorhabditis elegans, homodimeric [kinesin family (KIF) 17, osmotic avoidance abnormal-3 (OSM-3)] and heterotrimeric (KIF3) kinesin-2 motors are required to establish sensory cilia by intraflagellar transport (IFT) where KIF3 and KIF17 cooperate to build the axoneme core and KIF17 builds the distal segments. However, the function of KIF17 in vertebrates is unresolved. We expressed full-length and motorless KIF17 constructs in mouse rod photoreceptors using adeno-associated virus in Xenopus laevis rod photoreceptors using a transgene and in ciliated IMCD3 cells. We found that tagged KIF17 localized along the rod outer segment axoneme when expressed in mouse and X. laevis photoreceptors, whereas KIF3A was restricted to the proximal axoneme. Motorless KIF3A and KIF17 mutants caused photoreceptor degeneration, likely through dominant negative effects on IFT. KIF17 mutant lacking the motor domain translocated to nuclei after exposure of a C-terminal nuclear localization signal. Germ-line deletion of Kif17 in mouse did not affect photoreceptor function. A rod-specific Kif3/Kif17 double knockout mouse demonstrated that KIF17 and KIF3 do not act synergistically and did not prevent rhodopsin trafficking to rod outer segments. In summary, the nematode model of KIF3/KIF17 cooperation apparently does not apply to mouse photoreceptors in which the photosensory cilium is built exclusively by KIF3. PMID:26229057

  16. Validation of Spectral Analysis as a Noninvasive Tool to Assess Autonomic Regulation of Cardiovascular Function

    NASA Technical Reports Server (NTRS)

    Knapp, Charles F.; Evans, Joyce M.

    1996-01-01

    A major focus of our program has been to develop a sensitive noninvasive procedure to quantify early weightlessness-induced changes in cardiovascular function or potential dysfunction. Forty studies of healthy young volunteers (10 men and 10 women, each studied twice) were conducted to determine changes in the sympatho-vagal balance of autonomic control of cardiovascular regulation during graded headward and footward blood volume shifts. Changes in sympatho-vagal balance were classified by changes in the mean levels and spectral content of cardiovascular variables and verified by changes in circulating levels of catecholamines and pancreatic polypeptide. Possible shifts in intra/extravascular fluid were assessed from changes in hematocrit and plasma mass density while changes in the stimulus to regulate plasma volume were determined from Plasma Renin Activity (PRA). Autonomic blockade was used to unmask the relative contribution of sympathetic and parasympathetic efferent influences in response to 10 min each of 0, 20 and 40 mmHg Lower Body Negative Pressure (LBNP) and 15 and 30 mmHg Positive Pressure (LBPP). The combination of muscarinic blockade with graded LBNP and LBPP was used to evoke graded increases and decreases in sympathetic activity without parasympathetic contributions. The combination of beta blockade with graded LBNP and LBPP was used to produce graded increases and decreases in parasympathetic activity without beta sympathetic contributions. Finally, a combination of both beta and muscarinic blockades with LBNP and LBPP was used to determine the contribution from other, primarily alpha adrenergic, sources. Mean values, spectral analyses and time frequency analysis of R-R interval (HR), Arterial Pressure (AP), peripheral blood flow (RF), Stroke Volume (SV) and peripheral resistance (TPR) were performed for all phases of the study. Skin blood Flow (SF) was also measured in other studies and similarly analyzed. Spectra were examined for changes in

  17. Abnormal functional specialization within medial prefrontal cortex in high-functioning autism: a multi-voxel similarity analysis

    PubMed Central

    Meuwese, Julia D.I.; Towgood, Karren J.; Frith, Christopher D.; Burgess, Paul W.

    2009-01-01

    Multi-voxel pattern analyses have proved successful in ‘decoding’ mental states from fMRI data, but have not been used to examine brain differences associated with atypical populations. We investigated a group of 16 (14 males) high-functioning participants with autism spectrum disorder (ASD) and 16 non-autistic control participants (12 males) performing two tasks (spatial/verbal) previously shown to activate medial rostral prefrontal cortex (mrPFC). Each task manipulated: (i) attention towards perceptual versus self-generated information and (ii) reflection on another person's mental state (‘mentalizing'versus ‘non-mentalizing’) in a 2 × 2 design. Behavioral performance and group-level fMRI results were similar between groups. However, multi-voxel similarity analyses revealed strong differences. In control participants, the spatial distribution of activity generalized significantly between task contexts (spatial/verbal) when examining the same function (attention/mentalizing) but not when comparing different functions. This pattern was disrupted in the ASD group, indicating abnormal functional specialization within mrPFC, and demonstrating the applicability of multi-voxel pattern analysis to investigations of atypical populations. PMID:19174370

  18. Maternal-infant interaction and autonomic function in healthy infants and infants with transposition of the great arteries.

    PubMed

    Harrison, Tondi M; Ferree, Allison

    2014-12-01

    The quality of maternal-infant interaction is a critical factor in the development of infants' autonomic function and social engagement skills. In this secondary data analysis, relationships among infant and maternal affect and behavior and quality of dyadic interaction, as measured by the Parent-Child Early Relational Assessment, and infant autonomic function, as measured by heart rate variability, were examined during feeding at 2 weeks and 2 months of age in 16 healthy infants and in 15 infants with transposition of the great arteries (TGA). Contrary to previous research, at 2 weeks infant age, mothers of infants with TGA had significantly higher scores in affect and behavior than did mothers of healthy infants. The affect and behavior and quality of dyadic interaction of infants with TGA also did not differ from that of healthy infants. Although infants' social engagement skills did not differ by health condition (TGA or healthy), these skills did differ by parasympathetic nervous system function: infants better able to suppress vagal activity with challenge had more positive and less dysregulated affect and behavior, regardless of health status. These findings suggest that maternal-infant interactions for some cardiac disease subgroups may not differ from healthy dyads. Additional research is required to identify both healthy and ill infants with delayed autonomic maturation and to develop and test interventions to enhance critical interactive functions.

  19. Timing of obstetrical assistance affects peripartal cardiac autonomic function and early maternal behavior of dairy cows.

    PubMed

    Kovács, Levente; Kézér, Fruzsina Luca; Ruff, Ferenc; Szenci, Ottó

    2016-10-15

    Peripartal autonomic nervous system function and early maternal behavior were investigated in 79 multiparous Holstein-Friesian cows. Animals were allocated into four groups based on the technology of calving management: 1) unassisted calving in a group pen (UCG; N=19), 2) unassisted calving in an individual pen (UCI; N=21), 3) assisted calving with appropriately timed obstetrical assistance (ACA; N=20), and 4) assisted calving with premature obstetrical assistance (ACP; N=19). Heart rate, the high frequency (HF) component of heart rate variability (HRV) as a measure of vagal activity and the ratio between the low frequency (LF) and HF components (LF/HF ratio) as a parameter of sympathetic nervous system activity were calculated. Heart rate and HRV parameters were presented as areas under the curves (AUC) for the following periods: 1) prepartum period (between 96h before the onset of calving restlessness and the onset of restlessness), 2) parturition (between the onset calving restlessness and delivery), and 3) postpartum period (during a 48-h period after delivery). Pain-related behaviors were recorded during parturition (i.e., the occurrence of vocalization and stretching the neck towards the abdomen) and during a 2-h observation period after calving (i.e., the occurrence of vocalization, stretching the neck towards the abdomen and the duration of standing with an arched back). Early maternal behavior was observed during the first 2h following calving as follows: 1) latency and duration of sniffing calf's head/body, and 2) latency and duration of licking calf's head/body. No difference was found across groups in autonomic function before the onset of calving restlessness. Area under the heart rate curve was higher in ACP cows during parturition (39.6±2.5beats/min×h) compared to UCG, UCI and ACA animals (AUC=13.1±0.9beats/min×h, AUC=22.3±1.4beats/min×h and AUC=25.0±2.1beats/min×h, respectively). Area under the heart rate curve did not differ across the UCG

  20. Autonomous and Autonomic Swarms

    NASA Technical Reports Server (NTRS)

    Hinchey, Michael G.; Rash, James L.; Truszkowski, Walter F.; Rouff, Christopher A.; Sterritt, Roy

    2005-01-01

    A watershed in systems engineering is represented by the advent of swarm-based systems that accomplish missions through cooperative action by a (large) group of autonomous individuals each having simple capabilities and no global knowledge of the group s objective. Such systems, with individuals capable of surviving in hostile environments, pose unprecedented challenges to system developers. Design and testing and verification at much higher levels will be required, together with the corresponding tools, to bring such systems to fruition. Concepts for possible future NASA space exploration missions include autonomous, autonomic swarms. Engineering swarm-based missions begins with understanding autonomy and autonomicity and how to design, test, and verify systems that have those properties and, simultaneously, the capability to accomplish prescribed mission goals. Formal methods-based technologies, both projected and in development, are described in terms of their potential utility to swarm-based system developers.

  1. Relationship of abnormal Tamm-Horsfall glycoprotein localization to renal morphology and function.

    PubMed

    Chambers, R; Groufsky, A; Hunt, J S; Lynn, K L; McGiven, A R

    1986-07-01

    Tamm-Horsfall glycoprotein (TH) distribution was studied using a biotin-avidin immunoperoxidase technique in renal biopsies from 166 consecutive patients and 8 normal kidneys. Tubulointerstitial damage was independently assessed and graded. In 109 patients TH antibodies were measured by ELISA and in 30 of these urinary TH and beta 2-microglobulin excretions were measured by radioimmunoassay. In 124 biopsies only distal tubular epithelium and casts were stained. Glomerular space (8) or interstitial (34) deposits were seen in 42 biopsies; 16/68 with glomerulonephritis, 4/14 with systemic vasculitis, 12/33 with chronic interstitial nephritis, 1/8 with acute interstitial nephritis, 9/43 with other nephropathies. There was no correlation between TH distribution and the degree of tubulointerstitial damage (p greater than 0.5), urinary TH excretion (p greater than 0.05), urinary beta 2-microglobulin excretion (p greater than 0.05), glomerular filtration rate, urinary concentrating ability, or the incidence of pyuria. TH antibodies did not correlate with TH distribution (p greater than 0.5) or the degree of tubulointerstitial damage. Abnormal TH distribution showed no statistical relationship to the degree of tubulointerstitial damage, changes in renal function or levels of TH antibodies.

  2. Claudin-16 Deficiency Impairs Tight Junction Function in Ameloblasts, Leading to Abnormal Enamel Formation.

    PubMed

    Bardet, Claire; Courson, Frédéric; Wu, Yong; Khaddam, Mayssam; Salmon, Benjamin; Ribes, Sandy; Thumfart, Julia; Yamaguti, Paulo M; Rochefort, Gael Y; Figueres, Marie-Lucile; Breiderhoff, Tilman; Garcia-Castaño, Alejandro; Vallée, Benoit; Le Denmat, Dominique; Baroukh, Brigitte; Guilbert, Thomas; Schmitt, Alain; Massé, Jean-Marc; Bazin, Dominique; Lorenz, Georg; Morawietz, Maria; Hou, Jianghui; Carvalho-Lobato, Patricia; Manzanares, Maria Cristina; Fricain, Jean-Christophe; Talmud, Deborah; Demontis, Renato; Neves, Francisco; Zenaty, Delphine; Berdal, Ariane; Kiesow, Andreas; Petzold, Matthias; Menashi, Suzanne; Linglart, Agnes; Acevedo, Ana Carolina; Vargas-Poussou, Rosa; Müller, Dominik; Houillier, Pascal; Chaussain, Catherine

    2016-03-01

    Claudin-16 protein (CLDN16) is a component of tight junctions (TJ) with a restrictive distribution so far demonstrated mainly in the kidney. Here, we demonstrate the expression of CLDN16 also in the tooth germ and show that claudin-16 gene (CLDN16) mutations result in amelogenesis imperfecta (AI) in the 5 studied patients with familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC). To investigate the role of CLDN16 in tooth formation, we studied a murine model of FHHNC and showed that CLDN16 deficiency led to altered secretory ameloblast TJ structure, lowering of extracellular pH in the forming enamel matrix, and abnormal enamel matrix protein processing, resulting in an enamel phenotype closely resembling human AI. This study unravels an association of FHHNC owing to CLDN16 mutations with AI, which is directly related to the loss of function of CLDN16 during amelogenesis. Overall, this study indicates for the first time the importance of a TJ protein in tooth formation and underlines the need to establish a specific dental follow-up for these patients.

  3. Neonatal lupus manifests as isolated neutropenia and mildly abnormal liver functions.

    PubMed

    Kanagasegar, Sivalingam; Cimaz, Rolando; Kurien, Biji T; Brucato, Antonio; Scofield, R Hal

    2002-01-01

    Neonatal lupus is characterized by typical clinical features and the presence of maternal autoantibodies. Mothers can have systemic lupus erythematosus (SLE) or Sjögren's syndrome, but are commonly not affected with any clinical disease. The major clinical manifestations in the infants are cardiac, dermatological and hepatic with rare instances of hemolytic anemia, thrombocytopenia or neutropenia. We describe an infant born to a mother with anti-Ro and anti-La, who had neutropenia and mildly abnormal liver functions without other major clinical features of neonatal lupus such as cardiac or dermatological manifestations. Neutropenia improved as maternal antibody was metabolized. Antibodies from both the infant and mother bound intact neutrophils, and this binding was inhibited by 60 kDa Ro. These data imply neutropenia may be an isolated manifestation of neonatal lupus. We studied the anti-Ro antibodies of 2 other mothers who gave birth to infants with complete congenital heart block and neutropenia. Their sera also bound neutrophils. Because healthy infants do not commonly undergo complete blood counts, the incidence of neutropenia among infants of anti-Ro-positive mothers may be much higher than previously recognized. Furthermore, although other factors may contribute, these data suggest that anti-60 kDa Ro is directly involved in the pathogenesis of neutropenia.

  4. Serotonin transporter variant drives preventable gastrointestinal abnormalities in development and function

    PubMed Central

    Margolis, Kara Gross; Li, Zhishan; Stevanovic, Korey; Saurman, Virginia; Anderson, George M.; Snyder, Isaac; Blakely, Randy D.; Gershon, Michael D.

    2016-01-01

    Autism spectrum disorder (ASD) is an increasingly common behavioral condition that frequently presents with gastrointestinal (GI) disturbances. It is not clear, however, how gut dysfunction relates to core ASD features. Multiple, rare hyperfunctional coding variants of the serotonin (5-HT) transporter (SERT, encoded by SLC6A4) have been identified in ASD. Expression of the most common SERT variant (Ala56) in mice increases 5-HT clearance and causes ASD-like behaviors. Here, we demonstrated that Ala56-expressing mice display GI defects that resemble those seen in mice lacking neuronal 5-HT. These defects included enteric nervous system hypoplasia, slow GI transit, diminished peristaltic reflex activity, and proliferation of crypt epithelial cells. An opposite phenotype was seen in SERT-deficient mice and in progeny of WT dams given the SERT antagonist fluoxetine. The reciprocal phenotypes that resulted from increased or decreased SERT activity support the idea that 5-HT signaling regulates enteric neuronal development and can, when disturbed, cause long-lasting abnormalities of GI function. Administration of a 5-HT4 agonist to Ala56 mice during development prevented Ala56-associated GI perturbations, suggesting that excessive SERT activity leads to inadequate 5-HT4–mediated neurogenesis. We propose that deficient 5-HT signaling during development may contribute to GI and behavioral features of ASD. The consequences of therapies targeting SERT during pregnancy warrant further evaluation. PMID:27111230

  5. Serotonin transporter variant drives preventable gastrointestinal abnormalities in development and function.

    PubMed

    Margolis, Kara Gross; Li, Zhishan; Stevanovic, Korey; Saurman, Virginia; Israelyan, Narek; Anderson, George M; Snyder, Isaac; Veenstra-VanderWeele, Jeremy; Blakely, Randy D; Gershon, Michael D

    2016-06-01

    Autism spectrum disorder (ASD) is an increasingly common behavioral condition that frequently presents with gastrointestinal (GI) disturbances. It is not clear, however, how gut dysfunction relates to core ASD features. Multiple, rare hyperfunctional coding variants of the serotonin (5-HT) transporter (SERT, encoded by SLC6A4) have been identified in ASD. Expression of the most common SERT variant (Ala56) in mice increases 5-HT clearance and causes ASD-like behaviors. Here, we demonstrated that Ala56-expressing mice display GI defects that resemble those seen in mice lacking neuronal 5-HT. These defects included enteric nervous system hypoplasia, slow GI transit, diminished peristaltic reflex activity, and proliferation of crypt epithelial cells. An opposite phenotype was seen in SERT-deficient mice and in progeny of WT dams given the SERT antagonist fluoxetine. The reciprocal phenotypes that resulted from increased or decreased SERT activity support the idea that 5-HT signaling regulates enteric neuronal development and can, when disturbed, cause long-lasting abnormalities of GI function. Administration of a 5-HT4 agonist to Ala56 mice during development prevented Ala56-associated GI perturbations, suggesting that excessive SERT activity leads to inadequate 5-HT4-mediated neurogenesis. We propose that deficient 5-HT signaling during development may contribute to GI and behavioral features of ASD. The consequences of therapies targeting SERT during pregnancy warrant further evaluation. PMID:27111230

  6. Differential changes and interactions of autonomic functioning and sleep architecture before and after 50 years of age.

    PubMed

    Kuo, T B J; Li, Jia-Yi; Kuo, Hsu-Ko; Chern, Chang-Ming; Yang, C C H

    2016-02-01

    We hypothesize that the time when age-related changes in autonomic functioning and in sleep structure occur are different and that autonomic functioning modulates sleep architecture differently before and after 50 years of age. Sixty-eight healthy subjects (aged 20 to 79 years old, 49 of them women) were enrolled. Correlation analysis revealed that wake after sleep onset, the absolute and relative value of stage 1 (S1; S1%), and relative value of stage 2 (S2) were positively correlated with age; however, sleep efficiency, stage 3 (S3), S3%, and rapid-eye-movement latency (REML) were negatively correlated with age. Significant degenerations of sleep during normal aging were occurred after 50 years of age; however, significant declines of autonomic activity were showed before 50 years of age. Before 50 years of age, vagal function during sleep was negatively correlated with arousal index; however, after 50 years of age, it was positively correlated with S1 and S1%. In addition, sympathetic activity during wake stage was positively related to S2% only after 50 years of age. Our results imply that the age-related changes in autonomic functioning decline promptly as individuals leave the younger part of their adult life span and that age-related changes in sleep slowly develop as individuals enter the older part of their adult life span. Furthermore, while various aspects of sleep architecture are modulated by both the sympathetic and vagal nervous systems during adult life span, the sleep quality is mainly correlated with the sympathetic division after 50 years of age.

  7. Effect of long-term music therapy intervention on autonomic function in anthracycline-treated breast cancer patients.

    PubMed

    Chuang, Chih-Yuan; Han, Wei-Ru; Li, Pei-Chun; Song, Mi-Yun; Young, Shuenn-Tsong

    2011-12-01

    Anthracyclines are potent antineoplastic agents associated with cardiotoxicity, which may lead to congestive heart failure, causing impairment of autonomic cardiovascular function as assessed by heart rate variability (HRV). This decreases survival rates. This study aimed to determine whether music therapy intervention improves autonomic function in anthracycline-treated breast cancer patients, and if so, whether such improvements persist after cessation of the intervention. Participants were 12 women with breast cancer who had undergone mastectomy or breast-conserving treatment and adjuvant chemotherapy; they attended 8 weekly music therapy sessions, each lasting 2 hours. Electrocardiogram traces (5 minutes) for HRV analysis were recorded 4 times: prior to the first music session, T1; after the fourth music session, T2; after the eighth music session, T3; and 4 weeks after the completion of music therapy, T4. HRV parameters were subjected to a nonparametric Friedman test on the differences between T1 and T2, T3, and T4. The standard deviation of normal intervals and the total power of HRV parameters, related to global autonomic function, were significantly higher at T3 than at T1. The root-mean-square differences of successive normal R-R intervals and high-frequency (HF) HRV parameters, related to parasympathetic activity, were significantly increased, but no change was seen in the LF/HF ratio of HRV parameters (which is related to sympathetic activity) during the music therapy. Global autonomic function and parasympathetic activity had not changed significantly at T4 relative to T1. The authors provide preliminary evidence of the benefits of music therapy for anthracycline-treated breast cancer survivors.

  8. Cerebral Hemispheric Lateralization Associated with Hippocampal Sclerosis May Affect Interictal Cardiovascular Autonomic Functions in Temporal Lobe Epilepsy

    PubMed Central

    Ghchime, Rokia; Benjelloun, Halima; Kiai, Hajar; Belaidi, Halima; Lahjouji, Fatiha; Ouazzani, Reda

    2016-01-01

    It is well established that the temporal lobe epilepsy (TLE) is linked to the autonomic nervous system dysfunctions. Seizures alter the function of different systems such as the respiratory, cardiovascular, gastrointestinal, and urogenital systems. The aim of this work was to evaluate the possible factors which may be involved in interictal cardiovascular autonomic function in temporal lobe epilepsy with complex partial seizures, and with particular attention to hippocampal sclerosis. The study was conducted in 30 patients with intractable temporal lobe epilepsy (19 with left hippocampal sclerosis, 11 with right hippocampal sclerosis). All subjects underwent four tests of cardiac autonomic function: heart rate changes in response to deep breathing, heart rate, and blood pressure variations throughout resting activity and during hand grip, mental stress, and orthostatic tests. Our results show that the right cerebral hemisphere predominantly modulates sympathetic activity, while the left cerebral hemisphere mainly modulates parasympathetic activity, which mediated tachycardia and excessive bradycardia counterregulation, both of which might be involved as a mechanism of sudden unexpected death in epilepsy patients (SUDEP). PMID:27006827

  9. Analysis of functional abnormalities uncovered during preoperative evaluation of donor candidates for living-related liver transplantation.

    PubMed

    Morimoto, T; Awane, M; Tanaka, A; Ikai, I; Nakamura, Y; Yamamoto, Y; Takada, Y; Honda, K; Inamoto, T; Uemoto, S

    1995-02-01

    Functional abnormalities of the liver uncovered during preoperative routine evaluation were analyzed in 109 donor candidates for 100 cases of living-related liver transplantation (LRLT) performed during the period from June, 1990 to May, 1994 at the Second Department of Surgery, Kyoto University Hospital. High serum transaminase (GOT, GPT) levels were noted in 10 (9.2%) cases among 109 candidates, high alkaline phosphatase in 4 (3.7%), hyperbilirubinemia in 3 (2.8%), anemia in 3 and high choline esterase in 3 cases. Positive hepatitis C antibody (HCV) was also noted in 1 case. Fatty liver was detected in 10 (9.2%) cases, cholecystitis in 2 cases, 1 case each of cyst and calcification in the liver by diagnostic imaging (ultra sonograph and/or computed tomography). These abnormalities of the liver necessitated replacing the initial candidate with the other parent in 9 cases, including 1 case without any functional abnormality whose graft liver was too large to fit the recipient abdominal cavity. There were 14 cases of ABO blood type incompatible combination. Switching the initial candidate due to these abnormalities mentioned above resulted in incompatible combinations in 4 of these 14 cases. Although the advantages of the LRLT are the superior viability of the donor graft and the genetic histocompatibility between recipient and donor, to optimize the advantage of LRLT, all donor candidates should be strongly advised to make every effort preoperatively to improve their physical condition in preparation for the LRLT protocol, since many of these abnormalities are typically reversible.

  10. Abnormal functional global and local brain connectivity in female patients with anorexia nervosa

    PubMed Central

    Geisler, Daniel; Borchardt, Viola; Lord, Anton R.; Boehm, Ilka; Ritschel, Franziska; Zwipp, Johannes; Clas, Sabine; King, Joseph A.; Wolff-Stephan, Silvia; Roessner, Veit; Walter, Martin; Ehrlich, Stefan

    2016-01-01

    Background Previous resting-state functional connectivity studies in patients with anorexia nervosa used independent component analysis or seed-based connectivity analysis to probe specific brain networks. Instead, modelling the entire brain as a complex network allows determination of graph-theoretical metrics, which describe global and local properties of how brain networks are organized and how they interact. Methods To determine differences in network properties between female patients with acute anorexia nervosa and pairwise matched healthy controls, we used resting-state fMRI and computed well-established global and local graph metrics across a range of network densities. Results Our analyses included 35 patients and 35 controls. We found that the global functional network structure in patients with anorexia nervosa is characterized by increases in both characteristic path length (longer average routes between nodes) and assortativity (more nodes with a similar connectedness link together). Accordingly, we found locally decreased connectivity strength and increased path length in the posterior insula and thalamus. Limitations The present results may be limited to the methods applied during preprocessing and network construction. Conclusion We demonstrated anorexia nervosa–related changes in the network configuration for, to our knowledge, the first time using resting-state fMRI and graph-theoretical measures. Our findings revealed an altered global brain network architecture accompanied by local degradations indicating wide-scale disturbance in information flow across brain networks in patients with acute anorexia nervosa. Reduced local network efficiency in the thalamus and posterior insula may reflect a mechanism that helps explain the impaired integration of visuospatial and homeostatic signals in patients with this disorder, which is thought to be linked to abnormal representations of body size and hunger. PMID:26252451

  11. Forebrain regions associated with postexercise differences in autonomic and cardiovascular function during baroreceptor unloading.

    PubMed

    Kimmerly, D S; Wong, S W; Salzer, D; Menon, R; Shoemaker, J K

    2007-07-01

    The cortical regions representing peripheral autonomic reactions in humans are poorly understood. This study examined whether changes in forebrain activity were associated with the altered physiological responses to lower body negative pressure (LBNP) following a single bout of dynamic exercise (POST-EX). We hypothesized that, compared with the nonexercised condition (NO-EX), POST-EX would elicit greater reductions in stroke volume (SV) and larger increases in heart rate (HR) and muscle sympathetic nerve activity (MSNA) during LBNP (5, 15, and 35 mmHg). Forebrain neural activity (n = 11) was measured using blood oxygen level-dependent (BOLD) functional magnetic resonance imaging. HR, SV, arterial blood pressure (ABP), and MSNA were collected separately. Compared with NO-EX, baseline ABP was reduced, whereas HR and total vascular conductance (TVC) were elevated in POST-EX (P < 0.05). In both conditions, 5 mmHg LBNP did not elicit a change (from baseline) in any physiological parameter. Compared with NO-EX, 35 mmHg LBNP-mediated decreases in SV and TVC produced greater increases in HR and MSNA during POST-EX (P < 0.05). The right posterior insula and dorsal anterior cingulate cortex demonstrated a larger decrease in BOLD at 5 mmHg LBNP but greater BOLD increase at 15 and 35 mmHg LBNP POST-EX vs. NO-EX (P < 0.005). Conversely, the thalamus and ventral medial prefrontal cortex displayed the opposite BOLD activity pattern (i.e., larger increase at 5 mmHg LBNP but greater decrease at 15 and 35 mmHg LBNP POST-EX vs. NO-EX). Our findings suggest that discrete forebrain regions may be involved with the generation of baroreflex-mediated sympathetic and cardiovascular responses elicited by moderate LBNP. PMID:17351074

  12. Autonomic Function Predicts Fitness Response to Short-Term High-Intensity Interval Training.

    PubMed

    Kiviniemi, A M; Tulppo, M P; Eskelinen, J J; Savolainen, A M; Kapanen, J; Heinonen, I H A; Hautala, A J; Hannukainen, J C; Kalliokoski, K K

    2015-11-01

    We tested the hypothesis that baseline cardiac autonomic function and its acute response to all-out interval exercise explains individual fitness responses to high-intensity interval training (HIT). Healthy middle-aged sedentary men performed HIT (n=12, 4-6×30 s of all-out cycling efforts with 4-min recovery) or aerobic training (AET, n=9, 40-60 min at 60% of peak workload in exercise test [Loadpeak]), comprising 6 sessions within 2 weeks. Low (LF) and high frequency (HF) power of R-R interval oscillation were analyzed from data recorded at supine and standing position (5+5 min) every morning during the intervention. A significant training effect (p< 0.001), without a training*group interaction, was observed in Loadpeak and peak oxygen consumption (VO2peak). Pre-training supine LF/HF ratio, an estimate of sympathovagal balance, correlated with training outcome in Loadpeak (Spearman's rho [rs]=-0.74, p=0.006) and VO2peak (rs=- 0.59, p=0.042) in the HIT but not the AET group. Also, the mean change in the standing LF/HF ratio in the morning after an acute HIT exercise during the 1(st) week of intervention correlated with training response in Loadpeak (rs=- 0.68, p=0.014) and VO2peak (rs=-0.60, p=0.039) with HIT but not with AET. In conclusion, pre-training cardiac sympathovagal balance and its initial alterations in response to acute HIT exercise were related to fitness responses to short-term HIT.

  13. Cerebrospinal Fluid Orexin A Levels and Autonomic Function in Kleine-Levin Syndrome

    PubMed Central

    Wang, Jing Yu; Han, Fang; Dong, Song X.; Li, Jing; An, Pei; Zhang, Xiao Zhe; Chang, Yuan; Zhao, Long; Zhang, Xue Li; Liu, Ya Nan; Yan, Han; Li, Qing Hua; Hu, Yan; Lv, Chang Jun; Gao, Zhan Cheng; Strohl, Kingman P.

    2016-01-01

    Study Objectives: Kleine-Levin syndrome (KLS) is a rare disorder of relapsing sleepiness. The hypothesis was that the syndrome is related to a change in the vigilance peptide orexin A. Methods: From 2002 to 2013, 57 patients with relapsing hypersomnolence were clinically assessed in a referral academic center in Beijing, China, and 44 (28 males and 16 females; mean age 18.3 ± 8.9 y (mean ± standard deviation, range 9–57 y) were determined to have clinical and behavioral criteria consistent with KLS. Cerebrospinal fluid orexin A levels and diurnal blood pressure were measured in relapse versus remission in a subgroup of patients. Results: Presenting symptoms included relapsing or remitting excessive sleepiness–associated parallel complaints of cognitive changes (82%), eating disorders (84%); depression (45%); irritability (36%); hypersexuality (18%); and compulsions (11%). Episodes were 8.2 ± 3.3 days in duration. In relapse, diurnal values for blood pressure and heart rate were lower (P < 0.001). In a subgroup (n = 34), cerebrospinal fluid orexin A levels were ∼31% lower in a relapse versus remission (215.7 ± 81.5 versus 319.2 ± 95.92 pg/ml, P < 0.001); in three patients a pattern of lower levels during subsequent relapses was documented. Conclusions: There are lower orexin A levels in the symptomatic phase than in remission and a fall and rise in blood pressure and heart rate, suggesting a role for orexin dysregulation in KLS pathophysiology. Citation: Wang JY, Han F, Dong SX, Li J, An P, Zhang XZ, Chang Y, Zhao L, Zhang XL, Liu YN, Yan H, Li QH, Hu Y, Lv CJ, Gao ZC, Strohl KP. Cerebrospinal fluid orexin A levels and autonomic function in Kleine-Levin syndrome. SLEEP 2016;39(4):855–860. PMID:26943469

  14. Effect of partition board color on mood and autonomic nervous function.

    PubMed

    Sakuragi, Sokichi; Sugiyama, Yoshiki

    2011-12-01

    The purpose of this study was to evaluate the effects of the presence or absence (control) of a partition board and its color (red, yellow, blue) on subjective mood ratings and changes in autonomic nervous system indicators induced by a video game task. The increase in the mean Profile of Mood States (POMS) Fatigue score and mean Oppressive feeling rating after the task was lowest with the blue partition board. Multiple-regression analysis identified oppressive feeling and error scores on the second half of the task as statistically significant contributors to Fatigue. While explanatory variables were limited to the physiological indices, multiple-regression analysis identified a significant contribution of autonomic reactivity (assessed by heart rate variability) to Fatigue. These results suggest that a blue partition board would reduce task-induced subjective fatigue, in part by lowering the oppressive feeling of being enclosed during the task, possibly by increasing autonomic reactivity.

  15. Timing of obstetrical assistance affects peripartal cardiac autonomic function and early maternal behavior of dairy cows.

    PubMed

    Kovács, Levente; Kézér, Fruzsina Luca; Ruff, Ferenc; Szenci, Ottó

    2016-10-15

    Peripartal autonomic nervous system function and early maternal behavior were investigated in 79 multiparous Holstein-Friesian cows. Animals were allocated into four groups based on the technology of calving management: 1) unassisted calving in a group pen (UCG; N=19), 2) unassisted calving in an individual pen (UCI; N=21), 3) assisted calving with appropriately timed obstetrical assistance (ACA; N=20), and 4) assisted calving with premature obstetrical assistance (ACP; N=19). Heart rate, the high frequency (HF) component of heart rate variability (HRV) as a measure of vagal activity and the ratio between the low frequency (LF) and HF components (LF/HF ratio) as a parameter of sympathetic nervous system activity were calculated. Heart rate and HRV parameters were presented as areas under the curves (AUC) for the following periods: 1) prepartum period (between 96h before the onset of calving restlessness and the onset of restlessness), 2) parturition (between the onset calving restlessness and delivery), and 3) postpartum period (during a 48-h period after delivery). Pain-related behaviors were recorded during parturition (i.e., the occurrence of vocalization and stretching the neck towards the abdomen) and during a 2-h observation period after calving (i.e., the occurrence of vocalization, stretching the neck towards the abdomen and the duration of standing with an arched back). Early maternal behavior was observed during the first 2h following calving as follows: 1) latency and duration of sniffing calf's head/body, and 2) latency and duration of licking calf's head/body. No difference was found across groups in autonomic function before the onset of calving restlessness. Area under the heart rate curve was higher in ACP cows during parturition (39.6±2.5beats/min×h) compared to UCG, UCI and ACA animals (AUC=13.1±0.9beats/min×h, AUC=22.3±1.4beats/min×h and AUC=25.0±2.1beats/min×h, respectively). Area under the heart rate curve did not differ across the UCG

  16. Voiding and Sexual Function after Autonomic-Nerve-Preserving Surgery for Rectal Cancer in Disease-Free Male Patients

    PubMed Central

    Lee, Dong Kil; Song, Kanghyon; Park, Jong Wook; Moon, Sun-Mi

    2010-01-01

    Purpose We evaluated the effects of surgery for rectal cancer on postoperative voiding and sexual function over the course of time. Materials and Methods Data from 28 patients who underwent autonomic nerve preserving rectal cancer surgery were retrospectively analyzed. Operations were performed between October 2005 and July 2007 and all patients were followed-up for more than 3 years. Preoperatively, all patients underwent urodynamic studies including uroflowmetry, and filled out the International Prostate Symptom Score (IPSS). The evaluation of sexual function consisted of Erectile Function domain score in International Index of Erectile Function (IIEF-EFD) and Ejaculation domain score in Male Sexual Health Questionnaire (MSHQ-EjD). Data from uroflowmetry and questionnaires were examined. Results At 3 years postoperatively the prostate volume was similar to the preoperative value (p=0.727). There were no statistically significant postoperative changes in the average maximum flow rate (15.9 ml/s vs. 16.2 ml/s, p=0.637) and post-void residual urine volume (34.7 ml vs. 36.8 ml, p=0.809). No statistically significant differences were observed in the IPSS (13.2 vs. 12.2, p=0.374). However, although pelvic autonomic nerve preservation have been performed, a significant proportion of rectal cancer patients suffer from sexual dysfunction and the average of IIEF-EFD and MSHQ-EjD scores was decreased postoperatively until 3 years (25.1 vs. 16.1 and 28.3 vs. 14.2 respectively, p<0.001). Conclusions Voiding function was not affected after autonomic nerve-preserving rectal cancer surgery, however sexual function was significantly aggravated. We recommend that the baseline genitourinary function should be evaluated before the treatment for male rectal cancer patients, and penile rehabilitation is necessary for their quality of life after treatment. PMID:21221207

  17. Genetic mosaics reveal both cell-autonomous and cell-nonautonomous function of murine p27Kip1

    PubMed Central

    Chien, Wei-Ming; Rabin, Stuart; Macias, Everardo; Miliani de Marval, Paula L.; Garrison, Kendra; Orthel, Jason; Rodriguez-Puebla, Marcelo; Fero, Matthew L.

    2006-01-01

    Loss of the cyclin-dependent kinase inhibitor p27Kip1 leads to an overall increase in animal growth, pituitary tumors, and hyperplasia of hematopoietic organs, yet it is unknown whether all cells function autonomously in response to p27Kip1 activity or whether certain cells take cues from their neighbors. In addition, there is currently no genetic evidence that tumor suppression by p27Kip1 is cell-autonomous because biallelic gene inactivation is absent from tumors arising in p27Kip1 hemizygous mice. We have addressed these questions with tissue-specific targeted mouse mutants and radiation chimeras. Our results indicate that the suppression of pars intermedia pituitary tumors by p27Kip1 is cell-autonomous and does not contribute to overgrowth or infertility phenotypes. In contrast, suppression of spleen growth and hematopoietic progenitor expansion is a consequence of p27Kip1 function external to the hematopoietic compartment. Likewise, p27Kip1 suppresses thymocyte hyperplasia through a cell-nonautonomous mechanism. The interaction of p27Kip1 loss with epithelial cell-specific cyclin-dependent kinase 4 overexpression identifies the thymic epithelium as a relevant site of p27Kip1 activity for the regulation of thymus growth. PMID:16537495

  18. Peripheral circulation monitored by surface temperature and autonomic nervous function in hypobaric hypoxic environment: effects of submaximal exercise.

    PubMed

    Fukuda-Matsuda, Eri; Yamada, Makiko; Tanobe, Kyoko; Saito, Shigeru

    2007-02-01

    Hypothermia and frostbite are frequently seen in accidents in remote wilderness environment, especially in hypobaric hypoxic conditions. The aim of this study was to clarify how hypobaric hypoxic conditions affects peripheral circulation. Peripheral skin temperature and autonomic nervous functions were assessed in two 1000-m ascent exercises. Subjects (n = 15) ascended from 1000 m above sea level in Study 1, and ascended from 2400 m in Study 2. Conditions other than environmental oxygen pressure were mostly identical in both studies. The autonomic nervous activities were decreased solely in Study 2. The relative sympathetic activity was significantly increased in the lower barometric pressure in Study 2 (p < 0.01). Peripheral skin temperature was significantly decreased after the exercise in Study 2 (p < 0.01). In conclusion, hypobaric hypoxia itself induced peripheral low temperature during exercise at high altitudes. Relative sympathetic hyperactivity may be responsible for the compromised peripheral circulation.

  19. Abnormalities of motor function, transcription and cerebellar structure in mouse models of THAP1 dystonia.

    PubMed

    Ruiz, Marta; Perez-Garcia, Georgina; Ortiz-Virumbrales, Maitane; Méneret, Aurelie; Morant, Andrika; Kottwitz, Jessica; Fuchs, Tania; Bonet, Justine; Gonzalez-Alegre, Pedro; Hof, Patrick R; Ozelius, Laurie J; Ehrlich, Michelle E

    2015-12-20

    DYT6 dystonia is caused by mutations in THAP1 [Thanatos-associated (THAP) domain-containing apoptosis-associated protein] and is autosomal dominant and partially penetrant. Like other genetic primary dystonias, DYT6 patients have no characteristic neuropathology, and mechanisms by which mutations in THAP1 cause dystonia are unknown. Thap1 is a zinc-finger transcription factor, and most pathogenic THAP1 mutations are missense and are located in the DNA-binding domain. There are also nonsense mutations, which act as the equivalent of a null allele because they result in the generation of small mRNA species that are likely rapidly degraded via nonsense-mediated decay. The function of Thap1 in neurons is unknown, but there is a unique, neuronal 50-kDa Thap1 species, and Thap1 levels are auto-regulated on the mRNA level. Herein, we present the first characterization of two mouse models of DYT6, including a pathogenic knockin mutation, C54Y and a null mutation. Alterations in motor behaviors, transcription and brain structure are demonstrated. The projection neurons of the deep cerebellar nuclei are especially altered. Abnormalities vary according to genotype, sex, age and/or brain region, but importantly, overlap with those of other dystonia mouse models. These data highlight the similarities and differences in age- and cell-specific effects of a Thap1 mutation, indicating that the pathophysiology of THAP1 mutations should be assayed at multiple ages and neuronal types and support the notion of final common pathways in the pathophysiology of dystonia arising from disparate mutations. PMID:26376866

  20. Abnormalities of motor function, transcription and cerebellar structure in mouse models of THAP1 dystonia.

    PubMed

    Ruiz, Marta; Perez-Garcia, Georgina; Ortiz-Virumbrales, Maitane; Méneret, Aurelie; Morant, Andrika; Kottwitz, Jessica; Fuchs, Tania; Bonet, Justine; Gonzalez-Alegre, Pedro; Hof, Patrick R; Ozelius, Laurie J; Ehrlich, Michelle E

    2015-12-20

    DYT6 dystonia is caused by mutations in THAP1 [Thanatos-associated (THAP) domain-containing apoptosis-associated protein] and is autosomal dominant and partially penetrant. Like other genetic primary dystonias, DYT6 patients have no characteristic neuropathology, and mechanisms by which mutations in THAP1 cause dystonia are unknown. Thap1 is a zinc-finger transcription factor, and most pathogenic THAP1 mutations are missense and are located in the DNA-binding domain. There are also nonsense mutations, which act as the equivalent of a null allele because they result in the generation of small mRNA species that are likely rapidly degraded via nonsense-mediated decay. The function of Thap1 in neurons is unknown, but there is a unique, neuronal 50-kDa Thap1 species, and Thap1 levels are auto-regulated on the mRNA level. Herein, we present the first characterization of two mouse models of DYT6, including a pathogenic knockin mutation, C54Y and a null mutation. Alterations in motor behaviors, transcription and brain structure are demonstrated. The projection neurons of the deep cerebellar nuclei are especially altered. Abnormalities vary according to genotype, sex, age and/or brain region, but importantly, overlap with those of other dystonia mouse models. These data highlight the similarities and differences in age- and cell-specific effects of a Thap1 mutation, indicating that the pathophysiology of THAP1 mutations should be assayed at multiple ages and neuronal types and support the notion of final common pathways in the pathophysiology of dystonia arising from disparate mutations.

  1. Disruption of Ah Receptor Signaling during Mouse Development Leads to Abnormal Cardiac Structure and Function in the Adult

    PubMed Central

    Carreira, Vinicius S.; Fan, Yunxia; Kurita, Hisaka; Wang, Qin; Ko, Chia-I; Naticchioni, Mindi; Jiang, Min; Koch, Sheryl; Zhang, Xiang; Biesiada, Jacek; Medvedovic, Mario; Xia, Ying; Rubinstein, Jack; Puga, Alvaro

    2015-01-01

    The Developmental Origins of Health and Disease (DOHaD) Theory proposes that the environment encountered during fetal life and infancy permanently shapes tissue physiology and homeostasis such that damage resulting from maternal stress, poor nutrition or exposure to environmental agents may be at the heart of adult onset disease. Interference with endogenous developmental functions of the aryl hydrocarbon receptor (AHR), either by gene ablation or by exposure in utero to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent AHR ligand, causes structural, molecular and functional cardiac abnormalities and altered heart physiology in mouse embryos. To test if embryonic effects progress into an adult phenotype, we investigated whether Ahr ablation or TCDD exposure in utero resulted in cardiac abnormalities in adult mice long after removal of the agent. Ten-months old adult Ahr-/- and in utero TCDD-exposed Ahr+/+ mice showed sexually dimorphic abnormal cardiovascular phenotypes characterized by echocardiographic findings of hypertrophy, ventricular dilation and increased heart weight, resting heart rate and systolic and mean blood pressure, and decreased exercise tolerance. Underlying these effects, genes in signaling networks related to cardiac hypertrophy and mitochondrial function were differentially expressed. Cardiac dysfunction in mouse embryos resulting from AHR signaling disruption seems to progress into abnormal cardiac structure and function that predispose adults to cardiac disease, but while embryonic dysfunction is equally robust in males and females, the adult abnormalities are more prevalent in females, with the highest severity in Ahr-/- females. The findings reported here underscore the conclusion that AHR signaling in the developing heart is one potential target of environmental factors associated with cardiovascular disease. PMID:26555816

  2. Abnormal resting-state functional connectivity of the nucleus accumbens in multi-year abstinent heroin addicts.

    PubMed

    Zou, Feng; Wu, Xinhuai; Zhai, Tianye; Lei, Yu; Shao, Yongcong; Jin, Xiao; Tan, Shuwen; Wu, Bing; Wang, Lubin; Yang, Zheng

    2015-11-01

    Functional neuroimaging studies suggest that abnormal brain functional connectivity may be the neural underpinning of addiction to illicit drugs and of relapse after successful cessation therapy. Aberrant brain networks have been demonstrated in addicted patients and in newly abstinent addicts. However, it is not known whether abnormal brain connectivity patterns persist after prolonged abstinence. In this cross-sectional study, whole-brain resting-state functional magnetic resonance images (8 min) were collected from 30 heroin-addicted individuals after a long period of abstinence (more than 3 years) and from 30 healthy controls. We first examined the group differences in the resting-state functional connectivity of the nucleus accumbens (NAc), a brain region implicated in relapse-related processes, including craving and reactivity to stress following acute and protracted withdrawal from heroin. We then examined the relation between the duration of abstinence and the altered NAc functional connectivity in the heroin group. We found that, compared with controls, heroin-dependent participants exhibited significantly greater functional connectivity between the right ventromedial prefrontal cortex and the NAc and weaker functional connectivity between the NAc and the left putamen, left precuneus, and supplementary motor area. However, with longer abstinence time, the strength of NAc functional connectivity with the left putamen increased. These results indicate that dysfunction of the NAc functional network is still present in long-term-abstinent heroin-dependent individuals. PMID:26280556

  3. Ventilation, autonomic function, sleep and erythropoietin. Chronic mountain sickness of Andean natives.

    PubMed

    Bernardi, Luciano; Roach, Robert C; Keyl, Cornelius; Spicuzza, Lucia; Passino, Claudio; Bonfichi, Maurizio; Gamboa, Alfredo; Gamboa, Jorge; Malcovati, Luca; Schneider, Annette; Casiraghi, Nadia; Mori, Antonio; Leon-Velarde, Fabiola

    2003-01-01

    Polycythemia is one of the key factors involved in the chronic mountain sickness syndrome, a condition frequent in Andean natives but whose causes still remain unclear. In theory, polycythemia may be secondary to abnormalities in ventilation, occurring during day or night (e.g. due to sleep abnormalities) stimulating excessive erythropoietin (Epo) production, or else it may result from either autogenous production, or from co-factors like cobalt. To assess the importance of these points, we studied subjects with or without polycythemia, born and living in Cerro de Pasco (Peru, 4330m asl, CP) and evaluated the relationship between Epo and respiratory variables both in CP and sea level. We also assessed the relationship between sleep abnormalities and the circadian rhythm of Epo. Polycythemic subjects showed higher Epo in all conditions, lower SaO2 and hypoxic ventilatory response, higher physiological dead space and higher CO2, suggesting ventilatory inefficiency. Epo levels could be highly modified by the level of oxygenation, and were related to similar directional changes in SaO2. Cobalt levels were normal in all subjects and correlated poorly with hematologic variables. The diurnal variations in Epo were grossly abnormal in polycythemic subjects, with complete loss of the circadian rhythm. These abnormalities correlated with the levels of hypoxemia during the night, but not with sleep abnormalities, which were only minor even in polycythemic subjects. The increased Epo production is mainly related to a greater ventilatory inefficiency, and not to altered sensitivity to hypoxia, cobalt or sleep abnormalities. Improving oxygenation can represent a possible therapeutic option for this syndrome.

  4. [Changes in autonomic function and EEG power during mental arithmetic task and their mutual relationship].

    PubMed

    Hamada, Toshihiko; Murata, Tetsuhito; Takahashi, Tetsuya; Ohtake, Yuka; Saitoh, Minoru; Kimura, Hideki; Wada, Yuji; Yoshida, Haruyoshi

    2006-04-01

    Meditation is a specific consciousness state in which deep relaxation and increased internalized attention coexist. Autonomic nervous activity during meditation was reported to be characterized by decreased sympathetic activity and increased parasympathetic activity. And concerning EEG power, slow alpha power and fast theta power increased during meditation. On the other hand, mental arithmetic (MA) tasks have been reported to induce an increase in blood pressure and heart rate with enhanced sympathetic activity. However, changes in autonomic nervous activity and EEG power during MA tasks and their mutual relationship have not been adequately studied. In the present study, we quantitatively analyzed the changes in autonomic nervous activity using heart rate variability (HRV) and EEG power during MA task in 30 healthy volunteers. MA task induced significant increases in normalized LF, LF/HF ratio (as a sympathetic index), and a decrease in normalized HF (as a parasympathetic index). On the other hand, significant decrease in EEG power (slow theta: 4-6 Hz and fast alpha: 10-13 Hz in the posterior region and fast theta: 6-8 Hz and slow alpha: 8-10 Hz in all the regions) were induced by MA task. Further evaluation of these changes showed a negative correlation between the change rates (with the control resting condition as the baseline) in fast alpha power and that in LF/HF. These results suggest that specific correlated relationships exist between the change in autonomic nervous activity and EEG power depending on the difference in mental task (i.e., meditation or MA).

  5. Potential Interactions between the Autonomic Nervous System and Higher Level Functions in Neurological and Neuropsychiatric Conditions

    PubMed Central

    Bassi, Andrea; Bozzali, Marco

    2015-01-01

    The autonomic nervous system (ANS) maintains the internal homeostasis by continuously interacting with other brain structures. Its failure is commonly observed in many neurological and neuropsychiatric disorders, including neurodegenerative and vascular brain diseases, spinal cord injury, and peripheral neuropathies. Despite the different underlying pathophysiological mechanisms, ANS failure associates with various forms of higher level dysfunctions, and may also negatively impact on patients’ clinical outcome. In this review, we will discuss potential relationships between ANS and higher level dysfunctions in a selection of neurological and neuropsychiatric disorders. In particular, we will focus on the effect of a documented fall in blood pressure fulfilling the criteria for orthostatic hypotension and/or autonomic-reflex impairment on cognitive performances. Some evidence supports the hypothesis that cardiovascular autonomic failure may play a negative prognostic role in most neurological disorders. Despite a clear causal relationship between ANS involvement and higher level dysfunctions that is still controversial, this might have implications for neuro-rehabilitation strategies aimed at improving patients’ clinical outcome. PMID:26388831

  6. Pediatric autonomic disorders.

    PubMed

    Axelrod, Felicia B; Chelimsky, Gisela G; Weese-Mayer, Debra E

    2006-07-01

    The scope of pediatric autonomic disorders is not well recognized. The goal of this review is to increase awareness of the expanding spectrum of pediatric autonomic disorders by providing an overview of the autonomic nervous system, including the roles of its various components and its pervasive influence, as well as its intimate relationship with sensory function. To illustrate further the breadth and complexities of autonomic dysfunction, some pediatric disorders are described, concentrating on those that present at birth or appear in early childhood. PMID:16818580

  7. Autonomous control

    NASA Technical Reports Server (NTRS)

    Brown, Barbara

    1990-01-01

    KSC has been developing the Knowledge-Based Autonomous Test Engineer (KATE), which is a tool for performing automated monitoring, diagnosis, and control of electromechanical devices. KATE employs artificial intelligence computing techniques to perform these functions. The KATE system consists of a generic shell and a knowledge base. The KATE shell is the portion of the system which performs the monitoring, diagnosis, and control functions. It is generic in the sense that it is application independent. This means that the monitoring activity, for instance, will be performed with the same algorithms regardless of the particular physical device being used. The knowledge base is the portion of the system which contains specific functional and behavorial information about the physical device KATE is working with. Work is nearing completion on a project at KSC to interface a Texas Instruments Explorer running a LISP version of KATE with a Generic Checkout System (GCS) test-bed to control a physical simulation of a shuttle tanking system (humorously called the Red Wagon because of its color and mobility). The Autonomous Control System (ACS) project supplements and extends the KATE/GCS project by adding three other major activities. The activities include: porting KATE from the Texas Instruments Explorer machine to an Intel 80386-based UNIX workstation in the LISP language; rewriting KATE as necessary to run on the same 80386 workstation but in the Ada language; and investigating software and techniques to translate ANSI Standard Common LISP to Mil Standard Ada. Primary goals of this task are as follows: (1) establish the advantages of using expert systems to provide intelligent autonomous software for Space Station Freedom applications; (2) determine the feasibility of using Ada as the run-time environment for model-based expert systems; (3) provide insight into the advantages and disadvantagesof using LISP or Ada in the run-time environment for expert systems; and (4

  8. The GST T1 and CYP2E1 genotypes are possible factors causing vinyl chloride induced abnormal liver function.

    PubMed

    Huang, C Y; Huang, K L; Cheng, T J; Wang, J D; Hsieh, L L

    1997-01-01

    Vinyl chloride monomer (VCM) is hepatotoxic as well as carcinogenic in humans. There are reports that exposure to VCM seems to induce abnormal liver function, liver fibrosis, cirrhosis, portal hypertension, and angiosarcoma of the liver. In vivo, VCM is metabolized by cytochrome P450 2E1 (CYP2E1) to form the electrophilic metabolites, chloroethylene oxide (CEO) and chloroacetaldehyde (CAA), which may either cause cell damage or be further metabolized and detoxified by glutathione S-transferases (GSTs). This study investigated whether or not the genotypes CYP2E1, glutathione S-transferase theta (GST T1) and mu (GST M1) correlated with abnormal liver function found in vinyl chloride exposed workers. For this study, 251 workers from five polyvinyl chloride plants were enrolled. The workers were classified into two exposure groups (high and low) and the degree of exposure was determined based on their job titles and airborne VCM concentration. The activity of serum alanine aminotransferase (ALT) was used as the parameter of liver function. The genotypes CYP2E1, GST T1 and GST M1 were determined by polymerase chain reaction and restriction fragment length polymorphism on peripheral white blood cell DNA. Other potential risk factors were also ascertained and the confounding effect was adjusted accordingly. Stratified analyses were used to explore the correlation between the alteration of liver function and the genotypes CYP2E1, GST T1 and GST M1 among the workers exposed to different levels of VCM. The following results were obtained (1) at low VCM exposure, the odds ratio (OR) of positive GST T1 on abnormal ALT was 3.8 (95% CI 1.2-14.5) but the CYP2E1 genotype was not associated with abnormal ALT. (2) At high VCM exposure, a c2c2 CYP2E1 genotype was associated with increased OR on abnormal ALT (OR 5.4, 95% CI 0.7-35.1) and positive GST T1 was significantly associated with decreased OR on abnormal ALT (OR 0.3, 95% CI 0.1-0.9). (3) Multiple linear and logistic regression

  9. Assessment of cardiac autonomic functions by heart rate recovery, heart rate variability and QT dynamicity parameters in patients with acromegaly.

    PubMed

    Dural, Muhammet; Kabakcı, Giray; Cınar, Neşe; Erbaş, Tomris; Canpolat, Uğur; Gürses, Kadri Murat; Tokgözoğlu, Lale; Oto, Ali; Kaya, Ergün Barış; Yorgun, Hikmet; Sahiner, Levent; Dağdelen, Selçuk; Aytemir, Kudret

    2014-04-01

    Cardiovascular complications are the most common causes of morbidity and mortality in acromegaly. However, there is little data regarding cardiac autonomic functions in these patients. Herein, we aimed to investigate several parameters of cardiac autonomic functions in patients with acromegaly compared to healthy subjects. We enrolled 20 newly diagnosed acromegalic patients (55% female, age:45.7 ± 12.6 years) and 32 age- and gender-matched healthy subjects. All participants underwent 24 h Holter recording. Heart rate recovery (HRR) indices were calculated by subtracting 1st, 2nd and 3rd minute heart rates from maximal heart rate. All patients underwent heart rate variability (HRV) and QT dynamicity analysis. Baseline characteristics were similar except diabetes mellitus and hypertension among groups. Mean HRR1 (29.2 ± 12.3 vs 42.6 ± 6.5, p = 0.001), HRR2 (43.5 ± 15.6 vs 61.1 ± 10.8, p = 0.001) and HRR3 (46.4 ± 16.2 vs 65.8 ± 9.8, p = 0.001) values were significantly higher in control group. HRV parameters as, SDNN [standard deviation of all NN intervals] (p = 0.001), SDANN [SD of the 5 min mean RR intervals] (p = 0.001), RMSSD [root square of successive differences in RR interval] (p = 0.001), PNN50 [proportion of differences in successive NN intervals >50 ms] (p = 0.001) and high-frequency [HF] (p = 0.001) were significantly decreased in patients with acromegaly; but low frequency [LF] (p = 0.046) and LF/HF (p = 0.001) were significantly higher in acromegaly patients. QTec (p = 0.009), QTac/RR slope (p = 0.017) and QTec/RR slope (p = 0.01) were significantly higher in patients with acromegaly. Additionally, there were significant negative correlation of disease duration with HRR2, HRR3, SDNN, PNN50, RMSSD, variability index. Our study results suggest that cardiac autonomic functions are impaired in patients with acromegaly. Further large scale studies are needed to exhibit the prognostic significance of impaired autonomic functions in patients with

  10. Abnormal liver function in workers exposed to low levels of ethylene dichloride and vinyl chloride monomer.

    PubMed

    Cheng, T J; Huang, M L; You, N C; Du, C L; Chau, T T

    1999-12-01

    We investigated whether exposure to ethylene dichloride (EDC) and vinyl chloride monomer (VCM) resulted in increased risk of liver damage. Epidemiological information, including occupational, medical, smoking, and drinking history, was obtained by interview from 251 male workers. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyltransferase (GGT) were used as indicators of liver damage. Exposure to moderate or low levels of ECD and VCM resulted in a higher risk of developing abnormal ALT levels than did exposure to lower levels of the chemicals. Results were similar for AST. GGT was not associated with EDC or VCM exposure. Combined exposure to EDC and VCM showed a dose-response relationship in association with abnormal ALT levels. We concluded that relatively low concentrations of VCM and EDC cause liver damage.

  11. Abnormal NF-kappa B function characterizes human type 1 diabetes dendritic cells and monocytes.

    PubMed

    Mollah, Zia U A; Pai, Saparna; Moore, Craig; O'Sullivan, Brendan J; Harrison, Matthew J; Peng, Judy; Phillips, Karen; Prins, Johannes B; Cardinal, John; Thomas, Ranjeny

    2008-03-01

    Dendritic cell (DC) differentiation is abnormal in type 1 diabetes mellitus (T1DM). However, the nature of the relationship between this abnormality and disease pathogenesis is unknown. We studied the LPS response in monocytes and monocyte-derived DCs isolated from T1DM patients and from non-T1DM controls. In T1DM patients, late LPS-mediated nuclear DNA binding by RelA, p50, c-Rel, and RelB was impaired as compared with type 2 DM, rheumatoid arthritis, and healthy subjects, associated with impaired DC CD40 and MHC class I induction but normal cytokine production. In TIDM monocytes, RelA and RelB were constitutively activated, and the src homology 2 domain-containing protein tyrosine phosphatase (SHP-1), a negative regulator of NF-kappaB, was overexpressed. Addition of sodium stibogluconate, a SHP-1 inhibitor, to DCs differentiating from monocyte precursors restored their capacity to respond to LPS in approximately 60% of patients. The monocyte and DC NF-kappaB response to LPS is thus a novel phenotypic and likely pathogenetic marker for human T1DM. SHP-1 is at least one NF-kappaB regulatory mechanism which might be induced as a result of abnormal inflammatory signaling responses in T1DM monocytes. PMID:18292540

  12. Effects of reward and punishment on task performance, mood and autonomic nervous function, and the interaction with personality.

    PubMed

    Sakuragi, Sokichi; Sugiyama, Yoshiki

    2009-06-01

    The effects of reward and punishment are different, and there are individual differences in sensitivity to reward and punishment. The purpose of this study was to investigate the effects of reward and punishment on task performance, mood, and autonomic nervous function, along with the interaction with personality. Twenty-one healthy female subjects volunteered for the experiment. The task performance was evaluated by required time and total errors while performing a Wisconsin Card Sorting Test. We assessed their personalities using the Minnesota Multiphasic Personality Inventory (MMPI) questionnaire, and mood states by a profile of mood states. Autonomic nervous function was estimated by a spectral analysis of heart rate variability, baroreflex sensitivity, and blood pressure. Repeated measures analysis of variance (ANOVA) revealed significant interaction of condition x time course on mood and autonomic nervous activity, which would indicate a less stressed state under the rewarding condition, but revealed no significant interaction of condition x time course on the task performance. The interactions with personality were further analyzed by repeated measures ANOVA applying the clinical scales of MMPI as independent variables, and significant interactions of condition x time course x Pt (psychasthenia) on task performance, mood, and blood pressure, were revealed. That is, the high Pt group, whose members tend to be sensitive and prone to worry, showed gradual improvement of task performance under the punishing situation with slight increase in systolic blood pressure, while showed no improvement under the rewarding situation with fatigue sense attenuation. In contrast, the low Pt group, whose members tend to be adaptive and self-confident, showed gradual improvement under the rewarding situation. Therefore, we should carefully choose the strategy of reward or punishment, considering the interaction with personality as well as the context in which it is given. PMID

  13. Cardiac autonomic functions and the emergence of violence in a highly realistic model of social conflict in humans

    PubMed Central

    Haller, Jozsef; Raczkevy-Deak, Gabriella; Gyimesine, Katalin P.; Szakmary, Andras; Farkas, Istvan; Vegh, Jozsef

    2014-01-01

    Among the multitude of factors that can transform human social interactions into violent conflicts, biological features received much attention in recent years as correlates of decision making and aggressiveness especially in critical situations. We present here a highly realistic new model of human aggression and violence, where genuine acts of aggression are readily performed and which at the same time allows the parallel recording of biological concomitants. Particularly, we studied police officers trained at the International Training Centre (Budapest, Hungary), who are prepared to perform operations under extreme conditions of stress. We found that aggressive arousal can transform a basically peaceful social encounter into a violent conflict. Autonomic recordings show that this change is accompanied by increased heart rates, which was associated earlier with reduced cognitive complexity of perceptions (“attentional myopia”) and promotes a bias toward hostile attributions and aggression. We also observed reduced heart rate variability in violent subjects, which is believed to signal a poor functioning of prefrontal-subcortical inhibitory circuits and reduces self-control. Importantly, these autonomic particularities were observed already at the beginning of social encounters i.e., before aggressive acts were initiated, suggesting that individual characteristics of the stress-response define the way in which social pressure affects social behavior, particularly the way in which this develops into violence. Taken together, these findings suggest that cardiac autonomic functions are valuable external symptoms of internal motivational states and decision making processes, and raise the possibility that behavior under social pressure can be predicted by the individual characteristics of stress responsiveness. PMID:25374519

  14. Isolation and nucleotide sequence of an autonomously replicating sequence (ARS) element functional in Candida albicans and Saccharomyces cerevisiae.

    PubMed

    Cannon, R D; Jenkinson, H F; Shepherd, M G

    1990-04-01

    An 8.6-kb fragment was isolated from an EcoRI digest of Candida albicans ATCC 10261 genomic DNA which conferred the property of autonomous replication in Saccharomyces cervisiae on the otherwise non-replicative plasmid pMK155 (5.6 kb). The DNA responsible for the replicative function was subcloned as a 1.2-kb fragment onto a non-replicative plasmid (pRC3915) containing the C. albicans URA3 and LEU2 genes to form plasmid pRC3920. This plasmid was capable of autonomous replication in both S. cerevisiae and C. albicans and transformed S. cerevisiae AH22 (leu2-) to Leu+ at a frequency of 2.15 x 10(3) transformants per microgram DNA, and transformed C. albicans SGY-243 (delta ura3) to Ura+ at a frequency of 1.91 x 10(3) transformants per microgram DNA. Sequence analysis of the cloned DNA revealed the presence of two identical regions of eleven base pairs (5'TTTTATGTTTT3') which agreed with the consensus of autonomously replicating sequence (ARS) cores functional in S. cerevisiae. In addition there were two 10/11 and numerous 9/11 matches to the core consensus. The two 11/11 matches to the consensus, CaARS1 and CaARS2, were located on opposite strands in a non-coding AT-rich region and were separated by 107 bp. Also present on the C. albicans DNA, 538 bp from the ARS cores, was a gene for 5S rRNA which showed sequence homology with several other yeast 5S rRNA genes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2196431

  15. Associations Between Abnormal Rod-Mediated Dark Adaptation and Health and Functioning in Older Adults With Normal Macular Health

    PubMed Central

    Owsley, Cynthia; Huisingh, Carrie; Jackson, Gregory R.; Curcio, Christine A.; Szalai, Alexander J.; Dashti, Nassrin; Clark, Mark; Rookard, Kia; McCrory, Mark A.; Wright, Tyler T.; Callahan, Michael A.; Kline, Lanning B.; Witherspoon, C. Douglas; McGwin, Gerald

    2014-01-01

    Purpose. Delayed rod-mediated dark adaptation (DA) is characteristic of early age-related macular degeneration (AMD) and also can be observed in some older adults in normal macular health. We examine cross-sectional associations between rod-mediated DA and risk factors for AMD in older adults in normal macular health. Methods. The sample consisted of adults aged ≥60 years old in normal macular health per grading of fundus photos using an established disease classification system. Rod-mediated DA was measured psychophysically following a photobleach using a computer-automated dark adaptometer with targets centered at 5° on the inferior vertical meridian. The speed of DA was characterized by the rod-intercept value, with abnormal DA defined as rod-intercept ≥ 12.3 minutes. We assessed several health and functional characteristics that the literature has suggested increase AMD risk (e.g., smoking, alcohol use, inflammatory markers, apolipoproteins, low luminance visual acuity, chronic medical conditions, body mass, family history). Results. Among 381 participants (mean age, 68.5 years; SD, 5.5), 78% had normal and 22% had abnormal DA, with the prevalence of abnormal DA increasing with age. After age-adjustment, abnormal DA was associated with increased odds of elevated C-reactive protein (CRP), heavy use of or abstention from alcohol, high blood pressure, and drop in visual acuity under mesopic conditions. Conclusions. Despite having normal macular health according to accepted definitions of AMD presence, approximately one-quarter of older adults recruited from primary eye care clinics had abnormal DA, which was associated with known risk factors for AMD, including elevated CRP. PMID:24854857

  16. Abnormal aortic fatty acid composition and small artery function in offspring of rats fed a high fat diet in pregnancy

    PubMed Central

    Ghosh, P; Bitsanis, D; Ghebremeskel, K; Crawford, M A; Poston, L

    2001-01-01

    Disturbances of the in utero environment are associated with an increased risk of cardiovascular disease in adulthood. In this study we have determined whether abnormal vascular function in the adult offspring of rats fed a high saturated fat diet in pregnancy is associated with altered plasma lipids or vascular fatty acid content. Female Sprague-Dawley rats were fed a breeding diet (4 % fat) or a diet high in saturated fat (20 % fat) for 10 days prior to and throughout pregnancy, and during weaning. Female offspring were then fed a maintenance diet (3 % fat) until 160 days of age. Endothelium-dependent relaxation induced by acetylcholine was blunted in isolated branches of the femoral artery from 160-day-old female offspring of dams fed the saturated fat diet when compared with female offspring of dams fed the breeding diet. These offspring exhibited elevated plasma triglyceride and reduced plasma high density lipoprotein cholesterol concentrations. The fatty acid composition of the aortas was abnormal, with a marked reduction in the content of arachidonic and docosahexaenoic acids. This study demonstrates that a high fat diet in pregnant rats produces abnormal vascular function, plasma lipid disturbances and altered vascular fatty acid content in their female offspring during adulthood. PMID:11410637

  17. Cardiovascular autonomic neuropathy

    PubMed Central

    McCarty, Niamh

    2016-01-01

    Cardiovascular autonomic neuropathy often goes unrecognized. We present a case of a 22-year-old man with multiple manifestations of this disease, including weakness, dizziness, fatigue, tachycardia, abnormal QTc, and orthostasis, which occurred 2 years after his type 1 diabetes diagnosis. He exhibited parasympathetic denervation with resting tachycardia and exercise intolerance but also had evidence of orthostatic hypotension, which suggests sympathetic denervation. He did not have complete cardiovascular autonomic reflex testing, which would have been helpful, but improved with aggressive diabetes treatment and the increase of beta-blockade. It is important to identify these patients to understand their signs and symptoms and consider appropriate therapies. PMID:27034552

  18. Cardiovascular autonomic neuropathy.

    PubMed

    McCarty, Niamh; Silverman, Barry

    2016-04-01

    Cardiovascular autonomic neuropathy often goes unrecognized. We present a case of a 22-year-old man with multiple manifestations of this disease, including weakness, dizziness, fatigue, tachycardia, abnormal QTc, and orthostasis, which occurred 2 years after his type 1 diabetes diagnosis. He exhibited parasympathetic denervation with resting tachycardia and exercise intolerance but also had evidence of orthostatic hypotension, which suggests sympathetic denervation. He did not have complete cardiovascular autonomic reflex testing, which would have been helpful, but improved with aggressive diabetes treatment and the increase of beta-blockade. It is important to identify these patients to understand their signs and symptoms and consider appropriate therapies. PMID:27034552

  19. Social functioning and autonomic nervous system sensitivity across vocal and musical emotion in Williams syndrome and autism spectrum disorder.

    PubMed

    Järvinen, Anna; Ng, Rowena; Crivelli, Davide; Neumann, Dirk; Arnold, Andrew J; Woo-VonHoogenstyn, Nicholas; Lai, Philip; Trauner, Doris; Bellugi, Ursula

    2016-01-01

    Both Williams syndrome (WS) and autism spectrum disorders (ASD) are associated with unusual auditory phenotypes with respect to processing vocal and musical stimuli, which may be shaped by the atypical social profiles that characterize the syndromes. Autonomic nervous system (ANS) reactivity to vocal and musical emotional stimuli was examined in 12 children with WS, 17 children with ASD, and 20 typically developing (TD) children, and related to their level of social functioning. The results of this small-scale study showed that after controlling for between-group differences in cognitive ability, all groups showed similar emotion identification performance across conditions. Additionally, in ASD, lower autonomic reactivity to human voice, and in TD, to musical emotion, was related to more normal social functioning. Compared to TD, both clinical groups showed increased arousal to vocalizations. A further result highlighted uniquely increased arousal to music in WS, contrasted with a decrease in arousal in ASD and TD. The ASD and WS groups exhibited arousal patterns suggestive of diminished habituation to the auditory stimuli. The results are discussed in the context of the clinical presentation of WS and ASD.

  20. Function and Pharmacology of Spinally-Projecting Sympathetic Pre-Autonomic Neurones in the Paraventricular Nucleus of the Hypothalamus

    PubMed Central

    Nunn, Nicolas; Womack, Matthew; Dart, Caroline; Barrett-Jolley, Richard

    2011-01-01

    The paraventricular nucleus (PVN) of the hypothalamus has been described as the "autonomic master controller". It co-ordinates critical physiological responses through control of the hypothalamic-pituitary-adrenal (HPA)-axis, and by modulation of the sympathetic and parasympathetic branches of the central nervous system. The PVN comprises several anatomical subdivisions, including the parvocellular/ mediocellular subdivision, which contains neurones projecting to the medulla and spinal cord. Consensus indicates that output from spinally-projecting sympathetic pre-autonomic neurones (SPANs) increases blood pressure and heart rate, and dysfunction of these neurones has been directly linked to elevated sympathetic activity during heart failure. The influence of spinally-projecting SPANs on cardiovascular function high-lights their potential as targets for future therapeutic drug development. Recent studies have demonstrated pharmacological control of these spinally-projecting SPANs with glutamate, GABA, nitric oxide, neuroactive steroids and a number of neuropeptides (including angiotensin, substance P, and corticotrophin-releasing factor). The underlying mechanism of control appears to be a state of tonic inhibition by GABA, which is then strengthened or relieved by the action of other modulators. The physiological function of spinally-projecting SPANs has been subject to some debate, and they may be involved in physiological stress responses, blood volume regulation, glucose regulation, thermoregulation and/or circadian rhythms. This review describes the pharmacology of PVN spinally-projecting SPANs and discusses their likely roles in cardiovascular control. PMID:22131936

  1. Social functioning and autonomic nervous system sensitivity across vocal and musical emotion in Williams syndrome and autism spectrum disorder.

    PubMed

    Järvinen, Anna; Ng, Rowena; Crivelli, Davide; Neumann, Dirk; Arnold, Andrew J; Woo-VonHoogenstyn, Nicholas; Lai, Philip; Trauner, Doris; Bellugi, Ursula

    2016-01-01

    Both Williams syndrome (WS) and autism spectrum disorders (ASD) are associated with unusual auditory phenotypes with respect to processing vocal and musical stimuli, which may be shaped by the atypical social profiles that characterize the syndromes. Autonomic nervous system (ANS) reactivity to vocal and musical emotional stimuli was examined in 12 children with WS, 17 children with ASD, and 20 typically developing (TD) children, and related to their level of social functioning. The results of this small-scale study showed that after controlling for between-group differences in cognitive ability, all groups showed similar emotion identification performance across conditions. Additionally, in ASD, lower autonomic reactivity to human voice, and in TD, to musical emotion, was related to more normal social functioning. Compared to TD, both clinical groups showed increased arousal to vocalizations. A further result highlighted uniquely increased arousal to music in WS, contrasted with a decrease in arousal in ASD and TD. The ASD and WS groups exhibited arousal patterns suggestive of diminished habituation to the auditory stimuli. The results are discussed in the context of the clinical presentation of WS and ASD. PMID:26248474

  2. Alteration of cardiovascular autonomic functions by vegetarian diets in postmenopausal women is related to LDL cholesterol levels.

    PubMed

    Fu, Chin-Hua; Yang, Cheryl C H; Lin, Chin-Lon; Kuo, Terry B J

    2008-04-30

    This study was designed to test the hypothesis that alteration of cardiovascular autonomic functions by vegetarian diets in healthy postmenopausal women is related to lipid metabolism. A total of 70 healthy postmenopausal women not on hormone therapy participated in this study: 35 were vegetarians (mean age 55.0 years) and 35 were omnivores (mean age 55.1 years). Cardiovascular autonomic functions and baroreflex sensitivity were evaluated by specific frequency-domain measures of heart rate variability (HRV) and arterial blood pressure fluctuation. The vegetarians had statistically significant lowered blood pressure, total cholesterol, low-density lipoprotein (LDL) cholesterol, triglyceride, and fasting glucose levels compared with the omnivores. The vegetarians exhibited a significant higher total power, low-frequency (LF; 0.04-0.15 Hz) and high-frequency (HF; 0.15-0.4 Hz) of HRV and increased baroreflex sensitivity measures [Brr(LF) and Brr(HF)] compared with the omnivores. Total power, LF and HF of HRV, Brr(LF), and Brr(HF) were significantly and negatively correlated with LDL-cholesterol concentrations (P < 0.01). We concluded that the increases of cardiac vagal activity and baroreflex sensitivity by vegetarian diets in postmenopausal women are inversely related to LDL-cholesterol levels.

  3. Autonomic nervous function and localization of cerebral activity during lavender aromatic immersion.

    PubMed

    Duan, Xudong; Tashiro, Manabu; Wu, Di; Yambe, Tomoyuki; Wang, Qingtian; Sasaki, Takehisa; Kumagai, Kazuaki; Luo, Yun; Nitta, Shin-ichi; Itoh, Masatoshi

    2007-01-01

    Changes in the autonomic nervous activity can be induced by various sensory and emotional stimuli. The authors examined whether the power spectral analysis of heart rate variability (HRV) could detect changes in autonomic tone following a lavender aroma treatment or not. Healthy young women (n=10, 23+/-3 years old) underwent continuous electrocardiographic (ECG) monitoring before and after (10, 20, 30 minutes) the lavender fragrance stimuli. HRV was expressed by three indices: low (0.04-0.15 Hz) and high (0.15-0.40 Hz) frequency components (nLF and nHF, respectively) as well as LF/HF ratio. Increases in the parasympathetic tone were observed after the lavender fragrance stimulus as seen as increases in the HF component and decreases in the LF/HF. Additional measurement with positron emission tomography (PET) demonstrated the regional metabolic activation in the orbitofrontal, posterior cingulate gyrus, brainstem, thalamus and cerebellum, as well as the reductions in the pre/post-central gyrus and frontal eye field. These results suggested that lavender aromatic treatment induced not only relaxation but also increased arousal level in these subjects. PMID:17361051

  4. Autonomic nervous function and localization of cerebral activity during lavender aromatic immersion.

    PubMed

    Duan, Xudong; Tashiro, Manabu; Wu, Di; Yambe, Tomoyuki; Wang, Qingtian; Sasaki, Takehisa; Kumagai, Kazuaki; Luo, Yun; Nitta, Shin-ichi; Itoh, Masatoshi

    2007-01-01

    Changes in the autonomic nervous activity can be induced by various sensory and emotional stimuli. The authors examined whether the power spectral analysis of heart rate variability (HRV) could detect changes in autonomic tone following a lavender aroma treatment or not. Healthy young women (n=10, 23+/-3 years old) underwent continuous electrocardiographic (ECG) monitoring before and after (10, 20, 30 minutes) the lavender fragrance stimuli. HRV was expressed by three indices: low (0.04-0.15 Hz) and high (0.15-0.40 Hz) frequency components (nLF and nHF, respectively) as well as LF/HF ratio. Increases in the parasympathetic tone were observed after the lavender fragrance stimulus as seen as increases in the HF component and decreases in the LF/HF. Additional measurement with positron emission tomography (PET) demonstrated the regional metabolic activation in the orbitofrontal, posterior cingulate gyrus, brainstem, thalamus and cerebellum, as well as the reductions in the pre/post-central gyrus and frontal eye field. These results suggested that lavender aromatic treatment induced not only relaxation but also increased arousal level in these subjects.

  5. A functional Magnetic Resonance Imaging study of neurohemodynamic abnormalities during emotion processing in subjects at high risk for schizophrenia

    PubMed Central

    Venkatasubramanian, Ganesan; Puthumana, Dawn Thomas K.; Jayakumar, Peruvumba N.; Gangadhar, B. N.

    2010-01-01

    Background: Emotion processing abnormalities are considered among the core deficits in schizophrenia. Subjects at high risk (HR) for schizophrenia also show these deficits. Structural neuroimaging studies examining unaffected relatives at high risk for schizophrenia have demonstrated neuroanatomical abnormalities involving neo-cortical and sub-cortical brain regions related to emotion processing. The brain functional correlates of emotion processing in these HR subjects in the context of ecologically valid, real-life dynamic images using functional Magnetic Resonance Imaging (fMRI) has not been examined previously. Aim: To examine the neurohemodynamic abnormalities during emotion processing in unaffected subjects at high risk for schizophrenia in comparison with age-, sex-, handedness- and education-matched healthy controls, using fMRI. Materials and Methods: HR subjects for schizophrenia (n=17) and matched healthy controls (n=16) were examined. The emotion processing of fearful facial expression was examined using a culturally appropriate and valid tool for Indian subjects. The fMRI was performed in a 1.5-T scanner during an implicit emotion processing paradigm. The fMRI analyses were performed using the Statistical Parametric Mapping 2 (SPM2) software. Results: HR subjects had significantly reduced brain activations in left insula, left medial frontal gyrus, left inferior frontal gyrus, right cingulate gyrus, right precentral gyrus and right inferior parietal lobule. Hypothesis-driven region-of-interest analysis revealed hypoactivation of right amygdala in HR subjects. Conclusions: Study findings suggest that neurohemodynamic abnormalities involving limbic and frontal cortices could be potential indicators for increased vulnerability toward schizophrenia. The clinical utility of these novel findings in predicting the development of psychosis needs to be evaluated. PMID:21267363

  6. Thyroid Function Status and Echocardiographic Abnormalities in Patients with Beta Thalassemia Major in Bahrain

    PubMed Central

    Garadah, Taysir S.; Mahdi, Najat A.; Jaradat, Ahmed M.; Hasan, Zuheir A.; Nagalla, Das S.

    2013-01-01

    Background: Thyroid gland dysfunction and echocardiographic cardiac abnormalities are well-documented in patients with transfusion dependent beta-thalassemia major (β-TM). Aim: This cross-sectional analytic study was conducted to investigate left ventricle (LV) diastolic and systolic function using pulsed Doppler (PD) and tissue Doppler (TD) echocardiography and correlate that with serum level thyroid stimulating hormone in patients with β-TM. Methods: The study was conducted on patients with β-TM (n = 110, age 15.9 ± 8.9 years) and compared with a control group (n = 109, age 15.8 ± 8.9 years). In all participants, echocardiographic indices of PD and TD were performed and blood samples were withdrawn for measuring the serum level of TSH, free T4, and ferritin. A linear regression analysis was performed on TSH level as the dependent variable and serum ferritin as independent. Stepwise multiple regression analysis was used to determine the odds ratio of different biochemical and echo variables on the risk of developing hypothyroidism. Results: Patients with β-TM compared with controls had thicker LV septal wall index (0.65 ± 0.26 vs. 0.44 ± 0.21 cm/M2, P < 0.001), posterior wall index (0.65 ± 0.23 vs. 0.43 ± 0.21 cm/m2, P < 0.01) and larger LVEDD index (4.35 ± 0.69 vs.3.88 ± 0.153 mm/m2, P < 0.001). In addition, β-TM patients had higher transmitral E wave velocity (E) (70.81 ± 10.13 vs. 57.53 ± 10.13 cm/s, P = 0.02) and E/A ratio (1.54 ± 0.18 vs. 1.23 ± 0.17, P < 0.01) and shorter deceleration time (DT) (170.53 ± 13.3 vs. 210.50 ± 19.20 m sec, P < 0.01). Furthermore, the ratio of transmitral E wave velocity to the tissue Doppler E wave at the basal septal mitral annulus (E/Em) was significantly higher in the β-TM group (19.68 ± 2.81 vs. 13.86 ± 1.41, P < 0.05). The tissue Doppler systolic wave (Sm) velocity and the early diastolic wave (Em) were significantly lower in the β-TM group compared with controls with Sm, 4.82 ± 1.2 vs. 6.22 ± 2.1 mm

  7. Abnormal Intrinsic Functional Hubs in Severe Male Obstructive Sleep Apnea: Evidence from a Voxel-Wise Degree Centrality Analysis

    PubMed Central

    Shao, Yi; Gong, Honghan; Zhang, Wei; Zeng, Xianjun; Ye, Chenglong; Nie, Si; Chen, Liting; Peng, Dechang

    2016-01-01

    Purpose Obstructive sleep apnea (OSA) has been associated with changes in brain structure and regional function in certain brain areas. However, the functional features of network organization in the whole brain remain largely uncertain. The purpose of this study was to identify the OSA-related spatial centrality distribution of the whole brain functional network and to investigate the potential altered intrinsic functional hubs. Methods Forty male patients with newly confirmed severe OSA on polysomnography, and well-matched good sleepers, participated in this study. All participants underwent a resting-state functional MRI scan and clinical and cognitive evaluation. Voxel-wise degree centrality (DC) was measured across the whole brain, and group difference in DC was compared. The relationship between the abnormal DC value and clinical variables was assessed using a linear correlation analysis. Results Remarkably similar spatial distributions of the functional hubs (high DC) were found in both groups. However, OSA patients exhibited a pattern of significantly reduced regional DC in the left middle occipital gyrus, posterior cingulate cortex, left superior frontal gyrus, and bilateral inferior parietal lobule, and DC was increased in the right orbital frontal cortex, bilateral cerebellum posterior lobes, and bilateral lentiform nucleus, including the putamen, extending to the hippocampus, and the inferior temporal gyrus, which overlapped with the functional hubs. Furthermore, a linear correlation analysis revealed that the DC value in the posterior cingulate cortex and left superior frontal gyrus were positively correlated with Montreal cognitive assessment scores, The DC value in the left middle occipital gyrus and bilateral inferior parietal lobule were negatively correlated with apnea-hypopnea index and arousal index in OSA patients. Conclusion Our findings suggest that OSA patients exhibited specific abnormal intrinsic functional hubs including relatively

  8. Treatment of Posttraumatic Abdominal Autonomic Neuropathy Manifesting as Functional Dyspepsia and Chronic Constipation: An Integrative East-West Approach.

    PubMed

    Shubov, Andrew; Taw, Lawrence

    2015-07-01

    A 52-year-old male with a history of spinal cord injury and cauda equina syndrome resulting in neurogenic bladder presented with chronic constipation and functional dyspepsia that was refractory to medical management. He was treated with an integrative East-West approach including acupuncture, trigger point injections, and Tui Na massage. Both his pain and constipation improved after a series of treatments, and this improvement was largely sustained at 2-year follow-up. This patient's symptoms are consistent with damage to the visceral parasympathetic nervous system. Interestingly, many studies evaluating the mechanisms of acupuncture point to restoration of parasympathetic tone as a mechanism of action. In this article, we describe a case of complex functional gastrointestinal disorders associated with posttraumatic autonomic neuropathy that was refractory to pharmacotherapy and was successfully treated with an integrative East-West approach.

  9. Treatment of Posttraumatic Abdominal Autonomic Neuropathy Manifesting as Functional Dyspepsia and Chronic Constipation: An Integrative East-West Approach

    PubMed Central

    Taw, Lawrence

    2015-01-01

    A 52-year-old male with a history of spinal cord injury and cauda equina syndrome resulting in neurogenic bladder presented with chronic constipation and functional dyspepsia that was refractory to medical management. He was treated with an integrative East-West approach including acupuncture, trigger point injections, and Tui Na massage. Both his pain and constipation improved after a series of treatments, and this improvement was largely sustained at 2-year follow-up. This patient's symptoms are consistent with damage to the visceral parasympathetic nervous system. Interestingly, many studies evaluating the mechanisms of acupuncture point to restoration of parasympathetic tone as a mechanism of action. In this article, we describe a case of complex functional gastrointestinal disorders associated with posttraumatic autonomic neuropathy that was refractory to pharmacotherapy and was successfully treated with an integrative East-West approach PMID:26331105

  10. Preserved functional autonomic phenotype in adult mice overexpressing moderate levels of human alpha‐synuclein in oligodendrocytes

    PubMed Central

    Tank, Jens; da Costa‐Goncalves, Andrey C.; Kamer, Ilona; Qadri, Fatimunnisa; Ubhi, Kiren; Rockenstein, Edward; Diedrich, André; Masliah, Eliezer; Gross, Volkmar; Jordan, Jens

    2014-01-01

    Abstract Mice overexpressing human alpha‐synuclein in oligodendrocytes (MBP1‐α‐syn) recapitulate some key functional and neuropathological features of multiple system atrophy (MSA). Whether or not these mice develop severe autonomic failure, which is a key feature of human MSA, remains unknown. We explored cardiovascular autonomic regulation using long‐term blood pressure (BP) radiotelemetry and pharmacological testing. We instrumented 12 MBP1‐α‐syn mice and 11 wild‐type mice aged 9 months for radiotelemetry. Animals were tested with atropine, metoprolol, clonidine, and trimethaphan at 9 and 12 months age. We applied spectral and cross‐spectral analysis to assess heart rate (HR) and BP variability. At 9 months of age daytime BP (transgenic: 101 ± 2 vs. wild type: 99 ± 2 mmHg) and HR (497 ± 11 vs. 505 ± 16 beats/min) were similar. Circadian BP and HR rhythms were maintained. Nighttime BP (109 ± 2 vs. 108 ± 2 mmHg) and HR (575 ± 15 vs. 569 ± 14 beats/min), mean arterial BP responses to trimethaphan (−21 ± 8 vs. −10 ± 5 mmHg, P = 0.240) and to clonidine (−8 ± 3 vs. −5 ± 2 mmHg, P = 0.314) were similar. HR responses to atropine (+159 ± 24 vs. +146 ± 22 beats/min), and to clonidine (−188 ± 21 vs. −163 ± 33 beats/min) did not differ between strains. Baroreflex sensitivity (4 ± 1 vs. 4 ± 1 msec/mmHg) and HR variability (total power, 84 ± 17 vs. 65 ± 21 msec²) were similar under resting conditions and during pharmacological testing. Repeated measurements at 12 months of age provided similar results. In mice, moderate overexpression of human alpha‐synuclein in oligodendrocytes is not sufficient to induce overt autonomic failure. Additional mechanisms may be required to express the autonomic failure phenotype including higher levels of expression or more advanced age. PMID:25428949

  11. Clinical validation of software for a versatile variability analyzer: Assessment of autonomic function

    PubMed Central

    Ananthakrishnan, T. S.; Jindal, G. D.; Sinha, Vineet; Jain, Rajesh K.; Kataria, S. K.; Deshpande, Alaka K.

    2007-01-01

    Study of physiological variability is an upcoming area of research having manifold clinical applications. Considerable work has been done on heart rate variability and blood pressure variability during the past four decades. Electronics division, Bhabha Atomic Research Centre, has developed an instrument called medical analyzer, which can be used to study several variabilities simultaneously. This instrument has been used to collect data from control subjects and patients with established diagnosis. The data has been analyzed with the help of a software package developed for this purpose and has been found to be consistent with expected manifestations of the disease on the autonomic nervous system. The description of the software package and results of the study are briefly described in this paper. PMID:21157528

  12. Ictal Cardiac Ryhthym Abnormalities

    PubMed Central

    Ali, Rushna

    2016-01-01

    Cardiac rhythm abnormalities in the context of epilepsy are a well-known phenomenon. However, they are under-recognized and often missed. The pathophysiology of these events is unclear. Bradycardia and asystole are preceded by seizure onset suggesting ictal propagation into the cortex impacting cardiac autonomic function, and the insula and amygdala being possible culprits. Sudden unexpected death in epilepsy (SUDEP) refers to the unanticipated death of a patient with epilepsy not related to status epilepticus, trauma, drowning, or suicide. Frequent refractory generalized tonic-clonic seizures, anti-epileptic polytherapy, and prolonged duration of epilepsy are some of the commonly identified risk factors for SUDEP. However, the most consistent risk factor out of these is an increased frequency of generalized tonic–clonic seizures (GTC). Prevention of SUDEP is extremely important in patients with chronic, generalized epilepsy. Since increased frequency of GTCS is the most consistently reported risk factor for SUDEP, effective seizure control is the most important preventive strategy. PMID:27347227

  13. Ictal Cardiac Ryhthym Abnormalities.

    PubMed

    Ali, Rushna

    2016-01-01

    Cardiac rhythm abnormalities in the context of epilepsy are a well-known phenomenon. However, they are under-recognized and often missed. The pathophysiology of these events is unclear. Bradycardia and asystole are preceded by seizure onset suggesting ictal propagation into the cortex impacting cardiac autonomic function, and the insula and amygdala being possible culprits. Sudden unexpected death in epilepsy (SUDEP) refers to the unanticipated death of a patient with epilepsy not related to status epilepticus, trauma, drowning, or suicide. Frequent refractory generalized tonic-clonic seizures, anti-epileptic polytherapy, and prolonged duration of epilepsy are some of the commonly identified risk factors for SUDEP. However, the most consistent risk factor out of these is an increased frequency of generalized tonic-clonic seizures (GTC). Prevention of SUDEP is extremely important in patients with chronic, generalized epilepsy. Since increased frequency of GTCS is the most consistently reported risk factor for SUDEP, effective seizure control is the most important preventive strategy. PMID:27347227

  14. Liver Function Test Abnormalities in Depressed Patients Treated with Antidepressants: A Real-World Systematic Observational Study in Psychiatric Settings

    PubMed Central

    Verstuyft, Céline; Corruble, Emmanuelle; Perlemuter, Gabriel; Colle, Romain

    2016-01-01

    Background Concerning the risk of antidepressant induced liver injury, it is not clear whether psychiatrists perform a liver function test (LFT) and whether an increase in aminotransferase levels should contraindicate antidepressant treatment. Aim To evaluate LFT availability, the prevalence of LFT abnormalities and the probable cause of an altered LFT in patients with a major depressive episode (MDE) requiring an antidepressant drug. Methods We studied LFT evaluation in a real world psychiatric setting, in a sample of 321 consecutive patients with a current major depressive episode (MDE) requiring an antidepressant drug treatment, but without current alcohol or drug dependence or unstable medical disease. Results An LFT is performed in 36.1% (116/321) of depressed patients. One fifth of antidepressant-treated patients who had an LFT evaluation had abnormal results. The most frequent causes of LFT abnormalities were: NAFLD (nonalcoholic fatty liver disease) (7/321; 2.1%), acute alcohol consumption (4/321; 1.2%), antidepressant-induced liver injury (3/321; 0.9%), hepatitis C virus infection (2/321; 0.6%) and heart failure (1/321; 0.3%). The cause of LFT abnormalities was unknown in 32% of patients (8/25) due to the absence of etiological investigations. Conclusion These results demonstrate that an LFT is infrequently performed by psychiatrists in depressed patients requiring an antidepressant drug. Baseline LFT assessment and observations during the first six months of antidepressant treatment may be useful for detection of patients with pre-existing liver disease such as NAFLD, and early identification of cases of antidepressant-induced liver injury. An increase in aminotransferase levels may be related to an underlying liver disease, but does not contraindicate antidepressant treatment. PMID:27171561

  15. Respiratory symptoms in rheumatoid arthritis: relation to pulmonary abnormalities detected by high-resolution CT and pulmonary functional testing.

    PubMed

    Youssef, Amir A; Machaly, Shereen A; El-Dosoky, Mohammed E; El-Maghraby, Nermeen M

    2012-07-01

    Pulmonary disease is the most frequent and among the most severe extra-articular manifestation of rheumatoid arthritis (RA). However, this issue has not been sufficiently studied in Egyptian patients. The objectives of the present study are to investigate the prevalence and types of pulmonary involvement using high-resolution computed tomography scan (HRCT) and pulmonary function tests (PFT) and evaluate the association between respiratory symptoms and RA-lung disease in a group of Egyptian RA patients. Thirty-six RA patients were recruited; 34 females (94.4%) and 2 males (5.6%) with median age of 48.5 years, and none of them was smoker. Detailed medical and drug histories were obtained. PFT, plain X-ray of the chest, and HRCT were performed to all subjects involved. Nearly 64% of RA patients demonstrated abnormalities in PFT and 47% in HRCT. Mixed restrictive and obstructive pattern was the commonest. Nearly two-thirds of our patients reported one or more pulmonary symptom whether dyspnea, cough, wheezing, or phlegm. Dyspnea was the most frequent symptom. Respiratory symptoms were statistically more common in patients with lung disease. The advanced age, high radiological score, and severity of rheumatoid disease were found to be predictive of lung involvement. Among respiratory symptoms, dyspnea and cough were associated with any pulmonary abnormalities. When specific pulmonary abnormalities were considered, only dyspnea was identified as predictor for restriction. For obstructive abnormality, both cough and wheezing provided valid prediction. We conclude that pulmonary involvement is a common manifestation in Egyptian RA patients, and the pattern of involvement is generally consistent with other studies that were performed worldwide. Specific respiratory symptoms could be used as practical, easy, and cost-effective method, especially in older and with more severe RA patients, to discriminate patients in need of subsequent PFT and HRCT imaging.

  16. Patterns of Sensitivity to Emotion in Children with Williams Syndrome and Autism: Relations between Autonomic Nervous System Reactivity and Social Functioning

    ERIC Educational Resources Information Center

    Järvinen, Anna; Ng, Rowena; Crivelli, Davide; Neumann, Dirk; Grichanik, Mark; Arnold, Andrew J.; Lai, Philip; Trauner, Doris; Bellugi, Ursula

    2015-01-01

    Williams syndrome (WS) and autism spectrum disorder (ASD) are associated with atypical social-emotional functioning. Affective visual stimuli were used to assess autonomic reactivity and emotion identification, and the social responsiveness scale was used to determine the level social functioning in children with WS and ASD contrasted with typical…

  17. Sex ratio of congenital abnormalities in the function of maternal age: a population-based study.

    PubMed

    Csermely, Gyula; Urbán, Robert; Czeizel, Andrew E; Veszprémi, Béla

    2015-05-01

    Maternal age effect is well-known in the origin of numerical chromosomal aberrations and some isolated congenital abnormalities (CAs). The sex ratio (SR), i.e. number of males divided by the number of males and females together, of most CAs deviates from the SR of newborn population (0.51). The objective of this analysis was to evaluate the possible association of maternal age with the SR of isolated CAs in a population-based large dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996. First, SR of 24 CA entities/groups was estimated in 21,494 patients with isolated CA. In the next step SR of different maternal age groups was compared to the mean SR of the given CA-groups. The SR of four CA-groups showed some deviation in certain maternal age groups. Cases with anencephaly had female excess in young mothers (<25 years). Cases with skull's CAs particularly craniosynostosis had a male excess in cases born to women over 30 years. Two other CA groups (cleft lip ± palate and valvar pulmonic stenosis within the group of right-sided obstructive defect of heart) had significant deviation in SR of certain maternal age groups from the mean SR, but these deviations were not harmonized with joining age groups and thus were considered as a chance effect due to multiple testing. In conclusion, our study did not suggest that in general SR of isolated CAs might be modified by certain maternal age groups with some exception such as anencephaly and craniosynostosis.

  18. Catechin averts experimental diabetes mellitus-induced vascular endothelial structural and functional abnormalities.

    PubMed

    Bhardwaj, Pooja; Khanna, Deepa; Balakumar, Pitchai

    2014-03-01

    Diabetes mellitus is associated with an induction of vascular endothelial dysfunction (VED), an initial event that could lead to the pathogenesis of atherosclerosis and hypertension. Previous studies showed that catechin, a key component of green tea, possesses vascular beneficial effects. We investigated the effect of catechin hydrate in diabetes mellitus-induced experimental vascular endothelial abnormalities (VEA). Streptozotocin (50 mg/kg, i.p., once) administration to rats produced diabetes mellitus, which subsequently induced VEA in 8 weeks by markedly attenuating acetylcholine-induced endothelium-dependent relaxation in the isolated aortic ring preparation, decreasing aortic and serum nitrite/nitrate concentrations and impairing aortic endothelial integrity. These abnormalities in diabetic rats were accompanied with elevated aortic superoxide anion generation and serum lipid peroxidation in addition to hyperglycemia. Catechin hydrate treatment (50 mg/kg/day p.o., 3 weeks) markedly prevented diabetes mellitus-induced VEA and vascular oxidative stress. Intriguingly, in vitro incubation of L-NAME (100 μM), an inhibitor of nitric oxide synthase, or Wortmannin (100 nM), a selective inhibitor of phosphatidylinositol 3-kinase (PI3K), markedly prevented catechin hydrate-induced improvement in acetylcholine-provoked endothelium-dependent relaxation in the diabetic rat aorta. Moreover, catechin hydrate treatment considerably reduced the elevated level of serum glucose in diabetic rats. In conclusion, catechin hydrate treatment prevents diabetes mellitus-induced VED through the activation of endothelial PI3K signal and subsequent activation of eNOS and generation of nitric oxide. In addition, reduction in high glucose, vascular oxidative stress, and lipid peroxidation might additionally contribute to catechin hydrate-associated prevention of diabetic VEA. PMID:24048981

  19. Sex ratio of congenital abnormalities in the function of maternal age: a population-based study.

    PubMed

    Csermely, Gyula; Urbán, Robert; Czeizel, Andrew E; Veszprémi, Béla

    2015-05-01

    Maternal age effect is well-known in the origin of numerical chromosomal aberrations and some isolated congenital abnormalities (CAs). The sex ratio (SR), i.e. number of males divided by the number of males and females together, of most CAs deviates from the SR of newborn population (0.51). The objective of this analysis was to evaluate the possible association of maternal age with the SR of isolated CAs in a population-based large dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996. First, SR of 24 CA entities/groups was estimated in 21,494 patients with isolated CA. In the next step SR of different maternal age groups was compared to the mean SR of the given CA-groups. The SR of four CA-groups showed some deviation in certain maternal age groups. Cases with anencephaly had female excess in young mothers (<25 years). Cases with skull's CAs particularly craniosynostosis had a male excess in cases born to women over 30 years. Two other CA groups (cleft lip ± palate and valvar pulmonic stenosis within the group of right-sided obstructive defect of heart) had significant deviation in SR of certain maternal age groups from the mean SR, but these deviations were not harmonized with joining age groups and thus were considered as a chance effect due to multiple testing. In conclusion, our study did not suggest that in general SR of isolated CAs might be modified by certain maternal age groups with some exception such as anencephaly and craniosynostosis. PMID:25354028

  20. A new method of assessing cardiac autonomic function and its comparison with spectral analysis and coefficient of variation of R-R interval.

    PubMed

    Toichi, M; Sugiura, T; Murai, T; Sengoku, A

    1997-01-12

    A new non-linear method of assessing cardiac autonomic function was examined in a pharmacological experiment in ten healthy volunteers. The R-R interval data obtained under a control condition and in autonomic blockade by atropine and by propranolol were analyzed by each of the new methods employing Lorenz plot, spectral analysis and the coefficient of variation. With our method we derived two measures, the cardiac vagal index and the cardiac sympathetic index, which indicate vagal and sympathetic function separately. These two indices were found to be more reliable than those obtained by the other two methods. We anticipate that the non-invasive assessment of short-term cardiac autonomic function will come to be performed more reliably and conveniently by this method.

  1. Exercise and the autonomic nervous system.

    PubMed

    Fu, Qi; Levine, Benjamin D

    2013-01-01

    The autonomic nervous system plays a crucial role in the cardiovascular response to acute (dynamic) exercise in animals and humans. During exercise, oxygen uptake is a function of the triple-product of heart rate and stroke volume (i.e., cardiac output) and arterial-mixed venous oxygen difference (the Fick principle). The degree to which each of the variables can increase determines maximal oxygen uptake (V˙O2max). Both "central command" and "the exercise pressor reflex" are important in determining the cardiovascular response and the resetting of the arterial baroreflex during exercise to precisely match systemic oxygen delivery with metabolic demand. In general, patients with autonomic disorders have low levels of V˙O2max, indicating reduced physical fitness and exercise capacity. Moreover, the vast majority of the patients have blunted or abnormal cardiovascular response to exercise, especially during maximal exercise. There is now convincing evidence that some of the protective and therapeutic effects of chronic exercise training are related to the impact on the autonomic nervous system. Additionally, training induced improvement in vascular function, blood volume expansion, cardiac remodeling, insulin resistance and renal-adrenal function may also contribute to the protection and treatment of cardiovascular, metabolic and autonomic disorders. Exercise training also improves mental health, helps to prevent depression, and promotes or maintains positive self-esteem. Moderate-intensity exercise at least 30 minutes per day and at least 5 days per week is recommended for the vast majority of people. Supervised exercise training is preferable to maximize function capacity, and may be particularly important for patients with autonomic disorders. PMID:24095123

  2. Abnormal Functional Lateralization and Activity of Language Brain Areas in Typical Specific Language Impairment (Developmental Dysphasia)

    ERIC Educational Resources Information Center

    de Guibert, Clement; Maumet, Camille; Jannin, Pierre; Ferre, Jean-Christophe; Treguier, Catherine; Barillot, Christian; Le Rumeur, Elisabeth; Allaire, Catherine; Biraben, Arnaud

    2011-01-01

    Atypical functional lateralization and specialization for language have been proposed to account for developmental language disorders, yet results from functional neuroimaging studies are sparse and inconsistent. This functional magnetic resonance imaging study compared children with a specific subtype of specific language impairment affecting…

  3. Preserved local but disrupted contextual figure-ground influences in an individual with abnormal function of intermediate visual areas.

    PubMed

    Brooks, Joseph L; Gilaie-Dotan, Sharon; Rees, Geraint; Bentin, Shlomo; Driver, Jon

    2012-06-01

    Visual perception depends not only on local stimulus features but also on their relationship to the surrounding stimulus context, as evident in both local and contextual influences on figure-ground segmentation. Intermediate visual areas may play a role in such contextual influences, as we tested here by examining LG, a rare case of developmental visual agnosia. LG has no evident abnormality of brain structure and functional neuroimaging showed relatively normal V1 function, but his intermediate visual areas (V2/V3) function abnormally. We found that contextual influences on figure-ground organization were selectively disrupted in LG, while local sources of figure-ground influences were preserved. Effects of object knowledge and familiarity on figure-ground organization were also significantly diminished. Our results suggest that the mechanisms mediating contextual and familiarity influences on figure-ground organization are dissociable from those mediating local influences on figure-ground assignment. The disruption of contextual processing in intermediate visual areas may play a role in the substantial object recognition difficulties experienced by LG.

  4. Microbial community structure and function during abnormal curve development of substrate-induced respiration measurements.

    PubMed

    Bartling, Johanna; Kotzerke, Anja; Mai, Maike; Esperschütz, Jürgen; Buegger, Franz; Schloter, Michael; Wilke, Berndt-Michael

    2009-12-01

    Soil respiration measurements are an established method to test the abundance, activity and vitality of the soil microorganisms. However, abnormal progressions of soil respiration curves impede a clear interpretation of the data. The aim of this study was to investigate the changes in the microbial structure during the formation of phenomena like double peaks and terraces by analysis of the PLFA composition (phospholipid fatty acid composition). Moreover, 13C labeled glucose was used as substrate; therefore it was possible to measure delta13C values both within the PLFA fraction as well as within the carbon dioxide evolved during respiration. As contaminants trinitrotoluene, cycloheximide, and hexadecane were used. The results showed that the appearance of double peaks was mainly related to the growth of fungi with the marker 18:2delta9,12 due to a toxic effect of trinitrotoluene and cycloheximide. In contrast, the phenomenon of terrace formation was related to the utilization of hexadecane as a carbon source mainly by bacteria.

  5. A Computationally Inexpensive Optimal Guidance via Radial-Basis-Function Neural Network for Autonomous Soft Landing on Asteroids.

    PubMed

    Zhang, Peng; Liu, Keping; Zhao, Bo; Li, Yuanchun

    2015-01-01

    Optimal guidance is essential for the soft landing task. However, due to its high computational complexities, it is hardly applied to the autonomous guidance. In this paper, a computationally inexpensive optimal guidance algorithm based on the radial basis function neural network (RBFNN) is proposed. The optimization problem of the trajectory for soft landing on asteroids is formulated and transformed into a two-point boundary value problem (TPBVP). Combining the database of initial states with the relative initial co-states, an RBFNN is trained offline. The optimal trajectory of the soft landing is determined rapidly by applying the trained network in the online guidance. The Monte Carlo simulations of soft landing on the Eros433 are performed to demonstrate the effectiveness of the proposed guidance algorithm. PMID:26367382

  6. A Computationally Inexpensive Optimal Guidance via Radial-Basis-Function Neural Network for Autonomous Soft Landing on Asteroids.

    PubMed

    Zhang, Peng; Liu, Keping; Zhao, Bo; Li, Yuanchun

    2015-01-01

    Optimal guidance is essential for the soft landing task. However, due to its high computational complexities, it is hardly applied to the autonomous guidance. In this paper, a computationally inexpensive optimal guidance algorithm based on the radial basis function neural network (RBFNN) is proposed. The optimization problem of the trajectory for soft landing on asteroids is formulated and transformed into a two-point boundary value problem (TPBVP). Combining the database of initial states with the relative initial co-states, an RBFNN is trained offline. The optimal trajectory of the soft landing is determined rapidly by applying the trained network in the online guidance. The Monte Carlo simulations of soft landing on the Eros433 are performed to demonstrate the effectiveness of the proposed guidance algorithm.

  7. A Computationally Inexpensive Optimal Guidance via Radial-Basis-Function Neural Network for Autonomous Soft Landing on Asteroids

    PubMed Central

    Zhang, Peng; Liu, Keping; Zhao, Bo; Li, Yuanchun

    2015-01-01

    Optimal guidance is essential for the soft landing task. However, due to its high computational complexities, it is hardly applied to the autonomous guidance. In this paper, a computationally inexpensive optimal guidance algorithm based on the radial basis function neural network (RBFNN) is proposed. The optimization problem of the trajectory for soft landing on asteroids is formulated and transformed into a two-point boundary value problem (TPBVP). Combining the database of initial states with the relative initial co-states, an RBFNN is trained offline. The optimal trajectory of the soft landing is determined rapidly by applying the trained network in the online guidance. The Monte Carlo simulations of soft landing on the Eros433 are performed to demonstrate the effectiveness of the proposed guidance algorithm. PMID:26367382

  8. Abnormal resting-state functional connectivity of the left caudate nucleus in obsessive-compulsive disorder.

    PubMed

    Chen, Yunhui; Juhás, Michal; Greenshaw, Andrew J; Hu, Qiang; Meng, Xin; Cui, Hongsheng; Ding, Yongzhuo; Kang, Lu; Zhang, Yubo; Wang, Yuhua; Cui, Guangcheng; Li, Ping

    2016-06-01

    Altered brain activities in the cortico-striato-thalamocortical (CSTC) circuitry are implicated in the pathophysiology of obsessive-compulsive disorder (OCD). However, whether the underlying changes occur only within this circuitry or in large-scale networks is still not thoroughly understood. This study performed voxel-based functional connectivity analysis on resting-state functional magnetic resonance imaging (fMRI) data from thirty OCD patients and thirty healthy controls to investigate whole-brain intrinsic functional connectivity patterns in OCD. Relative to the healthy controls, OCD patients showed decreased functional connectivity within the CSTC circuitry but increased functional connectivity in other brain regions. Furthermore, decreased left caudate nucleus-thalamus connectivity within the CSTC circuitry was positively correlated with the illness duration of OCD. This study provides additional evidence that CSTC circuitry may play an essential role and alteration of large-scale brain networks may be involved in the pathophysiology of OCD. PMID:27143323

  9. Modification of the association of bisphenol A with abnormal liver function by polymorphisms of oxidative stress-related genes.

    PubMed

    Kim, Jin Hee; Lee, Mee-Ri; Hong, Yun-Chul

    2016-05-01

    Some studies suggested oxidative stress as a possible mechanism for the relation between exposure to bisphenol A (BPA) and liver damage. Therefore, we evaluated modification of genetic polymorphisms of cyclooxygenase 2 (COX2 or PTGS2), epoxide hydrolase 1 (EPHX1), catalase (CAT), and superoxide dismutase 2 (SOD2 or MnSOD), which are oxidative stress-related genes, on the relation between exposure to BPA and liver function in the elderly. We assessed the association of visit-to-visit variations in BPA exposure with abnormal liver function by each genotype or haplotype after controlling for age, sex, BMI, alcohol consumption, exercise, urinary cotinine levels, and low density lipoprotein cholesterol using a GLIMMIX model. A significant association of BPA with abnormal liver function was observed only in participants with COX2 GG genotype at rs5277 (odds ratio (OR)=3.04 and p=0.0231), CAT genotype at rs769218 (OR=4.16 and p=0.0356), CAT CT genotype at rs769217 (OR=4.19 and p=0.0348), SOD2 TT genotype at rs4880 (OR=2.59 and p=0.0438), or SOD2 GG genotype at rs2758331 (OR=2.57 and p=0.0457). Moreover, we also found higher OR values in participants with a pair of G-G haplotypes for COX2 (OR=2.81 and p=0.0384), G-C-A haplotype for EPHX1 (OR=4.63 and p=0.0654), A-T haplotype for CAT (OR=4.48 and p=0.0245), or T-G-A haplotype for SOD2 (OR=2.91 and p=0.0491) compared with those with the other pair of haplotypes for each gene. Furthermore, the risk score composed of 4 risky pair of haplotypes showed interactive effect with BPA on abnormal liver function (p=0.0057). Our study results suggest that genetic polymorphisms of COX2, EPHX1, CAT, and SOD2 modify the association of BPA with liver function. PMID:26922413

  10. Increasing or stabilizing renal epoxyeicosatrienoic acid production attenuates abnormal renal function and hypertension in obese rats.

    PubMed

    Huang, Hui; Morisseau, Christophe; Wang, JingFeng; Yang, Tianxin; Falck, John R; Hammock, Bruce D; Wang, Mong-Heng

    2007-07-01

    Since epoxyeicosatrienoic acids (EETs) affect sodium reabsorption in renal tubules and dilate the renal vasculature, we have examined their effects on renal hemodynamics and sodium balance in male rats fed a high-fat (HF) diet by fenofibrate, a peroxisome proliferator-activated receptor-alpha (PPAR-alpha) agonist and an inducer of cytochrome P-450 (CYP) epoxygenases; by N-methanesulfonyl-6-(2-proparyloxyphenyl)hexanamide (MSPPOH), a selective EET biosynthesis inhibitor; and by 12-(3-adamantane-1-yl-ureido)dodecanoic acid (AUDA), a selective inhibitor of soluble epoxide hydrolase. In rats treated with fenofibrate (30 mg.kg(-1).day(-1) ig) or AUDA (50 mg/l in drinking water) for 2 wk, mean arterial pressure, renal vascular resistance, and glomerular filtration rate were lower but renal blood flow was higher than in vehicle-treated control rats. In addition, fenofibrate and AUDA decreased cumulative sodium balance in the HF rats. Treatment with MSPPOH (20 mg.kg(-1).day(-1) iv) + fenofibrate for 2 wk reversed renal hemodynamics and sodium balance to the levels in control HF rats. Moreover, fenofibrate caused a threefold increase in renal cortical CYP epoxygenase activity, whereas the fenofibrate-induced elevation of this activity was attenuated by MSPPOH. Western blot analysis showed that fenofibrate induced the expression of CYP epoxygenases in renal cortex and microvessels and that the induction effect of fenofibrate was blocked by MSPPOH. These results demonstrate that the fenofibrate-induced increase of CYP epoxygenase expression and the AUDA-induced stabilization of EET production in the kidneys cause renal vascular dilation and reduce sodium retention, contributing to the improvement of abnormal renal hemodynamics and hypertension in HF rats.

  11. Degranulation and abnormal bactericidal function of granulocytes procured by reversible adhesion to nylon wool.

    PubMed

    Klock, J C; Bainton, D F

    1976-07-01

    Granylocyte bactericidal capacity, chemotaxis, hexose monophosphate shung activity (before and after phagocytic stimulus), and quantitative nitroblue tetrazolium reduction and enzyme content were examined in cells obtained by filtration leukaphresis (FL) and continuous-flow centrifugation (CFC). A decrease in the bactericidal efficiency of FL-produced cells compared to that of both normal and CFC-procured granulocytes was found; the decrease was 17% with a cell-to-bacteria ratio of 5:1, and 55% with a 1:1 ratio. Moreover, FL-acquired cells were often vacuolated and consistently contained less acid phosphatase and beta-glucuronidase than did normal granulocytes. When normal cells were incubated for 1-2 hr with nylon wool, 30% of the total acid phosphatase and beta-glucuronidase was released, with no evidence of cell death, thus suggesting degranulation. Similar results were obtained with glass, cotton, or polysulfone plastic fibers. Electron microscopic and peroxidase cytochemical studies of the adherence of normal granulocytes to nylon fibers were also carried out. After 30 min of incubation, cell-to-fiber attachment and cellular aggregation had occurred, although the cells per se appeared normal. After 60 and 120 min, other changes became apparent: (1) a decrease in the amount of cytoplasmic granules; (2) large, intracytoplasmic vaculoles; and (3) extracellular peroxidase on fiber surfaces. We conclude that granulocytes obtained by adherence to nylon fibers show both morphological and biochemical evidence of degranulation and diminished bactericidal capacity, and that these abnormalities may be causally related to decreased granulocyte survival in transfusion recipients.

  12. Autonomic neuropathies

    NASA Technical Reports Server (NTRS)

    Low, P. A.

    1998-01-01

    A limited autonomic neuropathy may underlie some unusual clinical syndromes, including the postural tachycardia syndrome, pseudo-obstruction syndrome, heat intolerance, and perhaps chronic fatigue syndrome. Antibodies to autonomic structures are common in diabetes, but their specificity is unknown. The presence of autonomic failure worsens prognosis in the diabetic state. Some autonomic neuropathies are treatable. Familial amyloid polyneuropathy may respond to liver transplantation. There are anecdotal reports of acute panautonomic neuropathy responding to intravenous gamma globulin. Orthostatic hypotension may respond to erythropoietin or midodrine.

  13. P53 functional abnormality in mesenchymal stem cells promotes osteosarcoma development

    PubMed Central

    Velletri, T; Xie, N; Wang, Y; Huang, Y; Yang, Q; Chen, X; Chen, Q; Shou, P; Gan, Y; Cao, G; Melino, G; Shi, Y

    2016-01-01

    It has been shown that p53 has a critical role in the differentiation and functionality of various multipotent progenitor cells. P53 mutations can lead to genome instability and subsequent functional alterations and aberrant transformation of mesenchymal stem cells (MSCs). The significance of p53 in safeguarding our body from developing osteosarcoma (OS) is well recognized. During bone remodeling, p53 has a key role in negatively regulating key factors orchestrating the early stages of osteogenic differentiation of MSCs. Interestingly, changes in the p53 status can compromise bone homeostasis and affect the tumor microenvironment. This review aims to provide a unique opportunity to study the p53 function in MSCs and OS. In the context of loss of function of p53, we provide a model for two sources of OS: MSCs as progenitor cells of osteoblasts and bone tumor microenvironment components. Standing at the bone remodeling point of view, in this review we will first explain the determinant function of p53 in OS development. We will then summarize the role of p53 in monitoring MSC fidelity and in regulating MSC differentiation programs during osteogenesis. Finally, we will discuss the importance of loss of p53 function in tissue microenvironment. We expect that the information provided herein could lead to better understanding and treatment of OS. PMID:26775693

  14. Cardiac autonomic function and vascular profile in subclinical hypothyroidism: Increased beat-to-beat QT variability

    PubMed Central

    Kalra, Pramila; Yeragani, Vikram K.; Prasanna Kumar, K. M.

    2016-01-01

    Background: Patients with subclinical hypothyroidism (SH) may have higher incidence of coronary heart disease and autonomic dysfunction. Design of the Study: Prospective case control study. Aim and Objectives: To evaluate beat-to-beat QT variability and vascular stiffness in patients with SH compared to normal controls. Materials and Methods: We compared linear and nonlinear measures of cardiac repolarization liability using beat-to-beat QT intervals derived from the surface electrocardiogram during supine posture and vascular indices including pulse wave velocity and ankle-brachial index (ABI) during supine posture between female patients with SH and age- and sex-matched normal controls. Spectral analysis was done at very low frequency (LF) (0.003–0.04 Hz), Low frequency (LF) (0.04–0.15 Hz), and high frequency (HF) (0.15–0.4 Hz). The HF represents vagal regulation (parasympathetic) and LF represents both parasympathetic and sympathetic regulation. Results: We recruited 58 women with a mean age of 31.83 ± 8.9 years and 49 controls with mean age of 32.4 ± 9.9 years (P = NS). QT variability index (QTvi) was higher in cases compared to controls (P = 0.01). The ratio of LF/HF of R-R interval which is an index of sympathovagal tone was significantly more in cases compared to controls (P = 0.02). The difference in the left minus the right ABI was significant between cases and controls (P = 0.03). Conclusions: The cases had lower parasympathetic activity as compared to controls, and there was a predominance of sympathetic activity in cases. QTvi may be an important noninvasive tool in this group of patients to study the risk of cardiovascular mortality. PMID:27730068

  15. Pulmonary function abnormalities and asthma are prevalent in children with sickle cell disease and are associated with acute chest syndrome.

    PubMed

    Intzes, Stefanos; Kalpatthi, Ram V; Short, Robert; Imran, Hamayun

    2013-11-01

    Pulmonary diseases form major sources of morbidity and mortality in children with sickle cell disease (SCD). The objective of the study was to determine the prevalence of lung function abnormalities and asthma and their association with acute chest syndrome (ACS) in children with SCD. This was a cross-sectional retrospective study of 127 children with SCD; we collected information regarding ACS and asthma and pulmonary function test (PFT) data. Based on PFT results, the patients were assigned to one pattern of lung function [normal, obstructive lung disease (OLD), restrictive lung disease (RLD)]. Statistical analyses included Pearson correlation, prevalence odds ratio (POR), cross-tabulation, and multiple binary logistic regression. OLD was noted in 35% and RLD in 23% of the patients, with the remainder exhibiting a normal PFT pattern. Forty-six percent of patients had asthma, 64% of whom had a history of ACS. OLD (r = .244, P = .008, POR = 2.8) and asthma (r = .395, P < .001, POR = 5.4) were significantly associated with a history of ACS. There was a negative correlation between having normal PFT data and a history of ACS (r = -.289, P = .002, POR = .3). Asthma and pulmonary function abnormalities are prevalent in children with SCD, with OLD being more common than RLD. There is an association between asthma, OLD, and ACS, however causality cannot be proven due to the study design. We stress the importance of actively investigating for a clinical diagnosis of asthma in all patients with SCD and suggest that PFT data may help detect patients at lower risk for ACS.

  16. Abnormal spontaneous regional brain activity in primary insomnia: a resting-state functional magnetic resonance imaging study

    PubMed Central

    Li, Chao; Ma, Xiaofen; Dong, Mengshi; Yin, Yi; Hua, Kelei; Li, Meng; Li, Changhong; Zhan, Wenfeng; Li, Cheng; Jiang, Guihua

    2016-01-01

    Objective Investigating functional specialization is crucial for a complete understanding of the neural mechanisms of primary insomnia (PI). Resting-state functional magnetic resonance imaging (fMRI) is a useful tool to explore the functional specialization of PI. However, only a few studies have focused on the functional specialization of PI using resting-state fMRI and results of these studies were far from consistent. Thus, the current study aimed to investigate functional specialization of PI using resting-state fMRI with amplitude of low frequency fluctuations (ALFFs) algorithm. Methods In this study, 55 PI patients and 44 healthy controls were included. ALFF values were compared between the two groups using two-sample t-test. The relationship of abnormal ALFF values with clinical characteristics and duration of insomnia was investigated using Pearson’s correlation analysis. Results PI patients showed lower ALFF values in the left orbitofrontal cortex/inferior frontal gyrus, right middle frontal gyrus, left inferior parietal lobule, and bilateral cerebellum posterior lobes, while higher ALFF values in the right middle/inferior temporal that extended to the right occipital lobe. In addition, we found that the duration of PI negatively correlated with ALFF values in the left orbitofrontal cortex/inferior frontal gyrus, and the Pittsburgh Sleep Quality Index score negatively correlated with ALFF values in the left inferior parietal lobule. Conclusion The present study added information to limited studies on functional specialization and provided evidence for hyperarousal hypothesis in PI. PMID:27366068

  17. Abnormal functional connectivity density in patients with ischemic white matter lesions

    PubMed Central

    Ding, Ju-Rong; Ding, Xin; Hua, Bo; Xiong, Xingzhong; Wang, Qingsong; Chen, Huafu

    2016-01-01

    Abstract White matter lesions (WMLs) are frequently detected in elderly people. Previous structural and functional studies have demonstrated that WMLs are associated with cognitive and motor decline. However, the underlying mechanism of how WMLs lead to cognitive decline and motor disturbance remains unclear. We used functional connectivity density mapping (FCDM) to investigate changes in brain functional connectivity in 16 patients with ischemic WMLs and 13 controls. Both short- and long-range FCD maps were computed, and group comparisons were performed between the 2 groups. A correlation analysis was further performed between regions with altered FCD and cognitive test scores (Mini-Mental State Examination [MMSE] and Montreal Cognitive Assessment [MoCA]) in the patient group. We found that patients with ischemic WMLs showed reduced short-range FCD in the temporal cortex, primary motor cortex, and subcortical region, which may account for inadequate top-down attention, impaired motor, memory, and executive function associated with WMLs. The positive correlation between primary motor cortex and MoCA scores may provide evidence for the influences of cognitive function on behavioral performance. The inferior parietal cortex exhibited increased short-range FCD, reflecting a hyper bottom-up attention to compensate for the inadequate top-down attention for language comprehension and information retrieval in patients with WMLs. Moreover, the prefrontal and primary motor cortex showed increased long-range FCD and the former positively correlated with MoCA scores, which may suggest a strategy of cortical functional reorganization to compensate for motor and executive deficits. Our findings provide new insights into how WMLs cause cognitive and motor decline from cortical functional connectivity perspective. PMID:27603353

  18. Abnormal functional connectivity density in patients with ischemic white matter lesions: An observational study.

    PubMed

    Ding, Ju-Rong; Ding, Xin; Hua, Bo; Xiong, Xingzhong; Wang, Qingsong; Chen, Huafu

    2016-09-01

    White matter lesions (WMLs) are frequently detected in elderly people. Previous structural and functional studies have demonstrated that WMLs are associated with cognitive and motor decline. However, the underlying mechanism of how WMLs lead to cognitive decline and motor disturbance remains unclear. We used functional connectivity density mapping (FCDM) to investigate changes in brain functional connectivity in 16 patients with ischemic WMLs and 13 controls. Both short- and long-range FCD maps were computed, and group comparisons were performed between the 2 groups. A correlation analysis was further performed between regions with altered FCD and cognitive test scores (Mini-Mental State Examination [MMSE] and Montreal Cognitive Assessment [MoCA]) in the patient group. We found that patients with ischemic WMLs showed reduced short-range FCD in the temporal cortex, primary motor cortex, and subcortical region, which may account for inadequate top-down attention, impaired motor, memory, and executive function associated with WMLs. The positive correlation between primary motor cortex and MoCA scores may provide evidence for the influences of cognitive function on behavioral performance. The inferior parietal cortex exhibited increased short-range FCD, reflecting a hyper bottom-up attention to compensate for the inadequate top-down attention for language comprehension and information retrieval in patients with WMLs. Moreover, the prefrontal and primary motor cortex showed increased long-range FCD and the former positively correlated with MoCA scores, which may suggest a strategy of cortical functional reorganization to compensate for motor and executive deficits. Our findings provide new insights into how WMLs cause cognitive and motor decline from cortical functional connectivity perspective. PMID:27603353

  19. Obesity: systemic and pulmonary complications, biochemical abnormalities, and impairment of lung function.

    PubMed

    Mafort, Thiago Thomaz; Rufino, Rogério; Costa, Cláudia Henrique; Lopes, Agnaldo José

    2016-01-01

    Obesity is currently one of the major epidemics of this millennium and affects individuals throughout the world. It causes multiple systemic complications, some of which result in severe impairment of organs and tissues. These complications involve mechanical changes caused by the accumulation of adipose tissue and the numerous cytokines produced by adipocytes. Obesity also significantly interferes with respiratory function by decreasing lung volume, particularly the expiratory reserve volume and functional residual capacity. Because of the ineffectiveness of the respiratory muscles, strength and resistance may be reduced. All these factors lead to inspiratory overload, which increases respiratory effort, oxygen consumption, and respiratory energy expenditure. It is noteworthy that patterns of body fat distribution significantly influence the function of the respiratory system, likely via the direct mechanical effect of fat accumulation in the chest and abdominal regions. Weight loss caused by various types of treatment, including low-calorie diet, intragastric balloon, and bariatric surgery, significantly improves lung function and metabolic syndrome and reduces body mass index. Despite advances in the knowledge of pulmonary and systemic complications associated with obesity, longitudinal randomized studies are needed to assess the impact of weight loss on metabolic syndrome and lung function. PMID:27408717

  20. Abnormal Functional MRI BOLD Contrast in the Vegetative State after Severe Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Heelmann, Volker

    2010-01-01

    For the rehabilitation process, the treatment of patients surviving brain injury in a vegetative state is still a serious challenge. The aim of this study was to investigate patients exhibiting severely disturbed consciousness using functional magnetic resonance imaging. Five cases of posttraumatic vegetative state and one with minimal…

  1. Distinct Patterns of Grey Matter Abnormality in High-Functioning Autism and Asperger's Syndrome

    ERIC Educational Resources Information Center

    McAlonan, Grainne M.; Suckling, John; Wong, Naikei; Cheung, Vinci; Lienenkaemper, Nina; Cheung, Charlton; Chua, Siew E.

    2008-01-01

    Background: Autism exists across a wide spectrum and there is considerable debate as to whether children with Asperger's syndrome, who have normal language milestones, should be considered to comprise a subgroup distinct other from high-functioning children with autism (HFA), who have a history of delayed language development. Magnetic resonance…

  2. Co-Localisation of Abnormal Brain Structure and Function in Specific Language Impairment

    ERIC Educational Resources Information Center

    Badcock, Nicholas A.; Bishop, Dorothy V. M.; Hardiman, Mervyn J.; Barry, Johanna G.; Watkins, Kate E.

    2012-01-01

    We assessed the relationship between brain structure and function in 10 individuals with specific language impairment (SLI), compared to six unaffected siblings, and 16 unrelated control participants with typical language. Voxel-based morphometry indicated that grey matter in the SLI group, relative to controls, was increased in the left inferior…

  3. Post mTBI fatigue is associated with abnormal brain functional connectivity.

    PubMed

    Nordin, Love Engström; Möller, Marika Christina; Julin, Per; Bartfai, Aniko; Hashim, Farouk; Li, Tie-Qiang

    2016-02-16

    This study set out to investigate the behavioral correlates of changes in resting-state functional connectivity before and after performing a 20 minute continuous psychomotor vigilance task (PVT) for patients with chronic post-concussion syndrome. Ten patients in chronic phase after mild traumatic brain injury (mTBI) with persisting symptoms of fatigue and ten matched healthy controls participated in the study. We assessed the participants' fatigue levels and conducted resting-state fMRI before and after a sustained PVT. We evaluated the changes in brain functional connectivity indices in relation to the subject's fatigue behavior using a quantitative data-driven analysis approach. We found that the PVT invoked significant mental fatigue and specific functional connectivity changes in mTBI patients. Furthermore, we found a significant linear correlation between self-reported fatigue and functional connectivity in the thalamus and middle frontal cortex. Our findings indicate that resting-state fMRI measurements may be a useful indicator of performance potential and a marker of fatigue level in the neural attentional system.

  4. Post mTBI fatigue is associated with abnormal brain functional connectivity

    PubMed Central

    Nordin, Love Engström; Möller, Marika Christina; Julin, Per; Bartfai, Aniko; Hashim, Farouk; Li, Tie-Qiang

    2016-01-01

    This study set out to investigate the behavioral correlates of changes in resting-state functional connectivity before and after performing a 20 minute continuous psychomotor vigilance task (PVT) for patients with chronic post-concussion syndrome. Ten patients in chronic phase after mild traumatic brain injury (mTBI) with persisting symptoms of fatigue and ten matched healthy controls participated in the study. We assessed the participants’ fatigue levels and conducted resting-state fMRI before and after a sustained PVT. We evaluated the changes in brain functional connectivity indices in relation to the subject’s fatigue behavior using a quantitative data-driven analysis approach. We found that the PVT invoked significant mental fatigue and specific functional connectivity changes in mTBI patients. Furthermore, we found a significant linear correlation between self-reported fatigue and functional connectivity in the thalamus and middle frontal cortex. Our findings indicate that resting-state fMRI measurements may be a useful indicator of performance potential and a marker of fatigue level in the neural attentional system. PMID:26878885

  5. Post mTBI fatigue is associated with abnormal brain functional connectivity.

    PubMed

    Nordin, Love Engström; Möller, Marika Christina; Julin, Per; Bartfai, Aniko; Hashim, Farouk; Li, Tie-Qiang

    2016-01-01

    This study set out to investigate the behavioral correlates of changes in resting-state functional connectivity before and after performing a 20 minute continuous psychomotor vigilance task (PVT) for patients with chronic post-concussion syndrome. Ten patients in chronic phase after mild traumatic brain injury (mTBI) with persisting symptoms of fatigue and ten matched healthy controls participated in the study. We assessed the participants' fatigue levels and conducted resting-state fMRI before and after a sustained PVT. We evaluated the changes in brain functional connectivity indices in relation to the subject's fatigue behavior using a quantitative data-driven analysis approach. We found that the PVT invoked significant mental fatigue and specific functional connectivity changes in mTBI patients. Furthermore, we found a significant linear correlation between self-reported fatigue and functional connectivity in the thalamus and middle frontal cortex. Our findings indicate that resting-state fMRI measurements may be a useful indicator of performance potential and a marker of fatigue level in the neural attentional system. PMID:26878885

  6. Identification of abnormal motor cortex activation patterns in children with cerebral palsy by functional near-infrared spectroscopy

    NASA Astrophysics Data System (ADS)

    Khan, Bilal; Tian, Fenghua; Behbehani, Khosrow; Romero, Mario I.; Delgado, Mauricio R.; Clegg, Nancy J.; Smith, Linsley; Reid, Dahlia; Liu, Hanli; Alexandrakis, George

    2010-05-01

    We demonstrate the utility of functional near-infrared spectroscopy (fNIRS) as a tool for physicians to study cortical plasticity in children with cerebral palsy (CP). Motor cortex activation patterns were studied in five healthy children and five children with CP (8.4+/-2.3 years old in both groups) performing a finger-tapping protocol. Spatial (distance from center and area difference) and temporal (duration and time-to-peak) image metrics are proposed as potential biomarkers for differentiating abnormal cortical activation in children with CP from healthy pediatric controls. In addition, a similarity image-analysis concept is presented that unveils areas that have similar activation patterns as that of the maximum activation area, but are not discernible by visual inspection of standard activation images. Metrics derived from the images presenting areas of similarity are shown to be sensitive identifiers of abnormal activation patterns in children with CP. Importantly, the proposed similarity concept and related metrics may be applicable to other studies for the identification of cortical activation patterns by fNIRS.

  7. Developmental Abnormalities of Neuronal Structure and Function in Prenatal Mice Lacking the Prader-Willi Syndrome Gene Necdin

    PubMed Central

    Pagliardini, Silvia; Ren, Jun; Wevrick, Rachel; Greer, John J.

    2005-01-01

    Necdin (Ndn) is one of a cluster of genes deleted in the neurodevelopmental disorder Prader-Willi syndrome (PWS). Ndntm2Stw mutant mice die shortly after birth because of abnormal respiratory rhythmogenesis generated by a key medullary nucleus, the pre-Bötzinger complex (preBötC). Here, we address two fundamental issues relevant to its pathogenesis. First, we performed a detailed anatomical study of the developing medulla to determine whether there were defects within the preBötC or synaptic inputs that regulate respiratory rhythmogenesis. Second, in vitro studies determined if the unstable respiratory rhythm in Ndntm2Stw mice could be normalized by neuromodulators. Anatomical defects in Ndntm2Stw mice included defasciculation and irregular projections of axonal tracts, aberrant neuronal migration, and a major defect in the cytoarchitecture of the cuneate/gracile nuclei, including dystrophic axons. Exogenous application of neuromodulators alleviated the long periods of slow respiratory rhythms and apnea, but some instability of rhythmogenesis persisted. We conclude that deficiencies in the neuromodulatory drive necessary for preBötC function contribute to respiratory dysfunction of Ndntm2Stw mice. These abnormalities are part of a more widespread deficit in neuronal migration and the extension, arborization, and fasciculation of axons during early stages of central nervous system development that may account for respiratory, sensory, motor, and behavioral problems associated with PWS. PMID:15972963

  8. Tumor suppression in basal keratinocytes via dual non-cell-autonomous functions of a Na,K-ATPase beta subunit

    PubMed Central

    Hatzold, Julia; Beleggia, Filippo; Herzig, Hannah; Altmüller, Janine; Nürnberg, Peter; Bloch, Wilhelm; Wollnik, Bernd; Hammerschmidt, Matthias

    2016-01-01

    The molecular pathways underlying tumor suppression are incompletely understood. Here, we identify cooperative non-cell-autonomous functions of a single gene that together provide a novel mechanism of tumor suppression in basal keratinocytes of zebrafish embryos. A loss-of-function mutation in atp1b1a, encoding the beta subunit of a Na,K-ATPase pump, causes edema and epidermal malignancy. Strikingly, basal cell carcinogenesis only occurs when Atp1b1a function is compromised in both the overlying periderm (resulting in compromised epithelial polarity and adhesiveness) and in kidney and heart (resulting in hypotonic stress). Blockade of the ensuing PI3K-AKT-mTORC1-NFκB-MMP9 pathway activation in basal cells, as well as systemic isotonicity, prevents malignant transformation. Our results identify hypotonic stress as a (previously unrecognized) contributor to tumor development and establish a novel paradigm of tumor suppression. DOI: http://dx.doi.org/10.7554/eLife.14277.001 PMID:27240166

  9. A lack of functional NK1 receptors explains most, but not all, abnormal behaviours of NK1R-/- mice1

    PubMed Central

    Porter, A J; Pillidge, K; Tsai, Y C; Dudley, J A; Hunt, S P; Peirson, S N; Brown, L A; Stanford, S C

    2015-01-01

    Mice lacking functional neurokinin-1 receptors (NK1R-/-) display abnormal behaviours seen in Attention Deficit Hyperactivity Disorder (hyperactivity, impulsivity and inattentiveness). These abnormalities were evident when comparing the behaviour of separate (inbred: ‘Hom’) wildtype and NK1R-/- mouse strains. Here, we investigated whether the inbreeding protocol could influence their phenotype by comparing the behaviour of these mice with that of wildtype (NK1R+/+) and NK1R-/- progeny of heterozygous parents (‘Het’, derived from the same inbred strains). First, we recorded the spontaneous motor activity of the two colonies/genotypes, over 7 days. This continuous monitoring also enabled us to investigate whether the diurnal rhythm in motor activity differs in the two colonies/genotypes. NK1R-/- mice from both colonies were hyperactive compared with their wildtypes and their diurnal rhythm was also disrupted. Next, we evaluated the performance of the four groups of mice in the 5-Choice Serial Reaction-Time Task (5-CSRTT). During training, NK1R-/- mice from both colonies expressed more impulsive and perseverative behaviour than their wildtypes. During testing, only NK1R-/- mice from the Hom colony were more impulsive than their wildtypes, but NK1R-/- mice from both colonies were more perseverative. There were no colony differences in inattentiveness. Moreover, a genotype difference in this measure depended on time of day. We conclude that the hyperactivity, perseveration and, possibly, inattentiveness of NK1R-/- mice is a direct consequence of a lack of functional NK1R. However, the greater impulsivity of NK1R-/- mice depended on an interaction between a functional deficit of NK1R and other (possibly environmental and/or epigenetic) factors. PMID:25558794

  10. Genetic Variations in the Promoter of the APE1 Gene Are Associated with DMF-Induced Abnormal Liver Function: A Case-Control Study in a Chinese Population

    PubMed Central

    Tong, Zhimin; Shen, Huanxi; Yang, Dandan; Zhang, Feng; Bai, Ying; Li, Qian; Shi, Jian; Zhang, Hengdong; Zhu, Baoli

    2016-01-01

    Acute or long-term exposure to N,N-dimethylformamide (DMF) can induce abnormal liver function. It is well known that DMF is mainly metabolized in the liver and thereby produces reactive oxygen species (ROS). The base excision repair (BER) pathway is regarded as a very important pathway involved in repairing ROS-induced DNA damage. Several studies have explored the associations between GSTM1, GSTT1, CYP2E1 polymorphisms and DMF-induced abnormal liver function; however, little is known about how common hOGG1, XRCC1 and APE1 polymorphisms and DMF induce abnormal liver function. The purpose of this study was to investigate whether the polymorphisms in the hOGG1 (rs159153 and rs2072668), XRCC1 (rs25487, rs25489, and rs1799782), APE1 (rs1130409 and 1760944) genes in the human BER pathway were associated with the susceptibility to DMF-induced abnormal liver function in a Chinese population. These polymorphisms were genotyped in 123 workers with DMF-induced abnormal liver function and 123 workers with normal liver function. We found that workers with the APE1 rs1760944 TG/GG genotypes had a reduced risk of abnormal liver function, which was more pronounced in the subgroups that were exposed to DMF for <10 years, exposed to ≥10 mg/m3 DMF, never smoked and never drank. In summary, our study supported the hypothesis that the APE1 rs1760944 T > G polymorphism may be associated with DMF-induced abnormal liver function in the Chinese Han population. PMID:27463724

  11. Genetic Variations in the Promoter of the APE1 Gene Are Associated with DMF-Induced Abnormal Liver Function: A Case-Control Study in a Chinese Population.

    PubMed

    Tong, Zhimin; Shen, Huanxi; Yang, Dandan; Zhang, Feng; Bai, Ying; Li, Qian; Shi, Jian; Zhang, Hengdong; Zhu, Baoli

    2016-01-01

    Acute or long-term exposure to N,N-dimethylformamide (DMF) can induce abnormal liver function. It is well known that DMF is mainly metabolized in the liver and thereby produces reactive oxygen species (ROS). The base excision repair (BER) pathway is regarded as a very important pathway involved in repairing ROS-induced DNA damage. Several studies have explored the associations between GSTM1, GSTT1, CYP2E1 polymorphisms and DMF-induced abnormal liver function; however, little is known about how common hOGG1, XRCC1 and APE1 polymorphisms and DMF induce abnormal liver function. The purpose of this study was to investigate whether the polymorphisms in the hOGG1 (rs159153 and rs2072668), XRCC1 (rs25487, rs25489, and rs1799782), APE1 (rs1130409 and 1760944) genes in the human BER pathway were associated with the susceptibility to DMF-induced abnormal liver function in a Chinese population. These polymorphisms were genotyped in 123 workers with DMF-induced abnormal liver function and 123 workers with normal liver function. We found that workers with the APE1 rs1760944 TG/GG genotypes had a reduced risk of abnormal liver function, which was more pronounced in the subgroups that were exposed to DMF for <10 years, exposed to ≥10 mg/m³ DMF, never smoked and never drank. In summary, our study supported the hypothesis that the APE1 rs1760944 T > G polymorphism may be associated with DMF-induced abnormal liver function in the Chinese Han population. PMID:27463724

  12. The influence of mean heart rate on measures of heart rate variability as markers of autonomic function: a model study.

    PubMed

    Chiu, Hung-Wen; Wang, Ti-Ho; Huang, Lu-Chou; Tso, Han-Wen; Kao, Tsair

    2003-07-01

    Some studies have demonstrated that the assessments of autonomic activities from the alterations of heart rate variations (HRVs) after autonomic blockade and during exercise of high intensity by the spectral analysis of HRV seemed inconsistent with actual situation. The inconsistency is probably caused by the contributions of fluctuating magnitudes and mean levels of autonomic activities on HRV having not been clarified. The alterations of HRV after autonomic blockade and during exercise of high intensity using a mathematical model were simulated. The autonomic activity in normal condition was assumed first according to some experimental evidence. Then autonomic activities after sympathetic blockade, vagal blockade and during exercise of high intensity were appropriately adjusted accordingly. The HRVs in response to these given autonomic activities were simulated. We found that the effect on HRV influenced by the mean level of autonomic activity is helpful to explain alterations of HRV in these conditions. After vagal blockade, a largely reduced low frequency (LF) power could be caused by the reduced mean heartbeat interval induced by a decreased mean level of vagal activity. Increased low and high frequency powers after sympathetic blockade could be caused by the increased mean heartbeat interval induced by a decreased mean level of sympathetic activity. A decreased LF power during exercise of high intensity, in addition to the withdrawal of vagal activity, could also be caused by the decreased mean heartbeat interval induced by an increased mean level of sympathetic activity.

  13. Functional brain abnormalities localized in 55 chronic tinnitus patients: fusion of SPECT coincidence imaging and MRI

    PubMed Central

    Farhadi, Mohammad; Mahmoudian, Saeid; Saddadi, Fariba; Karimian, Ali Reza; Mirzaee, Mohammad; Ahmadizadeh, Majid; Ghasemikian, Khosro; Gholami, Saeid; Ghoreyshi, Esmaeel; Beyty, Saeid; Shamshiri, Ahmadreza; Madani, Sedighe; Bakaev, Valery; Moradkhani, Seddighe; Raeisali, Gholamreza

    2010-01-01

    Tinnitus is often defined as the perception of sounds or noise in the absence of any external auditory stimuli. The pathophysiology of subjective idiopathic tinnitus remains unclear. The aim of this study was to investigate the functional brain activities and possible involved cerebral areas in subjective idiopathic tinnitus patients by means of single photon emission computerized tomography (SPECT) coincidence imaging, which was fused with magnetic resonance imaging (MRI). In this cross-sectional study, 56 patients (1 subject excluded) with subjective tinnitus and 8 healthy controls were enrolled. After intravenous injection of 5 mCi F18-FDG (fluorodeoxyglucose), all subjects underwent a brain SPECT coincidence scan, which was then superimposed on their MRIs. In the eight regions of interest (middle temporal, inferotemporal, medial temporal, lateral temporal, temporoparietal, frontal, frontoparietal, and parietal areas), the more pronounced values were represented in medial temporal, inferotemporal, and temporoparietal areas, which showed more important proportion of associative auditory cortices in functional attributions of tinnitus than primary auditory cortex. Brain coincidence SPECT scan, when fused on MRI is a valuable technique in the assessment of patients with tinnitus and could show the significant role of different regions of central nervous system in functional attributions of tinnitus. PMID:20068582

  14. Functional brain abnormalities localized in 55 chronic tinnitus patients: fusion of SPECT coincidence imaging and MRI.

    PubMed

    Farhadi, Mohammad; Mahmoudian, Saeid; Saddadi, Fariba; Karimian, Ali Reza; Mirzaee, Mohammad; Ahmadizadeh, Majid; Ghasemikian, Khosro; Gholami, Saeid; Ghoreyshi, Esmaeel; Beyty, Saeid; Shamshiri, Ahmadreza; Madani, Sedighe; Bakaev, Valery; Moradkhani, Seddighe; Raeisali, Gholamreza

    2010-04-01

    Tinnitus is often defined as the perception of sounds or noise in the absence of any external auditory stimuli. The pathophysiology of subjective idiopathic tinnitus remains unclear. The aim of this study was to investigate the functional brain activities and possible involved cerebral areas in subjective idiopathic tinnitus patients by means of single photon emission computerized tomography (SPECT) coincidence imaging, which was fused with magnetic resonance imaging (MRI). In this cross-sectional study, 56 patients (1 subject excluded) with subjective tinnitus and 8 healthy controls were enrolled. After intravenous injection of 5 mCi F18-FDG (fluorodeoxyglucose), all subjects underwent a brain SPECT coincidence scan, which was then superimposed on their MRIs. In the eight regions of interest (middle temporal, inferotemporal, medial temporal, lateral temporal, temporoparietal, frontal, frontoparietal, and parietal areas), the more pronounced values were represented in medial temporal, inferotemporal, and temporoparietal areas, which showed more important proportion of associative auditory cortices in functional attributions of tinnitus than primary auditory cortex. Brain coincidence SPECT scan, when fused on MRI is a valuable technique in the assessment of patients with tinnitus and could show the significant role of different regions of central nervous system in functional attributions of tinnitus.

  15. Artificial stone dust-induced functional and inflammatory abnormalities in exposed workers monitored quantitatively by biometrics

    PubMed Central

    Ophir, Noa; Shai, Amir Bar; Alkalay, Yifat; Israeli, Shani; Korenstein, Rafi; Kramer, Mordechai R.

    2016-01-01

    The manufacture of kitchen and bath countertops in Israel is based mainly on artificial stone that contains 93% silica as natural quartz, and ∼3500 workers are involved in cutting and processing it. Artificial stone produces high concentrations of silica dust. Exposure to crystalline silica may cause silicosis, an irreversible lung disease. Our aim was to screen exposed workers by quantitative biometric monitoring of functional and inflammatory parameters. 68 exposed artificial stone workers were compared to 48 nonexposed individuals (controls). Exposed workers filled in questionnaires, and all participants underwent pulmonary function tests and induced sputum analyses. Silica was quantitated by a Niton XL3 X-ray fluorescence spectrometer. Pulmonary function test results of exposed workers were significantly lower and induced sputa showed significantly higher neutrophilic inflammation compared to controls; both processes were slowed down by the use of protective measures in the workplace. Particle size distribution in induced sputum samples of exposed workers was similar to that of artificial stone dust, which contained aluminium, zirconium and titanium in addition to silica. In conclusion, the quantitation of biometric parameters is useful for monitoring workers exposed to artificial stone in order to avoid deterioration over time. PMID:27730180

  16. Abnormal functional integration of thalamic low frequency oscillation in the BOLD signal after acute heroin treatment.

    PubMed

    Denier, Niklaus; Schmidt, André; Gerber, Hana; Vogel, Marc; Huber, Christian G; Lang, Undine E; Riecher-Rossler, Anita; Wiesbeck, Gerhard A; Radue, Ernst-Wilhelm; Walter, Marc; Borgwardt, Stefan

    2015-12-01

    Heroin addiction is a severe relapsing brain disorder associated with impaired cognitive control, including deficits in attention allocation. The thalamus has a high density of opiate receptors and is critically involved in orchestrating cortical activity during cognitive control. However, there have been no studies on how acute heroin treatment modulates thalamic activity. In a cross-over, double-blind, vehicle-controlled study, 29 heroin-maintained outpatients were studied after heroin and placebo administration, while 20 healthy controls were included for the placebo condition only. Resting-state functional magnetic resonance imaging was used to analyze functional integration of the thalamus by three different resting state analysis techniques. Thalamocortical functional connectivity (FC) was analyzed by seed-based correlation, while intrinsic thalamic oscillation was assessed by analysis of regional homogeneity (ReHo) and the fractional amplitude of low frequency fluctuations (fALFF). Relative to the placebo treatment and healthy controls, acute heroin administration reduced thalamocortical FC to cortical regions, including the frontal cortex, while the reductions in FC to the mediofrontal cortex, orbitofrontal cortex, and frontal pole were positively correlated with the plasma level of morphine, the main psychoactive metabolite of heroin. Furthermore, heroin treatment was associated with increased thalamic ReHo and fALFF values, whereas fALFF following heroin exposure correlated negatively with scores of attentional control. The heroin-associated increase in fALFF was mainly dominated by slow-4 (0.027-0.073 Hz) oscillations. Our findings show that there are acute effects of heroin within the thalamocortical system and may shed new light on the role of the thalamus in cognitive control in heroin addiction. Future research is needed to determine the underlying physiological mechanisms and their role in heroin addiction.

  17. Detecting abnormalities in left ventricular function during exercise by respiratory measurement

    SciTech Connect

    Koike, A.; Itoh, H.; Taniguchi, K.; Hiroe, M. )

    1989-12-01

    The degree of exercise-induced cardiac dysfunction and its relation to the anaerobic threshold were evaluated in 23 patients with chronic heart disease. A symptom-limited exercise test was performed with a cycle ergometer with work rate increased by 1 W every 6 seconds. Left ventricular function, as reflected by ejection fraction, was continuously monitored with a computerized cadmium telluride detector after the intravenous injection of technetium-labeled red blood cells. The anaerobic threshold (mean, 727 {plus minus} 166 ml/min) was determined by the noninvasive measurement of respiratory gas exchange. As work rate rose, the left ventricular ejection fraction increased but reached a peak value at the anaerobic threshold and then fell below resting levels. Ejection fraction at rest, anaerobic threshold, and peak exercise were 41.4 {plus minus} 11.3%, 46.5 {plus minus} 12.0%, and 37.2 {plus minus} 11.0%, respectively. Stroke volume also increased from rest (54.6 {plus minus} 17.0 ml/beat) to the point of the anaerobic threshold (65.0 {plus minus} 21.2 ml/beat) and then decreased at peak exercise (52.4 {plus minus} 18.7 ml/beat). The slope of the plot of cardiac output versus work rate decreased above the anaerobic threshold. The anaerobic threshold occurred at the work rate above which left ventricular function decreased during exercise. Accurate determination of the anaerobic threshold provides an objective, noninvasive measure of the oxygen uptake above which exercise-induced deterioration in left ventricular function occurs in patients with chronic heart disease.

  18. Abnormal functional integration of thalamic low frequency oscillation in the BOLD signal after acute heroin treatment.

    PubMed

    Denier, Niklaus; Schmidt, André; Gerber, Hana; Vogel, Marc; Huber, Christian G; Lang, Undine E; Riecher-Rossler, Anita; Wiesbeck, Gerhard A; Radue, Ernst-Wilhelm; Walter, Marc; Borgwardt, Stefan

    2015-12-01

    Heroin addiction is a severe relapsing brain disorder associated with impaired cognitive control, including deficits in attention allocation. The thalamus has a high density of opiate receptors and is critically involved in orchestrating cortical activity during cognitive control. However, there have been no studies on how acute heroin treatment modulates thalamic activity. In a cross-over, double-blind, vehicle-controlled study, 29 heroin-maintained outpatients were studied after heroin and placebo administration, while 20 healthy controls were included for the placebo condition only. Resting-state functional magnetic resonance imaging was used to analyze functional integration of the thalamus by three different resting state analysis techniques. Thalamocortical functional connectivity (FC) was analyzed by seed-based correlation, while intrinsic thalamic oscillation was assessed by analysis of regional homogeneity (ReHo) and the fractional amplitude of low frequency fluctuations (fALFF). Relative to the placebo treatment and healthy controls, acute heroin administration reduced thalamocortical FC to cortical regions, including the frontal cortex, while the reductions in FC to the mediofrontal cortex, orbitofrontal cortex, and frontal pole were positively correlated with the plasma level of morphine, the main psychoactive metabolite of heroin. Furthermore, heroin treatment was associated with increased thalamic ReHo and fALFF values, whereas fALFF following heroin exposure correlated negatively with scores of attentional control. The heroin-associated increase in fALFF was mainly dominated by slow-4 (0.027-0.073 Hz) oscillations. Our findings show that there are acute effects of heroin within the thalamocortical system and may shed new light on the role of the thalamus in cognitive control in heroin addiction. Future research is needed to determine the underlying physiological mechanisms and their role in heroin addiction. PMID:26441146

  19. Abnormal structure or function of the amygdala is a common component of neurodevelopmental disorders

    PubMed Central

    Schumann, Cynthia M.; Bauman, Melissa D.; Amaral, David G.

    2010-01-01

    The amygdala, perhaps more than any other brain region, has been implicated in numerous neuropsychiatric and neurodevelopmental disorders. It is part of a system initially evolved to detect dangers in the environment and modulate subsequent responses, which can profoundly influence human behavior. If its threshold is set too low, normally benign aspects of the environment are perceived as dangers, interactions are limited, and anxiety may arise. If set too high, risk taking increases and inappropriate sociality may occur. Given that many neurodevelopmental disorders involve too little or too much anxiety or too little of too much social interaction, it is not surprising that the amygdala has been implicated in many of them. In this chapter, we begin by providing a brief overview of the phylogeny, ontogeny, and function of the amygdala and then appraise data from neurodevelopmental disorders which suggest amygdala dysregulation. We focus on neurodevelopmental disorders where there is evidence of amygdala dysregulation from postmortem studies, structural MRI analyses or functional MRI. However, the results are often disparate and it is not totally clear whether this is due to inherent heterogeneity or differences in methodology. Nonetheless, the amygdala is a common site for neuropathology in neurodevelopmental disorders and is therefore a potential target for therapeutics to alleviate associated symptoms. PMID:20950634

  20. Abnormal EEG Complexity and Functional Connectivity of Brain in Patients with Acute Thalamic Ischemic Stroke

    PubMed Central

    Liu, Shuang; Guo, Jie; Meng, Jiayuan; Wang, Zhijun; Yao, Yang; Yang, Jiajia; Qi, Hongzhi; Ming, Dong

    2016-01-01

    Ischemic thalamus stroke has become a serious cardiovascular and cerebral disease in recent years. To date the existing researches mostly concentrated on the power spectral density (PSD) in several frequency bands. In this paper, we investigated the nonlinear features of EEG and brain functional connectivity in patients with acute thalamic ischemic stroke and healthy subjects. Electroencephalography (EEG) in resting condition with eyes closed was recorded for 12 stroke patients and 11 healthy subjects as control group. Lempel-Ziv complexity (LZC), Sample Entropy (SampEn), and brain network using partial directed coherence (PDC) were calculated for feature extraction. Results showed that patients had increased mean LZC and SampEn than the controls, which implied the stroke group has higher EEG complexity. For the brain network, the stroke group displayed a trend of weaker cortical connectivity, which suggests a functional impairment of information transmission in cortical connections in stroke patients. These findings suggest that nonlinear analysis and brain network could provide essential information for better understanding the brain dysfunction in the stroke and assisting monitoring or prognostication of stroke evolution. PMID:27403202

  1. Microstructural abnormalities of uncinate fasciculus as a function of impaired cognition in schizophrenia: A DTI study.

    PubMed

    Singh, Sadhana; Singh, Kavita; Trivedi, Richa; Goyal, Satnam; Kaur, Prabhjot; Singh, Namita; Bhatia, Triptish; Deshpande, Smita N; Khushu, Subash

    2016-09-01

    Neuropsychological studies have reported that attention, memory, language, motor and emotion processing are impaired in schizophrenia. It is known that schizophrenia involves structural alterations in the white matter of brain that contribute to the pathophysiology of the disorder. Uncinate fasciculus (UNC), a bundle of white matter fibres, plays an important role in the pathology of this disorder and involved in cognitive functions such as memory, language and emotion processing. Therefore, the present study aimed to investigate microstructural changes in UNC fibre in schizophrenia patients relative to controls and its correlation with neuropsychological scores. Diffusion tensor imaging (DTI) and Hindi version of Penn Computerised Neuropsychological Battery test was performed in 14 schizophrenia patients and 14 controls. DTI measures [fractional anisotropy (FA) and mean diffusivity (MD)] from UNC fibre were calculated and a comparison was made between patients and controls. Pearson's correlation was performed between neuropsychological scores and DTI measures.Schizophrenia patients showed significantly reduced FA values in UNC fibre compared to controls. In schizophrenia patients, a positive correlation of attention, spatial memory, sensorimotor dexterity and emotion with FA was observed. These findings suggest that microstructural changes in UNC fibre may contribute to underlying dysfunction in the cognitive functions associated with schizophrenia. PMID:27581933

  2. Disorder-specific functional abnormalities during sustained attention in youth with Attention Deficit Hyperactivity Disorder (ADHD) and with autism.

    PubMed

    Christakou, A; Murphy, C M; Chantiluke, K; Cubillo, A I; Smith, A B; Giampietro, V; Daly, E; Ecker, C; Robertson, D; Murphy, D G; Rubia, K

    2013-02-01

    Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) are often comorbid and share behavioural-cognitive abnormalities in sustained attention. A key question is whether this shared cognitive phenotype is based on common or different underlying pathophysiologies. To elucidate this question, we compared 20 boys with ADHD to 20 age and IQ matched ASD and 20 healthy boys using functional magnetic resonance imaging (fMRI) during a parametrically modulated vigilance task with a progressively increasing load of sustained attention. ADHD and ASD boys had significantly reduced activation relative to controls in bilateral striato-thalamic regions, left dorsolateral prefrontal cortex (DLPFC) and superior parietal cortex. Both groups also displayed significantly increased precuneus activation relative to controls. Precuneus was negatively correlated with the DLPFC activation, and progressively more deactivated with increasing attention load in controls, but not patients, suggesting problems with deactivation of a task-related default mode network in both disorders. However, left DLPFC underactivation was significantly more pronounced in ADHD relative to ASD boys, which furthermore was associated with sustained performance measures that were only impaired in ADHD patients. ASD boys, on the other hand, had disorder-specific enhanced cerebellar activation relative to both ADHD and control boys, presumably reflecting compensation. The findings show that ADHD and ASD boys have both shared and disorder-specific abnormalities in brain function during sustained attention. Shared deficits were in fronto-striato-parietal activation and default mode suppression. Differences were a more severe DLPFC dysfunction in ADHD and a disorder-specific fronto-striato-cerebellar dysregulation in ASD.

  3. Abnormal Resting-State Functional Connectivity in Patients with Chronic Fatigue Syndrome: Results of Seed and Data-Driven Analyses.

    PubMed

    Gay, Charles W; Robinson, Michael E; Lai, Song; O'Shea, Andrew; Craggs, Jason G; Price, Donald D; Staud, Roland

    2016-02-01

    Although altered resting-state functional connectivity (FC) is a characteristic of many chronic pain conditions, it has not yet been evaluated in patients with chronic fatigue. Our objective was to investigate the association between fatigue and altered resting-state FC in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Thirty-six female subjects, 19 ME/CFS and 17 healthy controls, completed a fatigue inventory before undergoing functional magnetic resonance imaging. Two methods, (1) data driven and (2) model based, were used to estimate and compare the intraregional FC between both groups during the resting state (RS). The first approach using independent component analysis was applied to investigate five RS networks: the default mode network, salience network (SN), left frontoparietal networks (LFPN) and right frontoparietal networks, and the sensory motor network (SMN). The second approach used a priori selected seed regions demonstrating abnormal regional cerebral blood flow (rCBF) in ME/CFS patients at rest. In ME/CFS patients, Method-1 identified decreased intrinsic connectivity among regions within the LFPN. Furthermore, the FC of the left anterior midcingulate with the SMN and the connectivity of the left posterior cingulate cortex with the SN were significantly decreased. For Method-2, five distinct clusters within the right parahippocampus and occipital lobes, demonstrating significant rCBF reductions in ME/CFS patients, were used as seeds. The parahippocampal seed and three occipital lobe seeds showed altered FC with other brain regions. The degree of abnormal connectivity correlated with the level of self-reported fatigue. Our results confirm altered RS FC in patients with ME/CFS, which was significantly correlated with the severity of their chronic fatigue.

  4. Altered Striatal Synaptic Function and Abnormal Behaviour in Shank3 Exon4-9 Deletion Mouse Model of Autism.

    PubMed

    Jaramillo, Thomas C; Speed, Haley E; Xuan, Zhong; Reimers, Jeremy M; Liu, Shunan; Powell, Craig M

    2016-03-01

    Shank3 is a multi-domain, synaptic scaffolding protein that organizes proteins in the postsynaptic density of excitatory synapses. Clinical studies suggest that ∼ 0.5% of autism spectrum disorder (ASD) cases may involve SHANK3 mutation/deletion. Patients with SHANK3 mutations exhibit deficits in cognition along with delayed/impaired speech/language and repetitive and obsessive/compulsive-like (OCD-like) behaviors. To examine how mutation/deletion of SHANK3 might alter brain function leading to ASD, we have independently created mice with deletion of Shank3 exons 4-9, a region implicated in ASD patients. We find that homozygous deletion of exons 4-9 (Shank3(e4-9) KO) results in loss of the two highest molecular weight isoforms of Shank3 and a significant reduction in other isoforms. Behaviorally, both Shank3(e4-9) heterozygous (HET) and Shank3(e4-9) KO mice display increased repetitive grooming, deficits in novel and spatial object recognition learning and memory, and abnormal ultrasonic vocalizations. Shank3(e4-9) KO mice also display abnormal social interaction when paired with one another. Analysis of synaptosome fractions from striata of Shank3(e4-9) KO mice reveals decreased Homer1b/c, GluA2, and GluA3 expression. Both Shank3(e4-9) HET and KO demonstrated a significant reduction in NMDA/AMPA ratio at excitatory synapses onto striatal medium spiny neurons. Furthermore, Shank3(e4-9) KO mice displayed reduced hippocampal LTP despite normal baseline synaptic transmission. Collectively these behavioral, biochemical and physiological changes suggest Shank3 isoforms have region-specific roles in regulation of AMPAR subunit localization and NMDAR function in the Shank3(e4-9) mutant mouse model of autism. PMID:26559786

  5. Sensor fusion of inertial-odometric navigation as a function of the actual manoeuvres of autonomous guided vehicles

    NASA Astrophysics Data System (ADS)

    DeCecco, Mariolino

    2003-05-01

    This paper presents a description of the 'sensor-fusion' algorithm for a navigation system suitable for autonomous guided vehicles that use two navigation systems: an odometric one which uses encoders mounted on the vehicle's wheels and an inertial one which uses a gyroscope. In the proposed algorithm the accuracy of both navigation systems is estimated as a function of the actual manoeuvre being carried out, which is identified by navigation data, and then the outputs of both sensors are fused taking into account the accuracy ratios. The method is explained starting from the measurement models and its calibration as a function of the different manoeuvres. Experimental calibration of the proposed algorithm was carried out using a scaled mock-up of an industrial robot. While the mean absolute value of the estimated error in distance over the path is 49 mm when using odometric navigation and 28 mm when using odometric plus inertial attitude navigation, it is only 15 mm when carrying out data fusion between the two measurement systems. A recursive method for estimating the evolution of spatial uncertainty, which also takes into account the systematic effects, is proposed.

  6. Abnormal functioning of the left temporal lobe in language-impaired children.

    PubMed

    Helenius, Päivi; Sivonen, Päivi; Parviainen, Tiina; Isoaho, Pia; Hannus, Sinikka; Kauppila, Timo; Salmelin, Riitta; Isotalo, Leena

    2014-03-01

    Specific language impairment is associated with enduring problems in language-related functions. We followed the spatiotemporal course of cortical activation in SLI using magnetoencephalography. In the experiment, children with normal and impaired language development heard spoken real words and pseudowords presented only once or two times in a row. In typically developing children, the activation in the bilateral superior temporal cortices was attenuated to the second presentation of the same word. In SLI children, this repetition effect was nearly nonexistent in the left hemisphere. Furthermore, the activation was equally strong to words and pseudowords in SLI children whereas in the typically developing children the left hemisphere activation persisted longer for pseudowords than words. Our results indicate that the short-term maintenance of linguistic activation that underlies spoken word recognition is defective in SLI particularly in the left language-dominant hemisphere. The unusually rapid decay of speech-evoked activation can contribute to impaired vocabulary growth.

  7. Abnormal functioning of the left temporal lobe in language-impaired children.

    PubMed

    Helenius, Päivi; Sivonen, Päivi; Parviainen, Tiina; Isoaho, Pia; Hannus, Sinikka; Kauppila, Timo; Salmelin, Riitta; Isotalo, Leena

    2014-03-01

    Specific language impairment is associated with enduring problems in language-related functions. We followed the spatiotemporal course of cortical activation in SLI using magnetoencephalography. In the experiment, children with normal and impaired language development heard spoken real words and pseudowords presented only once or two times in a row. In typically developing children, the activation in the bilateral superior temporal cortices was attenuated to the second presentation of the same word. In SLI children, this repetition effect was nearly nonexistent in the left hemisphere. Furthermore, the activation was equally strong to words and pseudowords in SLI children whereas in the typically developing children the left hemisphere activation persisted longer for pseudowords than words. Our results indicate that the short-term maintenance of linguistic activation that underlies spoken word recognition is defective in SLI particularly in the left language-dominant hemisphere. The unusually rapid decay of speech-evoked activation can contribute to impaired vocabulary growth. PMID:24568877

  8. Dynamic testing of hypothalamic-pituitary function in abnormalities of ovulation.

    PubMed

    Jones, G E; Wentz, A C; Rosenwaks, Z; Shoemaker, J

    1977-12-01

    A review of 26 unusual patients indicates that a combined luteinizing hormone-releasing hormone (LRH)-clomiphene test in conjunction with an estrogen provocation test not only was helpful in identifying underlying pathophysiology of anovulation but also proved useful in the clinical management of the patients. Dynamic testing per se does not establish a diagnosis but, in conjunction with history and other laboratory findings, it does make possible further subdivisions of groups of patients who otherwise appear similar, both clinically and from routine laboratory evaluations. It, therefore, tends to pinpoint a lesion and establish the area in which further tests should be made. It is concluded that the value of such investigations will be more evident as gynecologic endocrinology moves into investigation of the supratentorial control of hypothalamic function and as hypothalamic LRH becomes available as a therapeutic agent.

  9. Abnormalities of follicular helper T-cell number and function in Wiskott-Aldrich syndrome

    PubMed Central

    Zhang, Xuan; Dai, Rongxin; Li, Wenyan; Zhao, Hongyi; Zhang, Yongjie; Zhou, Lina; Du, Hongqiang; Luo, Guangjin; Wu, Junfeng; Niu, Linlin; An, Yunfei; Zhang, Zhiyong; Ding, Yuan; Song, Wenxia; Liu, Chaohong

    2016-01-01

    Wiskott-Aldrich syndrome protein (WASp) is a hematopoietic-specific regulator of actin nucleation. Wiskott-Aldrich syndrome (WAS) patients show immunodeficiencies, most of which have been attributed to defective T-cell functions. T follicular helper (Tfh) cells are the major CD4+ T-cell subset with specialized B-cell helper capabilities. Aberrant Tfh cells activities are involved in immunopathologies such as autoimmunity, immunodeficiencies, and lymphomas. We found that in WAS patients, the number of circulating Tfh cells was significantly reduced due to reduced proliferation and increased apoptosis, and Tfh cells were Th2 and Th17 polarized. The expression of inducible costimulator (ICOS) in circulating Tfh cells was higher in WAS patients than in controls. BCL6 expression was decreased in total CD4+ T and Tfh cells of WAS patients. Mirroring the results in patients, the frequency of Tfh cells in WAS knockout (KO) mice was decreased, as was the frequency of BCL6+ Tfh cells, but the frequency of ICOS+ Tfh cells was increased. Using WAS chimera mice, we found that the number of ICOS+ Tfh cells was decreased in WAS chimera mice, indicating that the increase in ICOS+ Tfh cells in WAS KO mice was cell extrinsic. The data from in vivo CD4+ naive T-cell adoptive transfer mice as well as in vitro coculture of naive B and Tfh cells showed that the defective function of WASp-deficient Tfh cells was T-cell intrinsic. Consistent findings in both WAS patients and WAS KO mice suggested an essential role for WASp in the development and memory response of Tfh cells and that WASp deficiency causes a deficient differentiation defect in Tfh cells by downregulating the transcription level of BCL6. PMID:27170596

  10. Acid sphingomyelinase (aSMase) deficiency leads to abnormal microglia behavior and disturbed retinal function

    SciTech Connect

    Dannhausen, Katharina; Karlstetter, Marcus; Caramoy, Albert; Volz, Cornelia; Jägle, Herbert; Liebisch, Gerhard; Utermöhlen, Olaf; Langmann, Thomas

    2015-08-21

    Mutations in the acid sphingomyelinase (aSMase) coding gene sphingomyelin phosphodiesterase 1 (SMPD1) cause Niemann-Pick disease (NPD) type A and B. Sphingomyelin storage in cells of the mononuclear phagocyte system cause hepatosplenomegaly and severe neurodegeneration in the brain of NPD patients. However, the effects of aSMase deficiency on retinal structure and microglial behavior have not been addressed in detail yet. Here, we demonstrate that retinas of aSMase{sup −/−} mice did not display overt neuronal degeneration but showed significantly reduced scotopic and photopic responses in electroretinography. In vivo fundus imaging of aSMase{sup −/−} mice showed many hyperreflective spots and staining for the retinal microglia marker Iba1 revealed massive proliferation of retinal microglia that had significantly enlarged somata. Nile red staining detected prominent phospholipid inclusions in microglia and lipid analysis showed significantly increased sphingomyelin levels in retinas of aSMase{sup −/−} mice. In conclusion, the aSMase-deficient mouse is the first example in which microglial lipid inclusions are directly related to a loss of retinal function. - Highlights: • aSMase-deficient mice show impaired retinal function and reactive microgliosis. • aSMase-deficient microglia express pro-inflammatory transcripts. • aSMase-deficient microglia proliferate and have increased cell body size. • In vivo imaging shows hyperreflective spots in the fundus of aSMase-deficient mice. • aSMase-deficient microglia accumulate sphingolipid-rich intracellular deposits.

  11. Effect of Head-Down Bed Rest and Artificial Gravity Countermeasure on Cardiac Autonomic and Advanced Electrocardiographic Function

    NASA Technical Reports Server (NTRS)

    Schlegel, T. T.; Platts, S.; Stenger, M.; Ribeiro, C.; Natapoff, A.; Howarth, M.; Evans, J.

    2007-01-01

    To study the effects of 21 days of head-down bed rest (HDBR), with versus without an artificial gravity (AG) countermeasure, on cardiac autonomic and advanced electrocardiographic function. Fourteen healthy men participated in the study: seven experienced 21 days of HDBR alone ("HDBR controls") and seven the same degree and duration of HDBR but with approximately 1hr daily short-arm centrifugation as an AG countermeasure ("AG-treated"). Five minute supine high-fidelity 12-lead ECGs were obtained in all subjects: 1) 4 days before HDBR; 2) on the last day of HDBR; and 3) 7 days after HDBR. Besides conventional 12-lead ECG intervals and voltages, all of the following advanced ECG parameters were studied: 1) both stochastic (time and frequency domain) and deterministic heart rate variability (HRV); 2) beat-to-beat QT interval variability (QTV); 3) T-wave morphology, including signal-averaged T-wave residua (TWR) and principal component analysis ratios; 4) other SAECG-related parameters including high frequency QRS ECG and late potentials; and 5) several advanced ECG estimates of left ventricular (LV) mass. The most important results by repeated measures ANOVA were that: 1) Heart rates, Bazett-corrected QTc intervals, TWR, LF/HF power and the alpha 1 of HRV were significantly increased in both groups (i.e., by HDBR), but with no relevant HDBR*group differences; 2) All purely "vagally-mediated" parameters of HRV (e.g., RMSSD, HF power, Poincare SD1, etc.), PR intervals, and also several parameters of LV mass (Cornell and Sokolow-Lyon voltages, spatial ventricular activation times, ventricular gradients) were all significantly decreased in both groups (i.e., by HDBR), but again with no relevant HDBR*group differences); 3) All "generalized" or "vagal plus sympathetic" parameters of stochastic HRV (i.e., SDNN, total power, LF power) were significantly more decreased in the AG-treated group than in the HDBR-only group (i.e., here there was a relevant HDBR*group difference

  12. Abnormal affective decision making revealed in adolescent binge drinkers using a functional magnetic resonance imaging study.

    PubMed

    Xiao, Lin; Bechara, Antoine; Gong, Qiyong; Huang, Xiaoqi; Li, Xiangrui; Xue, Gui; Wong, Savio; Lu, Zhong-Lin; Palmer, Paula; Wei, Yonglan; Jia, Yong; Johnson, C Anderson

    2013-06-01

    The goal of this study was to investigate the neural correlates of affective decision making, as measured by the Iowa Gambling Task (IGT), which are associated with adolescent binge drinking. Fourteen adolescent binge drinkers (16-18 years of age) and 14 age-matched adolescents who had never consumed alcohol--never drinkers--were recruited from local high schools in Chengdu, China. Questionnaires were used to assess academic performance, drinking experience, and urgency. Brain regions activated by the IGT performance were identified with functional magnetic resonance imaging. Results showed that, compared to never drinkers, binge drinkers performed worse on the IGT and showed higher activity in the subcomponents of the decision-making neural circuitry implicated in the execution of emotional and incentive-related behaviors, namely, the left amygdala and insula bilaterally. Moreover, measures of the severity of drinking problems in real life, as well as high urgency scores, were associated with increased activity within the insula, combined with decreased activity within the orbitofrontal cortex. These results suggest that hyperreactivity of a neural system implicated in the execution of emotional and incentive-related behaviors can be associated with socially undesirable behaviors, such as binge drinking, among adolescents. These findings have social implications because they potentially reveal underlying neural mechanisms for making poor decisions, which may increase an individual's risk and vulnerability for alcoholism.

  13. Abnormal gastric morphology and function in CCK-B/gastrin receptor-deficient mice.

    PubMed Central

    Rindi, G.; Langhans, N.; Rehfeld, J. F.; Beinborn, M.; Kopin, A. S.

    1998-01-01

    Mice lacking the cholecystokinin (CCK)-B/gastrin receptor have been generated by targeted gene disruption. The roles of this receptor in controlling gastric acid secretion and gastric mucosal growth have been assessed. The analysis of homozygous mutant mice vs. wild type included measurement of basal gastric pH, plasma gastrin concentrations as well as quantification of gastric mucosal cell types by immunohistochemistry. Mutant mice exhibited a marked increase in basal gastric pH (from 3.2 to 5.2) and about a 10-fold elevation in circulating carboxyamidated gastrin compared with wild-type controls. Histologic analysis revealed a decrease in both parietal and enterochromaffin-like (ECL) cells, thus explaining the reduction in acid output. Consistent with the elevation in circulating gastrin, antral gastrin cells were increased in number while somatostatin cells were decreased. These data support the importance of the CCK-B/gastrin receptor in maintaining the normal cellular composition and function of the gastric mucosa. Images Figure 1 Figure 2 Figure 3 PMID:10461365

  14. Abnormal pituitary-gonadal axis may be responsible for rat decreased testicular function under simulated microgravity

    NASA Astrophysics Data System (ADS)

    Zhou, Yi; Tan, Xin; Zhu, Bao-an; Qi, Meng-di; Ding, Su-ling

    Space flight and simulated microgravity lead to suppression of mammalian spermatogenesis and decreased plasma testosterone level. In order to explain the mechanism behind the depression, we used rat tail-suspended model to simulate weightless conditions. To prevent cryptorchidism caused by tail-suspension, some experimental animals received inguinal canal ligation. The results showed that mass of testis decreased significantly and seminiferous tubules became atrophied in rats after tail-suspension. The levels of plasma testosterone (T), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) in tail-suspended rats with or without inguinal canal ligation decreased significantly compared with controls, and an increased level of plasma estradiol (E) was revealed in tail-suspended rats. The results indicate that besides the direct influence of fluid shift upon testis under short-term simulated microgravity, the pituitary function is also disturbed as a result of either immobilization stress or weight loss during tail-suspension treatment, which is responsible to some extent for the decreased testosterone secretion level and the atrophia of testis. The conversion of testosterone into E under simulated microgravity is another possible cause for the decline of plasma testosterone.

  15. Structural, Metabolic, and Functional Brain Abnormalities as a Result of Prenatal Exposure to Drugs of Abuse: Evidence from Neuroimaging

    PubMed Central

    Roussotte, Florence; Soderberg, Lindsay

    2010-01-01

    Prenatal exposure to alcohol and stimulants negatively affects the developing trajectory of the central nervous system in many ways. Recent advances in neuroimaging methods have allowed researchers to study the structural, metabolic, and functional abnormalities resulting from prenatal exposure to drugs of abuse in living human subjects. Here we review the neuroimaging literature of prenatal exposure to alcohol, cocaine, and methamphetamine. Neuroimaging studies of prenatal alcohol exposure have reported differences in the structure and metabolism of many brain systems, including in frontal, parietal, and temporal regions, in the cerebellum and basal ganglia, as well as in the white matter tracts that connect these brain regions. Functional imaging studies have identified significant differences in brain activation related to various cognitive domains as a result of prenatal alcohol exposure. The published literature of prenatal exposure to cocaine and methamphetamine is much smaller, but evidence is beginning to emerge suggesting that exposure to stimulant drugs in utero may be particularly toxic to dopamine-rich basal ganglia regions. Although the interpretation of such findings is somewhat limited by the problem of polysubstance abuse and by the difficulty of obtaining precise exposure histories in retrospective studies, such investigations provide important insights into the effects of drugs of abuse on the structure, function, and metabolism of the developing human brain. These insights may ultimately help clinicians develop better diagnostic tools and devise appropriate therapeutic interventions to improve the condition of children with prenatal exposure to drugs of abuse. PMID:20978945

  16. Functional and structural abnormalities associated with empathy in patients with schizophrenia: An fMRI and VBM study.

    PubMed

    Singh, Sadhana; Modi, Shilpi; Goyal, Satnam; Kaur, Prabhjot; Singh, Namita; Bhatia, Triptish; Deshpande, Smita N; Khushu, Subash

    2015-06-01

    Empathy deficit is a core feature of schizophrenia which may lead to social dysfunction. The present study was carried out to investigate functional and structural abnormalities associated with empathy in patients with schizophrenia using functional magnetic resonance imaging (fMRI) and voxel-based morphometry (VBM). A sample of 14 schizophrenia patients and 14 healthy control subjects matched for age, sex and education were examined with structural highresolution T1-weighted MRI; fMRI images were obtained during empathy task in the same session. The analysis was carried out using SPM8 software. On behavioural assessment, schizophrenic patients (83.00+-29.04) showed less scores for sadness compared to healthy controls (128.70+-22.26) (p less than 0.001). fMRI results also showed reduced clusters of activation in the bilateral fusiform gyrus, left lingual gyrus, left middle and inferior occipital gyrus in schizophrenic subjects as compared to controls during empathy task. In the same brain areas, VBM results also showed reduced grey and white matter volumes. The present study provides an evidence for an association between structural alterations and disturbed functional brain activation during empathy task in persons affected with schizophrenia. These findings suggest a biological basis for social cognition deficits in schizophrenics. PMID:25963262

  17. Prevalence of Abnormalities in Vestibular Function and Balance among HIV-Seropositive and HIV-Seronegative Women and Men

    PubMed Central

    Cohen, Helen S.; Cox, Christopher; Springer, Gayle; Hoffman, Howard J.; Young, Mary A.; Margolick, Joseph B.; Plankey, Michael W.

    2012-01-01

    Background Most HIV-seropositive subjects in western countries receive highly active antiretroviral therapy (HAART). Although many aspects of their health have been studied, little is known about their vestibular and balance function. The goals of this study were to determine the prevalences of vestibular and balance impairments among HIV-seropositive and comparable seronegative men and women and to determine if those groups differed. Methods Standard screening tests of vestibular and balance function, including head thrusts, Dix-Hallpike maneuvers, and Romberg balance tests on compliant foam were performed during semiannual study visits of participants who were enrolled in the Baltimore and Washington, D. C. sites of the Multicenter AIDS Cohort Study and the Women's Interagency HIV Study. Results No significant differences by HIV status were found on most tests, but HIV-seropositive subjects who were using HAART had a lower frequency of abnormal Dix-Hallpike nystagmus than HIV-seronegative subjects. A significant number of nonclassical Dix-Hallpike responses were found. Age was associated with Romberg scores on foam with eyes closed. Sex was not associated with any of the test scores. Conclusion These findings suggest that HAART-treated HIV infection has no harmful association with vestibular function in community-dwelling, ambulatory men and women. The association with age was expected, but the lack of association with sex was unexpected. The presence of nonclassical Dix-Hallpike responses might be consistent with central nervous system lesions. PMID:22675462

  18. Fyn kinase genetic ablation causes structural abnormalities in mature retina and defective Müller cell function.

    PubMed

    Chavez-Solano, Marbella; Ibarra-Sanchez, Alfredo; Treviño, Mario; Gonzalez-Espinosa, Claudia; Lamas, Monica

    2016-04-01

    Fyn kinase is widely expressed in neuronal and glial cells of the brain, where it exerts multiple functional roles that affect fundamental physiological processes. The aim of our study was to investigate the, so far unknown, functional role of Fyn in the retina. We report that Fyn is expressed, in vivo, in a subpopulation of Müller glia. We used a mouse model of Fyn genetic ablation and Müller-enriched primary cultures to demonstrate that Fyn deficiency induces morphological alterations in the mature retina, a reduction in the thickness of the outer and inner nuclear layers and alterations in postnatal Müller cell physiology. These include shortening of Müller cell processes, a decrease in cell proliferation, inactivation of the Akt signal transduction pathway, a reduced number of focal adhesions points and decreased adhesion of these cells to the ECM. As abnormalities in Müller cell physiology have been previously associated to a compromised retinal function we evaluated behavioral responses to visual stimulation. Our results associate Fyn deficiency with impaired visual optokinetic responses under scotopic and photopic light conditions. Our study reveals novel roles for Fyn kinase in retinal morphology and Müller cell physiology and suggests that Fyn is required for optimal visual processing.

  19. Functional and structural abnormalities associated with empathy in patients with schizophrenia: An fMRI and VBM study

    PubMed Central

    Singh, Sadhana; Modi, Shilpi; Goyal, Satnam; Kaur, Prabhjot; Singh, Namita; Bhatia, Triptish; Deshpande, Smita N; Khushu, Subash

    2016-01-01

    Empathy deficit is a core feature of schizophrenia which may lead to social dysfunction. The present study was carried out to investigate functional and structural abnormalities associated with empathy in patients with schizophrenia using functional magnetic resonance imaging (fMRI) and voxel-based morphometry (VBM). A sample of 14 schizophrenia patients and 14 healthy control subjects matched for age, sex and education were examined with structural high-resolution T1-weighted MRI; fMRI images were obtained during empathy task in the same session. The analysis was carried out using SPM8 software. On behavioural assessment, schizophrenic patients (83.00±29.04) showed less scores for sadness compared to healthy controls (128.70±22.26) (p<0.001). fMRI results also showed reduced clusters of activation in the bilateral fusiform gyrus, left lingual gyrus, left middle and inferior occipital gyrus in schizophrenic subjects as compared to controls during empathy task. In the same brain areas, VBM results also showed reduced grey and white matter volumes. The present study provides an evidence for an association between structural alterations and disturbed functional brain activation during empathy task in persons affected with schizophrenia. These findings suggest a biological basis for social cognition deficits in schizophrenics. PMID:25963262

  20. Functional and structural abnormalities associated with empathy in patients with schizophrenia: An fMRI and VBM study.

    PubMed

    Singh, Sadhana; Modi, Shilpi; Goyal, Satnam; Kaur, Prabhjot; Singh, Namita; Bhatia, Triptish; Deshpande, Smita N; Khushu, Subash

    2015-06-01

    Empathy deficit is a core feature of schizophrenia which may lead to social dysfunction. The present study was carried out to investigate functional and structural abnormalities associated with empathy in patients with schizophrenia using functional magnetic resonance imaging (fMRI) and voxel-based morphometry (VBM). A sample of 14 schizophrenia patients and 14 healthy control subjects matched for age, sex and education were examined with structural highresolution T1-weighted MRI; fMRI images were obtained during empathy task in the same session. The analysis was carried out using SPM8 software. On behavioural assessment, schizophrenic patients (83.00+-29.04) showed less scores for sadness compared to healthy controls (128.70+-22.26) (p less than 0.001). fMRI results also showed reduced clusters of activation in the bilateral fusiform gyrus, left lingual gyrus, left middle and inferior occipital gyrus in schizophrenic subjects as compared to controls during empathy task. In the same brain areas, VBM results also showed reduced grey and white matter volumes. The present study provides an evidence for an association between structural alterations and disturbed functional brain activation during empathy task in persons affected with schizophrenia. These findings suggest a biological basis for social cognition deficits in schizophrenics.

  1. Fyn kinase genetic ablation causes structural abnormalities in mature retina and defective Müller cell function.

    PubMed

    Chavez-Solano, Marbella; Ibarra-Sanchez, Alfredo; Treviño, Mario; Gonzalez-Espinosa, Claudia; Lamas, Monica

    2016-04-01

    Fyn kinase is widely expressed in neuronal and glial cells of the brain, where it exerts multiple functional roles that affect fundamental physiological processes. The aim of our study was to investigate the, so far unknown, functional role of Fyn in the retina. We report that Fyn is expressed, in vivo, in a subpopulation of Müller glia. We used a mouse model of Fyn genetic ablation and Müller-enriched primary cultures to demonstrate that Fyn deficiency induces morphological alterations in the mature retina, a reduction in the thickness of the outer and inner nuclear layers and alterations in postnatal Müller cell physiology. These include shortening of Müller cell processes, a decrease in cell proliferation, inactivation of the Akt signal transduction pathway, a reduced number of focal adhesions points and decreased adhesion of these cells to the ECM. As abnormalities in Müller cell physiology have been previously associated to a compromised retinal function we evaluated behavioral responses to visual stimulation. Our results associate Fyn deficiency with impaired visual optokinetic responses under scotopic and photopic light conditions. Our study reveals novel roles for Fyn kinase in retinal morphology and Müller cell physiology and suggests that Fyn is required for optimal visual processing. PMID:26808221

  2. Unique functional abnormalities in youth with combined marijuana use and depression: an FMRI study.

    PubMed

    Ford, Kristen A; Wammes, Michael; Neufeld, Richard W; Mitchell, Derek; Théberge, Jean; Williamson, Peter; Osuch, Elizabeth A

    2014-01-01

    Prior research has shown a relationship between early onset marijuana (MJ) use and depression; however, this relationship is complex and poorly understood. Here, we utilized passive music listening and fMRI to examine functional brain activation to a rewarding stimulus in 75 participants [healthy controls (HC), patients with major depressive disorder (MDD), frequent MJ users, and the combination of MDD and MJ (MDD + MJ)]. For each participant, a preferred and neutral piece of instrumental music was determined (utilizing ratings on a standardized scale), and each completed two 6-min fMRI scans of a passive music listening task. Data underwent pre-processing and 61 participants were carried forward for analysis (17 HC, 15 MDD, 15 MJ, 14 MDD + MJ). Two statistical analyses were performed using SPM8, an analysis of covariance with two factors (group × music type) and a whole brain, multiple regression analysis incorporating two predictors of interest [MJ use in past 28 days; and Beck Depression Inventory (BDI) score]. We identified a significant group × music type interaction. Post hoc comparisons showed that the preferred music had significantly greater activation in the MDD + MJ group in areas including the right middle and inferior frontal gyri extending into the claustrum and putamen and the anterior cingulate. No significant differences were identified in MDD, MJ, or HC groups. Multiple regression analysis showed that activation in medial frontal cortex was positively correlated with amount of MJ use, and activation in areas including the insula was negatively correlated with BDI score. Results showed modulation in brain activation during passive music listening specific to MDD, frequent MJ users. This supports the suggestion that frequent MJ use, when combined with MDD, is associated with changes in neurocircuitry involved in reward processing in ways that are absent with either frequent MJ use or MDD alone. This could help inform

  3. Unique Functional Abnormalities in Youth with Combined Marijuana Use and Depression: An fMRI Study

    PubMed Central

    Ford, Kristen A.; Wammes, Michael; Neufeld, Richard W.; Mitchell, Derek; Théberge, Jean; Williamson, Peter; Osuch, Elizabeth A.

    2014-01-01

    Prior research has shown a relationship between early onset marijuana (MJ) use and depression; however, this relationship is complex and poorly understood. Here, we utilized passive music listening and fMRI to examine functional brain activation to a rewarding stimulus in 75 participants [healthy controls (HC), patients with major depressive disorder (MDD), frequent MJ users, and the combination of MDD and MJ (MDD + MJ)]. For each participant, a preferred and neutral piece of instrumental music was determined (utilizing ratings on a standardized scale), and each completed two 6-min fMRI scans of a passive music listening task. Data underwent pre-processing and 61 participants were carried forward for analysis (17 HC, 15 MDD, 15 MJ, 14 MDD + MJ). Two statistical analyses were performed using SPM8, an analysis of covariance with two factors (group × music type) and a whole brain, multiple regression analysis incorporating two predictors of interest [MJ use in past 28 days; and Beck Depression Inventory (BDI) score]. We identified a significant group × music type interaction. Post hoc comparisons showed that the preferred music had significantly greater activation in the MDD + MJ group in areas including the right middle and inferior frontal gyri extending into the claustrum and putamen and the anterior cingulate. No significant differences were identified in MDD, MJ, or HC groups. Multiple regression analysis showed that activation in medial frontal cortex was positively correlated with amount of MJ use, and activation in areas including the insula was negatively correlated with BDI score. Results showed modulation in brain activation during passive music listening specific to MDD, frequent MJ users. This supports the suggestion that frequent MJ use, when combined with MDD, is associated with changes in neurocircuitry involved in reward processing in ways that are absent with either frequent MJ use or MDD alone. This could help inform

  4. Abnormal functional activation during a simple word repetition task: A PET study of adult dyslexics.

    PubMed

    McCrory, E; Frith, U; Brunswick, N; Price, C

    2000-09-01

    Eight dyslexic subjects, impaired on a range of tasks requiring phonological processing, were matched for age and general ability with six control subjects. Participants were scanned using positron emission tomography (PET) during three conditions: repeating real words, repeating pseudowords, and rest. In both groups, speech repetition relative to rest elicited widespread bilateral activation in areas associated with auditory processing of speech; there were no significant differences between words and pseudowords. However, irrespective of word type, the dyslexic group showed less activation than the control group in the right superior temporal and right post-central gyri and also in the left cerebellum. Notably, the right anterior superior temporal cortex (Brodmann's area 22 [BA 22]) was less activated in each of the eight dyslexic subjects, compared to each of the six control subjects. This deficit appears to be specific to auditory repetition as it was not detected in a previous study of reading which used the same sets of stimuli (Brunswick, N., McCrory, E., Price, C., Frith, C.D., & Frith, U. [1999]. Explicit and implicit processing of words and pseudowords by adult developmental dyslexics: A search for Wernicke's Wortschatz? Brain, 122, 1901-1917). This implies that the observed neural manifestation of developmental dyslexia is task-specific (i.e., functional rather than structural). Other studies of normal subjects indicate that attending to the phonetic structure of speech leads to a decrease in right-hemisphere processing. Lower right hemisphere activation in the dyslexic group may therefore indicate less processing of non-phonetic aspects of speech, allowing greater salience to be accorded to phonological aspects of attended speech. PMID:11054918

  5. Autonomic dysfunction in Guillain-Barré syndrome.

    PubMed Central

    Tuck, R R; McLeod, J G

    1981-01-01

    The following tests of autonomic function were performed on seven patients with the Guillain-Barré syndrome and compared with controls: (1) measurement of heart rate and blood pressure in the supine and erect positions, (2) measurement of baroreflex sensitivity, (3) Valsalva's manoeuvre, (4) sweat test. In two patients the heart rates were fixed and greater than 100/min and in three there was postural hypotension. The baroflex sensitivity of four patients was abnormal and heart rate response to Valsalva's manoeuvre was impaired in two of the three patients who were able to perform the manoeuvre. Areas of anhidrosis were found in all seven patients. These abnormalities probably reflect pathological alterations of the sympathetic and parasympathetic components of the autonomic nervous system of patients with Guillain-Barré syndrome. The severity of autonomic involvement is not related to the degree of sensory and motor disturbance which is consistent with the patchy distribution of lesions throughout the peripheral and autonomic nervous systems. PMID:7334398

  6. Association of Abnormal Liver Function Parameters with HIV Serostatus and CD4 Count in Antiretroviral-Naive Rwandan Women

    PubMed Central

    Hoover, Donald R.; Shi, Qiuhu; Mutimura, Eugene; Rudakemwa, Emmanuel; Ndacyayisenga, Victorien; Gakindi, Léonard; Mulvihill, Michael; Sinayobye, Jean D'Amour; Musabeyezu, Emmanuel; Anastos, Kathryn

    2015-01-01

    Abstract We determined the associations of HIV infection/CD4 count with markers of hepatocellular damage [elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT)] and liver synthetic function (decreased albumin) in HIV-infected (HIV+) antiretroviral therapy (ART)-naive and uninfected (HIV−) Rwandan women. In 2005, 710 HIV+ ART-naive and 226 HIV− women enrolled in the Rwanda Women's Interassociation Study and Assessment. Liver enzymes were measured with abnormality defined as either AST or ALT ≥1.25 times the upper limit of normal. Low serum albumin level was defined as <3.5 g/dl. Multivariable logistic regression analysis identified independent predictors of elevated AST/ALT and low serum albumin. HIV− women had the lowest prevalence (6.6%) of abnormal AST/ALT, with the highest prevalence (16.4%) in HIV+ women with CD4 <200 cells/μl (p=0.01). The odds of having serum albumin <3.5 g/dl was 5.7-fold higher in HIV+ than HIV− women (OR=5.68, 95% CI: 3.32–9.71). The risk of low albumin decreased from low to high CD4 count, with OR=2.62, 95% CI: 1.66, 4.14 and OR=1.57, 95% CI: 1.01, 2.43 in HIV+ women with a CD4 count <200 and 200–350 cells/μl, respectively vs. HIV+ with CD4 >350 (p<0.001 and p<0.05 for all comparisons). Our findings suggest that HIV-associated liver damage may occur in ART-naive patients. Although liver abnormality prevalences in this cohort of HIV-infected Rwandan women are less than reported in developed countries, caution is needed for risk assessment measures to monitor and screen HIV-infected patients pre- and post-ART initiation in African clinical settings to curtail potential risks associated with HIV infection. PMID:25924728

  7. Abnormal Functional Specialization within Medial Prefrontal Cortex in High-Functioning Autism: A Multi-Voxel Similarity Analysis

    ERIC Educational Resources Information Center

    Gilbert, Sam J.; Meuwese, Julia D. I.; Towgood, Karren J.; Frith, Christopher D.; Burgess, Paul W.

    2009-01-01

    Multi-voxel pattern analyses have proved successful in "decoding" mental states from fMRI data, but have not been used to examine brain differences associated with atypical populations. We investigated a group of 16 (14 males) high-functioning participants with autism spectrum disorder (ASD) and 16 non-autistic control participants (12 males)…

  8. Bacterial cell wall biogenesis is mediated by SEDS and PBP polymerase families functioning semi-autonomously.

    PubMed

    Cho, Hongbaek; Wivagg, Carl N; Kapoor, Mrinal; Barry, Zachary; Rohs, Patricia D A; Suh, Hyunsuk; Marto, Jarrod A; Garner, Ethan C; Bernhardt, Thomas G

    2016-01-01

    Multi-protein complexes organized by cytoskeletal proteins are essential for cell wall biogenesis in most bacteria. Current models of the wall assembly mechanism assume that class A penicillin-binding proteins (aPBPs), the targets of penicillin-like drugs, function as the primary cell wall polymerases within these machineries. Here, we use an in vivo cell wall polymerase assay in Escherichia coli combined with measurements of the localization dynamics of synthesis proteins to investigate this hypothesis. We find that aPBP activity is not necessary for glycan polymerization by the cell elongation machinery, as is commonly believed. Instead, our results indicate that cell wall synthesis is mediated by two distinct polymerase systems, shape, elongation, division, sporulation (SEDS)-family proteins working within the cytoskeletal machines and aPBP enzymes functioning outside these complexes. These findings thus necessitate a fundamental change in our conception of the cell wall assembly process in bacteria. PMID:27643381

  9. Vascular Function, Inflammation, and Variations in Cardiac Autonomic Responses to Particulate Matter Among Welders

    PubMed Central

    Cavallari, Jennifer M.; Eisen, Ellen A.; Chen, Jiu-Chiuan; Mittleman, Murray A.; Christiani, David C.

    2009-01-01

    Patients with health conditions associated with impaired vascular function and inflammation may be more susceptible to the adverse health effects of fine particulate (particulate matter with a mass median aerodynamic diameter of ≤2.5 μm (PM2.5)) exposure. In 2006, the authors conducted a panel study to investigate directly whether vascular function and inflammation (assessed by C-reactive protein) modify PM2.5-associated reductions in heart rate variability among 23 young male workers (mean age, 40 years) from Massachusetts. Concurrent 24-hour ambulatory electrocardiogram and personal PM2.5 exposure information was collected over a total of 36 person-days, including either or both welding and nonwelding days. Linear mixed models were used to examine the 5-minute standard deviation of normal-to-normal intervals (SDNN) in relation to the moving PM2.5 averages in the preceding 1–4 hours. C-reactive protein levels and 3 measures of vascular function (augmentation index, mean arterial pressure, and pulse pressure) were determined at baseline. The authors observed an inverse association between the 1-hour PM2.5 and 5-minute SDNN. Greater SDNN declines were observed among those with C-reactive protein (Pinteraction < 0.001) and augmentation index (P = 0.06) values at or above the 75th percentile and pulse pressure values below the 75th percentile (P < 0.001). Systemic inflammation and poorer vascular function appear to aggravate particle-related declines in heart rate variability among workers. PMID:19153215

  10. Multimodal functional cardiac MRI in creatine kinase-deficient mice reveals subtle abnormalities in myocardial perfusion and mechanics.

    PubMed

    Nahrendorf, Matthias; Streif, Jörg U; Hiller, Karl-Heinz; Hu, Kai; Nordbeck, Peter; Ritter, Oliver; Sosnovik, David; Bauer, Lisa; Neubauer, Stefan; Jakob, Peter M; Ertl, Georg; Spindler, Matthias; Bauer, Wolfgang R

    2006-06-01

    A decrease in the supply of ATP from the creatine kinase (CK) system is thought to contribute to the evolution of heart failure. However, previous studies on mice with a combined knockout of the mitochondrial and cytosolic CK (CK(-/-)) have not revealed overt left ventricular dysfunction. The aim of this study was to employ novel MRI techniques to measure maximal myocardial velocity (V(max)) and myocardial perfusion and thus determine whether abnormalities in the myocardial phenotype existed in CK(-/-) mice, both at baseline and 4 wk after myocardial infarction (MI). As a result, myocardial hypertrophy was seen in all CK(-/-) mice, but ejection fraction (EF) remained normal. V(max), however, was significantly reduced in the CK(-/-) mice [wild-type, 2.32 +/- 0.09 vs. CK(-/-), 1.43 +/- 0.16 cm/s, P < 0.05; and wild-type MI, 1.53 +/- 0.11 vs. CK(-/-) MI, 1.26 +/- 0.11 cm/s, P = not significant (NS), P < 0.05 vs. baseline]. Myocardial perfusion was also lower in the CK(-/-) mice (wild-type, 6.68 +/- 0.27 vs. CK(-/-), 4.12 +/- 0.63 ml/g.min, P < 0.05; and wild-type MI, 3.97 +/- 0.65 vs. CK(-/-) MI, 3.71 +/- 0.57 ml/g.min, P = NS, P < 0.05 vs. baseline), paralleled by a significantly reduced capillary density (histology). In conclusion, myocardial function in transgenic mice may appear normal when only gross indexes of performance such as EF are assessed. However, the use of a combination of novel MRI techniques to measure myocardial perfusion and mechanics allowed the abnormalities in the CK(-/-) phenotype to be detected. The myocardium in CK-deficient mice is characterized by reduced perfusion and reduced maximal contraction velocity, suggesting that the myocardial hypertrophy seen in these mice cannot fully compensate for the absence of the CK system.

  11. Abnormal development of sensory-motor, visual temporal and parahippocampal cortex in children with learning disabilities and borderline intellectual functioning

    PubMed Central

    Baglio, Francesca; Cabinio, Monia; Ricci, Cristian; Baglio, Gisella; Lipari, Susanna; Griffanti, Ludovica; Preti, Maria G.; Nemni, Raffaello; Clerici, Mario; Zanette, Michela; Blasi, Valeria

    2014-01-01

    Borderline intellectual functioning (BIF) is a condition characterized by an intelligence quotient (IQ) between 70 and 85. BIF children present with cognitive, motor, social, and adaptive limitations that result in learning disabilities and are more likely to develop psychiatric disorders later in life. The aim of this study was to investigate brain morphometry and its relation to IQ level in BIF children. Thirteen children with BIF and 14 age- and sex-matched typically developing (TD) children were enrolled. All children underwent a full IQ assessment (WISC-III scale) and a magnetic resonance (MR) examination including conventional sequences to assess brain structural abnormalities and high resolution 3D images for voxel-based morphometry analysis. To investigate to what extent the group influenced gray matter (GM) volumes, both univariate and multivariate generalized linear model analysis of variance were used, and the varimax factor analysis was used to explore variable correlations and clusters among subjects. Results showed that BIF children, compared to controls have increased regional GM volume in bilateral sensorimotor and right posterior temporal cortices and decreased GM volume in the right parahippocampal gyrus. GM volumes were highly correlated with IQ indices. The present work is a case study of a group of BIF children showing that BIF is associated with abnormal cortical development in brain areas that have a pivotal role in motor, learning, and behavioral processes. Our findings, although allowing for little generalization to the general population, contribute to the very limited knowledge in this field. Future longitudinal MR studies will be useful in verifying whether cortical features can be modified over time even in association with rehabilitative intervention. PMID:25360097

  12. Myoadenylate deaminase deficiency. Functional and metabolic abnormalities associated with disruption of the purine nucleotide cycle.

    PubMed Central

    Sabina, R L; Swain, J L; Olanow, C W; Bradley, W G; Fishbein, W N; DiMauro, S; Holmes, E W

    1984-01-01

    To assess the role of the purine nucleotide cycle in human skeletal muscle function, we evaluated 10 patients with AMP deaminase deficiency (myoadenylate deaminase deficiency; MDD). 4 MDD and 19 non-MDD controls participated in an exercise protocol. The latter group was composed of a patient cohort (n = 8) exhibiting a constellation of symptoms similar to those of the MDD patients, i.e., postexertional aches, cramps, and pains; as well as a cohort of normal, unconditioned volunteers (n = 11). The individuals with MDD fatigued after performing only 28% as much work as their non-MDD counterparts. Muscle biopsies were obtained from the four MDD patients and the eight non-MDD patients at rest and following exercise to the point of fatigue. Creatine phosphate content fell to a comparable extent in the MDD (69%) and non-MDD (52%) patients at the onset of fatigue. Following exercise the 34% decrease in ATP content of muscle from the non-MDD subjects was significantly greater than the 6% decrease in ATP noted in muscle from the MDD patients (P = 0.048). Only one of four MDD patients had a measurable drop in ATP compared with seven of eight non-MDD patients. At end-exercise the muscle content of inosine 5'-monophosphate (IMP), a product of AMP deaminase, was 13-fold greater in the non-MDD patients than that observed in the MDD group (P = 0.008). Adenosine content of muscle from the MDD patients increased 16-fold following exercise, while there was only a twofold increase in adenosine content of muscle from the non-MDD patients (P = 0.028). Those non-MDD patients in whom the decrease in ATP content following exercise was measurable exhibited a stoichiometric increase in IMP, and total purine content of the muscle did not change significantly. The one MDD patient in whom the decrease in ATP was measurable, did not exhibit a stoichiometric increase in IMP. Although the adenosine content increased 13-fold in this patient, only 48% of the ATP catabolized could be accounted for

  13. Correlation between vestibular and autonomous function after 6 months of spaceflight: Data of the SPIN and GAZE-SPIN experiments.

    NASA Astrophysics Data System (ADS)

    Wuyts, Floris; Clement, Gilles; Naumov, Ivan; Kornilova, Ludmila; Glukhikh, Dmitriy; Hallgren, Emma; MacDougall, Hamish; Migeotte, Pierre-Francois; Delière, Quentin; Weerts, Aurelie; Moore, Steven; Diedrich, Andre

    In 13 cosmonauts, the vestibulo-autonomic reflex was investigated before and after 6 months duration spaceflight. Cosmonauts were rotated on the mini-centrifuge VVIS, which is installed in Star City. Initially, this mini-centrifuge flew on board of the Neurolab mission (STS-90), and served to generate intermittent artificial gravity during that mission, with apparent very positive effects on the preservation of the orthostatic tolerance upon return to earth in the 4 crew members that were subjected to the rotations in space. The current experiments SPIN and GAZE-SPIN are control experiments to test the hypothesis that intermittent artificial gravity in space can serve as a counter measure against several deleterious effects of microgravity. Additionally, the effect of microgravity on the gaze holding system is studied as well. Cosmonauts from a long duration stay in the International Space Station were tested on the VVIS (1 g centripetal interaural acceleration; consecutive right-ear-out anti-clockwise and left-ear-out clockwise measurement) on 5 different days. Two measurements were scheduled about one month and a half prior to launch and the remaining three immediately after their return from space (typically on R+2, R+4, R+9; R = return day from space). The ocular counter roll (OCR) as a measure of otolith function was measured on before, during and after the rotation in the mini centrifuge, using infrared video goggles. The perception of verticality was monitored using an ultrasound system. Gaze holding was tested before, during and after rotation. After the centrifugation part, the crew was installed on a tilt table, and instrumented with several cardiovascular recording equipment (ECG, continuous blood pressure monitoring, respiratory monitoring), as well as with impedance measurement devices to investigate fluid redistribution throughout the operational tilt test. To measure heart rate variability parameters, imposed breathing periods were included in the

  14. Meiotic abnormalities

    SciTech Connect

    1993-12-31

    Chapter 19, describes meiotic abnormalities. These include nondisjunction of autosomes and sex chromosomes, genetic and environmental causes of nondisjunction, misdivision of the centromere, chromosomally abnormal human sperm, male infertility, parental age, and origin of diploid gametes. 57 refs., 2 figs., 1 tab.

  15. Assessing autonomic function by analysis of heart rate recovery from exercise in healthy subjects.

    PubMed

    Pierpont, Gordon L; Voth, Eric J

    2004-07-01

    Although delayed recovery of heart rate (HR) after exercise indicates poor prognosis, the relative role of parasympathetic reactivation versus sympathetic withdrawal in controlling exercise HR recovery remains controversial. Quantifying HR recovery is difficult because the rate of recovery varies with exercise level. This study develops a model of HR recovery applicable to multiple exercise levels simultaneously. Using the Levenberg-Marquardt method for nonlinear models, HR curves for 11 healthy volunteers recovering from 4 different levels of exercise were fit to equations incorporating 1 first-order time constant for parasympathetic reactivation and 1 for sympathetic withdrawal. Results provided time constants for parasympathetic reactivation of 44 +/- 37 seconds and for sympathetic withdrawal of 65 +/- 56 seconds. The model fit the HR recovery curves very closely, explaining 99.7 +/- 0.1% of the variance in the data. In conclusion, this study presents a unique method for quantitatively testing theories on the relative roles of sympathetic withdrawal and parasympathetic reactivation during recovery from exercise. It provides indexes of dynamic sympathetic and parasympathetic functions, with the parasympathetic system having a faster response time. It supports theories of coordinated interaction of parasympathetic reactivation and sympathetic withdrawal during exercise recovery and does not support using simple measures of exercise HR recovery as indexes of vagal function alone.

  16. Sensitivity of the resting-state haemodynamic response function estimation to autonomic nervous system fluctuations.

    PubMed

    Wu, Guo-Rong; Marinazzo, Daniele

    2016-05-13

    The haemodynamic response function (HRF) is a key component of the blood oxygen level-dependent (BOLD) signal, providing the mapping between neural activity and the signal measured with functional magnetic resonance imaging (fMRI). Most of the time the HRF is associated with task-based fMRI protocols, in which its onset is explicitly included in the design matrix. On the other hand, the HRF also mediates the relationship between spontaneous neural activity and the BOLD signal in resting-state protocols, in which no explicit stimulus is taken into account. It has been shown that resting-state brain dynamics can be characterized by looking at sparse BOLD 'events', which can be retrieved by point process analysis. These events can be then used to retrieve the HRF at rest. Crucially, cardiac activity can also induce changes in the BOLD signal, thus affecting both the number of these events and the estimation of the haemodynamic response. In this study, we compare the resting-state haemodynamic response retrieved by means of a point process analysis, taking the cardiac fluctuations into account. We find that the resting-state HRF estimation is significantly modulated in the brainstem and surrounding cortical areas. From the analysis of two high-quality datasets with different temporal and spatial resolution, and through the investigation of intersubject correlation, we suggest that spontaneous point process response durations are associated with the mean interbeat interval and low-frequency power of heart rate variability in the brainstem. PMID:27044997

  17. Autonomic Dysregulation in Multiple Sclerosis

    PubMed Central

    Pintér, Alexandra; Cseh, Domonkos; Sárközi, Adrienn; Illigens, Ben M.; Siepmann, Timo

    2015-01-01

    Multiple sclerosis (MS) is a chronic, progressive central neurological disease characterized by inflammation and demyelination. In patients with MS, dysregulation of the autonomic nervous system may present with various clinical symptoms including sweating abnormalities, urinary dysfunction, orthostatic dysregulation, gastrointestinal symptoms, and sexual dysfunction. These autonomic disturbances reduce the quality of life of affected patients and constitute a clinical challenge to the physician due to variability of clinical presentation and inconsistent data on diagnosis and treatment. Early diagnosis and initiation of individualized interdisciplinary and multimodal strategies is beneficial in the management of autonomic dysfunction in MS. This review summarizes the current literature on the most prevalent aspects of autonomic dysfunction in MS and provides reference to underlying pathophysiological mechanisms as well as means of diagnosis and treatment. PMID:26213927

  18. Abnormal immune system development and function in schizophrenia helps reconcile diverse findings and suggests new treatment and prevention strategies.

    PubMed

    Anders, Sherry; Kinney, Dennis K

    2015-08-18

    Extensive research implicates disturbed immune function and development in the etiology and pathology of schizophrenia. In addition to reviewing evidence for immunological factors in schizophrenia, this paper discusses how an emerging model of atypical immune function and development helps explain a wide variety of well-established - but puzzling - findings about schizophrenia. A number of theorists have presented hypotheses that early immune system programming, disrupted by pre- and perinatal adversity, often combines with abnormal brain development to produce schizophrenia. The present paper focuses on the hypothesis that disruption of early immune system development produces a latent immune vulnerability that manifests more fully after puberty, when changes in immune function and the thymus leave individuals more susceptible to infections and immune dysfunctions that contribute to schizophrenia. Complementing neurodevelopmental models, this hypothesis integrates findings on many contributing factors to schizophrenia, including prenatal adversity, genes, climate, migration, infections, and stress, among others. It helps explain, for example, why (a) schizophrenia onset is typically delayed until years after prenatal adversity, (b) individual risk factors alone often do not lead to schizophrenia, and (c) schizophrenia prevalence rates actually tend to be higher in economically advantaged countries. Here we discuss how the hypothesis explains 10 key findings, and suggests new, potentially highly cost-effective, strategies for treatment and prevention of schizophrenia. Moreover, while most human research linking immune factors to schizophrenia has been correlational, these strategies provide ethical ways to experimentally test in humans theories about immune function and schizophrenia. This article is part of a Special Issue entitled SI: Neuroimmunology in Health And Disease.

  19. Endogenous Brain Derived Neurotrophic Factor in the Nucleus Tractus Solitarius Tonically Regulates Synaptic and Autonomic Function

    PubMed Central

    Clark, Catharine G.; Hasser, Eileen M.; Kunze, Diana L.; Katz, David M.; Kline, David D.

    2012-01-01

    Brain derived neurotrophic factor (BDNF) and its receptor, TrkB, are highly expressed in the nucleus tractus solitarius (nTS), the principal target of cardiovascular primary afferent input to the brainstem. However, little is known about the role of BDNF signaling in nTS in cardiovascular homeostasis. We examined whether BDNF in nTS modulates cardiovascular function in vivo and regulates synaptic and/or neuronal activity in isolated brainstem slices. Microinjection of BDNF into the rat medial nTS (mnTS), a region critical for baroreflex control of sympathetic outflow, produced dose-dependent increases in mean arterial pressure (MAP), heart rate (HR) and lumbar sympathetic nerve activity (LSNA) that were blocked by the tyrosine kinase inhibitor K252a. In contrast, immunoneutralization of endogenous BDNF (antiBDNF), or microinjection of K252a alone, decreased MAP, HR and LSNA. The effects of antiBDNF were abolished by blockade of ionotropic glutamate receptors, indicating a role for glutamate signaling in the response to BDNF. In vitro, BDNF reduced the amplitude of miniature excitatory postsynaptic currents (mEPSCs) as well as solitary tract (TS)-evoked EPSC amplitude and action potential discharge (APD) in second-order nTS neurons. BDNF effects on EPSCs were independent of GABAergic signaling and ablated by AMPA receptor blockade. In contrast, K252a increased spontaneous EPSC frequency and TS-evoked EPSC amplitude. BDNF also attenuated APD evoked by injection of depolarizing current into second-order neurons, indicating reduced intrinsic neuronal excitability. Our data demonstrate that BDNF signaling in mnTS plays a tonic role in regulating cardiovascular function, likely via modulation of primary afferent glutamatergic excitatory transmission and neural activity. PMID:21865474

  20. High-frequency transformation of a methylotrophic yeast, Candida boidinii, with autonomously replicating plasmids which are also functional in Saccharomyces cerevisiae.

    PubMed

    Sakai, Y; Goh, T K; Tani, Y

    1993-06-01

    We have developed a transformation system which uses autonomous replicating plasmids for a methylotrophic yeast, Candida boidinii. Two autonomous replication sequences, CARS1 and CARS2, were newly cloned from the genome of C. boidinii. Plasmids having both a CARS fragment and the C. boidinii URA3 gene transformed C. boidinii ura3 cells to Ura+ phenotype at frequencies of up to 10(4) CFU/micrograms of DNA. From Southern blot analysis, CARS plasmids seemed to exist in polymeric forms as well as in monomeric forms in C. boidinii cells. The C. boidinii URA3 gene was overexpressed in C. boidinii on these CARS vectors. CARS1 and CARS2 were found to function as an autonomous replicating element in Saccharomyces cerevisiae as well. Different portions of the CARS1 sequence were needed for autonomous replicating activity in C. boidinii and S. cerevisiae. C. boidinii could also be transformed with vectors harboring a CARS fragment and the S. cerevisiae URA3 gene.

  1. High-frequency transformation of a methylotrophic yeast, Candida boidinii, with autonomously replicating plasmids which are also functional in Saccharomyces cerevisiae.

    PubMed

    Sakai, Y; Goh, T K; Tani, Y

    1993-06-01

    We have developed a transformation system which uses autonomous replicating plasmids for a methylotrophic yeast, Candida boidinii. Two autonomous replication sequences, CARS1 and CARS2, were newly cloned from the genome of C. boidinii. Plasmids having both a CARS fragment and the C. boidinii URA3 gene transformed C. boidinii ura3 cells to Ura+ phenotype at frequencies of up to 10(4) CFU/micrograms of DNA. From Southern blot analysis, CARS plasmids seemed to exist in polymeric forms as well as in monomeric forms in C. boidinii cells. The C. boidinii URA3 gene was overexpressed in C. boidinii on these CARS vectors. CARS1 and CARS2 were found to function as an autonomous replicating element in Saccharomyces cerevisiae as well. Different portions of the CARS1 sequence were needed for autonomous replicating activity in C. boidinii and S. cerevisiae. C. boidinii could also be transformed with vectors harboring a CARS fragment and the S. cerevisiae URA3 gene. PMID:8501059

  2. Effects of Escitalopram on Autonomic Function in Posttraumatic Stress Disorder Among Veterans of Operations Enduring Freedom and Iraqi Freedom (OEF/OIF)

    PubMed Central

    Selvaraj, Vithyalakshmi; Driscoll, David; Madabushi, Jayakrishna S.; Bhatia, Subhash C.; Yeragani, Vikram

    2015-01-01

    Objective: Posttraumatic stress disorder is a chronic, debilitating condition that has become a growing concern among combat veterans. Previous research suggests that posttraumatic stress disorder disrupts normal autonomic responding and may increase the risk of cardiovascular disease and mortality. Measures of heart rate variability and QT interval variability have been used extensively to characterize sympathetic and parasympathetic influences on heart rate in a variety of psychiatric populations. The objective of this study was to better understand the effects of pharmacological treatment on autonomic reactivity in posttraumatic stress disorder. Design: A 12-week, Phase IV, prospective, open-label trial of escitalopram in veterans with combat-related posttraumatic stress disorder and comorbid depression. Setting: An outpatient mental health clinic at a Veterans Affairs Medical Center. Participants: Eleven male veterans of Operations Enduring Freedom and Iraqi Freedom diagnosed with posttraumatic stress disorder and comorbid depression. Measurements: Autonomic reactivity was measured by examining heart rate variability and QT interval variability. Treatment safety and efficacy were also evaluated pre- and post-treatment. Results: We observed a reduction in posttraumatic stress disorder and depression symptoms from pre- to post-treatment, and escitalopram was generally well tolerated in our sample. In addition, we observed a decrease in high frequency heart rate variability and an increase in QT variability, indicating a reduction in cardiac vagal function and heightened sympathetic activation. Conclusion: These findings suggest that escitalopram treatment in patients with posttraumatic stress disorder and depression can trigger changes in autonomic reactivity that may adversely impact cardiovascular health. PMID:26155373

  3. Plasticity of cardiovascular function in snapping turtle embryos (Chelydra serpentina): chronic hypoxia alters autonomic regulation and gene expression.

    PubMed

    Eme, John; Rhen, Turk; Tate, Kevin B; Gruchalla, Kathryn; Kohl, Zachary F; Slay, Christopher E; Crossley, Dane A

    2013-06-01

    Reptile embryos tolerate large decreases in the concentration of ambient oxygen. However, we do not fully understand the mechanisms that underlie embryonic cardiovascular short- or long-term responses to hypoxia in most species. We therefore measured cardiac growth and function in snapping turtle embryos incubated under normoxic (N21; 21% O₂) or chronic hypoxic conditions (H10; 10% O₂). We determined heart rate (fH) and mean arterial pressure (Pm) in acute normoxic (21% O₂) and acute hypoxic (10% O₂) conditions, as well as embryonic responses to cholinergic, adrenergic, and ganglionic pharmacological blockade. Compared with N21 embryos, chronic H10 embryos had smaller bodies and relatively larger hearts and were hypotensive, tachycardic, and following autonomic neural blockade showed reduced intrinsic fH at 90% of incubation. Unlike other reptile embryos, cholinergic and ganglionic receptor blockade both increased fH. β-Adrenergic receptor blockade with propranolol decreased fH, and α-adrenergic blockade with phentolamine decreased Pm. We also measured cardiac mRNA expression. Cholinergic tone was reduced in H10 embryos, but cholinergic receptor (Chrm2) mRNA levels were unchanged. However, expression of adrenergic receptor mRNA (Adrb1, Adra1a, Adra2c) and growth factor mRNA (Igf1, Igf2, Igf2r, Pdgfb) was lowered in H10 embryos. Hypoxia altered the balance between cholinergic receptors, α-adrenoreceptor and β-adrenoreceptor function, which was reflected in altered intrinsic fH and adrenergic receptor mRNA levels. This is the first study to link gene expression with morphological and cardioregulatory plasticity in a developing reptile embryo. PMID:23552497

  4. Circumventricular organs: definition and role in the regulation of endocrine and autonomic function.

    PubMed

    Ganong, W F

    2000-01-01

    1. The circumventricular organs (CVO) are structures that permit polypeptide hypothalamic hormones to leave the brain without disrupting the blood-brain barrier (BBB) and permit substances that do not cross the BBB to trigger changes in brain function. 2. In mammals, CVO include only the median eminence and adjacent neurohypophysis, organum vasculosum lamina terminalis, subfornical organ and the area postrema. 3. The CVO are characterized by their small size, high permeability and fenestrated capillaries. The subcommissural organ is not highly permeable and does not have fenestrated capillaries, but new evidence indicates that it may be involved in the hypertension produced by aldosterone acting on the brain. 4. Feedback control of corticotropin-releasing hormone (CRH) secretion is exerted by free steroids diffusing into the brain, but substances such as cytokines and angiotensin II act on CVO to produce increases in CRH secretion. Gonadal steroids also diffuse into the brain to regulate gonadotrophin-releasing hormone secretion. Thyrotropin-releasing hormone secretion is regulated by thyroid hormones transported across cerebral capillaries. However, CVO may be involved in the negative feedback control of growth hormone and prolactin secretion.

  5. Maladaptive autonomic regulation in PTSD accelerates physiological aging

    PubMed Central

    Williamson, John B.; Porges, Eric C.; Lamb, Damon G.; Porges, Stephen W.

    2015-01-01

    A core manifestation of post-traumatic stress disorder (PTSD) is a disconnection between physiological state and psychological or behavioral processes necessary to adequately respond to environmental demands. Patients with PTSD experience abnormal oscillations in autonomic states supporting either fight and flight behaviors or withdrawal, immobilization, and dissociation without an intervening “calm” state that would provide opportunities for positive social interactions. This defensive autonomic disposition is adaptive in dangerous and life threatening situations, but in the context of every-day life may lead to significant psychosocial distress and deteriorating social relationships. The perpetuation of these maladaptive autonomic responses may contribute to the development of comorbid mental health issues such as depression, loneliness, and hostility that further modify the nature of cardiovascular behavior in the context of internal and external stressors. Over time, changes in autonomic, endocrine, and immune function contribute to deteriorating health, which is potently expressed in brain dysfunction and cardiovascular disease. In this theoretical review paper, we present an overview of the literature on the chronic health effects of PTSD. We discuss the brain networks underlying PTSD in the context of autonomic efferent and afferent contributions and how disruption of these networks leads to poor health outcomes. Finally, we discuss treatment approaches based on our theoretical model of PTSD. PMID:25653631

  6. Cell-autonomous iodothyronine deiodinase expression mediates seasonal plasticity in immune function.

    PubMed

    Stevenson, Tyler J; Onishi, Kenneth G; Bradley, Sean P; Prendergast, Brian J

    2014-02-01

    Annual rhythms in morbidity and mortality are well-documented, and host defense mechanisms undergo marked seasonal phenotypic change. Siberian hamsters (Phodopus sungorus) exhibit striking immunological plasticity following adaptation to short winter day lengths (SD), including increases in blood leukocytes and in the magnitude of T cell-mediated immune responses. Thyroid hormone (TH) signaling is rate-limited by tissue-level expression of iodothyronine deiodinase types II and III (dio2, dio3), and dio2/dio3 expression in the central nervous system gate TH-dependent transduction of photoperiod information into the neuroendocrine system. THs are also potent immunomodulators, but their role in seasonal immunobiology remains unexamined. Here we report that photoperiod-driven changes in triiodothyronine (T3) signaling mediate seasonal changes in multiple aspects of immune function. Transfer from long days (LD) to SD inhibited leukocyte dio3 expression, which increased cellular T4→T3 catabolism. T3 was preferentially localized in the lymphocyte cytoplasm, consistent with a non-nuclear role of T3 in lymphoid cell differentiation and maturation. Exposure to SD upregulated leukocyte DNA methyltransferase expression and markedly increased DNA methylation in the dio3 proximal promoter region. Lastly, to bypass low endogenous T3 biosynthesis in LD lymphocytes, LD hamsters were treated with T3, which enhanced T cell-dependent delayed-type hypersensitivity inflammatory responses and blood leukocyte concentrations in a dose-dependent manner, mimicking effects of SD on these immunophenotypes. T3 signaling represents a novel mechanism by which environmental day length cues impact the immune system: changes in day length alter lymphoid cell T3-signaling via epigenetic transcriptional control of dio3 expression.

  7. Cell-autonomous iodothyronine deiodinase expression mediates seasonal plasticity in immune function

    PubMed Central

    Stevenson, Tyler J; Onishi, Kenneth G; Bradley, Sean P; Prendergast, Brian J

    2013-01-01

    Annual rhythms in morbidity and mortality are well-documented, and host defense mechanisms undergo marked seasonal phenotypic change. Siberian hamsters (Phodopus sungorus) exhibit striking immunological plasticity following adaptation to short winter day lengths (SD), including increases in blood leukocytes and in the magnitude of T cell-mediated immune responses. Thyroid hormone (TH) signaling is rate-limited by tissue-level expression of iodothyronine deiodinase types II and III (dio2, dio3), and dio2/dio3 expression in the central nervous system gate TH-dependent transduction of photoperiod information into the neuroendocrine system. THs are also potent immunomodulators, but their role in seasonal immunobiology remains unexamined. Here we report that photoperiod-driven changes in triiodothyronine (T3) signaling mediate seasonal changes in multiple aspects of immune function. Transfer from long days (LD) to SD inhibited leukocyte dio3 expression, which increased cellular T4→T3 catabolism. T3 was preferentially localized in the lymphocyte cytoplasm, consistent with a non-nuclear role of T3 in lymphoid cell differentiation and maturation. Exposure to SD upregulated leukocyte DNA methyltransferase expression and markedly increased DNA methylation in the dio3 proximal promoter region. Lastly, to bypass low endogenous T3 biosynthesis in LD lymphocytes, LD hamsters were treated with T3, which enhanced T cell-dependent delayed-type hypersensitivity inflammatory responses and blood leukocyte concentrations in a dose-dependent manner, mimicking effects of SD on these immunophenotypes. T3 signaling represents a novel mechanism by which environmental day length cues impact the immune system: changes in day length alter lymphoid cell T3-signaling via epigenetic transcriptional control of dio3 expression. PMID:24145050

  8. Carotid body denervation improves autonomic and cardiac function and attenuates disordered breathing in congestive heart failure

    PubMed Central

    Marcus, Noah J; Rio, Rodrigo; Schultz, Evan P; Xia, Xiao-Hong; Schultz, Harold D

    2014-01-01

    In congestive heart failure (CHF), carotid body (CB) chemoreceptor activity is enhanced and is associated with oscillatory (Cheyne–Stokes) breathing patterns, increased sympathetic nerve activity (SNA) and increased arrhythmia incidence. We hypothesized that denervation of the CB (CBD) chemoreceptors would reduce SNA, reduce apnoea and arrhythmia incidence and improve ventricular function in pacing-induced CHF rabbits. Resting breathing, renal SNA (RSNA) and arrhythmia incidence were measured in three groups of animals: (1) sham CHF/sham–CBD (sham–sham); (2) CHF/sham–CBD (CHF–sham); and (3) CHF/CBD (CHF–CBD). Chemoreflex sensitivity was measured as the RSNA and minute ventilatory () responses to hypoxia and hypercapnia. Respiratory pattern was measured by plethysmography and quantified by an apnoea–hypopnoea index, respiratory rate variability index and the coefficient of variation of tidal volume. Sympatho-respiratory coupling (SRC) was assessed using power spectral analysis and the magnitude of the peak coherence function between tidal volume and RSNA frequency spectra. Arrhythmia incidence and low frequency/high frequency ratio of heart rate variability were assessed using ECG and blood pressure waveforms, respectively. RSNA and responses to hypoxia were augmented in CHF–sham and abolished in CHF–CBD animals. Resting RSNA was greater in CHF–sham compared to sham–sham animals (43 ± 5% max vs. 23 ± 2% max, P < 0.05), and this increase was not found in CHF–CBD animals (25 ± 1% max, P < 0.05 vs. CHF–sham). Low frequency/high frequency heart rate variability ratio was similarly increased in CHF and reduced by CBD (P < 0.05). Respiratory rate variability index, coefficient of variation of tidal volume and apnoea–hypopnoea index were increased in CHF–sham animals and reduced in CHF–CBD animals (P < 0.05). SRC (peak coherence) was increased in CHF–sham animals (sham–sham 0.49 ± 0.05; CHF–sham 0.79

  9. Architecture of autonomous systems

    NASA Technical Reports Server (NTRS)

    Dikshit, Piyush; Guimaraes, Katia; Ramamurthy, Maya; Agrawala, Ashok; Larsen, Ronald L.

    1989-01-01

    Automation of Space Station functions and activities, particularly those involving robotic capabilities with interactive or supervisory human control, is a complex, multi-disciplinary systems design problem. A wide variety of applications using autonomous control can be found in the literature, but none of them seem to address the problem in general. All of them are designed with a specific application in mind. In this report, an abstract model is described which unifies the key concepts underlying the design of automated systems such as those studied by the aerospace contractors. The model has been kept as general as possible. The attempt is to capture all the key components of autonomous systems. With a little effort, it should be possible to map the functions of any specific autonomous system application to the model presented here.

  10. Architecture of autonomous systems

    NASA Technical Reports Server (NTRS)

    Dikshit, Piyush; Guimaraes, Katia; Ramamurthy, Maya; Agrawala, Ashok; Larsen, Ronald L.

    1986-01-01

    Automation of Space Station functions and activities, particularly those involving robotic capabilities with interactive or supervisory human control, is a complex, multi-disciplinary systems design problem. A wide variety of applications using autonomous control can be found in the literature, but none of them seem to address the problem in general. All of them are designed with a specific application in mind. In this report, an abstract model is described which unifies the key concepts underlying the design of automated systems such as those studied by the aerospace contractors. The model has been kept as general as possible. The attempt is to capture all the key components of autonomous systems. With a little effort, it should be possible to map the functions of any specific autonomous system application to the model presented here.

  11. Abnormal reward functioning across substance use disorders and major depressive disorder: Considering reward as a transdiagnostic mechanism.

    PubMed

    Baskin-Sommers, Arielle R; Foti, Dan

    2015-11-01

    A common criticism of the Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Association, 2013) is that its criteria are based more on behavioral descriptions than on underlying biological mechanisms. Increasingly, calls have intensified for a more biologically-based approach to conceptualizing, studying, and treating psychological disorders, as exemplified by the Research Domain Criteria Project (RDoC). Among the most well-studied neurobiological mechanisms is reward processing. Moreover, individual differences in reward sensitivity are related to risk for substance abuse and depression. The current review synthesizes the available preclinical, electrophysiological, and neuroimaging literature on reward processing from a transdiagnostic, multidimensional perspective. Findings are organized with respect to key reward constructs within the Positive Valence Systems domain of the RDoC matrix, including initial responsiveness to reward (physiological 'liking'), approach motivation (physiological 'wanting'), and reward learning/habit formation. In the current review, we (a) describe the neural basis of reward, (b) elucidate differences in reward activity in substance abuse and depression, and (c) suggest a framework for integrating these disparate literatures and discuss the utility of shifting focus from diagnosis to process for understanding liability and co-morbidity. Ultimately, we believe that an integrative focus on abnormal reward functioning across the full continuum of clinically heterogeneous samples, rather than within circumscribed diagnostic categories, might actually help to refine the phenotypes and improve the prediction of onset and recovery of these disorders.

  12. Craniofacial Abnormalities

    MedlinePlus

    ... of the skull and face. Craniofacial abnormalities are birth defects of the face or head. Some, like cleft ... palate, are among the most common of all birth defects. Others are very rare. Most of them affect ...

  13. Chromosome Abnormalities

    MedlinePlus

    ... decade, newer techniques have been developed that allow scientists and doctors to screen for chromosomal abnormalities without using a microscope. These newer methods compare the patient's DNA to a normal DNA ...

  14. Walking abnormalities

    MedlinePlus

    ... include: Arthritis of the leg or foot joints Conversion disorder (a psychological disorder) Foot problems (such as a ... injuries. For an abnormal gait that occurs with conversion disorder, counseling and support from family members are strongly ...

  15. Nail abnormalities

    MedlinePlus

    Beau's lines; Fingernail abnormalities; Spoon nails; Onycholysis; Leukonychia; Koilonychia; Brittle nails ... Just like the skin, the fingernails tell a lot about your health: ... the fingernail. These lines can occur after illness, injury to ...

  16. Effect of pioglitazone on systemic inflammation is independent of metabolic control and cardiac autonomic function in patients with type 2 diabetes.

    PubMed

    Nerla, Roberto; Pitocco, Dario; Zaccardi, Francesco; Scalone, Giancarla; Coviello, Ilaria; Mollo, Roberto; Ghirlanda, Giovanni; Lanza, Gaetano A; Crea, Filippo

    2010-12-01

    The aim of this article is to investigate the relation of the anti-inflammatory effect of pioglitazone with cardiac autonomic function and metabolic control in diabetic patients. In this prospective open label trial, 36 type 2 diabetic patients (age 60 ± 10, 20 M) without overt cardiovascular disease were randomized to add pioglitazone (30 mg) to their therapy or to continue standard therapy. C-reactive protein (CRP) serum levels, metabolic parameters and cardiac autonomic function (assessed by heart rate variability [HRV] on 24-h ECG Holter monitoring) were measured at baseline and after 3 months. Clinical and laboratory variables were similar in the two groups. No significant changes were observed after 3 months for metabolic and anthropometric parameters, except for a mild increase in HDL levels in the pioglitazone group only (P = 0.04 vs. controls). CRP levels decreased significantly at follow-up in the pioglitazone group (3.2 ± 1.97 vs. 2.37 ± 1.56 mg/l) but not in the control group (3.0 ± 1.92 vs. 3.93 ± 2.14 mg/l; P = 0.003). No differences were found in basal and follow-up HRV variables between the two groups. In type 2 diabetic patients pioglitazone exerts favourable effects on inflammation even after short-term therapy. This effect precedes those on metabolic and anthropometric parameters and is not associated with changes in cardiac autonomic function.

  17. Are Cardiac Autonomic Nervous System Activity and Perceived Stress Related to Functional Somatic Symptoms in Adolescents? The TRAILS Study

    PubMed Central

    Janssens, Karin A. M.; Riese, Harriëtte; Van Roon, Arie M.; Hunfeld, Joke A. M.; Groot, Paul F. C.; Oldehinkel, Albertine J.; Rosmalen, Judith G. M.

    2016-01-01

    Objective Stressors have been related to medically insufficiently explained or functional somatic symptoms (FSS). However, the underlying mechanism of this association is largely unclear. In the current study, we examined whether FSS are associated with different perceived stress and cardiac autonomic nervous system (ANS) levels during a standardized stressful situation, and whether these associations are symptom-specific. Methods We examined 715 adolescents (16.1 years, 51.3% girls) from the Dutch cohort study Tracking Adolescents’ Individual Lives Sample during the Groningen Social Stress Test (GSST). FSS were assessed by the Youth Self-Report, and clustered into a cluster of overtiredness, dizziness and musculoskeletal pain and a cluster of headache and gastrointestinal symptoms. Perceived stress levels (i.e. unpleasantness and arousal) were assessed by the Self-Assessment Manikin, and cardiac ANS activity by assessing heart rate variability (HRV-HF) and pre-ejection period (PEP). Perceived stress and cardiac ANS levels before, during, and after the GSST were studied as well as cardiac ANS reactivity. Linear regression analyses were used to examine the associations. Results Perceived arousal levels during (beta = 0.09, p = 0.04) and after (beta = 0.07, p = 0.047) the GSST, and perceived unpleasantness levels before (beta = 0.07, p = 0.048) and during (beta = 0.12, p = 0.001) the GSST were related to FSS during the past couple of months. The association between perceived stress and FSS was stronger for the FSS cluster of overtiredness, dizziness and musculoskeletal pain than for the cluster of headache and gastrointestinal symptoms. Neither ANS activity levels before, during, and after the GSST, nor maximal HF-HRV and PEP reactivity were related to FSS. Conclusions This study suggests that perceived stress levels during social stress are related to FSS, whereas cardiac ANS activity and reactivity are not related to FSS. PMID:27089394

  18. Autonomic and brain responses associated with empathy deficits in autism spectrum disorder

    PubMed Central

    Eilam‐Stock, Tehila; Zhou, Thomas; Anagnostou, Evdokia; Kolevzon, Alexander; Soorya, Latha; Hof, Patrick R.; Friston, Karl J.

    2015-01-01

    Abstract Accumulating evidence suggests that autonomic signals and their cortical representations are closely linked to emotional processes, and that related abnormalities could lead to social deficits. Although socio‐emotional impairments are a defining feature of autism spectrum disorder (ASD), empirical evidence directly supporting the link between autonomic, cortical, and socio‐emotional abnormalities in ASD is still lacking. In this study, we examined autonomic arousal indexed by skin conductance responses (SCR), concurrent cortical responses measured by functional magnetic resonance imaging, and effective brain connectivity estimated by dynamic causal modeling in seventeen unmedicated high‐functioning adults with ASD and seventeen matched controls while they performed an empathy‐for‐pain task. Compared to controls, adults with ASD showed enhanced SCR related to empathetic pain, along with increased neural activity in the anterior insular cortex, although their behavioral empathetic pain discriminability was reduced and overall SCR was decreased. ASD individuals also showed enhanced correlation between SCR and neural activities in the anterior insular cortex. Importantly, significant group differences in effective brain connectivity were limited to greater reduction in the negative intrinsic connectivity of the anterior insular cortex in the ASD group, indicating a failure in attenuating anterior insular responses to empathetic pain. These results suggest that aberrant interoceptive precision, as indexed by abnormalities in autonomic activity and its central representations, may underlie empathy deficits in ASD. Hum Brain Mapp 36:3323–3338, 2015. © 2015 The Authors Human Brain Mapping Published byWiley Periodicals, Inc. PMID:25995134

  19. High Intensity Aerobic Exercise Training Improves Deficits of Cardiovascular Autonomic Function in a Rat Model of Type 1 Diabetes Mellitus with Moderate Hyperglycemia

    PubMed Central

    Grisé, Kenneth N.; Olver, T. Dylan; McDonald, Matthew W.; Dey, Adwitia; Jiang, Mao; Lacefield, James C.; Shoemaker, J. Kevin; Noble, Earl G.; Melling, C. W. James

    2016-01-01

    Indices of cardiovascular autonomic neuropathy (CAN) in experimental models of Type 1 diabetes mellitus (T1DM) are often contrary to clinical data. Here, we investigated whether a relatable insulin-treated model of T1DM would induce deficits in cardiovascular (CV) autonomic function more reflective of clinical results and if exercise training could prevent those deficits. Sixty-four rats were divided into four groups: sedentary control (C), sedentary T1DM (D), control exercise (CX), or T1DM exercise (DX). Diabetes was induced via multiple low-dose injections of streptozotocin and blood glucose was maintained at moderate hyperglycemia (9–17 mM) through insulin supplementation. Exercise training consisted of daily treadmill running for 10 weeks. Compared to C, D had blunted baroreflex sensitivity, increased vascular sympathetic tone, increased serum neuropeptide Y (NPY), and decreased intrinsic heart rate. In contrast, DX differed from D in all measures of CAN (except NPY), including heart rate variability. These findings demonstrate that this T1DM model elicits deficits and exercise-mediated improvements to CV autonomic function which are reflective of clinical T1DM. PMID:26885531

  20. High Intensity Aerobic Exercise Training Improves Deficits of Cardiovascular Autonomic Function in a Rat Model of Type 1 Diabetes Mellitus with Moderate Hyperglycemia.

    PubMed

    Grisé, Kenneth N; Olver, T Dylan; McDonald, Matthew W; Dey, Adwitia; Jiang, Mao; Lacefield, James C; Shoemaker, J Kevin; Noble, Earl G; Melling, C W James

    2016-01-01

    Indices of cardiovascular autonomic neuropathy (CAN) in experimental models of Type 1 diabetes mellitus (T1DM) are often contrary to clinical data. Here, we investigated whether a relatable insulin-treated model of T1DM would induce deficits in cardiovascular (CV) autonomic function more reflective of clinical results and if exercise training could prevent those deficits. Sixty-four rats were divided into four groups: sedentary control (C), sedentary T1DM (D), control exercise (CX), or T1DM exercise (DX). Diabetes was induced via multiple low-dose injections of streptozotocin and blood glucose was maintained at moderate hyperglycemia (9-17 mM) through insulin supplementation. Exercise training consisted of daily treadmill running for 10 weeks. Compared to C, D had blunted baroreflex sensitivity, increased vascular sympathetic tone, increased serum neuropeptide Y (NPY), and decreased intrinsic heart rate. In contrast, DX differed from D in all measures of CAN (except NPY), including heart rate variability. These findings demonstrate that this T1DM model elicits deficits and exercise-mediated improvements to CV autonomic function which are reflective of clinical T1DM. PMID:26885531

  1. Autonomous Soaring

    NASA Technical Reports Server (NTRS)

    Lin, Victor P.

    2007-01-01

    This viewgraph presentation reviews the autonomous soaring flight of unmanned aerial vehicles (UAV). It reviews energy sources for UAVs, and two examples of UAV's that used alternative energy sources, and thermal currents for soaring. Examples of flight tests, plans, and results are given. Ultimately, the concept of a UAV harvesting energy from the atmosphere has been shown to be feasible with existing technology.

  2. The "Laparoscopic Neuro-Navigation" -- LANN: from a functional cartography of the pelvic autonomous neurosystem to a new field of laparoscopic surgery.

    PubMed

    Possover; Rhiem; Chiantera

    2004-12-01

    It is the objective of this study to etablish the technique of laparoscopic exposure of all pelvic somatic and autonomous nerves. In all our patients who underwent a laparoscopic surgical approach of the retroperitoneum, exposure and assessment of the exposed nerves using laparoscopic neuro-navigation were performed. Laparoscopic surgery allows the surgical approach to all pelvic nerves, particularly to the sciatic nerve, the pudendal nerve and the splanchnic pelvic nerves. We describe a cartography of the functional anatomy of the pelvic plexus and elaborate on the concept of "laparoscopic pelvic functional surgery".

  3. Ichthyosis in Sjögren-Larsson syndrome reflects defective barrier function due to abnormal lamellar body structure and secretion.

    PubMed

    Rizzo, William B; S'Aulis, Dana; Jennings, M Anitia; Crumrine, Debra A; Williams, Mary L; Elias, Peter M

    2010-08-01

    Sjögren-Larsson syndrome is a genetic disease characterized by ichthyosis, mental retardation, spasticity and mutations in the ALDH3A2 gene coding for fatty aldehyde dehydrogenase, an enzyme necessary for oxidation of fatty aldehydes and fatty alcohols. We investigated the cutaneous abnormalities in 9 patients with Sjögren-Larsson syndrome to better understand how the enzymatic deficiency results in epidermal dysfunction. Histochemical staining for aldehyde oxidizing activity was profoundly reduced in the epidermis. Colloidal lanthanum perfusion studies showed abnormal movement of tracer into the extracellular spaces of the stratum corneum consistent with a leaky water barrier. The barrier defect could be attributed to the presence of abnormal lamellar bodies, many with disrupted limiting membranes or lacking lamellar contents. Entombed lamellar bodies were present in the cytoplasm of corneocytes suggesting blockade of lamellar body secretion. At the stratum granulosum-stratum corneum interface, non-lamellar material displaced or replaced secreted lamellar membranes, and in the stratum corneum, the number of lamellar bilayers declined and lamellar membrane organization was disrupted by foci of lamellar/non-lamellar phase separation. These studies demonstrate the presence of a permeability barrier abnormality in Sjögren-Larsson syndrome, which localizes to the stratum corneum interstices and can be attributed to abnormalities in lamellar body formation and secretion.

  4. In vivo functional connectome of human brainstem nuclei of the ascending arousal, autonomic and motor systems by high spatial resolution 7 Tesla fMRI

    PubMed Central

    Bianciardi, Marta; Toschi, Nicola; Eichner, Cornelius; Polimeni, Jonathan R.; Setsompop, Kawin; Brown, Emery N.; Hamalainen, Matti S.; Rosen, Bruce R.; Wald, Lawrence L.

    2016-01-01

    Object To map the in vivo human functional connectivity of several brainstem nuclei with the rest of the brain by using seed-based correlation of ultra-high magnetic field functional magnetic resonance imaging (fMRI) data. Materials and Methods We used the recently developed template of 11 brainstem nuclei derived from multi-contrast structural MRI at 7 Tesla as seed regions to determine their connectivity to the rest of the brain. To achieve this, we utilized the increased contrast-to-noise ratio of 7 Tesla fMRI compared to 3 Tesla and the time efficient simultaneous multi-slice imaging to cover the brain with high spatial resolution (1.1 mm-isotropic nominal resolution) while maintaining a short repetition time (2.5 s). Results The delineated Pearson’s correlation-based functional connectivity diagrams (connectomes) of 11 brainstem nuclei of the ascending arousal, motor and autonomic systems from 12 controls are presented and discussed in the context of existing histology and animal work. Conclusion Considering that the investigated brainstem nuclei play a crucial role in several vital functions, the delineated preliminary connectomes might prove useful for future in vivo research and clinical studies of human brainstem function and pathology, including disorders of consciousness, sleep disorders, autonomic disorders, Parkinson’s disease and other motor disorders. PMID:27126248

  5. Neurobiological substrates of cognitive rigidity and autonomic inflexibility in generalized anxiety disorder.

    PubMed

    Ottaviani, Cristina; Watson, David R; Meeten, Frances; Makovac, Elena; Garfinkel, Sarah N; Critchley, Hugo D

    2016-09-01

    Generalized anxiety disorder (GAD) is characterized by difficulties in inhibiting both perseverative thoughts (worry and rumination) and autonomic arousal. We investigated the neurobiological substrates of such abnormal inhibitory processes, hypothesizing aberrant functional coupling within 'default mode' (DMN) and autonomic brain networks. Functional imaging and heart rate variability (HRV) data were acquired from GAD patients and controls during performance of three tracking tasks interspersed with a perseverative cognition (PC) induction. After detection of infrequent target stimuli, activity within putative DMN hubs was suppressed, consistent with a redirection of attentional resources from internal to external focus. This magnitude of activity change was attenuated in patients and individuals with higher trait PC, but was predicted by individual differences in HRV. Following the induction of PC in controls, this pattern of neural reactivity became closer to that of GAD patients. Results support, at a neural level, the association between cognitive inflexibility and autonomic rigidity.

  6. Neurobiological substrates of cognitive rigidity and autonomic inflexibility in generalized anxiety disorder.

    PubMed

    Ottaviani, Cristina; Watson, David R; Meeten, Frances; Makovac, Elena; Garfinkel, Sarah N; Critchley, Hugo D

    2016-09-01

    Generalized anxiety disorder (GAD) is characterized by difficulties in inhibiting both perseverative thoughts (worry and rumination) and autonomic arousal. We investigated the neurobiological substrates of such abnormal inhibitory processes, hypothesizing aberrant functional coupling within 'default mode' (DMN) and autonomic brain networks. Functional imaging and heart rate variability (HRV) data were acquired from GAD patients and controls during performance of three tracking tasks interspersed with a perseverative cognition (PC) induction. After detection of infrequent target stimuli, activity within putative DMN hubs was suppressed, consistent with a redirection of attentional resources from internal to external focus. This magnitude of activity change was attenuated in patients and individuals with higher trait PC, but was predicted by individual differences in HRV. Following the induction of PC in controls, this pattern of neural reactivity became closer to that of GAD patients. Results support, at a neural level, the association between cognitive inflexibility and autonomic rigidity. PMID:27345596

  7. Cell autonomous phosphoinositide 3-kinase activation in oocytes disrupts normal ovarian function through promoting survival and overgrowth of ovarian follicles.

    PubMed

    Kim, So-Youn; Ebbert, Katherine; Cordeiro, Marilia H; Romero, Megan; Zhu, Jie; Serna, Vanida Ann; Whelan, Kelly A; Woodruff, Teresa K; Kurita, Takeshi

    2015-04-01

    In this study, we explored the effects of oocytic phosphoinositide 3-kinase (PI3K) activation on folliculogensis by generating transgenic mice, in which the oocyte-specific Cre-recombinase induces the expression of constitutively active mutant PI3K during the formation of primordial follicles. The ovaries of neonatal transgenic (Cre+) mice showed significantly reduced apoptosis in follicles, which resulted in an excess number of follicles per ovary. Thus, the elevation of phosphatidylinositol (3,4,5)-trisphosphate levels within oocytes promotes the survival of follicles during neonatal development. Despite the increase in AKT phosphorylation, primordial follicles in neonatal Cre+ mice remained dormant demonstrating a nuclear accumulation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN). These primordial follicles containing a high level of nuclear PTEN persisted in postpubertal females, suggesting that PTEN is the dominant factor in the maintenance of female reproductive lifespan through the regulation of primordial follicle recruitment. Although the oocytic PI3K activity and PTEN levels were elevated, the activation of primordial follicles and the subsequent accumulation of antral follicles with developmentally competent oocytes progressed normally in prepubertal Cre+ mice. However, mature Cre+ female mice were anovulatory. Because postnatal day 50 Cre+ mice released cumulus-oocyte complexes with developmentally competent oocytes in response to super-ovulation treatment, the anovulatory phenotype was not due to follicular defects but rather endocrine abnormalities, which were likely caused by the excess number of overgrown follicles. Our current study has elucidated the critical role of oocytic PI3K activity in follicular function, as well as the presence of a PTEN-mediated mechanism in the prevention of immature follicle activation.

  8. Cell Autonomous Phosphoinositide 3-Kinase Activation in Oocytes Disrupts Normal Ovarian Function Through Promoting Survival and Overgrowth of Ovarian Follicles

    PubMed Central

    Ebbert, Katherine; Cordeiro, Marilia H.; Romero, Megan; Zhu, Jie; Serna, Vanida Ann; Whelan, Kelly A.; Woodruff, Teresa K.

    2015-01-01

    In this study, we explored the effects of oocytic phosphoinositide 3-kinase (PI3K) activation on folliculogensis by generating transgenic mice, in which the oocyte-specific Cre-recombinase induces the expression of constitutively active mutant PI3K during the formation of primordial follicles. The ovaries of neonatal transgenic (Cre+) mice showed significantly reduced apoptosis in follicles, which resulted in an excess number of follicles per ovary. Thus, the elevation of phosphatidylinositol (3,4,5)-trisphosphate levels within oocytes promotes the survival of follicles during neonatal development. Despite the increase in AKT phosphorylation, primordial follicles in neonatal Cre+ mice remained dormant demonstrating a nuclear accumulation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN). These primordial follicles containing a high level of nuclear PTEN persisted in postpubertal females, suggesting that PTEN is the dominant factor in the maintenance of female reproductive lifespan through the regulation of primordial follicle recruitment. Although the oocytic PI3K activity and PTEN levels were elevated, the activation of primordial follicles and the subsequent accumulation of antral follicles with developmentally competent oocytes progressed normally in prepubertal Cre+ mice. However, mature Cre+ female mice were anovulatory. Because postnatal day 50 Cre+ mice released cumulus-oocyte complexes with developmentally competent oocytes in response to super-ovulation treatment, the anovulatory phenotype was not due to follicular defects but rather endocrine abnormalities, which were likely caused by the excess number of overgrown follicles. Our current study has elucidated the critical role of oocytic PI3K activity in follicular function, as well as the presence of a PTEN-mediated mechanism in the prevention of immature follicle activation. PMID:25594701

  9. Relationship between autonomic cardiovascular control, case definition, clinical symptoms, and functional disability in adolescent chronic fatigue syndrome: an exploratory study

    PubMed Central

    2013-01-01

    Chronic Fatigue Syndrome (CFS) is characterized by severe impairment and multiple symptoms. Autonomic dysregulation has been demonstrated in several studies. We aimed at exploring the relationship between indices of autonomic cardiovascular control, the case definition from Centers for Disease Control and Prevention (CDC criteria), important clinical symptoms, and disability in adolescent chronic fatigue syndrome. 38 CFS patients aged 12–18 years were recruited according to a wide case definition (ie. not requiring accompanying symptoms) and subjected to head-up tilt test (HUT) and a questionnaire. The relationships between variables were explored with multiple linear regression analyses. In the final models, disability was positively associated with symptoms of cognitive impairments (p<0.001), hypersensitivity (p<0.001), fatigue (p=0.003) and age (p=0.007). Symptoms of cognitive impairments were associated with age (p=0.002), heart rate (HR) at baseline (p=0.01), and HR response during HUT (p=0.02). Hypersensitivity was associated with HR response during HUT (p=0.001), high-frequency variability of heart rate (HF-RRI) at baseline (p=0.05), and adherence to the CDC criteria (p=0.005). Fatigue was associated with gender (p=0.007) and adherence to the CDC criteria (p=0.04). In conclusion, a) The disability of CFS patients is not only related to fatigue but to other symptoms as well; b) Altered cardiovascular autonomic control is associated with certain symptoms; c) The CDC criteria are poorly associated with disability, symptoms, and indices of altered autonomic nervous activity. PMID:23388153

  10. Autonomous vehicles

    SciTech Connect

    Meyrowitz, A.L.; Blidberg, D.R.; Michelson, R.C. |

    1996-08-01

    There are various kinds of autonomous vehicles (AV`s) which can operate with varying levels of autonomy. This paper is concerned with underwater, ground, and aerial vehicles operating in a fully autonomous (nonteleoperated) mode. Further, this paper deals with AV`s as a special kind of device, rather than full-scale manned vehicles operating unmanned. The distinction is one in which the AV is likely to be designed for autonomous operation rather than being adapted for it as would be the case for manned vehicles. The authors provide a survey of the technological progress that has been made in AV`s, the current research issues and approaches that are continuing that progress, and the applications which motivate this work. It should be noted that issues of control are pervasive regardless of the kind of AV being considered, but that there are special considerations in the design and operation of AV`s depending on whether the focus is on vehicles underwater, on the ground, or in the air. The authors have separated the discussion into sections treating each of these categories.

  11. Epididymal Hypo-Osmolality Induces Abnormal Sperm Morphology and Function in the Estrogen Receptor Alpha Knockout Mouse1

    PubMed Central

    Joseph, Avenel; Shur, Barry D.; Ko, CheMyong; Chambon, Pierre; Hess, Rex A.

    2010-01-01

    Estrogen receptor-alpha (ESR1) is highly expressed in the efferent ductules of all species studied as well as in the epididymal epithelium in mice and other select species. Male mice lacking ESR1 (Esr1KO) are infertile, but transplantation studies demonstrated that Esr1KO germ cells are capable of fertilization when placed in a wild-type reproductive tract. These results suggest that extratesticular regions, such as the efferent ductules and epididymis, are the major source of pathological changes in Esr1KO males. Previous studies have shown alterations in ion and fluid transporters in the efferent duct and epididymal epithelia of Esr1KO males, leading to misregulation of luminal fluid pH. To determine the effect of an altered epididymal milieu on Esr1KO sperm, we assayed sperm morphology in the different regions of the epididymis. Sperm recovered from the epididymis exhibited abnormal flagellar coiling and increased incidence of spontaneous acrosome reactions, both of which are consistent with exposure to abnormal epididymal fluid. Analysis of the epididymal fluid revealed that the osmolality of the Esr1KO fluid was reduced relative to wild type, consistent with prior reports of inappropriate fluid absorption from the efferent ductules. This, along with the finding that morphological defects increased with transit through the epididymal duct, suggests that the anomalies in sperm are a consequence of the abnormal luminal environment. Consistent with this, incubating Esr1KO sperm in a more wild-type-like osmotic environment significantly rescued the abnormal flagellar coiling. This work demonstrates that Esr1KO mice exhibit an abnormal fluid environment in the lumen of the efferent ducts and epididymis, precluding normal sperm maturation and instead resulting in progressive deterioration of sperm that contributes to infertility. PMID:20130266

  12. The hypertension of autonomic failure and its treatment

    NASA Technical Reports Server (NTRS)

    Shannon, J.; Jordan, J.; Costa, F.; Robertson, R. M.; Biaggioni, I.

    1997-01-01

    We studied the incidence and severity of supine hypertension in 117 patients with severe primary autonomic failure presenting to a referral center over a 9-year period. Patients were uniformly characterized by disabling orthostatic hypotension, lack of compensatory heart rate increase, abnormal autonomic function tests, and unresponsive plasma norepinephrine. Fifty-four patients had isolated autonomic impairment (pure autonomic failure). Sixty-three patients had central nervous system involvement in addition to autonomic impairment (multiple-system atrophy). Patients were studied off medications, in a metabolic ward, and on a controlled diet containing 150 mEq of sodium. Fifty-six percent of patients had supine diastolic blood pressure > or =90 mm Hg. The prevalence of hypertension was slightly greater in females (63%) than in males (52%). Potential mechanisms responsible for this hypertension were investigated. No correlation was found between blood volume and blood pressure. Similarly, plasma norepinephrine (92+/-15 pg/mL) and plasma renin activity (0.3+/-0.05 ng/mL per hour) were very low in the subset of patients with pure autonomic failure and supine hypertension (mean systolic/diastolic pressure, 177 +/- 6/108 +/- 2 mm Hg, range 167/97 to 219/121). Supine hypertension represents a challenge in the treatment of orthostatic hypotension. We found these patients to be particularly responsive to the hypotensive effects of transdermal nitroglycerin. Doses ranging from 0.025 to 0.1 mg/h decreased systolic blood pressure by 36+/-7 mm Hg and may effectively treat supine hypertension overnight, but the dose should be individualized and used with caution.

  13. Small mine size is associated with lung function abnormality and pneumoconiosis among underground coal miners in Kentucky, Virginia and West Virginia

    PubMed Central

    Blackley, David J; Halldin, Cara N; Wang, Mei Lin; Laney, A Scott

    2015-01-01

    Objectives To describe the prevalence of lung function abnormality and coal workers’ pneumoconiosis (CWP) by mine size among underground coal miners in Kentucky, Virginia and West Virginia. Methods During 2005–2012, 4491 miners completed spirometry and chest radiography as part of a health surveillance programme. Spirometry was interpreted according to American Thoracic Society and European Respiratory Society guidelines, and radiography per International Labour Office standards. Prevalence ratios (PR) were calculated for abnormal spirometry (obstructive, restrictive or mixed pattern using lower limits of normal derived from National Health and Nutrition Examination Survey (NHANES) III) and CWP among workers from small mines (≤50 miners) compared with those from large mines. Results Among 3771 eligible miners, those from small mines were more likely to have abnormal spirometry (18.5% vs 13.8%, p<0.01), CWP (10.8% vs 5.2%, p<0.01) and progressive massive fibrosis (2.4% vs 1.1%, p<0.01). In regression analysis, working in a small mine was associated with 37% higher prevalence of abnormal spirometry (PR 1.37, 95% CI 1.16 to 1.61) and 2.1 times higher prevalence of CWP (95% CI 1.68 to 2.70). Conclusions More than one in four of these miners had evidence of CWP, abnormal lung function or both. Although 96% of miners in the study have worked exclusively under dust regulations implemented following the 1969 Federal Coal Mine Safety and Health Act, we observed high rates of respiratory disease including severe cases. The current approach to dust control and provision of safe work conditions for central Appalachian underground coal miners is not adequate to protect them from adverse respiratory health effects. PMID:25052085

  14. Relations between social-perceptual ability in multi- and unisensory contexts, autonomic reactivity, and social functioning in individuals with Williams syndrome

    PubMed Central

    Järvinen, Anna; Ng, Rowena; Crivelli, Davide; Arnold, Andrew J.; Woo-VonHoogenstyn, Nicholas; Bellugi, Ursula

    2015-01-01

    Compromised social-perceptual ability has been proposed to contribute to social dysfunction in neurodevelopmental disorders. While such impairments have been identified in Williams syndrome (WS), little is known about emotion processing in auditory and multisensory contexts. Employing a multidimensional approach, individuals with WS and typical development (TD) were tested for emotion identification across fearful, happy, and angry multisensory and unisensory face and voice stimuli. Autonomic responses were monitored in response to unimodal emotion. The WS group was administered an inventory of social functioning. Behaviorally, individuals with WS relative to TD demonstrated impaired processing of unimodal vocalizations and emotionally incongruent audiovisual compounds, reflecting a generalized deficit in social-auditory processing in WS. The TD group outperformed their counterparts with WS in identifying negative (fearful and angry) emotion, with similar between-group performance with happy stimuli. Mirroring this pattern, electrodermal activity (EDA) responses to the emotional content of the stimuli indicated that whereas those with WS showed the highest arousal to happy, and lowest arousal to fearful stimuli, the TD participants demonstrated the contrasting pattern. In WS, more normal social functioning was related to higher autonomic arousal to facial expressions. Implications for underlying neural architecture and emotional functions are discussed. PMID:26002754

  15. Functional Ser205Leu polymorphism of the nerve growth factor receptor (NGFR) gene is associated with vagal autonomic dysregulation in humans.

    PubMed

    Chang, Chuan-Chia; Fang, Wen-Hui; Chang, Hsin-An; Huang, San-Yuan

    2015-01-01

    Evidence indicates that reduced cardiac vagal (parasympathetic) tone, a robust cardiovascular risk factor, is a trait vulnerability marker of major depressive disorder (MDD). The Ser205/Ser205 genotype of the functional polymorphism (Ser205Leu) of the nerve growth factor receptor (NGFR), also called p75 neurotrophin receptor (p75(NTR)), gene is reported to increase the risk of MDD. Here, we hypothesized that the NGFR Ser205Leu polymorphism may have an effect on vagal control. A sample of 810 healthy, drug-free, unrelated Han Chinese (413 males, 397 females; mean age 35.17 ± 8.53 years) was included in the NGFR genotyping. Short-term heart rate variability (HRV) was used to assess vagus-mediated autonomic function. Potential HRV covariates, such as mood/anxiety status and serum metabolic parameters, were assessed. Homozygotes of the Ser205 allele had significantly lower high frequency power and root mean square of successive heartbeat interval differences, both HRV indices of vagal modulation, compared to Leu205 allele carriers. Even after adjusting for relevant confounders, these associations remained significant. Further stratification by sex revealed that the associations were observed only in males. Our results implicate that decreased parasympathetic activity is associated with the NGFR Ser205/Ser205 genotype in a gender-specific manner, suggesting a potential role of NGFR polymorphism in modulating cardiac autonomic function. PMID:26278479

  16. Impact of aging on cardiac function in a female rat model of menopause: role of autonomic control, inflammation, and oxidative stress

    PubMed Central

    Machi, Jacqueline Freire; Dias, Danielle da Silva; Freitas, Sarah Cristina; de Moraes, Oscar Albuquerque; da Silva, Maikon Barbosa; Cruz, Paula Lázara; Mostarda, Cristiano; Salemi, Vera M C; Morris, Mariana; De Angelis, Kátia; Irigoyen, Maria-Cláudia

    2016-01-01

    Objective The aim of this study was to evaluate the effects of aging on metabolic, cardiovascular, autonomic, inflammatory, and oxidative stress parameters after ovarian hormone deprivation (OVX). Methods Female Wistar rats (3 or 22 months old) were divided into: young controls, young ovariectomized, old controls, and old ovariectomized (bilateral ovaries removal). After a 9-week follow-up, physical capacity, metabolic parameters, and morphometric and cardiac functions were assessed. Subsequently, arterial pressure was recorded and cardiac autonomic control was evaluated. Oxidative stress was measured on the cardiac tissue, while inflammatory profile was assessed in the plasma. Results Aging or OVX caused an increase in body and fat weight and triglyceride concentration and a decrease in both insulin sensitivity and aerobic exercise capacity. Left ventricular diastolic dysfunction and increased cardiac overload (myocardial performance index) were reported in old groups when compared with young groups. Aging and OVX led to an increased sympathetic tonus, and vagal tonus was lower only for the old groups. Tumor necrosis factor-α and interleukin-6 were increased in old groups when compared with young groups. Glutathione redox balance (GSH/GSSG) was reduced in young ovariectomized, old controls, and old ovariectomized groups when compared with young controls, indicating an increased oxidative stress. A negative correlation was found between GSH/GSSG and tumor necrosis factor-α (r=−0.6, P<0.003). Correlations were found between interleukin-6 with adipose tissue (r=0.5, P<0.009) and vagal tonus (r=−0.7, P<0.0002); and among myocardial performance index with interleukin-6 (r=0.65, P<0.0002), sympathetic tonus (r=0.55, P<0.006), and physical capacity (r=−0.55, P<0.003). The findings in this trial showed that ovariectomy aggravated the impairment of cardiac and functional effects of aging in female rats, probably associated with exacerbated autonomic dysfunction

  17. Maternal zinc supplementation during pregnancy affects autonomic function of Peruvian children assessed at 54 months of age.

    PubMed

    Caulfield, Laura E; Zavaleta, Nelly; Chen, Ping; Lazarte, Fabiola; Albornoz, Carla; Putnick, Diane L; Bornstein, Marc H; DiPietro, Janet A

    2011-02-01

    Maternal prenatal zinc supplementation improved fetal autonomic regulation in a nutrient-deficient population in Peru. To evaluate whether differences in autonomic regulation existed in early childhood, we studied 165 children from a zinc supplementation trial (80% of original sample) as part of a comprehensive evaluation at age 54 mo. Electrocardiogram (ECG) data were collected from the children at rest and while they underwent a cognitive testing battery following a standardized protocol. Of these, 79 were born to mothers receiving 25 mg/d zinc in addition to 60 mg/d iron and 250 μg/d folic acid during pregnancy, and 86 were born to mothers receiving iron and folic acid only. Derived cardiac measures included heart period (HP), range, HP variability (HPV), mean square of successive differences (MSSD), and a measure of vagal tone (V). Children in the zinc supplementation group had greater HP (i.e. slower heart rate), greater range, higher time-independent (HPV) and time-dependent (MSSD) variability in HP, and higher V (P < 0.05) during baseline. Analyses conducted across the cognitive testing period revealed similar effects of prenatal zinc supplementation on cardiac patterns. Concurrent child zinc plasma concentration was also associated with longer HP, greater variability, and marginally higher range and V (P < 0.10). Differences in cardiac patterns due to prenatal zinc supplementation were detectable in children at 54 mo of age during conditions of both rest and challenge, indicating that supplementing zinc-deficient pregnant women has beneficial long-term consequences for neural development associated with autonomic regulation. PMID:21178078

  18. Improved Stratification of Autonomic Regulation for risk prediction in post-infarction patients with preserved left ventricular function (ISAR-Risk)

    PubMed Central

    Bauer, Axel; Barthel, Petra; Schneider, Raphael; Ulm, Kurt; Müller, Alexander; Joeinig, Anke; Stich, Raphael; Kiviniemi, Antti; Hnatkova, Katerina; Huikuri, Heikki; Schömig, Albert; Malik, Marek; Schmidt, Georg

    2009-01-01

    Aims To investigate the combination of heart rate turbulence (HRT) and deceleration capacity (DC) as risk predictors in post-infarction patients with left ventricular ejection fraction (LVEF) > 30%. Methods and results We enrolled 2343 consecutive survivors of acute myocardial infarction (MI) (<76 years) in sinus rhythm. HRT and DC were obtained from 24 h Holter recordings. Patients with both abnormal HRT (slope ≤ 2.5 ms/RR and onset ≥ 0%) and abnormal DC (≤4.5 ms) were considered suffering from severe autonomic failure (SAF) and prospectively classified as high risk. Primary and secondary endpoints were all-cause, cardiac, and sudden cardiac mortality within the first 5 years of follow-up. During follow-up, 181 patients died; 39 deaths occurred in 120 patients with LVEF ≤ 30%, and 142 in 2223 patients with LVEF>30% (cumulative 5-year mortality rates of 37.9% and 7.8%, respectively). Among patients with LVEF > 30%, SAF identified another high-risk group of 117 patients with 37 deaths (cumulative 5-year mortality rates of 38.6% and 6.1%, respectively). Merging both high-risk groups (i.e. LVEF ≤ 30% and/or SAF) doubled the sensitivity of mortality prediction compared with LVEF ≤ 30% alone (21.1% vs. 42.1%, P < 0.001) while preserving 5-year mortality rate (38.2%). Conclusion In post-MI patients with LVEF>30%, SAF identifies a high-risk group equivalent in size and mortality risk to patients with LVEF ≤ 30%. PMID:19109245

  19. [Central autonomic failures].

    PubMed

    Senard, Jean-Michel; Despas, Fabien; Pathak, Atul

    2012-11-01

    Autonomic nervous system (ANS) modulates the function of all body organs through both parasympathetic and sympathetic fibers. Orthostatic hypotension is frequently observed in the course of central nervous system diseases including cortical (stroke, epilepsy, dementias), neurodegenerative (Parkinson's disease, multisystem atrophies) and spinal cord diseases. In some cases, the mechanism of orthostatic hypotension associated with central nervous system diseases involves a dysfunction of peripheral ANS fibers.

  20. Effects of autonomic balance and fluid and electrolyte changes on cardiac function in infarcted rats: A serial study of sexual dimorphism.

    PubMed

    Souza, N S; Dos-Santos, R C; Silveira, Anderson Luiz Bezerra da; R, Sonoda-Côrtes; Gantus, Michel Alexandre Villani; Fortes, F S; Olivares, Emerson Lopes

    2016-04-01

    Premenopausal women are known to show lower incidence of cardiovascular disease than men. During myocardial infarction (MI), homeostatic responses are activated, including the sympathetic autonomic nervous system and the rennin-angiotensin-aldosterone system, which is related to the fluid and electrolyte balance, both aiming to maintain cardiac output. This study sought to perform a serial evaluation of sexual dimorphism in cardiac autonomic control and fluid and electrolyte balance during the development of MI-induced heart failure in rats. Experimental MI was induced in male (M) and female (F) adult (7-9 weeks of age) Wistar rats. The animals were placed in metabolic cages to assess fluid intake and urine volume 1 and 4 weeks after inducing MI (male myocardial infarction (MMI) and female myocardial infarction (FMI) groups). They subsequently underwent echocardiographic evaluation and spectral analysis of heart rate variability. After completing each protocol, the animals were killed for postmortem evaluation and histology. The MMI group showed earlier and more intense cardiac morphological and functional changes than the FMI group, although the extent of MI did not differ between groups (P > 0.05). The MMI group showed higher sympathetic modulation and sodium and water retention than the FMI group (P < 0.05), which may partly explain both the echocardiographic and pathological findings. Females subjected to infarction seem to show attenuation of sympathetic modulation, more favourable fluid and electrolyte balances, and better preserved cardiac function compared to males subjected to the same infarction model. PMID:26748814

  1. [Changes in autonomic nerve function during the normal menstrual cycle measured by the coefficient of variation of R-R intervals].

    PubMed

    Kondo, M; Hirano, T; Okamura, Y

    1989-05-01

    The purpose of this study was to determine if there is a change in autonomic nerve function during the menstrual cycle. The subjects were 20 females (average age 26.1 years +/- 4.6) with a normal menstrual cycle. The coefficient of variation of R-R intervals (CV R.R) was measured to investigate autonomic function in the menstrual, follicular, ovulatory, luteal, and premenstrual phases. Average CV R-R for all phases was 5.2 +/- 1.9%. And the CV R-R tended to be lower in those in their 30s than in those in their 20s. And no noticeable difference was seen in the CV R-R among the 5 phases of the menstrual cycle. On the other hand, the CV R-R of 11 females with premenstrual syndrome was low in the ovulatory, luteal and premenstrual phases. These results, which provide basic data for clinical use, suggest the following. (1) The age of subjects should be taken into consideration. (2) Changes in the CV R-R during the menstrual cycle are negligible. (3) However, in those showing symptoms associated with the menstrual cycle such as premenstrual syndrome, changes during the menstrual cycle should be taken into account. At the same time psychological changes in the subjects were evaluated by the following tests: Cornell Medical Index, Taylor's manifest anxiety scale, and Zung's self-rating depression scale. The results of these tests did not vary significantly during the menstrual cycle.

  2. INL Autonomous Navigation System

    SciTech Connect

    2005-03-30

    The INL Autonomous Navigation System provides instructions for autonomously navigating a robot. The system permits high-speed autonomous navigation including obstacle avoidance, waypoing navigation and path planning in both indoor and outdoor environments.

  3. Micturition disturbance in acute idiopathic autonomic neuropathy

    PubMed Central

    Sakakibara, R; Uchiyama, T; Asahina, M; Suzuki, A; Yamanishi, T; Hattori, T

    2004-01-01

    Objective: To define the nature of micturition disturbance in patients with acute idiopathic autonomic neuropathy (AIAN). Methods: Micturitional symptoms were observed during hospital admissions and the in outpatient clinics in six patients with clinically definite AIAN (typical form in four, cholinergic variant in one, autonomic-sensory variant in one). Urodynamic studies included medium-fill water cystometry, external sphincter electromyography, and a bethanechol test. Results: Four patients had urinary retention and two had voiding difficulty as the initial presentation. Patients with retention became able to urinate within a week (two to seven days). The major symptoms at the time of urodynamic studies (three weeks to four months after disease onset in most cases) were voiding difficulty and nocturnal frequency. None had urinary incontinence. Complete recovery from the micturition disturbance took from three months to >18 years. The recovery period was shorter in a patient with cholinergic variant, and it was longer in two patients who had a longer duration of initial urinary retention. Micturition disturbance tended to improve earlier than orthostatic hypotension. The major urodynamic abnormalities were detrusor areflexia on voiding (5), denervation supersensitivity to bethanechol (3); low compliance detrusor (1); and impaired bladder sensation (2). None had neurogenic motor unit potentials of the external sphincter muscles. Conclusions: In patients with AIAN, urinary retention and voiding difficulty are common initial presentations. The underlying mechanisms seem to be pre- and postganglionic cholinergic dysfunction with preservation of somatic sphincter function. The bladder problems tend to improve earlier than orthostatic hypotension. PMID:14742606

  4. Architecture design of the multi-functional wavelet-based ECG microprocessor for realtime detection of abnormal cardiac events.

    PubMed

    Cheng, Li-Fang; Chen, Tung-Chien; Chen, Liang-Gee

    2012-01-01

    Most of the abnormal cardiac events such as myocardial ischemia, acute myocardial infarction (AMI) and fatal arrhythmia can be diagnosed through continuous electrocardiogram (ECG) analysis. According to recent clinical research, early detection and alarming of such cardiac events can reduce the time delay to the hospital, and the clinical outcomes of these individuals can be greatly improved. Therefore, it would be helpful if there is a long-term ECG monitoring system with the ability to identify abnormal cardiac events and provide realtime warning for the users. The combination of the wireless body area sensor network (BASN) and the on-sensor ECG processor is a possible solution for this application. In this paper, we aim to design and implement a digital signal processor that is suitable for continuous ECG monitoring and alarming based on the continuous wavelet transform (CWT) through the proposed architectures--using both programmable RISC processor and application specific integrated circuits (ASIC) for performance optimization. According to the implementation results, the power consumption of the proposed processor integrated with an ASIC for CWT computation is only 79.4 mW. Compared with the single-RISC processor, about 91.6% of the power reduction is achieved.

  5. Holoprosencephaly in RSH/Smith-Lemli-Opitz syndrome: Does abnormal cholesterol metabolism affect the function of sonic hedgehog?

    SciTech Connect

    Kelley, R.I.; Roessler, E.; Muenke, M.

    1996-12-30

    The RAH/Smith-Lemli-Opitz syndrome (RAH/SLOS) is an autosomal recessive malformation syndrome associated with increased levels of 7-dehydrocholesterol (7-DHC) and a defect of cholesterol biosynthesis at the level of 3{beta}-hydroxy-steroid-{Delta}{sup 7}-reductase (7-DHC reductase). Because rats exposed to inhibitors of 7-DHC reductase during development have a high frequency of holoprosencephaly (HPE), we have undertaken a search for biochemical evidence of RSH/SLOS and other possible defects of sterol metabolism among patients with various forms of HPE. We describe 4 patients, one with semilobar HPE and three others with less complete forms of the HPE sequence, in whom we have made a biochemical diagnosis of RAH/SLOS. The clinical and biochemical spectrum of these and other patients with RAH/SLOS suggests a role of abnormal sterol metabolism in the pathogenesis of their malformations. The association of HPE and RAH/SLOS is discussed in light of the recent discoveries that mutations in the embryonic patterning gene, Sonic Hedgehog (SHH), can cause HPE in humans and that the sonic hedgehog protein product undergoes autoproteolysis to form a cholesterol-modified active product. These clinical, biochemical, and molecular studies suggest that HPE and other malformations in SLOS may be caused by incomplete or abnormal modification of the sonic hedgehog protein and, possibly, other patterning proteins of the hedgehog class, a hypothesis testable in somatic cell systems. 37 refs., 1 fig.

  6. Autonomic Impairment in Borderline Personality Disorder: A Laboratory Investigation

    ERIC Educational Resources Information Center

    Weinberg, Anna; Klonsky, E. David; Hajcak, Greg

    2009-01-01

    Recent research suggests that emotional dysfunction in psychiatric disorders can be reflected in autonomic abnormalities. The present study examines sympathetic and parasympathetic autonomic nervous system activity in individuals with Borderline Personality Disorder (BPD) before, during, and following a social stressor task. Data were obtained…

  7. Diabetic autonomic neuropathy.

    PubMed

    Freeman, Roy

    2014-01-01

    Diabetes mellitus is the commonest cause of an autonomic neuropathy in the developed world. Diabetic autonomic neuropathy causes a constellation of symptoms and signs affecting cardiovascular, urogenital, gastrointestinal, pupillomotor, thermoregulatory, and sudomotor systems. Several discrete syndromes associated with diabetes cause autonomic dysfunction. The most prevalent of these are: generalized diabetic autonomic neuropathy, autonomic neuropathy associated with the prediabetic state, treatment-induced painful and autonomic neuropathy, and transient hypoglycemia-associated autonomic neuropathy. These autonomic manifestations of diabetes are responsible for the most troublesome and disabling features of diabetic peripheral neuropathy and result in a significant proportion of the mortality and morbidity associated with the disease.

  8. Cocaine addiction related reproducible brain regions of abnormal default-mode network functional connectivity: a group ICA study with different model orders.

    PubMed

    Ding, Xiaoyu; Lee, Seong-Whan

    2013-08-26

    Model order selection in group independent component analysis (ICA) has a significant effect on the obtained components. This study investigated the reproducible brain regions of abnormal default-mode network (DMN) functional connectivity related with cocaine addiction through different model order settings in group ICA. Resting-state fMRI data from 24 cocaine addicts and 24 healthy controls were temporally concatenated and processed by group ICA using model orders of 10, 20, 30, 40, and 50, respectively. For each model order, the group ICA approach was repeated 100 times using the ICASSO toolbox and after clustering the obtained components, centrotype-based anterior and posterior DMN components were selected for further analysis. Individual DMN components were obtained through back-reconstruction and converted to z-score maps. A whole brain mixed effects factorial ANOVA was performed to explore the differences in resting-state DMN functional connectivity between cocaine addicts and healthy controls. The hippocampus, which showed decreased functional connectivity in cocaine addicts for all the tested model orders, might be considered as a reproducible abnormal region in DMN associated with cocaine addiction. This finding suggests that using group ICA to examine the functional connectivity of the hippocampus in the resting-state DMN may provide an additional insight potentially relevant for cocaine-related diagnoses and treatments. PMID:23707901

  9. Nature's Autonomous Oscillators

    NASA Technical Reports Server (NTRS)

    Mayr, H. G.; Yee, J.-H.; Mayr, M.; Schnetzler, R.

    2012-01-01

    Nonlinearity is required to produce autonomous oscillations without external time dependent source, and an example is the pendulum clock. The escapement mechanism of the clock imparts an impulse for each swing direction, which keeps the pendulum oscillating at the resonance frequency. Among nature's observed autonomous oscillators, examples are the quasi-biennial oscillation and bimonthly oscillation of the Earth atmosphere, and the 22-year solar oscillation. The oscillations have been simulated in numerical models without external time dependent source, and in Section 2 we summarize the results. Specifically, we shall discuss the nonlinearities that are involved in generating the oscillations, and the processes that produce the periodicities. In biology, insects have flight muscles, which function autonomously with wing frequencies that far exceed the animals' neural capacity; Stretch-activation of muscle contraction is the mechanism that produces the high frequency oscillation of insect flight, discussed in Section 3. The same mechanism is also invoked to explain the functioning of the cardiac muscle. In Section 4, we present a tutorial review of the cardio-vascular system, heart anatomy, and muscle cell physiology, leading up to Starling's Law of the Heart, which supports our notion that the human heart is also a nonlinear oscillator. In Section 5, we offer a broad perspective of the tenuous links between the fluid dynamical oscillators and the human heart physiology.

  10. Autonomous power expert system

    NASA Technical Reports Server (NTRS)

    Walters, Jerry L.; Petrik, Edward J.; Roth, Mary Ellen; Truong, Long Van; Quinn, Todd; Krawczonek, Walter M.

    1990-01-01

    The Autonomous Power Expert (APEX) system was designed to monitor and diagnose fault conditions that occur within the Space Station Freedom Electrical Power System (SSF/EPS) Testbed. APEX is designed to interface with SSF/EPS testbed power management controllers to provide enhanced autonomous operation and control capability. The APEX architecture consists of three components: (1) a rule-based expert system, (2) a testbed data acquisition interface, and (3) a power scheduler interface. Fault detection, fault isolation, justification of probable causes, recommended actions, and incipient fault analysis are the main functions of the expert system component. The data acquisition component requests and receives pertinent parametric values from the EPS testbed and asserts the values into a knowledge base. Power load profile information is obtained from a remote scheduler through the power scheduler interface component. The current APEX design and development work is discussed. Operation and use of APEX by way of the user interface screens is also covered.

  11. Abnormal calcium homeostasis in heart failure with preserved ejection fraction is related to both reduced contractile function and incomplete relaxation: an electromechanically detailed biophysical modeling study

    PubMed Central

    Adeniran, Ismail; MacIver, David H.; Hancox, Jules C.; Zhang, Henggui

    2015-01-01

    Heart failure with preserved ejection fraction (HFpEF) accounts for about 50% of heart failure cases. It has features of incomplete relaxation and increased stiffness of the left ventricle. Studies from clinical electrophysiology and animal experiments have found that HFpEF is associated with impaired calcium homeostasis, ion channel remodeling and concentric left ventricle hypertrophy (LVH). However, it is still unclear how the abnormal calcium homeostasis, ion channel and structural remodeling affect the electro-mechanical dynamics of the ventricles. In this study we have developed multiscale models of the human left ventricle from single cells to the 3D organ, which take into consideration HFpEF-induced changes in calcium handling, ion channel remodeling and concentric LVH. Our simulation results suggest that at the cellular level, HFpEF reduces the systolic calcium level resulting in a reduced systolic contractile force, but elevates the diastolic calcium level resulting in an abnormal residual diastolic force. In our simulations, these abnormal electro-mechanical features of the ventricular cells became more pronounced with the increase of the heart rate. However, at the 3D organ level, the ejection fraction of the left ventricle was maintained due to the concentric LVH. The simulation results of this study mirror clinically observed features of HFpEF and provide new insights toward the understanding of the cellular bases of impaired cardiac electromechanical functions in heart failure. PMID:25852567

  12. Reflex and Tonic Autonomic Markers for Risk Stratification in Patients With Type 2 Diabetes Surviving Acute Myocardial Infarction

    PubMed Central

    Barthel, Petra; Bauer, Axel; Müller, Alexander; Junk, Nadine; Huster, Katharina M.; Ulm, Kurt; Malik, Marek; Schmidt, Georg

    2011-01-01

    OBJECTIVE Diabetic postinfarction patients are at increased mortality risk compared with nondiabetic postinfarction patients. In a substantial number of these patients, diabetic cardiac neuropathy already preexists at the time of the infarction. In the current study we investigated if markers of autonomic dysfunction can further discriminate diabetic postinfarction patients into low- and high-risk groups. RESEARCH DESIGN AND METHODS We prospectively enrolled 481 patients with type 2 diabetes who survived acute myocardial infarction (MI), were aged ≤80 years, and presented in sinus rhythm. Primary end point was total mortality at 5 years of follow-up. Severe autonomic failure (SAF) was defined as coincidence of abnormal autonomic reflex function (assessed by means of heart rate turbulence) and of abnormal autonomic tonic activity (assessed by means of deceleration capacity of heart rate). Multivariable risk analyses considered SAF and standard risk predictors including history of previous MI, arrhythmia on Holter monitoring, insulin treatment, and impaired left ventricular ejection fraction (LVEF) ≤30%. RESULTS During follow-up, 83 of the 481 patients (17.3%) died. Of these, 24 deaths were sudden cardiac deaths and 21 nonsudden cardiac deaths. SAF identified a high-risk group of 58 patients with a 5-year mortality rate of 64.0% at a sensitivity level of 38.0%. Multivariately, SAF was the strongest predictor of mortality (hazard ratio 4.9 [95% CI 2.4–9.9]), followed by age ≥65 years (3.4 [1.9–5.8]), and LVEF ≤30% (2.6 [1.5–4.4]). CONCLUSIONS Combined abnormalities of autonomic reflex function and autonomic tonic activity identifies diabetic postinfarction patients with very poor prognoses. PMID:21680727

  13. Autonomous Navigation Using Celestial Objects

    NASA Technical Reports Server (NTRS)

    Folta, David; Gramling, Cheryl; Leung, Dominic; Belur, Sheela; Long, Anne

    1999-01-01

    measurements from the command link carrier to autonomously estimate the spacecraft's orbit and reference oscillator's frequency. To support autonomous attitude determination and control and maneuver planning and control, the orbit determination accuracy should be on the order of kilometers in position and centimeters per second in velocity. A less accurate solution (one hundred kilometers in position) could be used for acquisition purposes for command and science downloads. This paper provides performance results for both libration point orbiting and high Earth orbiting satellites as a function of sensor measurement accuracy, measurement types, measurement frequency, initial state errors, and dynamic modeling errors.

  14. Relationships (II) of International Classification of High-resolution Computed Tomography for Occupational and Environmental Respiratory Diseases with ventilatory functions indices for parenchymal abnormalities

    PubMed Central

    TAMURA, Taro; SUGANUMA, Narufumi; HERING, Kurt G.; VEHMAS, Tapio; ITOH, Harumi; AKIRA, Masanori; TAKASHIMA, Yoshihiro; HIRANO, Harukazu; KUSAKA, Yukinori

    2015-01-01

    The International Classification of High-Resolution Computed Tomography (HRCT) for Occupational and Environmental Respiratory Diseases (ICOERD) is used to screen and diagnose respiratory illnesses. Using univariate and multivariate analysis, we investigated the relationship between subject characteristics and parenchymal abnormalities according to ICOERD, and the results of ventilatory function tests (VFT). Thirty-five patients with and 27 controls without mineral-dust exposure underwent VFT and HRCT. We recorded all subjects’ occupational history for mineral dust exposure and smoking history. Experts independently assessed HRCT using the ICOERD parenchymal abnormalities (Items) grades for well-defined rounded opacities (RO), linear and/or irregular opacities (IR), and emphysema (EM). High-resolution computed tomography showed that 11 patients had RO; 15 patients, IR; and 19 patients, EM. According to the multiple regression model, age and height had significant associations with many indices ventilatory functions such as vital capacity, forced vital capacity, and forced expiratory volume in 1 s (FEV1). The EM summed grades on the upper, middle, and lower zones of the right and left lungs also had significant associations with FEV1 and the maximum mid-expiratory flow rate. The results suggest the ICOERD notation is adequate based on the good and significant multiple regression modeling of ventilatory function with the EM summed grades. PMID:25810443

  15. Autonomic Involvement in Subacute and Chronic Immune-Mediated Neuropathies

    PubMed Central

    Mazzeo, Anna; Stancanelli, Claudia; Vita, Giuseppe

    2013-01-01

    Autonomic function can be impaired in many disorders in which sympathetic, parasympathetic, and enteric arms of the autonomic nervous system are affected. Signs and symptoms of autonomic involvement are related to impairment of cardiovascular, gastrointestinal, urogenital, thermoregulatory, sudomotor, and pupillomotor autonomic functions. Availability of noninvasive, sensitive, and reproducible tests can help to recognize these disorders and to better understand specific mechanisms of some, potentially treatable, immune-mediated autonomic neuropathies. This paper describes autonomic involvement in immune-mediated neuropathies with a subacute or chronic course. PMID:23853716

  16. MCT8 Deficiency in Male Mice Mitigates the Phenotypic Abnormalities Associated With the Absence of a Functional Type 3 Deiodinase.

    PubMed

    Stohn, J Patrizia; Martinez, M Elena; Matoin, Kassey; Morte, Beatriz; Bernal, Juan; Galton, Valerie Anne; St Germain, Donald; Hernandez, Arturo

    2016-08-01

    Mice deficient in the type 3 deiodinase (D3KO mice) manifest impaired clearance of thyroid hormone (TH), leading to elevated levels of TH action during development. This alteration causes reduced neonatal viability, growth retardation, and central hypothyroidism. Here we examined how these phenotypes are affected by a deficiency in the monocarboxylate transporter 8 (MCT8), which is a major contributor to the transport of the active thyroid hormone, T3, into the cell. MCT8 deficiency eliminated the neonatal lethality of type 3 deiodinase (D3)-deficient mice and significantly ameliorated their growth retardation. Double-mutant newborn mice exhibited similar peripheral thyrotoxicosis and increased brain expression of T3-dependent genes as mice with D3 deficiency only. Later in neonatal life and adulthood, double-mutant mice manifested central and peripheral TH status similar to mice with single MCT8 deficiency, with low serum T4, elevated serum TSH and T3, and decreased T3-dependent gene expression in the hypothalamus. In double-mutant adult mice, both thyroid gland size and the hypothyroidism-induced rise in TSH were greater than those in mice with single D3 deficiency but less than those in mice with MCT8 deficiency alone. Our results demonstrate that the marked phenotypic abnormalities observed in the D3-deficient mouse, including perinatal mortality, growth retardation, and central hypothyroidism in adult animals, require expression of MCT8, confirming the interdependent relationship between the TH transport into cells and the deiodination processes. PMID:27254003

  17. Local autonomic failure affecting a limb.

    PubMed Central

    Johnson, R H; Robinson, B J

    1987-01-01

    Three patients are described who presented with autonomic failure affecting predominantly one limb. Physiological studies revealed that there was sweating loss in the limb which appeared to be due to a preganglionic autonomic lesion and not to a sweat gland abnormality. In all three patients there was also evidence of failure of vasomotor control. There was no evidence of more generalised autonomic failure or neurological deficit. In two patients the condition appeared to be static and, according to the patients' accounts was life long. In the third the sweating loss was present for three years prior to pain loss becoming evident from C2/3 to T1 on the same side as the sweating loss. These patients, together with two recent case reports, indicate that isolated local autonomic failure, probably from a discrete cord lesion, can be a cause of presenting symptoms related to sweating loss or to change in temperature in a limb. PMID:3612155

  18. Cell-autonomous and non-cell-autonomous roles for IRF6 during development of the tongue.

    PubMed

    Goudy, Steven; Angel, Peggi; Jacobs, Britni; Hill, Cynthia; Mainini, Veronica; Smith, Arianna L; Kousa, Youssef A; Caprioli, Richard; Prince, Lawrence S; Baldwin, Scott; Schutte, Brian C

    2013-01-01

    Interferon regulatory factor 6 (IRF6) encodes a highly conserved helix-turn-helix DNA binding protein and is a member of the interferon regulatory family of DNA transcription factors. Mutations in IRF6 lead to isolated and syndromic forms of cleft lip and palate, most notably Van der Woude syndrome (VWS) and Popliteal Ptyerigium Syndrome (PPS). Mice lacking both copies of Irf6 have severe limb, skin, palatal and esophageal abnormalities, due to significantly altered and delayed epithelial development. However, a recent report showed that MCS9.7, an enhancer near Irf6, is active in the tongue, suggesting that Irf6 may also be expressed in the tongue. Indeed, we detected Irf6 staining in the mesoderm-derived muscle during development of the tongue. Dual labeling experiments demonstrated that Irf6 was expressed only in the Myf5+ cell lineage, which originates from the segmental paraxial mesoderm and gives rise to the muscles of the tongue. Fate mapping of the segmental paraxial mesoderm cells revealed a cell-autonomous Irf6 function with reduced and poorly organized Myf5+ cell lineage in the tongue. Molecular analyses showed that the Irf6-/- embryos had aberrant cytoskeletal formation of the segmental paraxial mesoderm in the tongue. Fate mapping of the cranial neural crest cells revealed non-cell-autonomous Irf6 function with the loss of the inter-molar eminence. Loss of Irf6 function altered Bmp2, Bmp4, Shh, and Fgf10 signaling suggesting that these genes are involved in Irf6 signaling. Based on these data, Irf6 plays important cell-autonomous and non-cell-autonomous roles in muscular differentiation and cytoskeletal formation in the tongue. PMID:23451037

  19. Abnormal Resting-State Functional Connectivity Strength in Mild Cognitive Impairment and Its Conversion to Alzheimer's Disease

    PubMed Central

    Li, Yuxia; Wang, Xiaoni; Li, Yongqiu; Sun, Yu; Sheng, Can; Li, Hongyan; Li, Xuanyu; Yu, Yang; Chen, Guanqun; Hu, Xiaochen; Jing, Bin; Wang, Defeng; Li, Kuncheng; Jessen, Frank; Han, Ying

    2016-01-01

    Individuals diagnosed with mild cognitive impairment (MCI) are at high risk of transition to Alzheimer's disease (AD). However, little is known about functional characteristics of the conversion from MCI to AD. Resting-state functional magnetic resonance imaging was performed in 25 AD patients, 31 MCI patients, and 42 well-matched normal controls at baseline. Twenty-one of the 31 MCI patients converted to AD at approximately 24 months of follow-up. Functional connectivity strength (FCS) and seed-based functional connectivity analyses were used to assess the functional differences among the groups. Compared to controls, subjects with MCI and AD showed decreased FCS in the default-mode network and the occipital cortex. Importantly, the FCS of the left angular gyrus and middle occipital gyrus was significantly lower in MCI-converters as compared with MCI-nonconverters. Significantly decreased functional connectivity was found in MCI-converters compared to nonconverters between the left angular gyrus and bilateral inferior parietal lobules, dorsolateral prefrontal and lateral temporal cortices, and the left middle occipital gyrus and right middle occipital gyri. We demonstrated gradual but progressive functional changes during a median 2-year interval in patients converting from MCI to AD, which might serve as early indicators for the dysfunction and progression in the early stage of AD. PMID:26843991

  20. Responses of Six-Weeks Aquatic Exercise on the Autonomic Nervous System, Peak Nasal Inspiratory Flow and Lung Functions in Young Adults with Allergic Rhinitis.

    PubMed

    Janyacharoen, Taweesak; Kunbootsri, Narupon; Arayawichanon, Preeda; Chainansamit, Seksun; Sawanyawisuth, Kittisak

    2015-06-01

    Allergic rhinitis is a chronic respiratory disease. Sympathetic hypofunction is identified in all of the allergic rhinitis patients. Moreover, allergic rhinitis is associated with decreased peak nasal inspiratory flow (PNIF) and impaired lung functions. The aim of this study was to investigate effects of six-week of aquatic exercise on the autonomic nervous system function, PNIF and lung functions in allergic rhinitis patients. Twenty-six allergic rhinitis patients, 12 males and 14 females were recruited in this study. Subjects were diagnosed by a physician based on history, physical examination, and positive reaction to a skin prick test. Subjects were randomly assigned to two groups. The control allergic rhinitis group received education and maintained normal life. The aquatic group performed aquatic exercise for 30 minutes a day, three days a week for six weeks. Heart rate variability, PNIF and lung functions were measured at the beginning, after three weeks and six weeks. There were statistically significant increased low frequency normal units (LF n.u.), PNIF and showed decreased high frequency normal units (HF n.u.) at six weeks after aquatic exercise compared with the control group. Six weeks of aquatic exercise could increase sympathetic activity and PNIF in allergic rhinitis patients.

  1. Abnormalities in intracellular calcium regulation and contractile function in myocardium from dogs with pacing-induced heart failure

    NASA Technical Reports Server (NTRS)

    Perreault, C. L.; Shannon, R. P.; Komamura, K.; Vatner, S. F.; Morgan, J. P.

    1992-01-01

    24 d of rapid ventricular pacing induced dilated cardiomyopathy with both systolic and diastolic dysfunction in conscious, chronically instrumented dogs. We studied mechanical properties and intracellular calcium (Ca2+i) transients of trabeculae carneae isolated from 15 control dogs (n = 32) and 11 dogs with pacing-induced cardiac failure (n = 26). Muscles were stretched to maximum length at 30 degrees C and stimulated at 0.33 Hz; a subset (n = 17 control, n = 17 myopathic) was loaded with the [Ca2+]i indicator aequorin. Peak tension was depressed in the myopathic muscles, even in the presence of maximally effective (i.e., 16 mM) [Ca2+] in the perfusate. However, peak [Ca2+]i was similar (0.80 +/- 0.13 vs. 0.71 +/- 0.05 microM; [Ca2+]o = 2.5 mM), suggesting that a decrease in Cai2+ availability was not responsible for the decreased contractility. The time for decline from the peak of the Cai2+ transient was prolonged in the myopathic group, which correlated with prolongation of isometric contraction and relaxation. However, similar end-diastolic [Ca2+]i was achieved in both groups (0.29 +/- 0.05 vs. 0.31 +/- 0.02 microM), indicating that Cai2+ homeostasis can be maintained in myopathic hearts. The inotropic response of the myopathic muscles to milrinone was depressed compared with the controls. However, when cAMP production was stimulated by pretreatment with forskolin, the response of the myopathic muscles to milrinone was improved. Our findings provide direct evidence that abnormal [Ca2+]i handling is an important cause of contractile dysfunction in dogs with pacing-induced heart failure and suggest that deficient production of cAMP may be an important cause of these changes in excitation-contraction coupling.

  2. Atomoxetine Changes Rat’s HR Response to Stress from Tachycardia to Bradycardia via Alterations in Autonomic Function

    PubMed Central

    Li, Winston Y.; Strang, Shara E.; Brown, David R.; Smith, Re’Gie; Silcox, Dennis L.; Li, Sheng-Gang; Baldridge, Bobby R.; Nesselroade, K. Paul; Randall, David C.

    2009-01-01

    Atomoxetine is a central norepinephrine reuptake inhibitor used to treat attention deficit hyperactivity disorder. We tested the effects of atomoxetine upon the heart rate (HR) and mean arterial blood pressure (mBP) response to aversive conditioning. In Protocol 1 the mBP and HR responses to a stress (15 sec. tone followed by shock) were tested in 8 Sprague Dawley rats given saline pretreatment for 3 days; the rats’ responses were then tested for 3 additional days following atomoxetine (1 mg/kg, sc). Atomoxetine decreased (p < 0.05) baseline mBP from 128 ± 11 mm Hg (mean ± SD) to 117 ± 19 mm Hg; baseline HR slowed from 380 ± 23 bpm to 351 ± 21 bpm. The mBP increase to acute stress was similar after saline vs. after drug, but the peak was attained more slowly. After atomoxetine HR tended to slow during stress rather than accelerate. In Protocol 2 the cardiovascular responses were tested (n=6) for 3 days post-saline and for 3 days after a higher dose of atomoxetine (2 mg/kg, sc). The average HR acceleration during the last 10 seconds of the stress after saline (+7.5 ± 14.7 bpm) was replaced by a HR slowing (−6.2 ± 10.5 bpm). We conclude that drug treatment (a) decreases baseline sympathetic tone and/or elevates cardiac parasympathetic tone; (b) slows sympathetic arousal to acute stress without changing its magnitude; and, (c) enables the emergence of elevated parasympathetic tone during the stress. These autonomic consequences are consistent with atomoxetine’s anxiolytic and transient sedative effects. PMID:20018569

  3. Experiential, Autonomic, and Neural Responses During Threat Anticipation Vary as a Function of Threat Intensity and Neuroticism

    PubMed Central

    Drabant, Emily M; Kuo, Janice R; Ramel, Wiveka; Blechert, Jens; Edge, Michael D; Cooper, Jeff R; Goldin, Philippe R; Hariri, Ahmad R; Gross, James J

    2011-01-01

    Anticipatory emotional responses play a crucial role in preparing individuals for impending challenges. They do this by triggering a coordinated set of changes in behavioral, autonomic, and neural response systems. In the present study, we examined the biobehavioral impact of varying levels of anticipatory anxiety, using a shock anticipation task in which unpredictable electric shocks were threatened and delivered to the wrist at variable intervals and intensities (safe, medium, strong). This permitted investigation of a dynamic range of anticipatory anxiety responses. In two studies, 95 and 51 healthy female participants, respectively, underwent this shock anticipation task while providing continuous ratings of anxiety experience and electrodermal responding (Study 1) and during fMRI BOLD neuroimaging (Study 2). Results indicated a step-wise pattern of responding in anxiety experience and electrodermal responses. Several brain regions showed robust responses to shock anticipation relative to safe trials, including the hypothalamus, periaqueductal gray, caudate, precentral gyrus, thalamus, insula, ventrolateral PFC, dorsomedial PFC, and ACC. A subset of these regions demonstrated a linear pattern of increased responding from safe to medium to strong trials, including the bilateral insula, ACC, and inferior frontal gyrus. These responses were modulated by individual differences in neuroticism, such that those high in neuroticism showed exaggerated anxiety experience across the entire task, and reduced brain activation from medium to strong trials in a subset of brain regions. These findings suggest that individual differences in neuroticism may influence sensitivity to anticipatory threat and provide new insights into the mechanism through which neuroticism may confer risk for developing anxiety disorders via dysregulated anticipatory responses. PMID:21093595

  4. Microwave-Induced Structural and Functional Injury of Hippocampal and PC12 Cells Is Accompanied by Abnormal Changes in the NMDAR-PSD95-CaMKII Pathway.

    PubMed

    Wang, Li-Feng; Wei, Li; Qiao, Si-Mo; Gao, Xiao-Na; Gao, Ya-Bing; Wang, Shui-Ming; Zhao, Li; Dong, Ji; Xu, Xin-Ping; Zhou, Hong-Mei; Hu, Xiang-Jun; Peng, Rui-Yun

    2015-01-01

    Recent studies have highlighted the important role of the postsynaptic NMDAR-PSD95-CaMKII pathway for synaptic transmission and related neuronal injury. Here, we tested changes in the components of this pathway upon microwave-induced neuronal structure and function impairments. Ultrastructural and functional changes were induced in hippocampal neurons of rats and in PC12 cells exposed to microwave radiation. We detected abnormal protein and mRNA expression, as well as posttranslational modifications in the NMDAR-PSD95-CaMKII pathway and its associated components, such as synapsin I, following microwave radiation exposure of rats and PC12 cells. Thus, microwave radiation may induce neuronal injury via changes in the molecular organization of postsynaptic density and modulation of the biochemical cascade that potentiates synaptic transmission.

  5. Information for Successful Interaction with Autonomous Systems

    NASA Technical Reports Server (NTRS)

    Malin, Jane T.; Johnson, Kathy A.

    2003-01-01

    Interaction in heterogeneous mission operations teams is not well matched to classical models of coordination with autonomous systems. We describe methods of loose coordination and information management in mission operations. We describe an information agent and information management tool suite for managing information from many sources, including autonomous agents. We present an integrated model of levels of complexity of agent and human behavior, which shows types of information processing and points of potential error in agent activities. We discuss the types of information needed for diagnosing problems and planning interactions with an autonomous system. We discuss types of coordination for which designs are needed for autonomous system functions.

  6. Toward autonomous spacecraft

    NASA Technical Reports Server (NTRS)

    Fogel, L. J.; Calabrese, P. G.; Walsh, M. J.; Owens, A. J.

    1982-01-01

    Ways in which autonomous behavior of spacecraft can be extended to treat situations wherein a closed loop control by a human may not be appropriate or even possible are explored. Predictive models that minimize mean least squared error and arbitrary cost functions are discussed. A methodology for extracting cyclic components for an arbitrary environment with respect to usual and arbitrary criteria is developed. An approach to prediction and control based on evolutionary programming is outlined. A computer program capable of predicting time series is presented. A design of a control system for a robotic dense with partially unknown physical properties is presented.

  7. Changes in autonomic function as determined by ECG R-R interval variability in sandal, shoe and leather workers exposed to n-hexane, xylene and toluene.

    PubMed

    Murata, K; Araki, S; Yokoyama, K; Yamashita, K; Okajima, F; Nakaaki, K

    1994-01-01

    To clarify if autonomic nervous system effects might be associated with exposure to organic solvents, 30 sandal, shoe and leather workers exposed to n-hexane, xylene, and toluene, and 25 unexposed controls were examined using the coefficient of variation in electrocardiographic R-R intervals (CVRR), combined with the distribution of nerve conduction velocities (DCV). The C-CVRSA and C-CVMWSA (two component CVs of the CVRR reflecting parasympathetic and sympathetic activities, respectively) were also computed from component spectral powers using autoregressive spectral and component analyses. Concentrations of the metabolites of the solvents in urine samples taken in the morning before work were 0-3.18 (mean 1.39) mg/l for 2,5-hexanedione, 0.10-0.43 (mean 0.19) g/g creatinine (Cn) for methylhippuric acid, and 0.05-2.53 (mean 0.41) g/g Cn for hippuric acid. In the solvent workers, the CVRR and C-CVRSA were reduced significantly when compared with the unexposed controls. The faster velocities of the DCV as well as the sensory median nerve conduction velocity (SCV) were significantly slowed in the solvent-exposed workers. The SCV was significantly correlated with the CVRR and C-CVMWSA among the solvent workers. These data suggest that chronic exposure to some organic solvents may affect cardiac autonomic function (mainly, parasympathetic activity) in addition to faster myelinated fibers of the peripheral nerves. However, the absence of significant dose-effect relations among the solvent workers makes it difficult to definitively attribute the differences to specific solvent exposures. PMID:7715857

  8. Planning Flight Paths of Autonomous Aerobots

    NASA Technical Reports Server (NTRS)

    Kulczycki, Eric; Elfes, Alberto; Sharma, Shivanjli

    2009-01-01

    Algorithms for planning flight paths of autonomous aerobots (robotic blimps) to be deployed in scientific exploration of remote planets are undergoing development. These algorithms are also adaptable to terrestrial applications involving robotic submarines as well as aerobots and other autonomous aircraft used to acquire scientific data or to perform surveying or monitoring functions.

  9. IL-10 Gene Polymorphisms Are Associated with Post-Bronchiolitis Lung Function Abnormalities at Six Years of Age

    PubMed Central

    Lauhkonen, Eero; Koponen, Petri; Teräsjärvi, Johanna; Gröndahl-Yli-Hannuksela, Kirsi; Vuononvirta, Juho; Nuolivirta, Kirsi; Toikka, Jyri O.; Helminen, Merja; He, Qiushui; Korppi, Matti

    2015-01-01

    Aim Interleukin-10 (IL-10) has been associated with wheezing and asthma in children and the genetic variation of the IL-10 cytokine production may be linked to post-bronchiolitis lung function. We used impulse oscillometry (IOS) to evaluate the associations of IL10 polymorphisms with lung function at a median age of 6.3 years in children hospitalised for bronchiolitis before six months of age. Methods We performed baseline and post-exercise IOS on 103 former bronchiolitis patients. Data on single nucleotide polymorphisms (SNP) of IL10 rs1800896 (–1082G/A), rs1800871 (–819C/T), rs1800872 (–592C/A) were available for 99 children and of IL10 rs1800890 (–3575T/A) for 98 children. Results IL10 rs1800896, rs1800871 and rs1800872 combined genotype AA+CT+CA and carriage of haplotype ATA, respectively, were associated with higher resistance and lower reactance in baseline IOS in adjusted analyses. At IL10 rs1800890, the A/A-genotype and carriers of A-allele were associated with lower reactance in baseline IOS. There were no significant associations between the studied SNPs and airway hyper-reactivity to exercise. Conclusion Low-IL-10-producing polymorphisms in the IL-10 encoding gene were associated with obstructive lung function parameters, suggesting an important role for IL-10 in development of lung function deficit in early bronchiolitis patients. PMID:26473365

  10. Whole-brain functional connectivity during emotional word classification in medication-free Major Depressive Disorder: Abnormal salience circuitry and relations to positive emotionality☆

    PubMed Central

    van Tol, Marie-José; Veer, Ilya M.; van der Wee, Nic J.A.; Aleman, André; van Buchem, Mark A.; Rombouts, Serge A.R.B.; Zitman, Frans G.; Veltman, Dick J.; Johnstone, Tom

    2013-01-01

    Major Depressive Disorder (MDD) has been associated with biased processing and abnormal regulation of negative and positive information, which may result from compromised coordinated activity of prefrontal and subcortical brain regions involved in evaluating emotional information. We tested whether patients with MDD show distributed changes in functional connectivity with a set of independently derived brain networks that have shown high correspondence with different task demands, including stimulus salience and emotional processing. We further explored if connectivity during emotional word processing related to the tendency to engage in positive or negative emotional states. In this study, 25 medication-free MDD patients without current or past comorbidity and matched controls (n = 25) performed an emotional word-evaluation task during functional MRI. Using a dual regression approach, individual spatial connectivity maps representing each subject's connectivity with each standard network were used to evaluate between-group differences and effects of positive and negative emotionality (extraversion and neuroticism, respectively, as measured with the NEO-FFI). Results showed decreased functional connectivity of the medial prefrontal cortex, ventrolateral prefrontal cortex, and ventral striatum with the fronto-opercular salience network in MDD patients compared to controls. In patients, abnormal connectivity was related to extraversion, but not neuroticism. These results confirm the hypothesis of a relative (para)limbic–cortical decoupling that may explain dysregulated affect in MDD. As connectivity of these regions with the salience network was related to extraversion, but not to general depression severity or negative emotionality, dysfunction of this network may be responsible for the failure to sustain engagement in rewarding behavior. PMID:24179829

  11. Testing the autonomic nervous system.

    PubMed

    Freeman, Roy; Chapleau, Mark W

    2013-01-01

    Autonomic testing is used to define the role of the autonomic nervous system in diverse clinical and research settings. Because most of the autonomic nervous system is inaccessible to direct physiological testing, in the clinical setting the most widely used techniques entail the assessment of an end-organ response to a physiological provocation. The noninvasive measures of cardiovascular parasympathetic function involve the assessment of heart rate variability while the measures of cardiovascular sympathetic function assess the blood pressure response to physiological stimuli. Tilt-table testing, with or without pharmacological provocation, has become an important tool in the assessment of a predisposition to neurally mediated (vasovagal) syncope, the postural tachycardia syndrome, and orthostatic hypotension. Distal, postganglionic, sympathetic cholinergic (sudomotor) function may be evaluated by provoking axon reflex mediated sweating, e.g., the quantitative sudomotor axon reflex (QSART) or the quantitative direct and indirect axon reflex (QDIRT). The thermoregulatory sweat test provides a nonlocalizing measure of global pre- and postganglionic sudomotor function. Frequency domain analyses of heart rate and blood pressure variability, microneurography, and baroreflex assessment are currently research tools but may find a place in the clinical assessment of autonomic function in the future. PMID:23931777

  12. Structural and functional MRI abnormalities of cerebellar cortex and nuclei in SCA3, SCA6 and Friedreich's ataxia.

    PubMed

    Stefanescu, Maria R; Dohnalek, Moritz; Maderwald, Stefan; Thürling, Markus; Minnerop, Martina; Beck, Andreas; Schlamann, Marc; Diedrichsen, Joern; Ladd, Mark E; Timmann, Dagmar

    2015-05-01

    Spinocerebellar ataxia type 3, spinocerebellar ataxia type 6 and Friedreich's ataxia are common hereditary ataxias. Different patterns of atrophy of the cerebellar cortex are well known. Data on cerebellar nuclei are sparse. Whereas cerebellar nuclei have long been thought to be preserved in spinocerebellar ataxia type 6, histology shows marked atrophy of the nuclei in Friedreich's ataxia and spinocerebellar ataxia type 3. In the present study susceptibility weighted imaging was used to assess atrophy of the cerebellar nuclei in patients with spinocerebellar ataxia type 6 (n = 12, age range 41-76 years, five female), Friedreich's ataxia (n = 12, age range 21-55 years, seven female), spinocerebellar ataxia type 3 (n = 10, age range 34-67 years, three female), and age- and gender-matched controls (total n = 23, age range 22-75 years, 10 female). T1-weighted magnetic resonance images were used to calculate the volume of the cerebellum. In addition, ultra-high field functional magnetic resonance imaging was performed with optimized normalization methods to assess function of the cerebellar cortex and nuclei during simple hand movements. As expected, the volume of the cerebellum was markedly reduced in spinocerebellar ataxia type 6, preserved in Friedreich's ataxia, and mildy reduced in spinocerebellar ataxia type 3. The volume of the cerebellar nuclei was reduced in the three patient groups compared to matched controls (P-values < 0.05; two-sample t-tests). Atrophy of the cerebellar nuclei was most pronounced in spinocerebellar ataxia type 6. On a functional level, hand-movement-related cerebellar activation was altered in all three disorders. Within the cerebellar cortex, functional magnetic resonance imaging signal was significantly reduced in spinocerebellar ataxia type 6 and Friedreich's ataxia compared to matched controls (P-values < 0.001, bootstrap-corrected cluster-size threshold; two-sample t-tests). The difference missed significance in spinocerebellar ataxia

  13. Misarticulation caused by abnormal lingual-palatal contact in patients with cleft palate with adequate velopharyngeal function.

    PubMed

    Yamashita, Y; Michi, K

    1991-10-01

    Misarticulations produced by three patients with cleft palate (2 isolated cleft palate; 1 unilateral cleft lip, alveolus, and palate) who attained adequate velopharyngeal function and normal palatal vault by early surgical repairs were examined using electropalatography (EPG) and sound spectrography (SG). Common characteristics of lingual-palatal contact in which the contact area was broader and/or was more posterior than normal were observed. These misarticulations can be divided into three types based on the direction of the breath emission: palatalized misarticulation (in which air passes along the midline of the palate), lateral misarticulation (in which air flows laterally through the occluded dental arch), and nasopharyngeal misarticulation (in which air flows out the nose). These three are considered to be similar to intractable posterior pattern of articulation in cleft palate patients previously reported. However, these types of misarticulations can be produced by cleft patients who have achieved adequate velopharyngeal function and normal palatal vault.

  14. Detecting Visual Function Abnormality with a Contrast-Dependent Visual Test in Patients with Type 2 Diabetes

    PubMed Central

    Jang, Yuh; Hu, Fu-Chang; Wu, Wei-Chi

    2016-01-01

    In addition to diabetic retinopathy, diabetes also causes early retinal neurodegeneration and other eye problems, which cause various types of visual deficits. This study used a computer-based visual test (Macular Multi-Function Assessment (MMFA)) to assess contrast-dependent macular visual function in patients with type 2 diabetes to collect more visual information than possible with only the visual acuity test. Because the MMFA is a newly developed test, this study first compared the agreement and discriminative ability of the MMFA and the Early Treatment Diabetic Retinopathy Study (ETDRS) contrast acuity charts. Then symbol discrimination performances of diabetic patients and controls were evaluated at 4 contrast levels using the MMFA. Seventy-seven patients and 45 controls participated. The agreement between MMFA and ETDRS scores was examined by fitting three-level linear mixed-effect models to estimate the intraclass correlation coefficients (ICCs). The estimated areas under the receiver operating characteristic (ROC) curve were used to compare the discriminative ability of diseased versus non-diseased participants between the two tests. The MMFA scores of patients and controls were compared with multiple linear regression analysis after adjusting the effects of age, sex, hypertension and cataract. Results showed that the scores of the MMFA and ETDRS tests displayed high levels of agreement and acceptable and similar discriminative ability. The MMFA performance was correlated with the severity of diabetic retinopathy. Most of the MMFA scores differed significantly between the diabetic patients and controls. In the low contrast condition, the MMFA scores were significantly lower for 006Eon-DR patients than for controls. The potential utility of the MMFA as an easy screening tool for contrast-dependent visual function and for detecting early functional visual change in patients with type 2 diabetes is discussed. PMID:27611680

  15. Detecting Visual Function Abnormality with a Contrast-Dependent Visual Test in Patients with Type 2 Diabetes.

    PubMed

    Tsai, Li-Ting; Liao, Kuo-Meng; Jang, Yuh; Hu, Fu-Chang; Wu, Wei-Chi

    2016-01-01

    In addition to diabetic retinopathy, diabetes also causes early retinal neurodegeneration and other eye problems, which cause various types of visual deficits. This study used a computer-based visual test (Macular Multi-Function Assessment (MMFA)) to assess contrast-dependent macular visual function in patients with type 2 diabetes to collect more visual information than possible with only the visual acuity test. Because the MMFA is a newly developed test, this study first compared the agreement and discriminative ability of the MMFA and the Early Treatment Diabetic Retinopathy Study (ETDRS) contrast acuity charts. Then symbol discrimination performances of diabetic patients and controls were evaluated at 4 contrast levels using the MMFA. Seventy-seven patients and 45 controls participated. The agreement between MMFA and ETDRS scores was examined by fitting three-level linear mixed-effect models to estimate the intraclass correlation coefficients (ICCs). The estimated areas under the receiver operating characteristic (ROC) curve were used to compare the discriminative ability of diseased versus non-diseased participants between the two tests. The MMFA scores of patients and controls were compared with multiple linear regression analysis after adjusting the effects of age, sex, hypertension and cataract. Results showed that the scores of the MMFA and ETDRS tests displayed high levels of agreement and acceptable and similar discriminative ability. The MMFA performance was correlated with the severity of diabetic retinopathy. Most of the MMFA scores differed significantly between the diabetic patients and controls. In the low contrast condition, the MMFA scores were significantly lower for 006Eon-DR patients than for controls. The potential utility of the MMFA as an easy screening tool for contrast-dependent visual function and for detecting early functional visual change in patients with type 2 diabetes is discussed. PMID:27611680

  16. Improvement of white matter and functional connectivity abnormalities by repetitive transcranial magnetic stimulation in crossed aphasia in dextral.

    PubMed

    Lu, Haitao; Wu, Haiyan; Cheng, Hewei; Wei, Dongjie; Wang, Xiaoyan; Fan, Yong; Zhang, Hao; Zhang, Tong

    2014-01-01

    As a special aphasia, the occurrence of crossed aphasia in dextral (CAD) is unusual. This study aims to improve the language ability by applying 1 Hz repetitive transcranial magnetic stimulation (rTMS). We studied multiple modality imaging of structural connectivity (diffusion tensor imaging), functional connectivity (resting fMRI), PET, and neurolinguistic analysis on a patient with CAD. Furthermore, we applied rTMS of 1 Hz for 40 times and observed the language function improvement. The results indicated that a significantly reduced structural and function connectivity was found in DTI and fMRI data compared with the control. The PET imaging showed hypo-metabolism in right hemisphere and left cerebellum. In conclusion, one of the mechanisms of CAD is that right hemisphere is the language dominance. Stimulating left Wernicke area could improve auditory comprehension, stimulating left Broca's area could enhance expression, and the results outlasted 6 months by 1 Hz rTMS balancing the excitability inter-hemisphere in CAD. PMID:25419415

  17. Towards an Autonomic Cluster Management System (ACMS) with Reflex Autonomicity

    NASA Technical Reports Server (NTRS)

    Truszkowski, Walt; Hinchey, Mike; Sterritt, Roy

    2005-01-01

    Cluster computing, whereby a large number of simple processors or nodes are combined together to apparently function as a single powerful computer, has emerged as a research area in its own right. The approach offers a relatively inexpensive means of providing a fault-tolerant environment and achieving significant computational capabilities for high-performance computing applications. However, the task of manually managing and configuring a cluster quickly becomes daunting as the cluster grows in size. Autonomic computing, with its vision to provide self-management, can potentially solve many of the problems inherent in cluster management. We describe the development of a prototype Autonomic Cluster Management System (ACMS) that exploits autonomic properties in automating cluster management and its evolution to include reflex reactions via pulse monitoring.

  18. Autonomous Integrated Receive System (AIRS) requirements definition. Volume 4: Functional specification for the prototype Automated Integrated Receive System (AIRS)

    NASA Technical Reports Server (NTRS)

    Chie, C. M.

    1984-01-01

    The functional requirements for the performance, design, and testing for the prototype Automated Integrated Receive System (AIRS) to be demonstrated for the TDRSS S-Band Single Access Return Link are presented.

  19. Autonomic dysfunction and microvascular damage in systemic sclerosis.

    PubMed

    Di Franco, Manuela; Paradiso, Michele; Riccieri, Valeria; Basili, Stefania; Mammarella, Antonio; Valesini, Guido

    2007-08-01

    Systemic sclerosis (SSc) is a connective tissue disease characterized by vascular damage and interstizial fibrosis of many organs. Our interest was focused on the evaluation of cardiac autonomic function by measurements of heart rate variability (HRV) and microvascular damage detected by nailfold capillaroscopy (NC) in SSc patients. We examined 25 consecutive outpatients affected by systemic sclerosis and 25 healthy controls. Exclusion criteria were the presence of cardiac disease, hypertension, diabetes mellitus, or neurological diseases. All subjects underwent 24-h ambulatory ECG Holter recording and NC examination. Heart rate variability was evaluated in the time domain, using appropriate software, computing the time series of all normal-to-normal (NN) QRS intervals throughout the 24-h recording period. A semiquantitative rating scale was adopted to score the NC abnormalities, as well as a rating system for avascular areas and morphological NC patterns. In SSc patients, HRV analysis showed significantly lower values of SDNN (standard deviation of all NN intervals) (p=0.009), SDANN (standard deviation of the averages of NN intervals in all 5-min segments of the entire recording) (p=0.01), and pNN50 (the percentage of adjacent NN intervals that differed by more than 50 ms) (p=0.02), compared to the control group. These parameters in SSc patients significantly decreased with the worsening of semiquantitative capillaroscopy score. In conclusion, an abnormal autonomic nervous control of the heart might contribute to identify subclinical cardiac involvement in SSc patients. The coexistence of autonomic dysfunction with a more severe microvascular damage could be considered a potential prognostic tool in the identification of those patients particularly at risk for cardiac mortality.

  20. Prolonged elevation of intraocular pressure results in retinal ganglion cell loss and abnormal retinal function in mice

    PubMed Central

    Khan, A Kareem; Tse, Dennis Y; van der Heijden, Meike; Shah, Priya; Nusbaum, Derek; Yang, Zhuo; Wu, Samuel M; Frankfort, Benjamin J

    2014-01-01

    The purpose of this study was to assess the impact of prolonged intraocular pressure (IOP) elevation on retinal anatomy and function in a mouse model of experimental glaucoma. IOP was elevated by anterior chamber injection of a fixed combination of polystyrene beads and sodium hyaluronate, and maintained via re-injection after 24 weeks. IOP was measured weekly with a rebound tonometer for 48 weeks. Histology was assessed with a combination of retrograde labeling and antibody staining. Retinal physiology and function was assessed with dark-adapted electroretinograms (ERGs). Comparisons between bead-injected animals and various controls were conducted at both 24 and 48 weeks after bead injection. IOP was elevated throughout the study. IOP elevation resulted in a reduction of retinal ganglion cell (RGCs) and an increase in axial length at both 24 and 48 weeks after bead injection. The b-wave amplitude of the ERG was increased to the same degree in bead-injected eyes at both time points, similar to previous studies. The positive scotopic threshold response (pSTR) amplitude, a measure of RGC electrical function, was diminished at both 24 and 48 weeks when normalized to the increased b-wave amplitude. At 48 weeks, the pSTR amplitude was reduced even without normalization, suggesting more profound RGC dysfunction. We conclude that injection of polystyrene beads and sodium hyaluronate causes chronic IOP elevation which results in phenotypes of stable b-wave amplitude increase and progressive pSTR amplitude reduction, as well as RGC loss and axial length elongation. PMID:25450059

  1. Evaluation of left atrial mechanical function and atrial conduction abnormalities in Maras powder (smokeless tobacco) users and smokers

    PubMed Central

    Akcay, Ahmet; Naci Aydin, M; Acar, Gurkan; Akgungor, Mehmet; Cabioglu, Eren; Ardic, İdris; Mese, Bulent; Bozoglan, Orhan; Çetin, Mustafa; Çakıcı, Musa

    2015-01-01

    Summary Objective In Turkey, a type of smokeless tobacco called Maras powder (MP) is widely used in the south-eastern region. Smokeless tobacco is found in preparations for chewing and for absorption by the nasal and oral mucosae. The purpose of this study was to investigate whether MP damages intra- and inter-atrial conduction delay and left atrial (LA) mechanical function as much as cigarette smoking. Method A total of 150 chronic MP users (50 males, 32.5 ± 5.4 years), smokers (50 males, 32.1 ± 6.0 years) and controls (50 males, 30.1 ± 5.8 years) were included in the study. LA volumes were measured echocardiographically according to the biplane area–length method. Atrial electromechanical coupling was measured with tissue Doppler imaging and LA mechanical function parameters were calculated. Results The LA passive emptying fraction was significantly decreased and LA active emptying volume (LAAEV) was significantly increased in the MP group (p = 0.012 and p = 0.024, respectively), and the LA active emptying fraction (LAAEF) was significantly increased in the smokers (p = 0.003). There was a positive correlation between the amount of MP used and smoking (pack years) with LAAEV and LAAEF (r = 0.26, p = 0.009 and r = 0.25, p = 0.013, respectively). Lateral atrial electromechanical intervals (PA) were significantly higher in MP users, and the septal mitral PA was statistically higher in the smokers (p = 0.05 and p = 0.04, respectively). Conclusion We suggest that atrial electromechanical coupling intervals were prolonged and LA mechanical function was impaired in MP users and smokers, but there was no significant difference between the MP users and smokers. These findings may be markers of subclinical cardiac involvement and tendency for atrial fibrillation. PMID:26592906

  2. Abnormal Degree Centrality of Bilateral Putamen and Left Superior Frontal Gyrus in Schizophrenia with Auditory Hallucinations: A Resting-state Functional Magnetic Resonance Imaging Study

    PubMed Central

    Chen, Cheng; Wang, Hui-Ling; Wu, Shi-Hao; Huang, Huan; Zou, Ji-Lin; Chen, Jun; Jiang, Tian-Zi; Zhou, Yuan; Wang, Gao-Hua

    2015-01-01

    Background: Dysconnectivity hypothesis of schizophrenia has been increasingly emphasized. Recent researches showed that this dysconnectivity might be related to occurrence of auditory hallucination (AH). However, there is still no consistent conclusion. This study aimed to explore intrinsic dysconnectivity pattern of whole-brain functional networks at voxel level in schizophrenic with AH. Methods: Auditory hallucinated patients group (n = 42 APG), no hallucinated patients group (n = 42 NPG) and normal controls (n = 84 NCs) were analyzed by resting-state functional magnetic resonance imaging. The functional connectivity metrics index (degree centrality [DC]) across the entire brain networks was calculated and evaluated among three groups. Results: DC decreased in the bilateral putamen and increased in the left superior frontal gyrus in all the patients. However, in APG, the changes of DC were more obvious compared with NPG. Symptomology scores were negatively correlated with the DC of bilateral putamen in all patients. AH score of APG positively correlated with the DC in left superior frontal gyrus but negatively correlated with the DC in bilateral putamen. Conclusion: Our findings corroborated that schizophrenia was characterized by functional dysconnectivity, and the abnormal DC in bilateral putamen and left superior frontal gyrus might be crucial in the occurrence of AH. PMID:26612293

  3. Structural and Functional Abnormalities of the Neuromuscular Junction in the Trembler-J Homozygote Mouse Model of Congenital Hypomyelinating Neuropathy.

    PubMed

    Scurry, Alexandra N; Heredia, Dante J; Feng, Cheng-Yuan; Gephart, Gregory B; Hennig, Grant W; Gould, Thomas W

    2016-04-01

    Mutations in peripheral myelin protein 22 (PMP22) result in the most common form of Charcot-Marie-Tooth (CMT) disease, CMT1A. This hereditary peripheral neuropathy is characterized by dysmyelination of peripheral nerves, reduced nerve conduction velocity, and muscle weakness. APMP22 point mutation in L16P (leucine 16 to proline) underlies a form of human CMT1A as well as the Trembler-J mouse model of CMT1A. Homozygote Trembler-J mice (Tr(J)) die early postnatally, fail to make peripheral myelin, and, therefore, are more similar to patients with congenital hypomyelinating neuropathy than those with CMT1A. Because recent studies of inherited neuropathies in humans and mice have demonstrated that dysfunction and degeneration of neuromuscular synapses or junctions (NMJs) often precede impairments in axonal conduction, we examined the structure and function of NMJs in Tr(J)mice. Although synapses appeared to be normally innervated even in end-stage Tr(J)mice, the growth and maturation of the NMJs were altered. In addition, the amplitudes of nerve-evoked muscle endplate potentials were reduced and there was transmission failure during sustained nerve stimulation. These results suggest that the severe congenital hypomyelinating neuropathy that characterizes Tr(J)mice results in structural and functional deficits of the developing NMJ.

  4. Small-molecule structure correctors target abnormal protein structure and function: structure corrector rescue of apolipoprotein E4-associated neuropathology.

    PubMed

    Mahley, Robert W; Huang, Yadong

    2012-11-01

    An attractive strategy to treat proteinopathies (diseases caused by malformed or misfolded proteins) is to restore protein function by inducing proper three-dimensional structure. We hypothesized that this approach would be effective in reversing the detrimental effects of apolipoprotein (apo) E4, the major allele that significantly increases the risk of developing Alzheimer's disease and other neurodegenerative disorders. ApoE4's detrimental effects result from its altered protein conformation ("domain interaction"), making it highly susceptible to proteolytic cleavage and the generation of neurotoxic fragments. Here, we review apoE structure and function and how apoE4 causes neurotoxicity, and describe the identification of potent small-molecule-based "structure correctors" that induce proper apoE4 folding. SAR studies identified a series of small molecules that significantly reduced apoE4's neurotoxic effects in cultured neurons and a series that reduced apoE4 fragment levels in vivo, providing proof-of-concept for our approach. Structure-corrector-based therapies could prove to be highly effective for the treatment of many protein-misfolding diseases.

  5. Autonomic Nervous System Disorders

    MedlinePlus

    Your autonomic nervous system is the part of your nervous system that controls involuntary actions, such as the beating of your heart ... breathing and swallowing Erectile dysfunction in men Autonomic nervous system disorders can occur alone or as the result ...

  6. Autonomous Soaring Flight Results

    NASA Technical Reports Server (NTRS)

    Allen, Michael J.

    2006-01-01

    A viewgraph presentation on autonomous soaring flight results for Unmanned Aerial Vehicles (UAV)'s is shown. The topics include: 1) Background; 2) Thermal Soaring Flight Results; 3) Autonomous Dolphin Soaring; and 4) Future Plans.

  7. Executive Function Deficits and Social-Behavioral Abnormality in Mice Exposed to a Low Dose of Dioxin In Utero and via Lactation

    PubMed Central

    Endo, Toshihiro; Kakeyama, Masaki; Uemura, Yukari; Haijima, Asahi; Okuno, Hiroyuki; Bito, Haruhiko; Tohyama, Chiharu

    2012-01-01

    An increasing prevalence of mental health problems has been partly ascribed to abnormal brain development that is induced upon exposure to environmental chemicals. However, it has been extremely difficult to detect and assess such causality particularly at low exposure levels. To address this question, we here investigated higher brain function in mice exposed to dioxin in utero and via lactation by using our recently developed automated behavioral flexibility test and immunohistochemistry of neuronal activation markers Arc, at the 14 brain areas. Pregnant C57BL/6 mice were given orally a low dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) at a dose of either 0, 0.6 or 3.0 µg/kg on gestation day 12.5. When the pups reached adulthood, they were group-housed in IntelliCage to assess their behavior. As a result, the offspring born to dams exposed to 0.6 µg TCDD/kg were shown to have behavioral inflexibility, compulsive repetitive behavior, and dramatically lowered competitive dominance. In these mice, immunohistochemistry of Arc exhibited the signs of hypoactivation of the medial prefrontal cortex (mPFC) and hyperactivation of the amygdala. Intriguingly, mice exposed to 3.0 µg/kg were hardly affected in both the behavioral and neuronal activation indices, indicating that the robust, non-monotonic dose-response relationship. In conclusion, this study showed for the first time that perinatal exposure to a low dose of TCDD in mice develops executive function deficits and social behavioral abnormality accompanied with the signs of imbalanced mPFC-amygdala activation. PMID:23251380

  8. Prevalence of abnormal findings when adopting new national and international Global Lung Function Initiative reference values for spirometry in the Finnish general population

    PubMed Central

    Kainu, Annette; Lindqvist, Ari; Sovijärvi, Anssi R. A.

    2016-01-01

    Background New Finnish (Kainu2015) and international Global Lung Function Initiative (GLI2012) reference values for spirometry were recently published. The aim of this study is to compare the interpretative consequences of adopting these new reference values with older, currently used Finnish reference values (Viljanen1982) in the general population of native Finns. Methods Two Finnish general population samples including 1,328 adults (45% males) aged 21–74 years were evaluated. Airway obstruction was defined as a reduced ratio of forced expiratory volume in one second (FEV1)/forced vital capacity (FVC), possible restrictive pattern as reduced FVC, and decreased ventilatory capacity as reduced FEV1 below their respective 2.5th percentiles. The severity gradings of reduced lung function were also compared. Results Using the Kainu2015 reference values, the prevalence of airway obstruction in the population was 5.6%; using GLI2012 it was 4.0% and with Viljanen1982 it was 13.0%. Possible restrictive pattern was found in 4.2% using the Kainu2015 values, in 2.0% with GLI2012, and 7.9% with the Viljanen1982 values. The prevalence of decreased ventilatory capacity was 6.8, 4.0, and 13.3% with the Kainu2015, GLI2012 and Viljanen1982 values, respectively. Conclusions The application of the GLI2012 reference values underestimates the prevalence of abnormal spirometric findings in native Finns. The adoption of the Kainu2015 reference values reduces the prevalences of airways obstruction, decreased ventilatory capacity, and restrictive impairment by approximately 50%. Changing from the 2.5th percentile, the previously used lower limit of normal, to the 5th percentile recommended by the American Thoracic Society/European Respiratory Society will not increase the prevalence of abnormal findings in the implementation of spirometry reference values. PMID:27608270

  9. Intelligent, autonomous systems in space

    NASA Technical Reports Server (NTRS)

    Lum, H.; Heer, E.

    1988-01-01

    The Space Station is expected to be equipped with intelligent, autonomous capabilities; to achieve and incorporate these capabilities, the required technologies need to be identitifed, developed and validated within realistic application scenarios. The critical technologies for the development of intelligent, autonomous systems are discussed in the context of a generalized functional architecture. The present state of this technology implies that it be introduced and applied in an evolutionary process which must start during the Space Station design phase. An approach is proposed to accomplish design information acquisition and management for knowledge-base development.

  10. [Trigeminal autonomic cephalgias].

    PubMed

    Maximova, M Yu; Piradov, M A; Suanova, E T; Sineva, N A

    2015-01-01

    Review of literature on the trigeminal autonomic cephalgias are presented. Trigeminal autonomic cephalgias are primary headaches with phenotype consisting of trigeminal pain with autonomic sign including lacrimation, rhinorrhea and miosis. Discussed are issues of classification, pathogenesis, clinical picture, diagnosis, differential diagnosis and treatment of this headache. Special attention is paid to cluster headache, paroxysmal hemicrania, SUNCT syndrome, hemicrania continua.

  11. Mesenteric lymph from rats with trauma-hemorrhagic shock causes abnormal cardiac myocyte function and induces myocardial contractile dysfunction.

    PubMed

    Sambol, Justin T; Lee, Marlon A; Jiang, Mingshan; Dosi, Garima; Dong, Wei; Deitch, Edwin A; Yatani, Atsuko

    2011-09-01

    Myocardial contractile dysfunction develops following trauma-hemorrhagic shock (T/HS). We have previously shown that, in a rat fixed pressure model of T/HS (mean arterial pressure of 30-35 mmHg for 90 min), mesenteric lymph duct ligation before T/HS prevented T/HS-induced myocardial contractile depression. To determine whether T/HS lymph directly alters myocardial contractility, we examined the functional effects of physiologically relevant concentrations of mesenteric lymph collected from rats undergoing trauma-sham shock (T/SS) or T/HS on both isolated cardiac myocytes and Langendorff-perfused whole hearts. Acute application of T/HS lymph (0.1-2%), but not T/SS lymph, induced dual inotropic effects on myocytes with an immediate increase in the amplitude of cell shortening (1.4 ± 0.1-fold) followed by a complete block of contraction. Similarly, T/HS lymph caused dual, positive and negative effects on cellular Ca²⁺ transients. These effects were associated with changes in the electrophysiological properties of cardiac myocytes; T/HS lymph initially prolonged the action potential duration (action potential duration at 90% repolarization, 3.3 ± 0.4-fold), and this was followed by a decrease in the plateau potential and membrane depolarization. Furthermore, intravenous infusion of T/HS lymph, but not T/SS lymph, caused myocardial contractile dysfunction at 24 h after injection, which mimicked actual T/HS-induced changes; left ventricular developed pressure (LVDP) and the maximal rate of LVDP rise and fall (±dP/dt(max)) were decreased and inotropic response to Ca²⁺ was blunted. However, the contractile responsiveness to β-adrenergic receptor stimulation in the T/HS lymph-infused hearts remained unchanged. These results suggest that T/HS lymph directly causes negative inotropic effects on the myocardium and that T/HS lymph-induced changes in myocyte function are likely to contribute to the development of T/HS-induced myocardial dysfunction.

  12. Mesenteric lymph from rats with trauma-hemorrhagic shock causes abnormal cardiac myocyte function and induces myocardial contractile dysfunction

    PubMed Central

    Sambol, Justin T.; Lee, Marlon A.; Jiang, Mingshan; Dosi, Garima; Dong, Wei; Deitch, Edwin A.

    2011-01-01

    Myocardial contractile dysfunction develops following trauma-hemorrhagic shock (T/HS). We have previously shown that, in a rat fixed pressure model of T/HS (mean arterial pressure of 30–35 mmHg for 90 min), mesenteric lymph duct ligation before T/HS prevented T/HS-induced myocardial contractile depression. To determine whether T/HS lymph directly alters myocardial contractility, we examined the functional effects of physiologically relevant concentrations of mesenteric lymph collected from rats undergoing trauma-sham shock (T/SS) or T/HS on both isolated cardiac myocytes and Langendorff-perfused whole hearts. Acute application of T/HS lymph (0.1–2%), but not T/SS lymph, induced dual inotropic effects on myocytes with an immediate increase in the amplitude of cell shortening (1.4 ± 0.1-fold) followed by a complete block of contraction. Similarly, T/HS lymph caused dual, positive and negative effects on cellular Ca2+ transients. These effects were associated with changes in the electrophysiological properties of cardiac myocytes; T/HS lymph initially prolonged the action potential duration (action potential duration at 90% repolarization, 3.3 ± 0.4-fold), and this was followed by a decrease in the plateau potential and membrane depolarization. Furthermore, intravenous infusion of T/HS lymph, but not T/SS lymph, caused myocardial contractile dysfunction at 24 h after injection, which mimicked actual T/HS-induced changes; left ventricular developed pressure (LVDP) and the maximal rate of LVDP rise and fall (±dP/dtmax) were decreased and inotropic response to Ca2+ was blunted. However, the contractile responsiveness to β-adrenergic receptor stimulation in the T/HS lymph-infused hearts remained unchanged. These results suggest that T/HS lymph directly causes negative inotropic effects on the myocardium and that T/HS lymph-induced changes in myocyte function are likely to contribute to the development of T/HS-induced myocardial dysfunction. PMID:21700891

  13. Abnormal degree centrality of functional hubs associated with negative coping in older Chinese adults who lost their only child.

    PubMed

    Liu, Wei; Liu, HuiJuan; Wei, Dongtao; Sun, Jiangzhou; Yang, Junyi; Meng, Jie; Wang, Lihong; Qiu, Jiang

    2015-12-01

    The loss of an only child is a negative life event and may potentially increase the risk of psychiatric disorders. However, the psychological consequences of the loss of an only child and the associated neural mechanisms remain largely unexplored. Degree centrality (DC), derived from resting-state functional magnetic resonance imaging (fMRI), was used to examine network communication in 22 older adults who lost their only child and 23 matched controls. The older adults who lost their only child exhibited an ineffective coping style. They also showed decreased distant and local DC in the precuneus and left inferior parietal lobule and decreased distant DC in the bilateral dorsolateral prefrontal cortex (DLPFC). Furthermore, the decreased local and distant DC of these regions and the decreased DLPFC-precuneus connectivity strength were negatively correlated with negative coping scores in the loss group but not in the controls. Overall, the results suggested a model that the impaired neural network communication of brain hubs within the default mode network (DMN) and central executive network (CEN) were associated with a negative coping style in older adults who lost their only child. The decreased connectivity of the hubs can be identified as a neural risk factor that is related to future psychopathology. PMID:26391339

  14. Functional magnetic resonance imaging reveals abnormal brain connectivity in EGR3 gene transfected rat model of schizophrenia.

    PubMed

    Song, Tianbin; Nie, Binbin; Ma, Ensen; Che, Jing; Sun, Shilong; Wang, Yuli; Shan, Baoci; Liu, Yawu; Luo, Senlin; Ma, Guolin; Li, Kefeng

    2015-05-01

    Schizophrenia is characterized by the disorder of "social brain". However, the alternation of connectivity density in brain areas of schizophrenia patients remains largely unknown. In this study, we successfully created a rat model of schizophrenia by the transfection of EGR3 gene into rat brain. We then investigated the connectivity density of schizophrenia susceptible regions in rat brain using functional magnetic resonance imaging (fMRI) in combination with multivariate Granger causality (GC) model. We found that the average signal strength in prefrontal lobe and hippocampus of schizophrenia model group was significantly higher than the control group. Bidirectional Granger causality connection was observed between hippocampus and thalamic in schizophrenia model group. Both connectivity density and Granger causality connection were changed in prefrontal lobe, hippocampus and thalamus after risperidone treatment. Our results indicated that fMRI in combination with GC connection analysis may be used as an important method in diagnosis of schizophrenia and evaluation the effect of antipsychotic treatment. These findings support the connectivity disorder hypothesis of schizophrenia and increase our understanding of the neural mechanisms of schizophrenia.

  15. Abnormal costimulatory phenotype and function of dendritic cells before and after the onset of severe murine lupus.

    PubMed

    Colonna, Lucrezia; Dinnall, Joudy-Ann; Shivers, Debra K; Frisoni, Lorenza; Caricchio, Roberto; Gallucci, Stefania

    2006-01-01

    We analyzed the activation and function of dendritic cells (DCs) in the spleens of diseased, lupus-prone NZM2410 and NZB-W/F1 mice and age-matched BALB/c and C57BL/6 control mice. Lupus DCs showed an altered ex vivo costimulatory profile, with a significant increase in the expression of CD40, decreased expression of CD80 and CD54, and normal expression of CD86. DCs from young lupus-prone NZM2410 mice, before the development of the disease, expressed normal levels of CD80 and CD86 but already overexpressed CD40. The increase in CD40-positive cells was specific for DCs and involved the subset of myeloid and CD8alpha+ DCs before disease onset, with a small involvement of plasmacytoid DCs in diseased mice. In vitro data from bone marrow-derived DCs and splenic myeloid DCs suggest that the overexpression of CD40 is not due to a primary alteration of CD40 regulation in DCs but rather to an extrinsic stimulus. Our analyses suggest that the defect of CD80 in NZM2410 and NZB-W/F1 mice, which closely resembles the costimulatory defect found in DCs from humans with systemic lupus erythematosus, is linked to the autoimmune disease. The increase in CD40 may instead participate in disease pathogenesis, being present months before any sign of autoimmunity, and its downregulation should be explored as an alternative to treatment with anti-CD40 ligand in lupus.

  16. Mitochondria-targeted ROS scavenger improves post-ischemic recovery of cardiac function and attenuates mitochondrial abnormalities in aged rats.

    PubMed

    Escobales, Nelson; Nuñez, Rebeca E; Jang, Sehwan; Parodi-Rullan, Rebecca; Ayala-Peña, Sylvette; Sacher, Joshua R; Skoda, Erin M; Wipf, Peter; Frontera, Walter; Javadov, Sabzali

    2014-12-01

    Mitochondria-generated reactive oxygen species (ROS) play a crucial role in the pathogenesis of aging and age-associated diseases. In this study, we evaluated the effects of XJB-5-131 (XJB), a mitochondria-targeted ROS and electron scavenger, on cardiac resistance to ischemia-reperfusion (IR)-induced oxidative stress in aged rats. Male adult (5-month old, n=17) and aged (29-month old, n=19) Fischer Brown Norway (F344/BN) rats were randomly assigned to the following groups: adult (A), adult+XJB (AX), aged (O), and aged+XJB (OX). XJB was administered 3 times per week (3mg/kg body weight, IP) for four weeks. At the end of the treatment period, cardiac function was continuously monitored in excised hearts using the Langendorff technique for 30 min, followed by 20 min of global ischemia, and 60-min reperfusion. XJB improved post-ischemic recovery of aged hearts, as evidenced by greater left ventricular developed-pressures and rate-pressure products than the untreated, aged-matched group. The state 3 respiration rates at complexes I, II and IV of mitochondria isolated from XJB-treated aged hearts were 57% (P<0.05), 25% (P<0.05) and 28% (P<0.05), respectively, higher than controls. Ca(2+)-induced swelling, an indicator of permeability transition pore opening, was reduced in the mitochondria of XJB-treated aged rats. In addition, XJB significantly attenuated the H2O2-induced depolarization of the mitochondrial inner membrane as well as the total and mitochondrial ROS levels in cultured cardiomyocytes. This study underlines the importance of mitochondrial ROS in aging-induced cardiac dysfunction and suggests that targeting mitochondrial ROS may be an effective therapeutic approach to protect the aged heart against IR injury.

  17. Time-based prospective memory functioning in mild cognitive impairment associated with Parkinson’s disease: relationship with autonomous management of daily living commitments

    PubMed Central

    Costa, Alberto; Zabberoni, Silvia; Peppe, Antonella; Serafini, Francesca; Scalici, Francesco; Caltagirone, Carlo; Carlesimo, Giovanni Augusto

    2015-01-01

    Objective: Prospective memory (PM), that is, the ability to keep in memory and carry out intentions in the future, is reported to be impaired in individuals with Parkinson’s disease (PD). PM failure may be also associated with reduced daily living functioning in these patients. Little is known, however, about the relationship between mild cognitive impairment (MCI) and time-based PM functioning in PD patients and the possible impact of PM deficits on patients’ autonomy in daily living. Here we aimed to investigate whether MCI associated with PD affects time-based PM. We also wished to determine whether PM impairment accounts for reduced autonomous management of medication in these patients. Method: The study included 48 PD patients with MCI, 33 PD patients without cognitive disorders (PDN) and 20 healthy controls. The time-based PM procedure required that subjects perform an action after a fixed time. The PM procedure was incorporated in the standard neuropsychological assessment. One score was computed for the ability to retrieve the intention (prospective component) and one for remembering the action to be executed (retrospective component). The Pill Questionnaire was administered to assess the ability to manage medication. Results: PD patients with MCI performed less accurately in the PM procedure than HC and tended to perform poorer than PDN. Moreover, in PD patients with MCI, accuracy on the prospective component of the PM task and performance on the Modified Card Sorting Test significantly predicted the ability to manage medication. Conclusions: Results document that reduced efficiency of time-based PM processes in PD is specifically related to the presence of MCI. The same data indicate that PM weakness may be associated with impaired daily living functioning and decreased autonomy. PMID:26106317

  18. Forebrain deletion of the vesicular acetylcholine transporter results in deficits in executive function, metabolic, and RNA splicing abnormalities in the prefrontal cortex.

    PubMed

    Kolisnyk, Benjamin; Al-Onaizi, Mohammed A; Hirata, Pedro H F; Guzman, Monica S; Nikolova, Simona; Barbash, Shahar; Soreq, Hermona; Bartha, Robert; Prado, Marco A M; Prado, Vania F

    2013-09-11

    One of the key brain regions in cognitive processing and executive function is the prefrontal cortex (PFC), which receives cholinergic input from basal forebrain cholinergic neurons. We evaluated the contribution of synaptically released acetylcholine (ACh) to executive function by genetically targeting the vesicular acetylcholine transporter (VAChT) in the mouse forebrain. Executive function was assessed using a pairwise visual discrimination paradigm and the 5-choice serial reaction time task (5-CSRT). In the pairwise test, VAChT-deficient mice were able to learn, but were impaired in reversal learning, suggesting that these mice present cognitive inflexibility. Interestingly, VAChT-targeted mice took longer to reach criteria in the 5-CSRT. Although their performance was indistinguishable from that of control mice during low attentional demand, increased attentional demand revealed striking deficits in VAChT-deleted mice. Galantamine, a cholinesterase inhibitor used in Alzheimer's disease, significantly improved the performance of control mice, but not of VAChT-deficient mice on the 5-CSRT. In vivo magnetic resonance spectroscopy showed altered levels of two neurochemical markers of neuronal function, taurine and lactate, suggesting altered PFC metabolism in VAChT-deficient mice. The PFC of these mice displayed a drastic reduction in the splicing factor heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2/B1), whose cholinergic-mediated reduction was previously demonstrated in Alzheimer's disease. Consequently, several key hnRNPA2/B1 target transcripts involved in neuronal function present changes in alternative splicing in VAChT-deficient mice, including pyruvate kinase M, a key enzyme involved in lactate metabolism. We propose that VAChT-targeted mice can be used to model and to dissect the neurochemical basis of executive abnormalities. PMID:24027290

  19. The Shark Strikes Twice: Hypervariable Loop 2 of Shark IgNAR Antibody Variable Domains and Its Potential to Function as an Autonomous Paratope.

    PubMed

    Zielonka, Stefan; Empting, Martin; Könning, Doreen; Grzeschik, Julius; Krah, Simon; Becker, Stefan; Dickgießer, Stephan; Kolmar, Harald

    2015-08-01

    In this present study, we engineered hypervariable loop 2 (HV2) of the IgNAR variable domain in a way that it solely facilitates antigen binding, potentially functioning as an autonomous paratope. For this, the surface-exposed loop corresponding to HV2 was diversified and antigen-specific variable domain of IgNAR antibody (vNAR) molecules were isolated by library screening using yeast surface display (YSD) as platform technology. An epithelial cell adhesion molecule (EpCAM)-specific vNAR was used as starting material, and nine residues in HV2 were randomized. Target-specific clones comprising a new HV2-mediated paratope were isolated against cluster of differentiation 3ε (CD3ε) and human Fcγ while retaining high affinity for EpCAM. Essentially, we demonstrate that a new paratope comprising moderate affinities against a given target molecule can be engineered into the vNAR scaffold that acts independent of the original antigen-binding site, composed of complementarity-determining region 3 (CDR3) and CDR1. PMID:26003538

  20. The Shark Strikes Twice: Hypervariable Loop 2 of Shark IgNAR Antibody Variable Domains and Its Potential to Function as an Autonomous Paratope.

    PubMed

    Zielonka, Stefan; Empting, Martin; Könning, Doreen; Grzeschik, Julius; Krah, Simon; Becker, Stefan; Dickgießer, Stephan; Kolmar, Harald

    2015-08-01

    In this present study, we engineered hypervariable loop 2 (HV2) of the IgNAR variable domain in a way that it solely facilitates antigen binding, potentially functioning as an autonomous paratope. For this, the surface-exposed loop corresponding to HV2 was diversified and antigen-specific variable domain of IgNAR antibody (vNAR) molecules were isolated by library screening using yeast surface display (YSD) as platform technology. An epithelial cell adhesion molecule (EpCAM)-specific vNAR was used as starting material, and nine residues in HV2 were randomized. Target-specific clones comprising a new HV2-mediated paratope were isolated against cluster of differentiation 3ε (CD3ε) and human Fcγ while retaining high affinity for EpCAM. Essentially, we demonstrate that a new paratope comprising moderate affinities against a given target molecule can be engineered into the vNAR scaffold that acts independent of the original antigen-binding site, composed of complementarity-determining region 3 (CDR3) and CDR1.

  1. Drug-like actions of autoantibodies against receptors of the autonomous nervous system and their impact on human heart function

    PubMed Central

    Herda, LR; Felix, SB; Boege, F

    2012-01-01

    Antibodies against cholinergic and adrenergic receptors (adrenoceptors) are frequent in serum of patients with chronic heart failure. Their prevalence is associated with Chagas' disease, idiopathic dilated cardiomyopathy (DCM), and ischaemic heart disease. Among the epitopes targeted are first and second extracellular loops of the β-adrenergic (β-adrenoceptor) and M2 muscarinic receptor. β1-adrenoceptor autoantibodies affect radioligand binding and cardiomyocyte function similar to agonists. Corresponding rodent immunizations induce symptoms compatible with chronic heart failure that are reversible upon removal of the antibodies, transferable via the serum and abrogated by adrenergic antagonists. In DCM patients, prevalence and stimulatory efficacy of β1-adrenoceptor autoantibodies are correlated to the decline in cardiac function, ventricular arrhythmia and higher incidence of cardiac death. In conclusion, such autoantibodies seem to cause or promote chronic human left ventricular dysfunction by acting on their receptor targets in a drug-like fashion. However, the pharmacology of this interaction is poorly understood. It is unclear how the autoantibodies trigger changes in receptor activity and second messenger coupling and how that is related to the pathogenesis and severity of the associated diseases. Here, we summarize the available evidence regarding these issues and discuss these findings in the light of recent knowledge about the conformational activation of the human β2-adrenoceptor and the properties of bona fide cardiopathogenic autoantibodies derived from immune-adsorption therapy of DCM patients. These considerations might contribute to the conception of therapy regimen aimed at counteracting or neutralizing cardiopathogenic receptor autoantibodies. PMID:22220626

  2. The ICH S8 immunotoxicity guidance. Immune function assessment and toxicological pathology: autonomous or synergistic methods to predict immunotoxicity?

    PubMed

    Spanhaak, Steven

    2006-07-01

    The new ICH S8 guideline on Immunotoxicology Studies for Human Pharmaceuticals indicates that additional, functional testing of pharmaceuticals is not mandatory to screen for unintended immunotoxicity. The usefulness of conventional parameters like clinical pathology, organ weights and histopathology as measured in Standard Toxicity Studies (STS) to screen for potential unintended immunotoxicity was investigated in an ICH survey. Data of this survey appear to support the notion that properly evaluated STS endpoints would be sufficient for the detection of the majority of unintended immunosuppression by investigational pharmaceutical compounds. Thus the ICH S8 guideline was based on a cause for concern approach using a weight of evidence review of various factors like: findings from STS, pharmacological properties of the drug, intended patient population, structural similarities to known immunomodulators, drug disposition and/or clinical information. Overall the S8 guideline allows for more flexible approaches, and requires a weight of evidence review for which there is no given set of rules. For a proper use this asks for a sensible, realistic and above all a responsible approach both from Industry and Regulators. Some examples regarding the use of clinical pathology parameters like immunoglobulin levels and lymphocyte phenotyping have been included to illustrate this. In conclusion, to detect and evaluate potential immunotoxic effects of human pharmaceuticals the ICH S8 guideline allows for a more flexible, scientifically sound approach. For a proper evaluation of potential immunotoxic effects integration of data from standard toxicological parameters like clinical pathology, histopathology and functional assays are important.

  3. Discerning non-autonomous dynamics

    NASA Astrophysics Data System (ADS)

    Clemson, Philip T.; Stefanovska, Aneta

    2014-09-01

    Structure and function go hand in hand. However, while a complex structure can be relatively safely broken down into the minutest parts, and technology is now delving into nanoscales, the function of complex systems requires a completely different approach. Here the complexity clearly arises from nonlinear interactions, which prevents us from obtaining a realistic description of a system by dissecting it into its structural component parts. At best, the result of such investigations does not substantially add to our understanding or at worst it can even be misleading. Not surprisingly, the dynamics of complex systems, facilitated by increasing computational efficiency, is now readily tackled in the case of measured time series. Moreover, time series can now be collected in practically every branch of science and in any structural scale-from protein dynamics in a living cell to data collected in astrophysics or even via social networks. In searching for deterministic patterns in such data we are limited by the fact that no complex system in the real world is autonomous. Hence, as an alternative to the stochastic approach that is predominantly applied to data from inherently non-autonomous complex systems, theory and methods specifically tailored to non-autonomous systems are needed. Indeed, in the last decade we have faced a huge advance in mathematical methods, including the introduction of pullback attractors, as well as time series methods that cope with the most important characteristic of non-autonomous systems-their time-dependent behaviour. Here we review current methods for the analysis of non-autonomous dynamics including those for extracting properties of interactions and the direction of couplings. We illustrate each method by applying it to three sets of systems typical for chaotic, stochastic and non-autonomous behaviour. For the chaotic class we select the Lorenz system, for the stochastic the noise-forced Duffing system and for the non-autonomous the

  4. Autonomic contributions to empathy: evidence from patients with primary autonomic failure.

    PubMed

    Chauhan, Bina; Mathias, Christopher J; Critchley, Hugo D

    2008-06-01

    Empathy for the emotions of others may require simulatory engagement of corresponding autonomic arousal states. We tested the hypothesis that disruption of autonomic control impairs the ability to empathize emotionally with others. Fifteen patients with primary autonomic failure showed attenuated scores on the Mehrabian Balanced Emotional Empathy Scale (BEES), compared to both younger and older controls. This effect was not accounted for by age, gender, mood state or functional disability. These early observations provide preliminary evidence for a direct contribution of autonomic responsivity to the 'higher-order' social cognitive process of empathy, and may inform the dynamics of supportive care.

  5. Cognitive load and autonomic response patterns under negative priming demand in depersonalization-derealization disorder.

    PubMed

    Lemche, Erwin; Sierra-Siegert, Mauricio; David, Anthony S; Phillips, Mary L; Gasston, David; Williams, Steven C R; Giampietro, Vincent P

    2016-04-01

    Previous studies have yielded evidence for cognitive processing abnormalities and alterations of autonomic functioning in depersonalization-derealization disorder (DPRD). However, multimodal neuroimaging and psychophysiology studies have not yet been conducted to test for functional and effective connectivity under cognitive stress in patients with DPRD. DPRD and non-referred control subjects underwent a combined Stroop/negative priming task, and the neural correlates of Stroop interference effect, negative priming effect, error rates, cognitive load span and average amplitude of skin conductance responses were ascertained for both groups. Evoked haemodynamic responses for basic Stroop/negative priming activations were compared. For basic Stroop to neutral contrast, patients with DPRD differed in the location (inferior vs. superior lobule) of the parietal region involved, but showed similar activations in the left frontal region. In addition, patients with DPRD also co-activated the dorsomedial prefrontal cortex (BA9) and posterior cingulate cortex (BA31), which were also found to be the main between-group difference regions. These regions furthermore showed connectivity with frequency of depersonalization states. Evoked haemodynamic responses drawn from regions of interest indicated significant between-group differences in 30-40% of time points. Brain-behaviour correlations differed mainly in laterality, yet only slightly in regions. A reversal of autonomic patterning became evident in patients with DPRD for cognitive load spans, indicating less effective arousal suppression under cognitive stress - patients with DPRD showed positive associations of cognitive load with autonomic responses, whereas controls exhibit respect