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• Implementation of IT2-FLCP-PID control scheme for mean arterial blood pressure regulation. • Automatic control of SNP drug administration in order to meet the required performance specifications. • The controller parameters and scaling gains are obtained with a recent meta-heuristic optimization technique CSA. • Comparison is done with T1-FLC-PID and conventional PID controllers. • Robustness testing is done for parameter variations and noise rejection. The main aim of this work is to present an optimal and robust controller design in order to improve the drug infusion to the automatic control of mean arterial blood pressure in conditions like critically-ill or post-operative or anaesthesia administration. The physiological systems also have uncertainty issues such as parameter variations with time or external disturbances and noise. Therefore, a controlled drug administration is necessary to regulate the mean arterial blood pressure of a person during surgery/observation. Over the years, the proportional-integral-derivative (PID) controller is the most commonly used controller in industries due to its easy structure and simplicity. However, this controller does not meet the desired performance with the complex and uncertain plants. Therefore, a robust controller is required to regulate the physiological variables that are uncertain in nature and can affect the human life. In this work, a hybrid control scheme consisting of an interval type-2-fuzzy logic controller which acts as pre-compensator to the traditional PID controller is presented, to regulate the mean arterial blood pressure of a patient by administering the drug sodium nitroprusside in a controlled manner. An effective and well-established nature-inspired optimization technique namely cuckoo search algorithm is employed for obtaining the optimal parameters for the presented scheme. Simulation results are presented to show the effectiveness and robustness of proposed interval type-2-fuzzy logic controller based PID controller scheme, for maintaining the mean arterial pressure to 100 mmHg within considerable limit through SNP infusion. The results are further compared with other two controllers namely type-1 fuzzy logic based PID and traditional PID controllers for the parameter variations and external noise. In this study, the proposed interval type-2-fuzzy logic controller pre-compensator based PID controller provides an effective control than traditional type-1 fuzzy logic based control scheme and PID controller in terms of overshoot, settling-time and error which are the prime performance objectives of the closed-loop controlled drug delivery of human blood pressure. The presented study provides a firm base for initial design considerations for development of a low-cost closed-loop drug delivery system for blood pressure regulation. [ABSTRACT FROM AUTHOR]

Lower body negative pressure (LBNP) has been employed in multiple countermeasure protocols against post spaceflight orthostatic hypotension. However, protocols utilizing oscillatory LBNP (oLBNP) have not been explored in this regard. oLBNP has shown promise in few studies to have good tolerance in conditions of hypovolemic stress and since the negative suction is only phasic, the extravascular fluid shifts associated with negative suction are also hypothesized to be less. Our study addressed the paucity of information on oLBNP by investigating the cardiovascular and neurohormonal effects of oLBNP of −15 and −45 mm Hg in 40 healthy adult males (mean age = 29.6 ± 4.7 years, BMI = 25.1 ± 3.6 kg/m2). After supine rest of 10 min (baseline), oLBNP was applied at −15 mm Hg and −45 mm Hg for 10 min each with a gap of 10 min. Blood sample for neurohormonal analysis was collected at the end of baseline and after each oLBNP exposure. Blood pressure, heart rate, respiratory rate and end tidal CO 2 (EtCO 2) were recorded for the entire duration. Serum angiotensin II (ATII), antidiuretic hormone (ADH) and atrial natriuretic peptide (ANP) were analyzed using ELISA. On comparison with the baseline [SBP: 114 ± 2.38, MBP: 75.8 ± 2.16 mm Hg] there was a significant fall in SBP on application of −15 mm Hg as well as −45 mm Hg oLBNP[-15 oLBNP: 107.4 ± 2.34 mm Hg; −45 oLBNP: 105.3 ± 2.28 mm Hg], while there was no significant difference observed in the DBP. There was a significant increase in the heart rate at both −15 [77.29(72.75–85.65) BPM] and −45 mm Hg [81.29 (73.93–86.09) BPM] oLBNP as compared to the baseline [70.41(64.32–79.80) BPM]. No significant difference in the serum ATII, ADH and ANP after 10 min of application of −15 or −45 mm Hg oLBNP as compared to baseline was observed. In conclusion, oLBNP induced legward pooling of blood causes a fall in the blood pressure which initiates the neural reflex mechanisms, most important being the baroreflex and the cardiopulmonary reflex. However, since there was no significant difference in the serum ATII, ADH and ANP from baseline, this suggests that 10 min oLBNP up to −45 mm Hg results in recruitment of cardiovascular neural reflex response but it does not evoke neurohormonal responses which mediate long term volume changes. • -45 mm Hg Oscillatory LBNP (oLBNP) evoked blood pressure drop & elevation in heart rate. • However, the serum ATII, ADH and ANP remain unchanged after the same protocol. • oLBNP causes recruitment of cardiovascular reflexes but not hormonal response. [ABSTRACT FROM AUTHOR]

Low-flow-mediated constriction (LFMC) has been used to assess resting endothelial function in peripheral conduit arteries. The literature describes discrepancies in the behaviour of radial versus brachial artery in response to low-flow state, the reasons for which were not addressed in a systematic and scientific way. Moreover, the influence of handedness on observed LFMC responses has not been investigated. The present study aimed at systematic measurement and comparison of the LFMC responses in radial and brachial arteries of both dominant and non-dominant arms of healthy human volunteers. We also investigated the physiological factors associated with differential LFMC response of radial versus brachial artery in the same group of subjects. Longitudinal B mode ultrasonographic cine loops of radial and brachial arteries were acquired at baseline and after producing distal circulatory arrest. Cine loops were screen grabbed and analyzed later using automated edge detection algorithms to measure end-diastolic diameters. Distal circulatory arrest was produced over the proximal forearm (for the brachial artery) and over the wrist (for the radial artery) at 250 mm Hg for 5 min after baseline measurements. Results suggested that arterial location (p = 0.0001) and baseline diameter (p < 0.0021) emerged as independent predictors of LFMC response. Differences in the LFMC responses are handedness independent and could be attributed to the arterial location along with the differences in their baseline diameters. [ABSTRACT FROM AUTHOR]

Dear Editor, Nonsegmental generalized vitiligo (NSGV) is the most common and progressive clinical form of vitiligo[1] and narrowband ultraviolet B (NB-UVB) is the preferred and most effective treatment modality in active NSGV (aNSGV).[2] The effect of NB-UVB treatment on microRNA (miRNA) expression and its association with clinical outcome in aNSGV is unknown. miRNA are noncoding oligonucleotides that are known to regulate various biological processes and are implicated in a variety of diseases.[3] Limited studies are available regarding the role of miRNA in vitiligo pathogenesis, but the precise mechanism of action is unknown.[4] This study aimed to investigate the expression of miRNA (peripheral blood, serum, lesional and nonlesional skin) and pigmentation-associated genes (lesional vs. nonlesional) in untreated aNSGV and NB-UVB-treated aNSGV (tNSGV). GLO:F03/01jul20:bjd18890-fig-0001.jpg PHOTO (COLOR): microRNA (miRNA) expression profile in peripheral blood mononuclear cells (PBMCs) of (a) active nonsegmental generalized vitiligo (aNSGV) (n = 26) and healthy controls (n = 20); (b) aNSGV(n = 26) and narrowband ultraviolet-B-treated aNSGV (tNSGV) (n = 21); (c) lesional and nonlesional skin in aNSGV (n = 26) and tNSGV (n = 21); and (d) miRNA expression levels of skin pigmentation-associated genes in lesional and nonlesional skin in aNSGV (n = 8), tNSGV (n = 8) and healthy controls (n = 6). The present study indicated that NB-UVB-induced repigmentation may occur by modulation of miRNA expression and enhanced expression of pigmentation-associated genes at a molecular level in aNSGV. [Extracted from the article]

Background: Autonomic dysfunction is common in children with Rett syndrome. They usually manifest with agitation, persistent screaming, constipation, gastroesophageal reflux, aerophagia, hyperventilation, and breath-holding episodes. Cardiovascular autonomic dysfunction may result in fatal a arrhythmia. Many of these events are mistaken for seizures and treated with antiepileptics.Methods: The present study was conducted in a tertiary care teaching hospital in north India for more than a six month period. MeCP2 mutation positive, 24 cases with Rett syndrome and 24 age-matched healthy girls were evaluated for cardiovascular autonomic dysfunction (heart rate variability, head-up tilt test, and cold pressor test).Results: The mean age was 9.06 years (±3.4) and 9.75 years (±3.13) for patients and control subjects, respectively. The heart rate variability contributed independently by parasympathetic and sympathetic nervous system was significantly reduced in cases compared with control subjects (P = 0.033 and P = 0.001, respectively). There was significant sympathovagal imbalance with sympathetic overactivity in cases compared with control subjects (P = 0.001). The mean longest QTc interval was significantly prolonged in cases compared with control subjects (P = 0.001). Cold pressor test and head-up tilt test could be done in 16 Rett syndrome patients (because of poor cooperation) and in all 24 control subjects. The change in blood pressure during cold pressor test and head-up tilt test was not significantly different in cases and control subjects.Conclusions: Children with Rett syndrome exhibited significant cardiovascular autonomic dysfunction in the form of sympathetic overactivity, parasympathetic underactivity, and sympathovagal imbalance. These findings have potentially important therapeutic- and outcome-related implications. [ABSTRACT FROM AUTHOR]

Summary: Purpose: Autonomic symptoms frequently occur during seizures. There are reports that the adult group of intractable epilepsy patients have different autonomic profile than the well controlled epilepsy, but there is no clear evidence in the children epilepsy group, therefore, we planned to study the autonomic profile in well controlled and refractory epilepsy children by recording the short-term heart rate variability (HRV). Methods: This cross sectional study was conducted in a tertiary care hospital between July 2008 and June 2009. Children with mean age of 9.1±3.3 years were enrolled. Three groups of children, 40 in each group namely, refractory epilepsy, well controlled epilepsy and normal control children were included. Children who had chronic systemic diseases and were on drugs that cause autonomic dysfunction were excluded. All children underwent short term heart rate variability testing. Data was analyzed in time domain and frequency domain. Results: pNN50 was significantly lower in children with refractory epilepsy than the well control as well as healthy controls. Rest of the parameters of time domain and frequency domain were comparable between the groups. Conclusions: Our study showed that parasympathetic activity is lower in refractory epilepsy children. However, autonomic tone is comparable in well control versus healthy controls. [Copyright &y& Elsevier]

Approximate entropy (ApEn) and sample entropy (SampEn) are the promising techniques for extracting complex characteristics of cardiovascular variability. Ectopic beats, originating from other than the normal site, are the artefacts contributing a serious limitation to heart rate variability (HRV) analysis. The approaches like deletion and interpolation are currently in use to eliminate the bias produced by ectopic beats. In this study, normal R–R interval time series of 10 healthy and 10 acute myocardial infarction (AMI) patients were analysed by inserting artificial ectopic beats. Then the effects of ectopic beats editing by deletion, degree-zero and degree-one interpolation on ApEn and SampEn have been assessed. Ectopic beats addition (even 2%) led to reduced complexity, resulting in decreased ApEn and SampEn of both healthy and AMI patient data. This reduction has been found to be dependent on level of ectopic beats. Editing of ectopic beats by interpolation degree-one method is found to be superior to other methods. [ABSTRACT FROM PUBLISHER]

Abstract: Cushing''s syndrome is associated with increased cardiovascular morbidity and mortality. It''s also associated with other cardiac risk factors like hypertension, diabetes mellitus and obesity. Cardiovascular autonomic function impairment could predict cardiovascular morbidity and mortality. Twenty five patients with Cushing''s syndrome without diabetes and twenty five age matched healthy controls underwent a battery of cardiovascular autonomic function tests including deep breath test, Valsalva test, hand grip test, cold pressor test and response to standing from lying position. The rise in diastolic blood pressure on hand grip test and diastolic BP response to cold pressor test in Cushing''s patients were significantly less compared to healthy controls (9.83±3.90 vs 20.64±9.55, p <0.001 and 10.09±4.07 vs 15.33±6.26, p <0.01 respectively). The E:I ratio on deep breathing test was also less in the patients in comparison to controls (1.36±0.21 vs 1.53±0.19, p <0.01). Seven patients underwent the same battery of tests 6months after a curative surgery showing a trend towards normalization with significant improvement in expiratory to inspiratory ratio and sinus arrhythmia delta heart rate. To conclude, this study showed that chronic endogenous hypercortisolism in Cushing''s is associated with an impaired sympathetic cardiovascular autonomic functioning. After a curative surgery, some of the parameters tend to improve. [Copyright &y& Elsevier]

Summary: Background: Epilepsy is associated with imbalance of sympathetic and parasympathetic activity which may lead to sudden unexplained death in epilepsy (SUDEP). Well-controlled (WcE) and intractable epilepsy (IE) subjects may present different autonomic profiles, which can be helpful in explaining the predisposition of the latter to SUDEP. Purpose: To compare inter-ictal cardiovascular autonomic function in subjects with partial WcE and IE. Methods: Thirty WcE and 31 IE subjects underwent a battery of autonomic function tests: deep breathing, Valsalva maneuver, isometric exercise, cold pressor and tilt-table. Autonomic tone was assessed by heart rate variability (HRV). Their autonomic severity score and anxiety status was also assessed. Results: IE subjects had elevated low frequency component (52.0 vs. 37.6, p =0.047) and decremented high frequency component (114 vs. 397, p =0.013) of HRV and higher diastolic BP (75.62±9.77 vs. 68.64±0.43, p =0.036). In deep breathing test, they had lesser HR changes (20±10.18 vs. 29.68±11.23, p =0.007) and lower E:I (1.29±0.16 vs. 1.43±0.21, p =0.008). IE subjects had higher dysautonomia (chi square 165.0, p <0.0001). Conclusions: We observed a higher vasomotor tone, higher sympathetic tone, lower parasympathetic tone, lower parasympathetic reactivity and more severe dysautonomia in the IE subjects. Refractoriness may lead to an alteration in cardiovascular autonomic regulation, which might be a predisposing factor for SUDEP. [Copyright &y& Elsevier]

Abstract: Cardiac autonomic functions were assessed in 145 consecutive recently detected type 2 diabetics. Ninety-nine healthy persons served as controls. Criteria for normalcy were, heart rate variation during deep breathing ≥15beats/min, deep breathing expiratory to inspiratory R–R ratio ≥1.21, Valsalva ratio ≥1.21, sustained handgrip test ≥16mm of mercury, cold pressor test ≥10, BP response to standing ≤10mm of mercury and 30:15 R–R ratio on standing ≥1.04. An abnormal test was defined as the above parameters being <10beats/min, <1.21, <1.21, ≤10mm of mercury, <10, ≥30mm of mercury and ≤1.0, respectively. A borderline test was defined as, heart rate variation during deep breathing 11–14, sustained handgrip test 11–15mm of mercury, BP response to standing 11–29mm of mercury and 30:15 R–R ratio on standing 1.01–1.03. Parasympathetic dysfunction was found in 44.2% and sympathetic dysfunction in 51.9% diabetics. Among healthy controls, these figures were 11.9% and 22.1%, respectively. Cardiac autonomic function was normal in 7.8% patients and 32.5% healthy controls. [Copyright &y& Elsevier]

Background: Heart rate variability (HRV) is a marker of cardiac autonomic tone. Depressed HRV has been reported in patients with AIDS. We conducted this study to find out if HRV is depressed in human immunodeficiency virus (HIV)-positive individuals without AIDS. Methods: We studied prospectively HRV by spectral analysis of short-term electrocardiography (ECG) monitoring in 21 HIV-positives (33±11 years) and in 18 healthy volunteers (31±9 years). None of the HIV-positives had any clinical evidence of autonomic or cardiac dysfunction. Echocardiography was also performed in HIV-seropositives to rule out left ventricular (LV) systolic dysfunction. All these individuals did not have any evidence of AIDS. Results: Mean CD4+ lymphocyte count was 426±166/mm3. The ejection fraction (EF%) of HIV patients was 62.4±6.4.The total power of HRV was reduced significantly in HIV-positive individuals (p<0.00001). All the components of HRV were reduced. Conclusions: HRV is reduced in HIV-seropositive individuals in early stages of infection as well without any clinical evidence of autonomic dysfunction. This may serve as an early marker of future global sympatho-vagal imbalance. [Copyright &y& Elsevier]

Introduction/Background Fibromyalgia (FM) is a multi-symptomatic disorder with a varying degree of widespread pain in the body. With emerging evidences pathophysiological concept shifted from peripheral damage or inflammation to central neural mechanism. Fibromyalgia is characterised by dysfunction in central pain processing, “central sensitivity”. In this cross-sectional study central sensitization was recorded in patients with fibromyalgia by observing cortical oxygenation in prefrontal cortex using Functional Near Infrared Spectroscopy (fNIRS). Material and method fNIRS 300B (BIOPAC), a wearable continuous fNIRS system with 4 optode and 16 detectors was used to assess changes in oxy-haemoglobin concentration (μM) from Brodmann areas 9, 10, 45 and 46. Number of activation (max and 60% max signals) was compared in time series of Oxygenated Haemoglobin level with Rt foot immersed in ice cold water. For comparison of categorical variable, sex Chi 2 test was used. For non-parametric data, i.e. age and fNIRS data Mann–Whitney U test was used. Both of the test was done in SPSS Statistics 23 by IBM, Chicago, IL with a confidence interval of 95% and a significance level lower than 5%. Results Fifty FM patients diagnosed according to ACR 2010 fibromyalgia criteria and equal number of age and sex matched controls were enrolled in the study. There was increased oxygenation in FM compared to control in prefrontal cortex. Conclusion This increased oxygenation in prefrontal cortex in FM group objectively demonstrates alteration in central activity in FM group. Changes in central activity along with pain hypersensitivity in FM points towards central sensitisation. Lack of 3D digitiser restrict us to comment on localisation of activation. fNIRS can be used as tool to evaluate central sensitization. [ABSTRACT FROM AUTHOR]

BACKGROUND: Faculty development lays the foundation for the quality enhancement in medical education. However, programs are not always based on the needs of the participants, and there is dearth of information on methods to derive faculty's needs. The Medical Education Unit at the University of Dammam, Saudi Arabia, carried out an innovative method to identify and prioritize faculty needs in order to plan future activities. METHODS: A questionnaire was designed, pilot-tested and administered to all faculty members (N=200). The respondents rated the perceived importance (high, moderate, low) and their performance (good, average, poor) on twelve competencies described in the literature. The ratings of perceived importance - high/moderate, and self-rated performance- average/poor, were summed up to determine priority rankings for continuing education. The respondents' rating of various continuing education activities, their willingness to participate and commit time, and their suggestions for strengthening faculty development were also analyzed. RESULTS: All the twelve competencies were perceived as 'highly important' by the subjects. They felt most confident in teaching in large and small groups, attitudes and ethical values, and decision making skills. The competencies prioritized as 'gaps' were knowing how to develop learning resources, plan curriculum, evaluate courses and conduct research. The prioritized activities were specialized courses, orientation workshops for the new faculty, and training in educational research skills. This implied a multi-phased approach to faculty development. A majority (62.4%) were willing to devote 2.2 hours per week to faculty development. Respondents suggested initiatives that should be undertaken by the Medical Education Unit and the broader institution. CONCLUSION: We demonstrated a participatory approach to needs assessment by identifying the gaps between 'perceived importance' and 'self-rated performance', as criteria for determining priorities. Findings also demonstrated the need for adopting a comprehensive approach to faculty development in which both departmental and organizational initiatives are required. Our findings are applicable to the Gulf Region context and our methodology can be applied anywhere. [ABSTRACT FROM AUTHOR]