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Purpose: Cerebral blood flow (CBF) tracks physiological effects of ictal or interictal epileptic discharges (IEDs) and neurostimulation. This study compared CBF changes between high-frequency (HF; 300 Hz) microburst, and standard, low-frequency (LF; 30 Hz) vagal nerve stimulation (VNS) Therapy in 2 baboons with genetic generalized epilepsy (GGE), including one with photosensitivity., Methods: The baboons were selected based on video recordings and scalp EEG studies. They were both implanted with Sentiva™ 1000 devices capable of stimulating at standard and microburst frequencies. Nine H 2 15 O (10-20 mCi) positron emission tomographic (PET) scans were performed each session (two PET sessions acquired for each animal). The baboons were sedated with ketamine, paralyzed, and monitored with scalp EEG. CBF changes were compared between the two modes of stimulation and resting scans in the first study, while in the second, VNS Therapy trials were combined with intermittent light stimulation (ILS) at 25 Hz and compared to CBF changes induced by ILS alone., Results: ILS-associated IED rates were slightly reduced by HF- and LF-VNS Therapies in B1, while spontaneous IEDs were completely suppressed by HF-VNS Therapy in B2. Regional CBF changes were consistent between the two modes of therapy in each baboon, in particular with respect to the activation of the superior colliculus and cerebellum. Neither VNS mode suppressed the photoepileptic response in B1. In B2, IED suppression was associated with bilateral deactivations of the frontal and temporal cortices, cingulate and anterior striatum, as well as bilateral cerebellar activations., Conclusions: This pilot study reveals similar activation/deactivation patterns between LF- and HF-VNS Therapies, but the most pronounced CBF differences between the two baboons and the two modes of stimulation may have been driven by the suppression of the epileptic network by HF-VNS Therapy in B2. Some therapeutic targets appear to be subcortical, including the putamen, superior colliculus, brainstem nuclei, as well as the cerebellum, all of which modulate corticothalamic networks, which is particularly reflected by CBF changes associated with HF-VNS Therapy. These findings need to be replicated in larger samples and correlated with long-term clinical outcomes., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: To identify candidate tear fluid biomarkers in patients with unilateral acute anterior uveitis (AAU) that can aid in the differentiation between these patients and patients with bacterial keratitis or healthy controls., Methods: Thirteen patients (40.1 ± 16.2 years of age) with unilateral AAU, seven patients with unilateral bacterial keratitis (40.2 ± 15.3 years of age), and 14 healthy subjects (41.1 ± 11.6 years of age) were included. The tear proteome of affected eyes was compared with that of the unaffected eye or healthy controls. Proteins were identified by liquid chromatography tandem mass spectrometry and enzyme-linked immunosorbent assay., Results: Relative protein ratios were detected and calculated for 272 unique proteins. Compared with healthy controls and the unaffected eye, the top upregulated proteins in AAU eyes were submaxillary gland androgen regulated protein 3B (SMR3B) and SMR3A. Similarly, the top upregulated proteins in bacterial keratitis were S100 calcium-binding protein A9 and orosomucoid 2. The acute phase response protein Serpin Family A Member 3 (SERPINA3) was increased in the healthy eye of AAU patients (P = 0.019) compared with healthy controls. Laser flare measurements in affected eyes of AAU patients showed positive logarithmic correlation with SERPINA3 in tear samples of the unaffected eye (P = 0.022). The use of SERPINA3 as a tear biomarker yielded a sensitivity of 85% and a specificity of 71% in detecting patients with AAU in the study population., Conclusions: The acute phase response protein SERPINA3 was increased in tear samples of unaffected eyes of patients with unilateral AAU compared with healthy controls. This study highlights SERPINA3 as a potential biomarker for AAU. Future research should explore the dynamic properties of SERPINA3 in the tear fluid of active and quiescent uveitis eyes.

The epileptic baboon provides a natural model of idiopathic generalized epilepsy and sudden unexpected death in epilepsy (SUDEP). This retrospective, case-controlled study aims to evaluate cardiac biomarkers of epilepsy, specifically QT-interval prolongation and heart rate variability (HRV), in pedigreed, captive baboons undergoing scalp electroencephalography (EEG). We retrospectively identified 21 epileptic (nine females, mean age = 11.4 ± 5.4 years) and 19 asymptomatic control (12 females, mean age = 10.5 ± 6.3 years) baboons, who had undergone scalp EEG studies with an artifact-free, 10-beat electrocardiogram sample. All baboons were sedated with subanesthetic doses of ketamine prior to electrode placement. PR, QT, and RR intervals were measured, and Fridericia-corrected QT duration (QTcF) and root mean square of successive differences between RR intervals (RMSSD; representative of HRV) values were compared between the groups. The epilepsy group had significantly prolonged QT and QTcF intervals (P = .005) compared to controls. RMSSD values were nonsignificantly decreased in epileptic baboons compared to the control group. This study demonstrates cardiac repolarization anomalies and reduction of HRV in epileptic baboons, providing new cardiac biomarkers in pedigreed baboons and potential risk factors for SUDEP., (Wiley Periodicals, Inc. © 2019 International League Against Epilepsy.)

Background: Use of and acute poisoning by substances of abuse represent a major health problem and are often linked to social destitution. We describe associations between place of residence, living conditions and the incidence of poisoning by substances of abuse in Oslo., Material and Method: All patients who were 12 years of age or older and resident in Oslo and who were treated for acute poisoning by substances of abuse at the Oslo Accident and Emergency Outpatient Clinic (OAEOC) were included prospectively for a continuous period of one year, from October 2011 to September 2012. The 15 districts of Oslo were categorised into three groups of living conditions, from the best (I) to the poorest (III) living conditions, based on the City of Oslo's living conditions index. Homeless people were grouped separately. The incidence of poisoning by substances of abuse treated in the OAEOC was estimated., Results: Of a total of 1,560 poisonings by substances of abuse, 1,094 cases (70%) affected men. The median age was 41 years. The most frequent toxic agents were ethanol, with 915 cases (59%), and heroin, with 249 cases (16%). The incidence of poisoning by substances of abuse treated in the OAEOC per year per 1,000 inhabitants amounted to 1.75 in living conditions group I, to 2.76 in living conditions group II and 3.41 in living conditions group III. Living conditions group III had a significantly higher incidence than living conditions group II (p < 0.001), and living conditions group II had a significantly higher incidence than living conditions group I (p < 0.001)., Interpretation: The incidence of acute poisoning by substances of abuse was higher, the poorer the living conditions in the district.

Background/study Context: Psychotropic drug treatment has been associated with increased risk for falls and hip fractures in elderly patients. The authors examined the association between drug treatment and hip fractures resulting from falls in elderly hospitalized patients, focusing on the medications' anticholinergic properties., Methods: This retrospective case-control study was conducted in an acute geriatric ward in a general medical center. Medical records, including demographic, clinical, biochemical, and pharmacological variables, of elderly patients with hip fractures from falls (N = 185), admitted during a 2-year period, were reviewed and compared with a control group (N = 187) of patients matched for age and gender and without hip fractures., Results: The usage rates of antipsychotics, antidepressants, mood stabilizers, and various nonpsychiatric medications were similar in the two groups, except for hypnotics-anxiolytics (higher rates in hip-fracture patients). The Cumulative Illness Rating Scale for Geriatrics (CIRS-G) and diastolic blood pressure constituted very modest predictors of falls (R(2) = .038, p = .004). There were no significant differences in the anticholinergic burden values, clinical dementia ratings, and comorbidity burden between the two groups., Conclusion: The rate of psychotropic drug use in general and their anticholinergic burden are similar in acutely admitted elderly patients with or without hip fractures. However, higher usage rate of anxiolytics found in the patients with hip fractures may indicate that this is a risk factor for hip fractures related to falls in elderly patients living in the community.

A nondipping BP pattern has been shown to be predictive of end-organ damage, cardiovascular events, and mortality. The mechanisms of blunted nocturnal BP fall are multifactorial. We assessed whether total corrected serum calcium and ionic calcium (iCa) are associated with a blunted nocturnal BP fall in both treated and untreated hypertensive patients with stages 1-3 of the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF KDOQI). Clinical data and 24-hour ambulatory blood pressure monitoring were obtained in a cohort of 231 essential hypertensive patients. Among the entire cohort, 107 were nondippers and 124 were dippers. Only in nondippers, we found significant correlations between iCa and 24-hour systolic blood pressure (SBP; r = 0.21, P < .03), diurnal SBP (r = 0.21, P < .03), and 24-hour pulse pressure (PP; r = 0.23, P < .02). The ambulatory arterial stiffness index (AASI) was significantly related with 24-hour PP in both dippers and nondippers after adjusting for age. Both AASI and 24-hour PP were higher in nondippers than in dippers. In addition, in nondippers, the prevalence of estimated glomerular filtration rate (eGFR) < 60 mL/minute/1.73 m2 was higher than in dippers (50% vs. 33.7%, P < .02). Logistic regression showed that patients with eGFR ≥ 60 mL/minute/1.73 m2 had lower risk of nondipper status than patients with eGFR < 60 mL/minute/1.73 m2 (odds ratio = 2.445; 95% confidence interval = 1.398-4.277, P < .002). In conclusion, serum iCa could participate in the pathogenesis of nondipping pattern. Increased large artery stiffness may be a mechanism of the deleterious influence of nondipping on cardiovascular outcome. Hypertensive subjects with stage 3 of NKF KDOQI had a greater loss of circadian BP rhythm than those in stages 1 and 2.

Our aims were to evaluate the prevalence and outcome of hypertension in patients with primary hyperparathyroidism (PHPT), previously and after follow-up of parathyroidectomy. A group of 46 consecutive patients with sporadic PHPT due to adenoma undergoing surgery were followed an average of 3.5 years (range 36 to 53 months). In 16 nonselected, consecutive parathyroidectomized patients, with normalized biochemical measurements, circadian rhythm of blood pressure was evaluated with ambulatory blood pressure monitoring (ABPM). Prevalence of hypertension in PHPT was 54.35%, and there was no significant association of PTH, total and ionic calcium levels with SBP and DBP. During follow-up, none of the patients with presurgical hypertension became normotensive and five of the normotensive patients developed clinical hypertension. In ABPM, 6/11 hypertensive and 3/5 normotensive subjects showed nondipper behavior. Serum total calcium was significantly related to night-time systolic blood pressure (SBP) (r = 0.620, P < 0.02), and night-time diastolic blood pressure (DBP) (r = 0.758, P < 0.002). In dippers, creatinine clearance was significantly higher (91.3 +/- 18.5 vs. 64.3 +/- 11.5 ml/min, P < 0.01), while serum total calcium was lower (2.42 +/- 0.13 vs. 2.23 +/- 0.17 mmol/L, P < 0.04) than in nondippers. In conclusion, our results suggest that parathyroidectomy has little effect on hypertension prevalence. Renal impairment, a condition that did not improve after parathyroidectomy, may be a causal factor of hypertension in PHPT. Also, the high prevalence of nondipper behavior in hypertensive and normotensive subjects after parathyroidectomy, suggests that target organ risk persists. We hypothesized that slight elevations of serum total calcium even in the normal range could be involved in the alteration of the circadian rhythm of blood pressure.

Obesity poses a serious threat for health, being a risk factor for development of heart diseases, diabetes type II, tumors, and reproductive function failure. The aim of this study is to investigate the effect of orlistat (xenical) on the character of menstrual cycle and some metabolic indicators in women with obesity. 17 patients of reproductive age with I-III degree of obesity were investigated. The visceral type of obesity and disorders of menstrual cycle were observed in all patients: oligomenorrhea was observed in 9 (52.9%), amenorrhea in 4 (23.5%)and metrorrhagia in 4 (23.5 %) patients. All the patients received orlistat (xenical) 120 mg 3 times per day during 6 months. Orlistat (xenical) therapy results in significant reduction of body weight (12.3%), body mass index (13.3%), improvement of lipid and carbohydrates metabolisms. Normalization of hormonal levels was registered. As a result of all this the restoration of menstrual cycle and ovulation is registered. Orlistat (xenical) is effective in the treatment of women with obesity and menstrual cycle disorders.

A correlation between the rate of ATP synthesis by F0F1 ATP-synthase and formate oxidation by formate hydrogen lyase (FHL) has been established in inverted membrane vesicles of Escherichia coli JW 136 mutant with double deletions (delta hya/ delta hyb) of hydrogenase 1 and 2 grown anaerobically on glucose in the absence of external electron acceptors (pH 6.5). ATP synthesis was suppressed by H+ -ATPase inhibitors N,N'-dicyclohexylcarbodiimide (DCCD) and sodium azide as well as by the protonophore carbonyl cyanide-m-chlorophenyhydrazone (CCCP). Copper ions inhibited formate-dependent hydrogenase and ATP-synthase activities but did not affect the ATPase activity of vesicles. The maximal rate of ATP synthesis (0.83 microM/min x mg protein) stimulated by K+ ions was determined when sodium formate, ADP and inorganic phosphate were applied simultaneously. The results confirm the assumption about the dual role of hydrogenase 3, formate hydrogen lyase subunit, which is able to couple the reduction of protons to H2 and their translocation through a membrane with chemiosmotic synthesis of ATP.

Background and Aim: To examine the relationship between 24-h ambulatory blood pressure monitoring (ABPM) and three commonest anthropometric measurements for obesity [body mass index (BMI), waist circumference (WC) and waist-hip ratio (WHR)] in patients with essential hypertension never treated or after a 3 week placebo period, living in Buenos Aires., Methods and Results: Cross-sectional survey among outpatients at the Hypertension Program of Buenos Aires University Hospital de Clinicas. Three-hundred seventy-seven essential hypertensives, aged 18-86 years, of either sex, were consecutively recruited. All subjects underwent 24 h ABPM performed with a blood pressure (BP) device. The prevalence of overweight-obesity was 56.76% in women and 75.86% in men. High WHR prevalence in non-obese women was 4.5% and 4.1% in non-obese men while high values of WC were observed in 3.0% of non-obese women and in 0% of non-obese men. The two-way ANCOVA showed that in women with high values of WHR, 24 h DBP was higher in those with BMI<25 than in those with BMI> or =25. Those females with a BMI> or =25 had a higher prevalence of top tertile values of PP (> or =68 mmHg) (P<0.05) than non-obese females. Only in women was mean pulse pressure (PP) significantly correlated with age (r=0.38; P<0.0001), WC (r=0.22; P<0.005), WHR (r=0.21, P<0.008), and BMI (r=0.20; P<0.01) while in men there was no significant correlation between variables. Logistic regression showed that the odds of morning blood pressure surge (MBPS) increased with age, central obesity (represented by high WHR and dipper status), while the odds of higher mean PP increased with age and high WHR., Conclusion: These results indicated a high prevalence of overweight-obesity (more than 56% of women and 75% of men) in our hospital-based sample of essential hypertension and that the WHR offers additional information beyond BMI and WC to predict the hypertension risk according to the ABPM.

A study was carried out within a 700-km river sector, including three types of ecosystems (a reservoir, a river and its estuary) to characterise the major features of zooplankton communities in the Seine Basin. In rivers, zooplankton biomass becomes significant only when the growth rate of the organisms is higher than the dilution rate (4-5th orders rivers, according to River Continuum Concept). Upstream, short residence times favour the development of small species (Rotifers) with low individual body weight and biomass. Conversely, larger species (microcrustaceans) develop more downstream, where increased residence time leads to autochthonous production (Riverine Productivity Model). Such a pattern is greatly modified by human impact. Zooplankton input from the Marne reservoir represents one type of disruption in the general upstream-downstream trend (according to the Serial Discontinuity Concept). This reservoir is a source of microcrustaceans; they rapidly disappear mainly through fish predation, and therefore have little impact on the river phytoplankton. Discontinuities, such as confluences, have a relatively small effect on the stock of zooplankton with regard to the water release from the reservoir, but they persist more downstream, because they have the same lotic origin. A few microhabitats with macrophytes play a small role for this canalised river, but they can modify locally the plankton community structure and composition. As a whole, the flux of zooplankton rises exponentially, whereas discharge increases linearly from upstream (4th order) to downstream (8th order). In the canalised sectors, Dreissena larvae build up an important biomass, adding to that of the zooplankton sensu stricto. Especially abundant in the downstream sector of the Marne and Seine Rivers, the larvae show a widespread colonisation of the benthic substrates by the adult Dreissena. One of the largest mussel colonies in the middle estuary can contribute to a rapid decrease of zooplankton. Estuary ecosystems form a transitional zone between freshwater and seawater, with zooplankton dynamics closely linked to the particular conditions on this part of the river system.

The aim of the study was to elucidate the role of hyperinsulinaemia/insulin resistance in hypertension of lean postmenopausal women. Twenty-four women with essential hypertension (systolic/diastolic > or =140/90 mm Hg) and a body mass index (BMI) less than 26 kg/m(2) not receiving antihypertensive treatment or who had been without treatment for a 4-week washout period, and 10 normotensive postmenopausal weight- and aged-matched controls were compared. Both groups were not receiving hormone replacement therapy. Hip and waist circumferences were measured and waist/hip ratios were calculated. Casual blood pressure was measured in triplicate. Neither the fasting plasma glucose nor serum insulin levels in hypertensive women and normotensives differed significantly. During 2 h oral glucose (75 g)-tolerance test the mean plasma glucose levels after 30 min (172.5 +/- 40.24 mg/dl vs. 143.67 +/- 20.16 mg/dl), 60 min (134.88 +/- 38.78 mg/dl vs. 112.33 +/- 5.44 mg/dl) and 120 min (116.08 +/- 26.65 mg/dl vs. 95.56 +/- 20.17 mg/dl) were significantly higher in hypertensives than that for normotensives (P < 0.05 for all three comparisons). The mean serum insulin levels of hypertensive women were significantly higher than that in normotensives after 15 min (92.04 +/- 59.90 microU/ml vs. 54.89 +/- 33.67 microU/ml) and 120 min (49.63 +/- 44.45 microU/ml vs. 19.22 +/- 24.10 microU/ml; P< 0.05 for both comparisons). The mean serum insulin: plasma glucose ratio for hypertensive women was significantly higher than that for normotensives after 15 min (0.596 +/- 0.46 vs. 0.359 +/- 0.20 microU/mg), 60 min (0.406 +/- 0.30 vs. 0.329 +/- 0.25 microU/mg) and 120 min (0.436 +/- 0.35 vs. 0.205 +/- 0.26 microU/mg) (P < 0.05 for all three comparisons). Significant correlations were observed between the daytime period and 24-h average ambulatory systolic blood pressure and the area under the serum insulin curve (r = 0.41 and 0.36, respectively). For non-dippers we found higher fasting insulinaemias but the AUC(insulin) did not differ. Plasma glucose levels did not differ either during fasting or during OGTT (AUC(glucose)). Insulinogenic index was higher in dippers than in non-dippers. We conclude that in lean, postmenopausal hypertensive women insulin resistance is increased compared with age- and weight-matched normotensive women. Also, hyperinsulinaemia correlates with ambulatory systolic blood pressure. Thus, insulin resistance may possibly be involved as a pathogenetic factor in lean, postmenopausal hypertensive women.

To determine the relationships between the circadian blood pressure profile and left ventricular mass, hormonal pattern and insulin sensitivity indices in patients with active acromegaly, ambulatory 24-h blood pressure monitoring (ABPM) was recorded in 25 subjects (47.0 +/- 15.1 years, range 23-72). Serum growth hormone (GH) and insulin-like growth factor-1, fasting and mean plasma glucose and insulin during oral glucose tolerance test (OGTT), insulinogenic index, the sum of the plasma insulin levels and the homeostasis model insulin resistance index (Homa's index) were determined. Left ventricular mass index (LVMI) was calculated from two-dimensional guided M-mode echocardiogram. The prevalence of hypertension was 56% (n = 14) and 40% (n = 10) according to sphygmomanometric measurements and ABPM, respectively. Non-dipping profile was observed in six of 10 hypertensives and in six of 15 normotensives. Serum growth hormone, fasting glucose, the area under the serum insulin curve and LVMI were higher for acromegalics with non-dipping profile than for dippers (all of them, P < 0.05). In non-dippers daytime heart rate was higher than night time (P < 0.001). In conclusion, the main observations in the present study suggested that both normotensive and hypertensive acromegalics had a highly prevalent non-dipping profile with a preserved circadian pattern of heart rate, that was associated with higher levels of serum GH. The disturbance in nocturnal blood fall in normotensives was associated with a decreased insulin sensitivity. The role of GH in blood pressure circadian rhythm regulation in essential hypertension deserves further studies.

Objective: To elucidate the role of hypertension as part of a state of insulin resistance., Methods: Thirty-one uncomplicated hypertensive men not receiving antihypertensive treatment or who had been without treatment for a 4-week washout period and 10 lean normotensive controls were compared. Hypertensive men were divided according to their body mass index into three groups. All subjects came to the clinic for measurements of height, weight, hip and waist circumferences, and sitting blood pressure, and to begin 24 h ambulatory blood pressure monitoring. Plasma glucose and insulin levels were measured during a 2 h oral glucose (75 g)-tolerance test. For the hypertensive population as a whole, behaviors of studied variables among dippers (n = 18) and nondippers (n = 13) were determined., Results: During oral glucose-tolerance testing blood glucose levels after 60 min and 120 min were significantly higher (P < 0.05) in members of the high body mass index group than they were in members of the low body mass index group. Insulin levels of members of the high and middle body mass index groups were higher than those of members of the low body mass index group after 60 min (P < 0.05 for both comparisons) and 120 min (P < 0.05 for both comparisons). The mean serum insulin level in members of the low body mass index group was significantly higher than that in normotensives after 30 min, 60 min and 120 min (P < 0.05 for all three comparisons). The mean serum insulin: plasma glucose ratio for men in the low BMI group was significantly higher than that for normotensives after 60 min and 120 min (P < 0.05 for both comparisons). Correlations of blood pressure and insulin levels were not significant. Levels of high-density lipoprotein cholesterol and triglycerides were lower in members of the group with high body mass index than they were in members of the group with low body mass index. Total cholesterol: high-density lipoprotein cholesterol ratio was higher for members of the high body mass index group than it was for members of the middle body mass index group. Weight, body mass index, casual systolic blood pressure, 24 h average systolic blood pressure and diastolic blood pressure, 0700-2300 h systolic blood pressure, and 24 h average heart rate-systolic blood pressure product of dippers were significantly lower than those of nondippers., Conclusions: These results suggest that hypertension and being overweight have additive effects increasing insulinemia and that being overweight is associated with a significantly lower nocturnal fall in blood pressure.