Treatment of hypertension by increasing impaired endothelial TRPV4-KCa2.3 interaction.

PubMed

He, Dongxu; Pan, Qiongxi; Chen, Zhen; Sun, Chunyuan; Zhang, Peng; Mao, Aiqin; Zhu, Yaodan; Li, Hongjuan; Lu, Chunxiao; Xie, Mingxu; Zhou, Yin; Shen, Daoming; Tang, Chunlei; Yang, Zhenyu; Jin, Jian; Yao, Xiaoqiang; Nilius, Bernd; Ma, Xin

2017-11-01

The currently available antihypertensive agents have undesirable adverse effects due to systemically altering target activity including receptors, channels, and enzymes. These effects, such as loss of potassium ions induced by diuretics, bronchospasm by beta-blockers, constipation by Ca 2+ channel blockers, and dry cough by ACEI, lead to non-compliance with therapies (Moser, 1990). Here, based on new hypertension mechanisms, we explored a new antihypertensive approach. We report that transient receptor potential vanilloid 4 (TRPV4) interacts with Ca 2+ -activated potassium channel 3 (KCa2.3) in endothelial cells (ECs) from small resistance arteries of normotensive humans, while ECs from hypertensive patients show a reduced interaction between TRPV4 and KCa2.3. Murine hypertension models, induced by high-salt diet, N(G)-nitro-l-arginine intake, or angiotensin II delivery, showed decreased TRPV4-KCa2.3 interaction in ECs. Perturbation of the TRPV4-KCa2.3 interaction in mouse ECs by overexpressing full-length KCa2.3 or defective KCa2.3 had hypotensive or hypertensive effects, respectively. Next, we developed a small-molecule drug, JNc-440, which showed affinity for both TRPV4 and KCa2.3. JNc-440 significantly strengthened the TRPV4-KCa2.3 interaction in ECs, enhanced vasodilation, and exerted antihypertensive effects in mice. Importantly, JNc-440 specifically targeted the impaired TRPV4-KCa2.3 interaction in ECs but did not systemically activate TRPV4 and KCa2.3. Together, our data highlight the importance of impaired endothelial TRPV4-KCa2.3 coupling in the progression of hypertension and suggest a novel approach for antihypertensive drug development. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

System Analysis for Decay Heat Removal in Lead-Bismuth Cooled Natural Circulated Reactors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Takaaki Sakai; Yasuhiro Enuma; Takashi Iwasaki

2002-07-01

Decay heat removal analyses for lead-bismuth cooled natural circulation reactors are described in this paper. A combined multi-dimensional plant dynamics code (MSG-COPD) has been developed to conduct the system analysis for the natural circulation reactors. For the preliminary study, transient analysis has been performed for a 100 MWe lead-bismuth-cooled reactor designed by Argonne National Laboratory (ANL). In addition, decay heat removal characteristics of a 400 MWe lead-bismuth-cooled natural circulation reactor designed by Japan Nuclear Cycle Development Institute (JNC) has been evaluated by using MSG-COPD. PRACS (Primary Reactor Auxiliary Cooling System) is prepared for the JNC's concept to get sufficient heatmore » removal capacity. During 2000 sec after the transient, the outlet temperature shows increasing tendency up to the maximum temperature of 430 Centigrade, because the buoyancy force in a primary circulation path is temporary reduced. However, the natural circulation is recovered by the PRACS system and the out let temperature decreases successfully. (authors)« less

System Analysis for Decay Heat Removal in Lead-Bismuth-Cooled Natural-Circulation Reactors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sakai, Takaaki; Enuma, Yasuhiro; Iwasaki, Takashi

2004-03-15

Decay heat removal analyses for lead-bismuth-cooled natural-circulation reactors are described in this paper. A combined multidimensional plant dynamics code (MSG-COPD) has been developed to conduct the system analysis for the natural-circulation reactors. For the preliminary study, transient analysis has been performed for a 300-MW(thermal) lead-bismuth-cooled reactor designed by Argonne National Laboratory. In addition, decay heat removal characteristics of a 400-MW(electric) lead-bismuth-cooled natural-circulation reactor designed by the Japan Nuclear Cycle Development Institute (JNC) has been evaluated by using MSG-COPD. The primary reactor auxiliary cooling system (PRACS) is prepared for the JNC concept to get sufficient heat removal capacity. During 2000 smore » after the transient, the outlet temperature shows increasing tendency up to the maximum temperature of 430 deg. C because the buoyancy force in a primary circulation path is temporarily reduced. However, the natural circulation is recovered by the PRACS system, and the outlet temperature decreases successfully.« less

The Relationship Between Cognitive Functioning and the JNC-8 Guidelines for Hypertension in Older Adults.

PubMed

Goldstein, Felicia C; Hajjar, Ihab M; Dunn, Callie B; Levey, Allan I; Wharton, Whitney

2017-01-01

Guidelines for hypertension treatment by the Eighth Joint National Committee (JNC-8) in 2014 recommended a target systolic blood pressure (BP) of <150/<90 mmHg in persons older than 60 years, in contrast to the 2003 JNC-7 recommendations of systolic BP <140 mmHg. This study evaluated the implications of raising the BP target on cognitive functioning and conversion from normal cognition to mild cognitive impairment (MCI). This was a longitudinal study of individuals older than 60 years enrolled in the NIH-NIA Alzheimer's Disease Centers. All had normal cognition at baseline. 453 participants were taking BP medications and had readings of <140/<90 mmHg at four annual visits (reference group). Two other groups consisted of participants with either systolic BP of 140-149 mmHg (n = 112) or ≥150 mmHg (n = 280) on three or four annual visits. Compared with the reference and the 140-149 mmHg groups, those with BP ≥150 mmHg exhibited poorer cognitive status by Year 4 on the Mini-Mental State Exam, and they had a higher risk of conversion to MCI. The 140-149 mmHg exhibited poorer performance than the reference group on domains assessing attention and executive functioning. In contrast, their performance was not significantly different from those with BP ≥150 mmHg. Persons with BP ≥150 mmHg show a faster global cognitive decline and transition to MCI than those with lower BP readings. However, the poor cognitive performance in the attention and executive functioning domains for the 140-149 mmHg group indicates the need for further research evaluating the newer recommended cutoff. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Antihypertensive medication classes used among medicare beneficiaries initiating treatment in 2007-2010.

PubMed

Kent, Shia T; Shimbo, Daichi; Huang, Lei; Diaz, Keith M; Kilgore, Meredith L; Oparil, Suzanne; Muntner, Paul

2014-01-01

After the 2003 publication of the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) guidelines, there was a 5-10% increase in patients initiating antihypertensive medication with a thiazide-type diuretic, but most patients still did not initiate treatment with this class. There are few contemporary published data on antihypertensive medication classes filled by patients initiating treatment. We used the 5% random Medicare sample to study the initiation of antihypertensive medication between 2007 and 2010. Initiation was defined by the first antihypertensive medication fill preceded by 365 days with no antihypertensive medication fills. We restricted our analysis to beneficiaries ≥ 65 years who had two or more outpatient visits with a hypertension diagnosis and full Medicare fee-for-service coverage for the 365 days prior to initiation of antihypertensive medication. Between 2007 and 2010, 32,142 beneficiaries in the 5% Medicare sample initiated antihypertensive medication. Initiation with a thiazide-type diuretic decreased from 19.2% in 2007 to 17.9% in 2010. No other changes in medication classes initiated occurred over this period. Among those initiating antihypertensive medication in 2010, 31.3% filled angiotensin-converting enzyme inhibitors (ACE-Is), 26.9% filled beta blockers, 17.2% filled calcium channel blockers, and 14.4% filled angiotensin receptor blockers (ARBs). Initiation with >1 antihypertensive medication class decreased from 25.6% in 2007 to 24.1% in 2010. Patients initiated >1 antihypertensive medication class most commonly with a thiazide-type diuretic and either an ACE-I or ARB. These results suggest that JNC 7 had a limited long-term impact on the choice of antihypertensive medication class and provide baseline data prior to the publication of the 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults from the Panel Members Appointed to the Eighth Joint National Committee (JNC 8).

Guidelines for hypertension treatment: applications for primary care practice--a review of the JNC VI report.

PubMed

Alexander, L M

1998-01-01

The Joint National Committee's report on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure was released in November 1997. With its release, an increased emphasis on "treating the patient, not just the number" has taken place. The report provides a comprehensive review of recent clinical evidence that helps guide clinical decision making in the care of the hypertensive patient. A new disease classification system entitled "risk stratification" is introduced and takes into account comorbid conditions that are present for many hypertensive individuals. This risk stratification is then linked to treatment strategies and provides a concise decision analysis framework to aid in clinical decision making. Community-based prevention strategies are also highlighted and should raise the awareness of clinicians to adopt these recommendations and integrate them more aggressively into daily practice. Increased emphasis on patient compliance to improve overall hypertension control rates is also presented. Maximum efficacy through once-daily dosing and fixed-dose combinations are reviewed in the report. The JNC report is a comprehensive resource for clinicians in primary care practice. Its evidenced-based approach is a wonderful teaching tool for those clinicians who also serve as clinical educators in primary care.

Lack of chart reminder effectiveness on family medicine resident JNC-VI and NCEP III guideline knowledge and attitudes.

PubMed

Echlin, Paul S; Upshur, Ross E G; Markova, Tsveti P

2004-07-05

The literature demonstrates that medical residents and practicing physicians have an attitudinal-behavioral discordance concerning their positive attitudes towards clinical practice guidelines (CPG), and the implementation of these guidelines into clinical practice patterns. A pilot study was performed to determine if change in a previously identified CPG compliance factor (accessibility) would produce a significant increase in family medicine resident knowledge and attitude toward the guidelines. The primary study intervention involved placing a summary of the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) and the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (NCEP III) CPGs in all patient (>18 yr.) charts for a period of three months. The JNC VI and NCEP III CPGs were also distributed to each Wayne State family medicine resident, and a copy of each CPG was placed in the preceptor's area of the involved clinics. Identical pre- and post- intervention questionnaires were administered to all residents concerning CPG knowledge and attitude. Post-intervention analysis failed to demonstrate a significant difference in CPG knowledge. A statistically significant post-intervention difference was found in only on attitude question. The barriers to CPG compliance were identified as 1) lack of CPG instruction; 2) lack of critical appraisal ability; 3) insufficient time; 4) lack of CPG accessibility; and 5) lack of faculty modeling. This study demonstrated no significant post intervention changes in CPG knowledge, and only one question that reflected attitude change. Wider resident access to dedicated clinic time, increased faculty modeling, and the implementation of an electronic record/reminder system that uses a team-based approach are compliance factors that should be considered for further investigation. The interpretation of CPG non-compliance will benefit from a causal matrix focused on physician knowledge, attitudes, and behavior. Recent findings in resident knowledge-behavior discordance may direct the future investigation of physician CPG non-compliance away from generalized barrier research, and toward the development of information that maximizes the sense of individual practitioner urgency and certainty.

Blood pressure level and hypertension awareness and control differ by marital status, sex, and ethnicity: a population-based study.

PubMed

Abu-Saad, Kathleen; Chetrit, Angela; Eilat-Adar, Sigal; Alpert, Gershon; Atamna, Ahmed; Gillon-Keren, Michal; Rogowski, Ori; Ziv, Arnona; Kalter-Leibovici, Ofra

2014-12-01

Population-based studies about factors associated with blood pressure (BP) levels and hypertension awareness and control are lacking in Israel. We aimed to identify covariables of BP level (across the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-7) categories) and hypertension awareness and control. Participants (n = 763; aged 25-74 years) were randomly selected from the population registry and stratified by sex, age, and ethnicity (Arab or Jewish). Sociodemographic, lifestyle, chronic morbidity, drug therapy, and measured anthropometric and BP data were collected. Hypertension was defined as physician diagnosis, antihypertension drug therapy, or systolic BP ≥140 mm Hg or diastolic BP ≥90 mm Hg. Standardized hypertension prevalence was 32.5%. Age and body mass index were positively associated with being in a higher JNC-7 category. In multivariable analysis, the association between gender and JNC-7 category depended upon marital status. Of those with hypertension (n = 315), 66.0% were aware of their status, and 26.0% exhibited adequate BP control. Using "aware-and-controlled" as the outcome reference category, the odds ratio (OR) of being aware and uncontrolled was 1.9 (95% confidence interval (CI) = 1.3-2.9) for 10-year age increment. The OR of being unaware and uncontrolled was 5.6 (95% CI = 2.0-15.8) for Arabs vs. Jews, 5.6 (95% CI = 1.4-22.3) for single/divorced vs. married participants, 3.9 (95% CI = 1.7-9.2) for those with <3 visits to the family physician per year, and 0.1 (95% CI = 0.02-0.4) for those with self-reported cardiovascular disease. Sociodemographic factors and primary healthcare service utilization are associated with hypertension awareness and control. Specially focused outreach may be needed to improve hypertension awareness among Arabs, certain subgroups not traditionally considered to be at high risk, and those who have less contact with the healthcare system. © American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

CTC Sentinel. Volume 7, Issue 7

DTIC Science & Technology

2014-07-01

provide other support activities to organizations operating outside of Europe.3 The largely laissez - faire attitude of Swiss authorities (an approach, it...Counterterrorism Strategy By J.N.C. Hill 18 Contrasting the Leadership of Mullah Fazlullah and Khan Said Sajna in Pakistan By Daud Khattak 20...the IMU’s leadership since 2009.5 The existing literature, however, fails to explore the role played by the IMU in recent high- profile attacks in

On the Analytical Inversion of Lidar Returns from an Inhomogeneous Atmosphere.

DTIC Science & Technology

1980-04-01

of Clouds and Precipitation (Reidel, Dordrecht, Holand , 1978), pp. 20-21. 5. T. Okita, J. Ileteorol. Soc. Japan, 40, 39 (1962). 6. R. T. Brown, Jr...Cnt %ftl 44b cA Ln. 0Co I (a 0 0 0 i rJnc RANlIe (PER !Ora) F1 "Sure 9 Znversiooms obased Oen Eqs. (14), (16), and (23), with and vithoutIteration, fo

The Racial, Cultural and Social Makeup of Hispanics as a potential Profile Risk for Intensifying the Need for Including this Ethnic Group in Clinical Trials.

PubMed

López-Candales, Angel; Aponte Rodríguez, Jaime; Harris, David

2015-01-01

Hypertension not only is the most frequently listed cause of death worldwide; but also a well-recognized major risk factor for cardiovascular disease and stroke. Based on the latest published statistics published by the American Heart Association, hypertension is very prevalent and found in one of every 3 US adults. Furthermore, data from NHANES 2007 to 2010 claims that almost 6% of US adults have undiagnosed hypertension. Despite this staggering statistic, previous US guidelines for the prevention, detection, and treatment of hypertension (The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure 7 [JNC 7]), released in 2003, stated that; "unfortunately, sufficient numbers of Mexican Americans and other Hispanic Americans... have not been included in most of the major clinical trials to allow reaching strong conclusions about their responses to individual antihypertensive therapies." However, the recently published JNC 8 offers no comment regarding recommendations or guideline treatment suggestions on Hispanics. The purpose of this article not only is to raise awareness of the lack of epidemiological data and treatment options regarding high blood pressure in the US Hispanic population; but also to make a case of the racial, cultural and social makeup of this ethnic group that places them at risk of cardiovascular complications related to hypertension.

Differences in prevalence of diastolic arterial hypertension in 1423 young individuals in two different interviews.

PubMed

De Lena, S M; Gende, O A; Almirón, M A; Cingolani, H E

1994-09-01

To determine prevalence of diastolic arterial hypertension (DAH) in young individuals using different criteria. Secondly, to test the possible different blood pressure reactions to mental stress and hand grip in two groups: group A, a 'low blood pressure group', and group B, diastolic blood pressure 90 mmHg or greater in one interview and below these values in a second interview. A total of 1423 volunteer medical students was recruited at La Plata School of Medicine, average age 21 +/- 3 years. Systolic and diastolic blood pressure were measured three times on two different occasions separated by one week. With the values obtained, prevalence of arterial hypertension was determined according to the criteria suggested by The Joint National Committee 4 (JNC-4) and the World Health Organization (WHO), and to statistical bases. Mental stress and hand grip tests were performed by groups A and B. The prevalence of DAH when only the first determination of the first interview was considered was 14.7%, 6.7% (considering the WHO criterion) or 5% (using the statistical criterion). These values are reduced if repeated measurements are averaged. The greatest reduction was obtained when the JNC-4 criterion was used (1.6%). The reactivity of stressors did not show any relationship with the initial blood pressure of the subjects. In epidemiological studies, the differences among the criteria should be considered when analyzing blood pressure of populations. Stress tests (mental stress and hand grip) do not help in identifying differences between the groups studied.

Ambiguities in the Guidelines for the Management of Arterial Hypertension: Indian Perspective with a Call for Global Harmonization.

PubMed

Rehan, Harmeet Singh; Grover, Abhinav; Hungin, A P S

2017-02-01

Many medical professional societies have formulated guidelines to treat hypertension, but there existed differences with respect to diagnosis, blood pressure (BP) targets, pharmacotherapy of hypertension, and grades of evidence. A MEDLINE search for hypertension guidelines was performed to compare Indian guidelines for hypertension (IGH) with these guidelines. A majority of the guidelines had consensus on the cutoff value (140/90 mmHg, recorded twice) to diagnose hypertension. The Joint National Committee 8 (JNC 8), IGH, Japanese Society of hypertension (JSH), Canadian Hypertension Education Program (CHEP), and American Society of Hypertension/International Society of Hypertension (ASH/ISH) guidelines provide a higher BP target for the elderly hypertensive populations, while the National Institute for Health and Care Excellence (NICE) and European Society of Hypertension (ESH) guidelines provided a lower BP target for the elderly patients. However, a meta-analysis showed benefits of having a systolic BP target of <130 mmHg for all patients. Treatment of hypertension according to JNC 8, NICE, and ASH/ISH guidelines varies among the black and the non-black population which recommended thiazide or calcium channel blockers for the black population. There is no special mention of pharmacotherapy or BP targets for the South Asian population in various guidelines including IGH despite evidence of higher risk of hypertension-associated complications in this population. It is suggested that all the available guidelines should be harmonized with highest level of evidence available to minimize ambiguities associated with management of hypertension.

[Guidelines for the management of hypertension].

PubMed

Prieto-Díaz, Miguel Ángel

2014-09-01

In the last year, several scientific societies have published guidelines for the management of arterial hypertension. In Spain, two clinical practice guidelines have had a strong impact and have been closely followed in the last few years: the first is the Guideline of the National Heart, Lung and Blood Institute, although their last report (JNC 7) was published in 2003; the second is the clinical practice guideline for the management of arterial hypertension of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH), whose latest version was published in 2007, although an update was published in 2009. A new ESC/ESH document, published in 2013, adopts a mainly educational stance, closely rooted in clinical practice. Many of the recommendations maintain the same criteria as previous guidelines. However, the new publication shows greater rigor and contains major contributions such as specification of the level of evidence and grade of recommendation for each recommendation, which was lacking in the previous guidelines of these societies. The document is both practical and easy to consult, consisting of 17 tables, 5 figures and 18 blocks of recommendations. The JNC 8 report, however, has a single objective: to respond to three questions that are considered a priority and which refer exclusively to drug therapy. Nine recommendations are made relating to these three questions. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Medicina Rural y Generalista (SEMERGEN). All rights reserved.

The need for defining- and redefining- hypertension: beyond the numbers.

PubMed

Giles, Thomas D; Sander, Gary E

2005-12-01

By definition, hypertension has been linked to blood pressure levels. This link is demonstrated in the various iterations of reports by the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC). Over the past few decades, the definition of hypertension has changed with each new report, and so have the levels of blood pressure that are considered satisfactory after treatment. In this article, Drs Giles and Sander review the current definitions of hypertension in clinical practice and its evaluation in light of total cardiovascular risk.

Factors predicting incremental administration of antihypertensive boluses during deep brain stimulator placement for Parkinson's disease.

PubMed

Rajan, Shobana; Deogaonkar, Milind; Kaw, Roop; Nada, Eman Ms; Hernandez, Adrian V; Ebrahim, Zeyd; Avitsian, Rafi

2014-10-01

Hypertension is common in deep brain stimulator (DBS) placement predisposing to intracranial hemorrhage. This retrospective review evaluates factors predicting incremental antihypertensive use intraoperatively. Medical records of Parkinson's disease (PD) patients undergoing DBS procedure between 2008-2011 were reviewed after Institutional Review Board approval. Anesthesia medication, preoperative levodopa dose, age, preoperative use of antihypertensive medications, diabetes mellitus, anxiety, motor part of the Unified Parkinson's Disease Rating Scale score and PD duration were collected. Univariate and multivariate analysis was done between each patient characteristic and the number of antihypertensive boluses. From the 136 patients included 60 were hypertensive, of whom 32 were on angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB), told to hold on the morning of surgery. Antihypertensive medications were given to 130 patients intraoperatively. Age (relative risk [RR] 1.01; 95% confidence interval [CI] 1.00-1.02; p=0.005), high Joint National Committee (JNC) class (p<0.0001), diabetes mellitus (RR 1.4; 95%CI 1.2-17; p<0.0001) and duration of PD >10 years (RR 1.2; 95%CI 1.1-1.3; p=0.001) were independent predictors for antihypertensive use. No difference was noted in the mean dose of levodopa (p=0.1) and levodopa equivalent dose (p=0.4) between the low (I/II) and high severity (III/IV) JNC groups. Addition of dexmedetomidine to propofol did not influence antihypertensive boluses required (p=0.38). Intraoperative hypertension during DBS surgery is associated with higher age group, hypertensive, diabetic patients and longer duration of PD. Withholding ACEI or ARB is an independent predictor of hypertension requiring more aggressive therapy. Levodopa withdrawal and choice of anesthetic agent is not associated with higher intraoperative antihypertensive medications. Copyright © 2014 Elsevier Ltd. All rights reserved.

Hydrochemical characteristics and groundwater evolution modeling in sedimentary rocks of the Tono mine, Japan

NASA Astrophysics Data System (ADS)

Sasamoto, Hiroshi; Yui, Mikazu; Arthur, Randolph C.

Based on geochemical data collected by Japan Nuclear Cycle Development Institute (JNC) in the Tono uranium mine, a conceptual groundwater evolution model developed by JNC is tested to evaluate whether equilibrium-based concepts of water-rock interaction are consistent with observed variations in the mineralogy and hydrochemistry of the Tono mine area. The chemical evolution of the groundwaters is modeled assuming local equilibrium for selected mineral-fluid reactions, taking into account the rainwater origin of these solutions. Results suggest that it is possible to interpret approximately the actual groundwater chemistry (i.e., pH, Eh, total dissolved concentrations of Si, Na, Ca, K, Al, carbonate and sulfate) if the following assumptions are adopted (a) CO 2 concentration in the gas phase contacting pore solutions in the overlying soil zone=10 -1 atm, and (b) minerals in the rock zone that control the solubility of respective elements in the groundwater include: chalcedony (Si), albite (Na), kaolinite (Al), calcite (Ca and carbonate), muscovite (K) and pyrite (Eh and sulfate). This result helps to build confidence in the use of simplified geochemical modeling techniques to develop an understanding of dominant geochemical reactions controlling groundwater chemistry in rocks similar to those that could be used for the geological disposal of radioactive wastes. It is noted, however, that the available field data may not be sufficient to adequately constrain parameters in the groundwater evolution model. In particular, more detailed information characterizing certain site properties are needed to improve the model. For this reason, a model that accounts for ion-exchange reactions among clay minerals, and which is based on the results of laboratory experiments, has also been evaluated in the present study. Further improvement of model considering ion-exchange reactions are needed in future, however.

Integrated Computer-Aided Manufacturing (ICAM) Architecture. Part 3. Volume 8. Technology Transfer.

DTIC Science & Technology

1983-09-01

AN’c MOp C O M P E T I T I V E D O S : 7 : .. .F ,- .,, Y T .. FINANCIAL RISK . "ON THE GO.ERM’" I2K_ IF, PROVIDES jNC-1.1,"L. TO-F, .NAKLS. ANC EIKN...RECENTLY, HO1WEVEP, :-XERNAL AND INTERNAL ENVIRONMENTAL PRESSURES HAVE FOCUSED; 7H GENERAL MANAGER’S AND HIS TOP FUNCTIONAL zTAF F’ S ATTENTION ON THE...SYSTieM DneFINITlO MEHOD Le He ~~~~h C~IDEF MEHDLGAIIAE etTERlog wNDElSTaDilG, tinTndaayisohhepolm COMMUNIATION, AN ANALYIS OF ESOLUTION. THE DENSIN IS

Mechanism of Protein Denaturation: Partial Unfolding of the P22 Coat Protein I-Domain by Urea Binding.

PubMed

Newcomer, Rebecca L; Fraser, LaTasha C R; Teschke, Carolyn M; Alexandrescu, Andrei T

2015-12-15

The I-domain is an insertion domain of the bacteriophage P22 coat protein that drives rapid folding and accounts for over half of the stability of the full-length protein. We sought to determine the role of hydrogen bonds (H-bonds) in the unfolding of the I-domain by examining (3)JNC' couplings transmitted through H-bonds, the temperature and urea-concentration dependence of (1)HN and (15)N chemical shifts, and native-state hydrogen exchange at urea concentrations where the domain is predominantly folded. The native-state hydrogen-exchange data suggest that the six-stranded β-barrel core of the I-domain is more stable against unfolding than a smaller subdomain comprised of a short α-helix and three-stranded β-sheet. H-bonds, separately determined from solvent protection and (3)JNC' H-bond couplings, are identified with an accuracy of 90% by (1)HN temperature coefficients. The accuracy is improved to 95% when (15)N temperature coefficients are also included. In contrast, the urea dependence of (1)HN and (15)N chemical shifts is unrelated to H-bonding. The protein segments with the largest chemical-shift changes in the presence of urea show curved or sigmoidal titration curves suggestive of direct urea binding. Nuclear Overhauser effects to urea for these segments are also consistent with specific urea-binding sites in the I-domain. Taken together, the results support a mechanism of urea unfolding in which denaturant binds to distinct sites in the I-domain. Disordered segments bind urea more readily than regions in stable secondary structure. The locations of the putative urea-binding sites correlate with the lower stability of the structure against solvent exchange, suggesting that partial unfolding of the structure is related to urea accessibility. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Relationship of Blood Pressure With Mortality and Cardiovascular Events Among Hypertensive Patients aged ≥60 years in Rural Areas of China

PubMed Central

Zheng, Liqiang; Li, Jue; Sun, Zhaoqing; Zhang, Xingang; Hu, Dayi; Sun, Yingxian

2015-01-01

Abstract The Eighth Joint National Committee (JNC-8) panel recently recommended a systolic blood pressure (BP) threshold of ≥150 mmHg for the initiation of drug therapy and a therapeutic target of <150/90 mmHg in patients ≥60 years of age. However, results from some post-hoc analysis of randomized controlled trials and observational studies did not support these recommendations. In the prospective cohort study, 5006 eligible hypertensive patients aged ≥60 years from rural areas of China were enrolled for the present analysis. The association between the average follow-up BP and outcomes (all-cause and cardiovascular death, incident coronary heart disease [CHD], and stroke), followed by a median of 4.8 years, were evaluated using Cox proportional hazards models adjusting for other potential confounders. The relationship between BP (systolic or diastolic) showed an increased or J-shaped curve association with adverse outcomes. Compared with the reference group of BP <140/90 mmHg, the risk of all-cause death (hazard ratio [HR]: 2.698; 95% confidence interval [CI]: 1.989–3.659), cardiovascular death (HR: 2.702; 95% CI: 1.855–3.935), incident CHD (HR: 3.263; 95% CI: 2.063–5.161), and stroke (HR: 2.334; 95% CI: 1.559–3.945) was still significantly increased in the group with BP of 140–149/<90 mmHg. Older hypertensive patients with BP of 140–149/<90 mmHg were at higher risk of developing adverse outcomes, implying that lenient BP control of 140–149/<90 mmHg, based on the JNC-8 guidelines, may not be appropriate for hypertensive patients aged ≥60 years in rural areas of China. PMID:26426621

Comparative effectiveness of antihypertensive therapeutic classes and treatment strategies in the initiation of therapy in primary care patients: a Distributed Ambulatory Research in Therapeutics Network (DARTNet) study.

PubMed

Bronsert, Michael R; Henderson, William G; Valuck, Robert; Hosokawa, Patrick; Hammermeister, Karl

2013-01-01

Few comparative effectiveness studies of treatment strategies using antihypertensive therapeutic classes in hypertension control have been assessed in a primary care environment. The objectives are to compare the effectiveness of common antihypertensive therapeutic classes initiated as monotherapy and of fixed-dose combinations (FDCs), free-equivalent combinations (FECs), and monotherapy on hypertension control. This article reports observational comparative effectiveness analyses of data electronically extracted from electronic health records. The study population consisted of 8,676 patients with an incident prescription for an antihypertensive agent of a total of 79,176 patients receiving antihypertensive therapy in 33 geographically diverse primary care clinics. The main measures were reductions in systolic blood pressure (SBP) and diastolic blood pressure (DBP) and rates of attaining goals per the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7). There were small, clinically insignificant differences in blood pressure reductions between the monotherapy classes. Higher rates of blood pressure control were obtained when patients were initiated on an angiotensin-converting enzyme inhibitor than a thiazide or thiazide-like diuretic (47.8% vs 39.9%) or a β-blocker versus a thiazide (45.9% vs 39.9%). Patients initiated on FDCs had significantly larger reductions in blood pressure than patients initiated on FECs (-17.3 vs -12.0 mm Hg SBP; -10.1 vs -6.0 mm Hg DBP) or monotherapy (-17.3 vs -13.6 mm Hg SBP; -10.1 vs -7.9 mm Hg DBP). Rates of attaining JNC7 goals also were better for FDCs than FECs (57.2% vs 42.5%) and for FDCs versus monotherapy (57.2% vs 44.9%). Patients initiated on angiotensin-converting enzyme inhibitors and β-blockers had slightly higher rates of blood pressure control. The use of FDCs as initial therapy is more effective in the control of hypertension than monotherapy or FECs.

Studies on Materials for Heavy-Liquid-Metal-Cooled Reactors in Japan

DOE Office of Scientific and Technical Information (OSTI.GOV)

Minoru Takahashi; Masayuki Igashira; Toru Obara

2002-07-01

Recent studies on materials for the development of lead-bismuth (Pb-Bi)-cooled fast reactors (FR) and accelerator-driven sub-critical systems (ADS) in Japan are reported. The measurement of the neutron cross section of Bi to produce {sup 210}Po, the removal experiment of Po contamination and steel corrosion test in Pb-Bi flow were performed in Tokyo Institute of Technology. A target material corrosion test was performed in the project of Transmutation Experimental Facility for ADS in Japan Atomic Energy Research Institute (JAERI). Steel corrosion test was started in Mitsui Engineering and Shipbuilding Co., LTD (MES). The feasibility study for FR cycle performed in Japanmore » Nuclear Cycle Institute (JNC) are described. (authors)« less

Baseline Blood Pressure, the 2017 ACC/AHA High Blood Pressure Guidelines, and Long-Term Cardiovascular Risk in SPRINT.

PubMed

Vaduganathan, Muthiah; Pareek, Manan; Qamar, Arman; Pandey, Ambarish; Olsen, Michael H; Bhatt, Deepak L

2018-02-05

The 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines include lower thresholds to define hypertension than previous guidelines. Little is known about the impact of these guideline changes in patients with or at high risk for cardiovascular disease. In this exploratory analysis using baseline blood pressure assessments in Systolic Blood Pressure Intervention Trial (SPRINT), we evaluated the prevalence and associated cardiovascular prognosis of patients newly reclassified with hypertension based on the 2017 ACC/AHA (systolic blood pressure ≥130 mm Hg or diastolic blood pressure ≥80 mm Hg) compared with the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC 7) guidelines (systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg). The primary endpoint was the composite of myocardial infarction, other acute coronary syndromes, stroke, heart failure, or cardiovascular death. In 4683 patients assigned to the standard treatment arm of SPRINT, 2328 (49.7%) met hypertension thresholds by JNC 7 guidelines, and another 1424 (30.4%) were newly reclassified as having hypertension based on the 2017 ACC/AHA guidelines. Over 3.3-year median follow-up, 319 patients experienced the primary endpoint (87 of whom were newly reclassified with hypertension based on the revised guidelines). Patients with hypertension based on prior guidelines compared with those newly identified with hypertension based on the new guidelines had similar risk of the primary endpoint (2.3 [95% confidence interval {CI}, 2.0-2.7] vs 2.0 [95% CI, 1.6-2.4] events per 100 patient-years; adjusted HR, 1.10 [95% CI, 0.84-1.44]; P = .48). The 2017 ACC/AHA high blood pressure guidelines are expected to significantly increase the prevalence of patients with hypertension (perhaps to a greater extent in higher-risk patient cohorts compared with the general population) and identify greater numbers of patients who will ultimately experience adverse cardiovascular events. Copyright © 2018 Elsevier Inc. All rights reserved.

JAEA's actions and contributions to the strengthening of nuclear non-proliferation

NASA Astrophysics Data System (ADS)

Suda, Kazunori; Suzuki, Mitsutoshi; Michiji, Toshiro

2012-06-01

Japan, a non-nuclear weapons state, has established a commercial nuclear fuel cycle including LWRs, and now is developing a fast neutron reactor fuel cycle as part of the next generation nuclear energy system, with commercial operation targeted for 2050. Japan Atomic Energy Agency (JAEA) is the independent administrative agency for conducting comprehensive nuclear R&D in Japan after the merger of Japan Atomic Energy Research Institute (JAERI) and Japan Nuclear Cycle Development Institute (JNC). JAEA and its predecessors have extensive experience in R&D, facility operations, and safeguards development and implementation for new types of nuclear facilities for the peaceful use of nuclear energy. As the operator of various nuclear fuel cycle facilities and numerous nuclear materials, JAEA makes international contributions to strengthen nuclear non-proliferation. This paper provides an overview of JAEA's development of nuclear non-proliferation and safeguards technologies, including remote monitoring of nuclear facilities, environmental sample analysis methods and new efforts since the 2010 Nuclear Security Summit in Washington D.C.

Specimen size effects on ductile?brittle transition temperature in Charpy impact testing

NASA Astrophysics Data System (ADS)

Kurishita, H.; Yamamoto, T.; Narui, M.; Suwarno, H.; Yoshitake, T.; Yano, Y.; Yamazaki, M.; Matsui, H.

2004-08-01

One key issue for small specimen test techniques is to clarify specimen size effects on test results. In consideration of size effects on determining the ductile-to-brittle transition temperature (DBTT) in Charpy impact testing, a method to evaluate the plastic constraint loss for differently sized Charpy V-notch (CVN) specimens is proposed and applied to a ferritic-martensitic steel, 2WFK, developed by JNC. In the method, a constraint factor, α, that is an index of the plastic constraint is defined as α=σ ∗/σ y∗. Here, σ ∗ is the critical cleavage fracture stress which is a material constant and σ y∗ is the uniaxial yield stress at the DBTT at the strain rate generated in the Charpy impact test. The procedures for evaluating each of σ ∗ and σ y∗ are described and a result of σ ∗ and σ y∗, thus the value of α, is presented for different types of miniaturized and full-sized CVN specimens of 2WFK.

2015 guidelines of the Taiwan Society of Cardiology and the Taiwan Hypertension Society for the management of hypertension.

PubMed

Chiang, Chern-En; Wang, Tzung-Dau; Ueng, Kwo-Chang; Lin, Tsung-Hsien; Yeh, Hung-I; Chen, Chung-Yin; Wu, Yih-Jer; Tsai, Wei-Chuan; Chao, Ting-Hsing; Chen, Chen-Huan; Chu, Pao-Hsien; Chao, Chia-Lun; Liu, Ping-Yen; Sung, Shih-Hsien; Cheng, Hao-Min; Wang, Kang-Ling; Li, Yi-Heng; Chiang, Fu-Tien; Chen, Jyh-Hong; Chen, Wen-Jone; Yeh, San-Jou; Lin, Shing-Jong

2015-01-01

It has been almost 5 years since the publication of the 2010 hypertension guidelines of the Taiwan Society of Cardiology (TSOC). There is new evidence regarding the management of hypertension, including randomized controlled trials, non-randomized trials, post-hoc analyses, subgroup analyses, retrospective studies, cohort studies, and registries. More recently, the European Society of Hypertension (ESH) and the European Society of Cardiology (ESC) published joint hypertension guidelines in 2013. The panel members who were appointed to the Eighth Joint National Committee (JNC) also published the 2014 JNC report. Blood pressure (BP) targets have been changed; in particular, such targets have been loosened in high risk patients. The Executive Board members of TSOC and the Taiwan Hypertension Society (THS) aimed to review updated information about the management of hypertension to publish an updated hypertension guideline in Taiwan. We recognized that hypertension is the most important risk factor for global disease burden. Management of hypertension is especially important in Asia where the prevalence rate grows faster than other parts of the world. In most countries in East Asia, stroke surpassed coronary heart disease (CHD) in causing premature death. A diagnostic algorithm was proposed, emphasizing the importance of home BP monitoring and ambulatory BP monitoring for better detection of night time hypertension, early morning hypertension, white-coat hypertension, and masked hypertension. We disagreed with the ESH/ESH joint hypertension guidelines suggestion to loosen BP targets to <140/90 mmHg for all patients. We strongly disagree with the suggestion by the 2014 JNC report to raise the BP target to <150/90 mmHg for patients between 60-80 years of age. For patients with diabetes, CHD, chronic kidney disease who have proteinuria, and those who are receiving antithrombotic therapy for stroke prevention, we propose BP targets of <130/80 mmHg in our guidelines. BP targets are <140/90 mmHg for all other patient groups, except for patients ≥80 years of age in whom a BP target of <150/90 mmHg would be optimal. For the management of hypertension, we proposed a treatment algorithm, starting with life style modification (LSM) including S-ABCDE (Sodium restriction, Alcohol limitation, Body weight reduction, Cigarette smoke cessation, Diet adaptation, and Exercise adoption). We emphasized a low-salt strategy instead of a no-salt strategy, and that excessively aggressive sodium restriction to <2.0 gram/day may be harmful. When drug therapy is considered, a strategy called "PROCEED" was suggested (Previous experience, Risk factors, Organ damage, Contraindications or unfavorable conditions, Expert's or doctor's judgment, Expenses or cost, and Delivery and compliance issue). To predict drug effects in lowering BP, we proposed the "Rule of 10" and "Rule of 5". With a standard dose of any one of the 5 major classes of anti-hypertensive agents, one can anticipate approximately a 10-mmHg decrease in systolic BP (SBP) (Rule of 10) and a 5-mmHg decrease in diastolic BP (DBP) (Rule of 5). When doses of the same drug are doubled, there is only a 2-mmHg incremental decrease in SBP and a 1-mmHg incremental decrease in DBP. Preferably, when 2 drugs with different mechanisms are to be taken together, the decrease in BP is the sum of the decrease of the individual agents (approximately 20 mmHg in SBP and 10 mmHg in DBP). Early combination therapy, especially single-pill combination (SPC), is recommended. When patient's initial treatment cannot get BP to targeted goals, we have proposed an adjustment algorithm, "AT GOALs" (Adherence, Timing of administration, Greater doses, Other classes of drugs, Alternative combination or SPC, and LSM + Laboratory tests). Treatment of hypertension in special conditions, including treatment of resistant hypertension, hypertension in women, and perioperative management of hypertension, were also mentioned. The TSOC/THS hypertension guidelines provide the most updated information available in the management of hypertension. The guidelines are not mandatory, and members of the task force fully realize that treatment of hypertension should be individualized to address each patient's circumstances. Ultimately, the decision of the physician decision remains of the utmost importance in hypertension management. Copyright © 2014. Published by Elsevier Taiwan.

All Prime Contract Awards by State or Country, Place, and Contractor, FY 88. Part 6. (Alachua, Florida-Woodstock, Georgia).

DTIC Science & Technology

1988-01-01

9W P.- 1 1 (000 1-4-4 1 1-44-- 4. -4 -4 -4 --- 4 4-4-4 -4 ~-4--4 -4-4 "-4 N-4,𔃾 4-4 -4 F- I MOLA (0 I IWNNN m WNCNiC.JNC’J .. NൌN" m"N C𔃾 I(OLA( W 4...4 -4 -41-4 -4-4 -4 c -4 -4 c - A- 4- 4- l’- I MOLA (0 I JN NN N NN N 0N N NNl’,N MN 0N MN"NNN it IC00In(0 -4. -1-4-4-4_4--4-4 -4 ~~~-4 ’-4-4-4 -4 .l...toNNNNNCJ C1 MU (N C 0 0 (0 4N 0 0 I MOLA (0 1-4 -4 -4 -4 -4-4 -4 -4 -4-4-4 -4 4 -4--1 -4 -4-4 14 4 -4444- --fI4--4 o I (00A4 I -00000 ’-0 -000000000000 ’-0

Protein Structure Validation and Refinement Using Amide Proton Chemical Shifts Derived from Quantum Mechanics

PubMed Central

Christensen, Anders S.; Linnet, Troels E.; Borg, Mikael; Boomsma, Wouter; Lindorff-Larsen, Kresten; Hamelryck, Thomas; Jensen, Jan H.

2013-01-01

We present the ProCS method for the rapid and accurate prediction of protein backbone amide proton chemical shifts - sensitive probes of the geometry of key hydrogen bonds that determine protein structure. ProCS is parameterized against quantum mechanical (QM) calculations and reproduces high level QM results obtained for a small protein with an RMSD of 0.25 ppm (r = 0.94). ProCS is interfaced with the PHAISTOS protein simulation program and is used to infer statistical protein ensembles that reflect experimentally measured amide proton chemical shift values. Such chemical shift-based structural refinements, starting from high-resolution X-ray structures of Protein G, ubiquitin, and SMN Tudor Domain, result in average chemical shifts, hydrogen bond geometries, and trans-hydrogen bond (h3 JNC') spin-spin coupling constants that are in excellent agreement with experiment. We show that the structural sensitivity of the QM-based amide proton chemical shift predictions is needed to obtain this agreement. The ProCS method thus offers a powerful new tool for refining the structures of hydrogen bonding networks to high accuracy with many potential applications such as protein flexibility in ligand binding. PMID:24391900

Pre-employment medical examination of Indonesian domestic helpers in a private clinic in Johor Bahru--an eight year review.

PubMed

Leong, C C

2006-12-01

On review of 3117 patients' records (all were female Indonesian foreign workers over the span of eight years (1997 to 2004 in a private clinic in Johor Bahru, 223 cases (7.2%) were found to have various medical problems. These 3117 foreigners were to be employed as domestic helpers in Malaysia. They were examined upon arrival in Johor Bahru even though our government did not require this pre-requisite (before 1st August 2005) as they were examined and certified fit in their country of origin before embarking to Malaysia. The proportion of female Indonesian foreign workers who were afflicted with category 1 conditions was 55.6% (which rendered them unfit for employment) and category 2 conditions was 44.4%. The medical problem detected most frequently was hypertension. Sixty-one (80.3%) out of 76 workers had stage 2 hypertension (JNC 7 report). Pulmonary tuberculosis ranked second in this review and is a category 1 condition. This paper supports the recent move by the Malaysian Ministry of Health to implement mandatory medical examinations for all foreign workers arriving in Malaysia within one month of arrival regardless of whether or not they are certified fit in their countries of origin.

Does "hidden undercuffing" occur among obese patients? Effect of arm sizes and other predictors of the difference between wrist and upper arm blood pressures.

PubMed

Doshi, Hardik; Weder, Alan B; Bard, Robert L; Brook, Robert D

2010-02-01

Arm size can affect the accuracy of blood pressure (BP) measurement, and "undercuffing" of large upper arms is likely to be a growing problem. Therefore, the authors investigated the relationship between upper arm and wrist readings. Upper arm and wrist circumferences and BP were measured in 261 consecutive patients. Upper arm auscultation and wrist BP was measured in triplicate, rotating measurements every 30 seconds between sites. Upper arm BP was 131.9+/-20.6/71.6+/-12.6 mm Hg in an obese population (body mass index, 30.6+/-6.6 kg/m(2)) with mean upper arm size of 30.7+/-5.1 cm. Wrist BP was higher (2.6+/-9.2 mm Hg and 4.9+/-6.6 mm Hg, respectively, P<.001); however, there was moderate concordance for the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) strata (kappa value=0.27-0.71), and the difference was >or=5 mm Hg in 72% of the patients. The authors conclude that there was poor concordance between arm and wrist BP measurement and found no evidence that "hidden undercuffing" was associated with obesity; therefore, they do not support routine use of wrist BP measurements.

Gender differences in prevalence and socioeconomic determinants of hypertension: findings from the WHO STEPs survey in a rural community of Vietnam.

PubMed

Minh, H Van; Byass, P; Chuc, N T K; Wall, S

2006-02-01

In Vietnam, hypertension was estimated to cause a large number of deaths in hospitals. However, population-based knowledge about the magnitude of hypertension in Vietnam and its relationship with socioeconomic status, especially in the rural communities, still remains scarce. This paper, taking advantage of a study on noncommunicable disease (NCD) risk factors in Bavi district, Vietnam, using the WHO STEPs approach, estimates the prevalence of hypertension in the setting and examines its association with some socioeconomic factors. A representative sample comprising 2000 adults aged 25-64 years were selected randomly and surveyed in 2002. The JNC VII criteria for hypertension were used. Socioeconomic status of the study subjects was estimated by assessing their education, occupation and economic conditions. Descriptive techniques and multivariate logistic regression were used. The prevalence of hypertension was 14.1%. Of hypertensives, only 17.4% were aware of their hypertensive status. Men were hypertensive more often than women and age was positively associated with hypertension. The association between hypertension and socioeconomic status was complex and differed between men and women. Among men, those with lower educational and occupational status but who were richer were more likely to be hypertensive. More women with lower occupational and economic status were hypertensive.

Is 60 the New 80 in Hypertension?

PubMed

Pflederer, Matthew C; Estacio, Raymond O; Krantz, Mori J

2016-08-01

Since the release of the "2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8)", much controversy has ensued over the appropriate systolic blood pressure goal for those over the age of 60 years. This guideline suggested liberalizing the target for this population to <150 mmHg, moving away from previous guidelines suggesting a target of <140 mmHg. While some national quality measures have accepted the new relaxed blood pressure goal, the American Heart Association and American College of Cardiology have not. Recently published data show that millions of adults over 60 years of age would be classified as controlled using a threshold of <150 mmHg, but not with a target of <140 mmHg. In addition, emerging randomized trial evidence suggests that targeting a systolic blood pressure well below 140 mmHg is beneficial in older adults. In light of the improved health and vitality of older adults, and the steady decline in cardiovascular and cerebrovascular mortality over recent decades, we do not think it is in good judgment to liberalize the treatment target in adults less than 80 years of age.

Association of DD genotype of angiotensin-converting enzyme gene (I/D) polymorphism with hypertension among a North Indian population.

PubMed

Rana, Garima; Yadav, Suniti; Joshi, Shipra; Saraswathy, K N

2018-01-01

Hypertension, a major risk factor for cardiovascular diseases, is among the leading causes of morbidity and mortality worldwide. Genetic predisposition to the risk of developing hypertension due to angiotensin-converting enzyme (ACE) gene insertion(I)/deletion(D) polymorphism (through altered serum ACE activity) is well documented among various populations. The present study investigated the possible association between ACE (DD) genotype and hypertension using a nested case-control study design including 451 individuals (of either sex in the age group 30-65 years) from a rural North Indian population practicing agriculture and lacto-vegetarianism. Blood Pressure was classified using JNC-7 criterion. Age- and sex-matched individuals were selected from normotensive (N-122), pre-hypertensive (N-123), hypertensive not on medication (N-122), and hypertensive on medication (N-84) categories. Amplification of DNA and genotyping of PCR product was done using standard protocols. From the analysis, comparatively higher frequency of individuals with DD genotype in the hypertensive category was observed, indicating a possible relation between DD genotype and hypertension. The odds ratio analysis revealed 2.225 (1.13-4.37)-fold significant increased risk for hypertension among cases, validating the vulnerability of individuals with DD genotype towards hypertension. Thus, the present study highlights the increased risk for developing hypertension due to ACE DD genotype in the studied population.

ALLHAT in perspective: implications to clinical practice and clinical trials.

PubMed

Yusoff, K

2005-06-01

ALLHAT study is the biggest randomized clinical trial in hypertension ever conducted. Its objective was to ompare the efficacy of newer (calcium channel blocker amlodipine and angiotensin-converting enzyme inhibitor inopril) to the older (diuretic chlorthalidone) antihypertensive agents in the treatment of patients with hypertension. After enrolling 42,000 patients who were followed for an average of 4.9 years, ALLHAT did not find significant differences in the primary end-points between these antihypertenive agents. ALLHAT however found significant differences in the secondary end-points such as heart failure and strokes between chlorthalidone and amlodipine or lisinopril. Based on these and on economic reasons, the investigators unequivocally recommended diuretics as the first line therapy for hypertension. Since its publication, ALLHAT has been much discussed, debated A and opined. The choice of drugs for study, the study design, the conduct of the study and the conclusions drawn by the investigators had all been criticised or controversial. Yet ALLHAT has been widely quoted, commented upon or referred to and it has been instrumental in initiating the JNC VII Guidelines. Thus a thorough understanding of ALLHAT is necessary for clinical practice and in designing and evaluating clinical trials in the future. Moving Points: in Medicine will capture the essence of ALLHAT, discusses its implications to clinical trials and explores its possible impact on the practice of medicine in this country.

Perceived Job Stress and Presence of Hypertension Among Administrative Officers in Sri Lanka

PubMed Central

Gamage, Anuji Upekshika; De Alwis Seneviratne, Rohini

2016-01-01

A cross-sectional survey was carried out among 275 and 760 randomly selected senior officers (SOs) and managerial assistants (MAs) aged between 30 and 60 years. Sum of scores of efforts, rewards, and overcommitment and effort–reward ratio assessed job stress. Blood pressure was measured and classified using JNC-7 guidelines. The response rates of SOs and MAs were 98.9% and 97.2%, respectively. The prevalence of job stress based on high effort–rewards imbalance among SOs and MAs was 74.6% and 80.5%, respectively. The prevalence of overcommitment among SOs and MAs was 35.3% and 29%, respectively. Statistically significant differences (P = .05) were observed between the prevalence of effort–reward imbalance and overcommitment among SOs and MAs. Multivariate analysis indicated effort–reward imbalance (odds ratio [OR] = 2.8; 95% confidence interval [CI] = 1.1–7.4), high efforts (OR = 2.5; 95% CI = 1.2–5.3), and overcommitment (OR = 2.5; 95% CI = 1.1–5.6) were significantly associated with hypertension among SOs. Similarly, effort–reward imbalance and high efforts increased the risk of hypertension by 2-fold (OR = 2.2; 95% CI = 1.1–4.2) and 3-fold (OR = 3.02; 95% CI = 1.9–4.8), respectively, among the MAs. A significant number of administrators are afflicted by job stress, and job stress was significantly associated with hypertension. PMID:26276363

Cardiovascular disease risk factors, CHD morbidity and mortality in the Federal Republic of Germany.

PubMed

Greiser, E; Joeckel, K H; Giersiepen, K; Maschewsky-Schneider, U; Zachcial, M

1989-01-01

Analyses of data from the first National Health Examination Survey undertaken from 1984-1986 within the framework of the German Cardiovascular Prevention Study, show the following risk factor prevalences in 25-69 year-old men and women: overweight (BMI males: greater than 25, females greater than 24) or obese (BMI greater than 30): men 65.0%, women 57.6%; total serum cholesterol (less than 5.17 mmol/dl): men 73.7%, women 74.0%; normal blood pressure (according to JNC definitions): men 45.0%, women 59.1%; hypertension according to WHO criteria: men 26.0%, women 21.1%; controlled hypertensives (WHO criteria): men 19.9%, women 33.9%; current smoking: men 40.8%, women 26.1%. For most of the cardiovascular risk factors there is a clear negative association between prevalence and length of school education. Three myocardial infarction (MI) registries (WHO MONICA Project) are operating in the Federal Republic of Germany. Incidence and case-fatality data are within comparable ranges. Coronary heart disease (CHD) mortality has been relatively stable in both sexes from 1970 to 1986 with a minor peak in 1976 and a slight downward trend since then. A study of the reliability of coding procedures in West German state statistical offices revealed major disagreements so that trends derived from national mortality data as aggregate data of the federal states might be spurious. An ecological correlation of regional smoking prevalences (1978) and regional CHD mortality rates (1977-9) showed significant coefficients in men, but not in women.

Hypertension and related lifestyle factors among persons living in rural Nicaragua.

PubMed

Alicea-Planas, Jessica; Greiner, Lydia; Greiner, Philip A

2016-02-01

Globally about 40% of adults are diagnosed with hypertension, with high-income countries having a lower prevalence than low-income countries. However, there are limited data about adult hypertension prevalence in Nicaragua. The purpose of this study was to determine the prevalence of hypertension in rural coffee farm workers. A convenience sample of 229 adult coffee farm workers was used. Blood pressure was measured using an established protocol and the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC-7) guidelines. Nearly 60% of the sample reported at least one prior blood pressure measurement. Hypertension was detected in 16.7% of males and 26.3% of females (20.7% of the total). Prehypertension was detected in 59.3% of males and 27.7% of females (46.2% of the total). Of the men, 51.4% reported smoking at least some days and just over one third of the sample reported adding extra salt to their food. While the prevalence of hypertension in this sample is lower than global estimates, almost half of the sample had prehypertension, demonstrating an area where health promotion efforts could be focused. Given the limited funding and resources often available in these areas, increasing disease prevention efforts (including health promotion and wellness programs) and establishing settings that provide outreach and education, may improve chronic disease management and prevent comorbidities from occurring. Copyright © 2015 Elsevier Inc. All rights reserved.

Hypertension and hyperlipidemia management in patients treated at community health centers.

PubMed

Kirchhoff, Anne C; Drum, Melinda L; Zhang, James X; Schlichting, Jennifer; Levie, Jessica; Harrison, James F; Lippold, Susan A; Schaefer, Cynthia T; Chin, Marshall H

2008-01-01

OBJECTIVE: Community health centers (HCs) provide care for millions of medically underserved Americans with disproportionate burdens of hypertension and hyperlipidemia. For both conditions, treatment guidelines recently became more stringent and quality improvement (QI) efforts have intensified. We assessed hypertension and hyperlipidemia management in HCs during this time of guideline revision and increased QI efforts. DESIGN: Cross-sectional chart review. SETTING AND PARTICIPANTS: Eleven Midwestern HCs for 2000 and 9 for 2002 provided audit data from 2,976 randomly chosen patients with hypertension and/or hyperlipidemia. MEASUREMENT: Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC VI/VII) and National Cholesterol Education Program Adult Treatment Panel (NCEP-ATP III) guidelines were used to assess management of these conditions. RESULTS: Hypertension (2000, N=808; 2002, N=692) and hyperlipidemia (2000, N=774; 2002, N=702) outcomes improved for specific clinical subgroups. Hypertensive patients with 1 or more cardiovascular risk factors demonstrated significant improvement (34% vs. 45% controlled at <140/90 mm Hg, p=0.02). Hypertension control for persons with diabetes, renal failure and heart failure increased (16% vs. 28% controlled at <130/85 mm Hg, p=0.006). LDL control increased significantly for patients with 2 or more risk factors (39% vs. 58% controlled at <130 mg/dl, p=0.008). Other clinical subgroups showed trends toward better control, although there was insufficient power to detect significant differences for these groups. CONCLUSION: Hypertension and hyperlipidemia outcomes improved for some risk groups; however, ongoing QI is necessary.

Serum Markers of Endothelial Dysfunction and Inflammation Increase in Hypertension with Prediabetes Mellitus.

PubMed

Huang, Zhouqing; Chen, Chen; Li, Sheng; Kong, Fanqi; Shan, Peiren; Huang, Weijian

2016-06-01

The aim of this study was to examine endothelial dysfunction and inflammation in hypertension and prediabetes by studying adhesion molecules and inflammatory factors. This study included 133 outpatients. Participants were categorized into three groups based on the presence or absence of hypertension and prediabetes: control subjects without prediabetes and hypertension (N group, n = 39); patients with hypertension only (H group, n = 34); and patients with hypertension and prediabetes (HD group, n = 60). Hypertension was diagnosed according to JNC7 criteria. Prediabetes was defined according to 2010 American Diabetes Association criteria. Plasma was isolated from overnight fasting blood samples for enzyme-linked immunosorbent assay (ELISA) analysis of concentrations of intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor-α (TNF-α), P-selectin, and interleukin-6 (IL-6) as indicators of endothelial function and inflammation. We found that the H and HD groups showed significantly higher levels of all four biomarkers compared with the N group (all p < 0.01). The HD group also showed significantly higher levels of ICAM-1 (p = 0.042) and TNF-α (p < 0.01) compared with the H group; no significant differences in P-selectin (p = 0.59) and IL-6 (p = 0.70) levels were observed among these groups. Prediabetes and hypertension induce endothelial dysfunction and inflammation by elevating levels of soluble adhesion molecules and inflammatory cytokines. The comorbidity of these diseases may exacerbate inflammation and endothelial dysfunction by enhancing the expression of ICAM-1 and TNF-α.

Prevalence, awareness, treatment and control of hypertension among the elderly in Bangladesh and India: a multicentre study.

PubMed Central

2001-01-01

OBJECTIVE: To evaluate the prevalence, awareness, treatment and control of hypertension among elderly individuals in Bangladesh and India. METHOD: A community-based sample of 1203 elderly individuals (670 women; mean age, 70 years) was selected using a multistage cluster sampling technique from two sites in Bangladesh and three sites in India. FINDINGS: The overall prevalence of hypertension (WHO-International Society for Hypertension criteria) was 65% (95% confidence interval = 62-67%). The prevalence was higher in urban than rural areas, but did not differ significantly between the sexes. Multiple logistic regression analyses identified a higher body mass index, higher education status and prevalent diabetes mellitus as important correlates of the prevalence of hypertension. Physical activity, rural residence, and current smoking were inversely related to the prevalence of hypertension. Among study subjects who had hypertension, 45% were aware of their condition, 40% were taking anti-hypertensive medications, but only 10% achieved the level established by the US Sixth Joint National Committee on Detection, Evaluation and Treatment of Hypertension (JNC VI)/WHO criteria. A visit to a physician in the previous year, higher educational attainment and being female emerged as important correlates of hypertension awareness. CONCLUSIONS: Our findings emphasize the need to implement effective and low cost management regimens based on absolute levels of cardiovascular risk appropriate for the economic context. From a public health perspective, the only sustainable approach to the high prevalence of hypertension in the Indian subcontinent is through a strategy to reduce the average blood pressure in the population. PMID:11436469

Differences in blood pressure control in a large population-based sample of older African Americans and non-Hispanic whites.

PubMed

Delgado, Jose; Jacobs, Elizabeth A; Lackland, Daniel T; Evans, Denis A; de Leon, Carlos F Mendes

2012-11-01

Cardiovascular disease is the main cause of death in older adults. Uncontrolled blood pressure is an important risk factor for cardiovascular disease. African Americans have poorer blood pressure control than non-Hispanic whites. Little is known about whether this difference persists in older ages or the factors that contribute to this racial gap. Data were obtained from participants of the Chicago Health and Aging Program. Blood pressure control was defined according to JNC-7 criteria. Univariate chi-square analyses were used to determine racial differences in hypertension and blood pressure control, whereas sequential multivariate logistic regression models were used to determine the effect of race on blood pressure control. African Americans had a higher prevalence of hypertension (74% vs 63%; p < .001), higher awareness of hypertension (81% vs 72%; p < .001), and poorer blood pressure control (45% vs 51%, p < .001) than non-Hispanic whites. Racial differences in blood pressure control persisted after adjustment for socioeconomic status, medical conditions, obesity, and use of antihypertensive medications (odds ratio = 0.84, 95% confidence interval = 0.70-0.94). From 1993 to 2008, blood pressure control improved more among non-Hispanic whites than among African Americans. Racial differences in blood pressure control in older adults were not explained by socioeconomic status. The racial disparity in the prevalence and control of hypertension remained consistent for older hypertensive individuals eligible for Medicare. Although the rates of hypertension control improved for both racial groups, the improvement was greater among whites, thus widening the gap in this older population at high risk for cardiovascular disease.

High Blood Pressure Increases the Risk of Poor Outcome at Discharge and 12-month Follow-up in Patients with Symptomatic Intracranial Large Artery Stenosis and Occlusions: Subgroup analysis of the CICAS Study.

PubMed

Yu, Dan-Dan; Pu, Yue-Hua; Pan, Yue-Song; Zou, Xin-Ying; Soo, Yannie; Leung, Thomas; Liu, Li-Ping; Wang, David Z; Wong, Ka-Sing; Wang, Yi-Long; Wang, Yong-Jun

2015-06-01

The purpose of this study was to discuss the relationship between blood pressure and prognosis of patients with symptomatic intracranial arterial stenosis. Data on 2426 patients with symptomatic intracranial large artery stenosis and occlusion who participated in the Chinese Intracranial Atherosclerosis (CICAS) study were analyzed. According to the JNC 7 criteria, blood pressure of all patients was classified into one of the four subgroups: normal, prehypertension, hypertension stage I, and hypertension stage II. Poor outcomes were defined as death and functional dependency (mRS 3-5) at discharge or at 1 year. For patients with intracranial stenosis of 70% to 99%, the rate of poor outcome at discharge was 19.3%, 23.5%, 26.8%, and 39.8% (P = 0.001) for each blood pressure subgroup. For patients with intracranial large artery occlusion, the rates were 17.6%, 22.1%, 29.5%, and 49.8%, respectively (P < 0.0001). The rate of poor outcome at 12-month follow-up was 12.6%, 15.3%, 28.5%, and 27.9% (P = 0.0038) in patients with stenosis of 70% to 99% for each blood pressure subgroup and 11.6%, 21.5%, 23.9%, 35.1% (P < 0.0001) in patients with occlusion. For patients with severe intracranial arterial stenosis or occlusion, higher hypertension stages are associated with an increased risk of poor outcome at discharge and 12-month follow-up. © 2015 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.

Nurse management for hypertension. A systems approach.

PubMed

Rudd, Peter; Miller, Nancy Houston; Kaufman, Judy; Kraemer, Helena C; Bandura, Albert; Greenwald, George; Debusk, Robert F

2004-10-01

Standard office-based approaches to controlling hypertension show limited success. Such suboptimal hypertension control reflects in part the absence of both an infrastructure for patient education and frequent, regular blood pressure (BP) monitoring. We tested the efficacy of a physician-directed, nurse-managed, home-based system for hypertension management with standardized algorithms to modulate drug therapy, based on patients' reports of home BP. We randomized outpatients requiring drug therapy for hypertension according to the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) criteria to receive usual medical care only (UC, n = 76) or usual care plus nurse care management intervention (INT, n = 74) over a 6-month period. Patients receiving INT achieved greater reductions in office BP values at 6 months than those receiving UC: 14.2 +/- 18.1 versus 5.7 +/- 18.7 mm Hg systolic (P < .01) and 6.5 +/- 10.0 versus 3.4 +/- 7.9 mm Hg diastolic, respectively (P < .05). At 6 months, we observed one or more changes in drug therapy in 97% of INT patients versus 43% of UC patients, and 70% of INT patients received two or more drugs versus 46% of UC. Average daily adherence to medication, measured by electronic drug event monitors, was superior among INT subjects (mean +/- SD, 80.5% +/- 23.0%) than among UC subjects (69.2 +/- 31.1%; t(113) = 2.199, P = .03). There were no significant adverse drug reactions in either group. Telephone-mediated nurse management can successfully address many of the systems-related and patient-related issues that limit pharmacotherapeutic effectiveness for hypertension.

Assessment of cognitive function in patients with essential hypertension treated with lercanidipine

PubMed Central

Tisaire-Sánchez, J; Roma, J; CamachoAzcargorta, Ignacio; Bueno-Gómez, J; Mora-Maciá, J; Navarro, Angel

2006-01-01

Objectives The aim of this longitudinal, open-label, comparative, multicenter study was to assess cognitive function in hypertensive patients receiving mid-term treatment with lercanidipine. Methods Hypertensive patients aged 40 years or older were treated with lercanidipine (10mg daily) after 7–10 days washout period. The duration of the study was 6 months. Blood pressure (BP) was measured every 4 weeks (JNC 6th report). In patients with inadequate BP control, doxazosin was added and up-titrated. At baseline and after 6 months of treatment, cognitive function was evaluated using the Spanish validated version of the Mini-Mental State Examination (MMSE) and the Trail Making Test (TMT). Results In the study population of 467 patients, BP decreased from 154.4/95.3 mmHg at baseline to 134.8/80.7 mmHg at 6 months. At the end of the study, 98% of patients were receiving lercanidipine, 20% an angiotensin-converting enzyme inhibitor, and 6% doxazosin. Adequate BP control was obtained in 68% of patients. The mean (standard deviation) MMSE scores improved from 32.35 (2.59) to 33.25 (2.36) (p<0.0001). Patients with good BP control scored significantly better than those with inadequate BP control (p<0.05), which was already observed at the first month. Conclusions The third-generation calcium channel antagonist, lercanidipine, improved cognitive function after 6 months of treatment especially in patients with good BP control, suggesting that improvements in cognitive function may be associated with a decrease in BP. PMID:17323604

Associated influence of hypertension and heart rate greater than 80 beats per minute on mortality rate in patients with anterior wall STEMI

PubMed Central

Davidovic, Goran; Iric-Cupic, Violeta; Milanov, Srdjan

2013-01-01

Acute myocardial infarction as a form of coronary heart disease is characterized by permanent damage/loss of anatomical and functional cardiac tissue. Diagnosis of STEMI includes data on anginal pain and persistent ST-segment elavation. According to the numerous epidemiological studies, arterial blood pressure and heart rate are offten increased especially during the first hours of pain due to domination of sympathetic response. We wanted to investigate the associated influence of heart rate greater than 80 beats per minute and hypertension on the mortality in patients with anterior wall STEMI. Research included 140 patients treated in Coronary Unit, Clinical Center Kragujevac form January 2001 to June 2006. Heart rate was calculated as the mean value of baseline and heart rate in the first 30 minutes after admission, recorded on monitor and electrocardiogram. Data for history of hypertension were collected and blood pressure levels were measured in a lying position after 5 minutes of rest, and classified according to the VII JNC recommendations as confirmation of hypertension. Collected data were analyzed in SPSS 13.0 for Windows. Heart rate greater than 80 bpm influences the hospital mortality. Systolic blood pressure levels were higher in the survivors, while for the diastolic there was no difference. History of hypertension was singled out as a significant predictor of mortality without difference between the respondents with heart rate greater and lower than 80 bpm in the survivors and fatal. Increased heart rate and hypertension at admission are significant predictors of mortality in patients with anterior wall STEMI. PMID:23724155

Towards Efficient Wireless Body Area Network Using Two-Way Relay Cooperation.

PubMed

Waheed, Maham; Ahmad, Rizwan; Ahmed, Waqas; Drieberg, Micheal; Alam, Muhammad Mahtab

2018-02-13

The fabrication of lightweight, ultra-thin, low power and intelligent body-borne sensors leads to novel advances in wireless body area networks (WBANs). Depending on the placement of the nodes, it is characterized as in/on body WBAN; thus, the channel is largely affected by body posture, clothing, muscle movement, body temperature and climatic conditions. The energy resources are limited and it is not feasible to replace the sensor's battery frequently. In order to keep the sensor in working condition, the channel resources should be reserved. The lifetime of the sensor is very crucial and it highly depends on transmission among sensor nodes and energy consumption. The reliability and energy efficiency in WBAN applications play a vital role. In this paper, the analytical expressions for energy efficiency (EE) and packet error rate (PER) are formulated for two-way relay cooperative communication. The results depict better reliability and efficiency compared to direct and one-way relay communication. The effective performance range of direct vs. cooperative communication is separated by a threshold distance. Based on EE calculations, an optimal packet size is observed that provides maximum efficiency over a certain link length. A smart and energy efficient system is articulated that utilizes all three communication modes, namely direct, one-way relay and two-way relay, as the direct link performs better for a certain range, but the cooperative communication gives better results for increased distance in terms of EE. The efficacy of the proposed hybrid scheme is also demonstrated over a practical quasi-static channel. Furthermore, link length extension and diversity is achieved by joint network-channel (JNC) coding the cooperative link.

Cardiovascular and Metabolic Predictors of Progression of Prehypertension into Hypertension: The Strong Heart Study

PubMed Central

De Marco, Marina; de Simone, Giovanni; Roman, Mary J; Chinali, Marcello; Lee, Elisa T; Russell, Marie; Howard, Barbara V; Devereux, Richard B

2009-01-01

Prehypertension (defined by JNC-7) frequently evolves to hypertension (HTN) and increases cardiovascular risk. It is unclear whether metabolic and/or cardiac characteristics favor development of HTN in prehypertensive subjects. We evaluated baseline anthropometric, laboratory and echocardiographic characteristics of 625 untreated prehypertensive participants in the Strong Heart Study (SHS), without prevalent cardiovascular disease (63% women; 22% diabetes; mean age 59±7 years) to identify predictors of 4-year incidence of hypertension. Diabetes was assessed by ADA criteria and diabetes-specific definition of hypertension was used. Four-year incidence of HTN was 38%. Incident HTN was independently predicted by baseline systolic blood pressure (OR= 1.60 per 10 mmHg, 95% CI=1.30-2.00; p<0.0001), waist circumference (OR=1.10 per 10 cm, 95% CI=1.01-1.30; p=0.04) and diabetes (OR= 2.73, 95% CI=1.77-4.21; p<0.0001), with no significant effect for age, gender, HbA1c, HOMA index, CRP, fibrinogen, LDL-HDL cholesterol, tryglicerides, plasma creatinine or urine albumin/creatinine. Higher left ventricular mass index (OR=1.15 per 5 g/m2.7, 95% CI=1.01-1.25; p= 0.03) or stroke volume index (OR=1.25 per 5 ml/m2.04, 95% CI=1.10-1.50; p= 0.03) were also identified, together with baseline systolic blood pressure and presence of diabetes, as independent predictors of incident HTN, without additional predictive contribution from other anthropometric, metabolic or echocardiographic parameters (all p>0.10). Thus, progression to HTN in 38% of SHS pre-hypertensive participants could be predicted by higher left ventricular mass and stroke volume in addition to baseline systolic blood pressure and prevalent diabetes. PMID:19720957

Counseling African Americans to Control Hypertension (CAATCH) Trial: A Multi-level Intervention to Improve Blood Pressure Control in Hypertensive African Americans

PubMed Central

Ogedegbe, Gbenga; Tobin, Jonathan N.; Fernandez, Senaida; Gerin, William; Diaz-Gloster, Marleny; Cassells, Andrea; Khalida, Chamanara; Pickering, Thomas; Schoenthaler, Antoinette; Ravenell, Joseph

2009-01-01

Background Despite strong evidence of effective interventions targeted at blood pressure (BP) control, there is little evidence on the translation of these approaches to routine clinical practice in care of hypertensive African Americans. The goal of this study is to evaluate the effectiveness of a multi-level, multi-component, evidence-based intervention compared to usual care in improving BP control among hypertensive African Americans who receive care in Community Health Centers (CHCs). The primary outcomes are BP control rate at 12 months; and maintenance of intervention one year after the trial. The secondary outcomes are within-patient change in BP from baseline to 12 months and cost effectiveness of the intervention. Methods and Results Counseling African Americans to Control Hypertension (CAATCH) is a group randomized clinical trial with two conditions: Intervention Condition (IC) and Usual Care (UC). Thirty CHCs were randomly assigned equally to the IC group (N=15) or the UC group (N=15). The intervention is comprised of three components targeted at patients (interactive computerized hypertension education; home BP monitoring; and monthly behavioral counseling on lifestyle modification) and two components targeted at physicians (monthly case rounds based on JNC-7 guidelines; chart audit and provision of feedback on clinical performance and patients’ home BP readings). All outcomes are assessed at quarterly study visits for one year. Chart review is conducted at 24 months to evaluate maintenance of intervention effects and sustainability of the intervention. Conclusions Poor BP control is one of the major reasons for the mortality gap between African Americans and whites. Findings from this study, if successful, will provide salient information needed for translation and dissemination of evidence-based interventions targeted at BP control into clinical practice for this high-risk population. PMID:20031845

P05.05. A Multidisciplinary Approach to Hypertension: Yes We Can!

PubMed Central

Cheng, Catherine; Burns, Virginia; Southard, Carol; Silberg, Aline; Crowley, Maggie; Feldman, Howard; Meyer, Mary Anne

2013-01-01

Focus Area: Integrative Approaches to Care Hypertension is one of the most common chronic diseases in our nation, affecting approximately 75 million adults, according to the American Heart Association. Data from the JNC-7 in 2003 demonstrated that about two-thirds of those individuals who are being treated with conventional antihypertensive agents did not have their blood pressure under control. Thus, there is a clear need for a complementary and integrative approach to fill in the gaps left by conventional medicine in the treatment of hypertension. In addition, many patients either cannot tolerate conventional antihypertensive medications or are more interested in trying other types of treatments to help control their blood pressure. There are myriad complementary and integrative approaches used for antihypertensive effects, and it is beneficial for practitioners to be aware of the available options. But beyond simply knowing about the choices they have to help their patients manage their hypertension, it is also important for providers to know what evidence exists for the different modalities in order to help direct their patients to make the best choices for their own overall health. The poster presentation will address segments on integrative treatment approaches for hypertension that will include (1) acupuncture and traditional Chinese medicine; (2) tobacco cessation; (3) massage therapy; (4) mindfulness meditation; (5) qi gong; and (6) overall lifestyle change—diet, exercise, and supplements. For most of the individual segments, there will be demonstrations of techniques to be done either with the group as a whole or with individual volunteers. The presenter will discuss the available research for each of the treatment modalities as well as the types of patients who might respond well to specific types of treatment.

Manganese- and 1-methyl-4-phenylpyridinium-induced neurotoxicity display differences in morphological, electrophysiological and genome-wide alterations: implications for idiopathic Parkinson's disease.

PubMed

Mythri, Rajeswara Babu; Raghunath, Narayana Reddy; Narwade, Santosh Chandrakant; Pandareesh, Mirazkar Dasharatha Rao; Sabitha, Kollarkandi Rajesh; Aiyaz, Mohamad; Chand, Bipin; Sule, Manas; Ghosh, Krittika; Kumar, Senthil; Shankarappa, Bhagyalakshmi; Soundararajan, Soundarya; Alladi, Phalguni Anand; Purushottam, Meera; Gayathri, Narayanappa; Deobagkar, Deepti Dileep; Laxmi, Thenkanidiyoor Rao; Srinivas Bharath, Muchukunte Mukunda

2017-11-01

Idiopathic Parkinson's disease and manganese-induced atypical parkinsonism are characterized by movement disorder and nigrostriatal pathology. Although clinical features, brain region involved and responsiveness to levodopa distinguish both, differences at the neuronal level are largely unknown. We studied the morphological, neurophysiological and molecular differences in dopaminergic neurons exposed to the Parkinson's disease toxin 1-methyl-4-phenylpyridinium ion (MPP + ) and manganese (Mn), followed by validation in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and Mn mouse models. Morphological analysis highlighted loss of neuronal processes in the MPP + and not the Mn model. Cellular network dynamics of dopaminergic neurons characterized by spike frequency and inter-spike intervals indicated major neuronal population (~ 93%) with slow discharge rates (0-5 Hz). While MPP + exposure suppressed the firing of these neurons, Mn neither suppressed nor elevated the neuronal activity. High-throughput transcriptomic analysis revealed up-regulation of 694 and 603 genes and down-regulation of 428 and 255 genes in the MPP + and Mn models respectively. Many differentially expressed genes were unique to either models and contributed to neuroinflammation, metabolic/mitochondrial function, apoptosis and nuclear function, synaptic plasticity, neurotransmission and cytoskeleton. Analysis of the Janus kinase-signal transducer and activator of transcription pathway with implications for neuritogenesis and neuronal proliferation revealed contrasting profile in both models. Genome-wide DNA methylomics revealed differences between both models and substantiated the epigenetic basis of the difference in the Janus kinase-signal transducer and activator of transcription pathway. We conclude that idiopathic Parkinson's disease and atypical parkinsonism have divergent neurotoxicological manifestation at the dopaminergic neuronal level with implications for pathobiology and evolution of novel therapeutics. Cover Image for this issue: doi. 10.1111/jnc.13821. © 2017 International Society for Neurochemistry.

Comparison of metabolic syndrome with growing epidemic syndrome Z in terms of risk factors and gender differences.

PubMed

Uyar, Meral; Davutoğlu, Vedat; Aydın, Neriman; Filiz, Ayten

2013-05-01

The aim of this study is to compare metabolic syndrome with syndrome Z growing epidemic in terms of risk factors, demographic variables, and gender differences in our large cohort at southeastern area in Turkey. Data of patients admitted to sleep clinic in University of Gaziantep from January 2006 to January 2011 were retrospectively evaluated. ATP III and JNC 7 were used for defining metabolic syndrome and hypertension. Data of 761 patients were evaluated. Hypertension, diabetes mellitus, coronary artery disease, pulmonary hypertension, and left ventricular hypertrophy were more common in patients with syndrome Z than in patients without metabolic syndrome. Age, waist/neck circumferences, BMI, triglyceride, glucose, and Epworth sleepiness scale score were detected higher, whereas the minimum oxygen saturation during sleep was lower in patients with syndrome Z. Metabolic syndrome was more common in sleep apneic subjects than in controls (58 versus 30 %). Female sleep apneics showed higher rate of metabolic syndrome than those of males (74 versus 52 %). Hypertension, diabetes mellitus, coronary artery disease, and left ventricular hypertrophy were detected higher in males with syndrome Z than in males without metabolic syndrome. Snoring and excessive daytime sleepiness were detected higher in females with syndrome Z than in females without metabolic syndrome. Systemic/pulmonary hypertension, diabetes mellitus, and left ventricular hypertrophy were more common in females with syndrome Z than in females without metabolic syndrome. Complaints of headache and systemic/pulmonary hypertension were more common among females than males with syndrome Z. Female syndrome Z patients had lower minimum oxygen saturation than male patients with syndrome Z. Metabolic syndrome in sleep apneic patients is more prevalent than in controls. All metabolic syndrome parameters were significantly different among obstructive sleep apneic patients with respect to gender with more severe coronary risk factors in males.

Association of aldosterone and cortisol with cardiovascular risk factors in prehypertension stage.

PubMed

Syed, Sadiqa Badar; Qureshi, Masood Anwar

2012-01-01

Background. The Pakistani population has higher incidence of cardiovascular (CV) diseases at younger ages, due to undiagnosed, uncontrolled hypertension (HTN). A variety of associated HTN stressors is also reported. The study plans to understand the variables associated with initiation of HTN in this population. Objective. To find plasma aldosterone and cortisol relationship with some CV risk factors (obesity, dyslipidemia, hyperglycemia, sodium and potassium) in different stages of HTN particularly prehypertension. Subjects and Methods. The study conducted on 276 subjects (25-60 years), classified into prehypertensive (n = 55), HTN stage-1 (n = 70) and II (n = 76) according to 7th JNC report and compared with normotensive controls (n = 75). The anthropometric profiles (height, weight, waist circumference, Body Mass index) and BP recorded. Serum cortisol, aldosterone, total cholesterol, Low density lipoproteins, blood glucose, Na(+) and K(+), using standard laboratory techniques, were determined in fasting blood samples. Results. Subjects were mostly overweight and obese (80%, 90%, and 76% in pre-HTN, stage-I and II versus 69% in controls). The aldosterone level (ng/dl) was in higher normal range (9.17-12.41) and significantly correlated to BMI (0.587) in controls, and to TC (0.726) and LDL (0.620) in pre-HTN stage-I. The cortisol level was positively correlated (P < 0.01) to BMI (0.538), Na(+) (0.690) and K(+) (0.578) in control, and to BMI (0.628) and WC (0.679) in pre-HTN group, showing its association with BMI > 25. Conclusion. Pre-HTN stage among Pakistani population with successive increase in various risk factors of HTN in relation to aldosterone and cortisol has been identified. Interaction of the risk factors with endogenous levels of these hormones may initiate stages of HTN.

Association of Aldosterone and Cortisol with Cardiovascular Risk Factors in Prehypertension Stage

PubMed Central

Syed, Sadiqa Badar; Qureshi, Masood Anwar

2012-01-01

Background. The Pakistani population has higher incidence of cardiovascular (CV) diseases at younger ages, due to undiagnosed, uncontrolled hypertension (HTN). A variety of associated HTN stressors is also reported. The study plans to understand the variables associated with initiation of HTN in this population. Objective. To find plasma aldosterone and cortisol relationship with some CV risk factors (obesity, dyslipidemia, hyperglycemia, sodium and potassium) in different stages of HTN particularly prehypertension. Subjects and Methods. The study conducted on 276 subjects (25–60 years), classified into prehypertensive (n = 55), HTN stage-1 (n = 70) and II (n = 76) according to 7th JNC report and compared with normotensive controls (n = 75). The anthropometric profiles (height, weight, waist circumference, Body Mass index) and BP recorded. Serum cortisol, aldosterone, total cholesterol, Low density lipoproteins, blood glucose, Na+ and K+, using standard laboratory techniques, were determined in fasting blood samples. Results. Subjects were mostly overweight and obese (80%, 90%, and 76% in pre-HTN, stage-I and II versus 69% in controls). The aldosterone level (ng/dl) was in higher normal range (9.17–12.41) and significantly correlated to BMI (0.587) in controls, and to TC (0.726) and LDL (0.620) in pre-HTN stage-I. The cortisol level was positively correlated (P < 0.01) to BMI (0.538), Na+ (0.690) and K+ (0.578) in control, and to BMI (0.628) and WC (0.679) in pre-HTN group, showing its association with BMI > 25. Conclusion. Pre-HTN stage among Pakistani population with successive increase in various risk factors of HTN in relation to aldosterone and cortisol has been identified. Interaction of the risk factors with endogenous levels of these hormones may initiate stages of HTN. PMID:22957211

Blood pressure trends and hypertension among rural and urban Jat women of Haryana, India.

PubMed

Kaur, Maninder

2012-03-01

Hypertension is an important public health problem and the major causes of cardiovascular morbidity and mortality among aged and elderly population in India. The present study is an attempt to assess age related trends of blood pressure and prevalence of hypertension in rural and urban women as well as correlation of blood pressure with obesity indicators (WC, BMI, and WHR). Data for present cross-sectional study were collected by purposive sampling method from six hundred Jat women (300 rural and 300 urban), aged 40 to 70 years. Karl Pearson's correlation coefficient (r) was employed to find the relationship between blood pressure and obesity indicators. The results revealed an age associated increase in mean values of systolic and diastolic blood pressure in rural and urban women. Urban women showed significantly higher overall mean value of systolic (mm of Hg) (133.93 vs. 130.79, p < 0.001), diastolic blood pressure (mm of Hg) (84.34 vs. 82.81, p < 0.01) and pulse rate (81.72 +/- 6.27 vs. 80.94 +/- 9.06, p > 0.05) as compared to rural women. The overall prevalence of hypertension was found to be 9% in rural and 26.66% in urban women as per JNC VII criteria. Increased prominence of hypertension among urban Jat women may be attributed to their modern lifestyle having more stress, less manual work and faulty dietary habits. There was a very low awareness of hypertension in the rural subjects (37%) than their urban (72%) counterparts. Rural and urban women revealed a positive and significant association of systolic blood pressure with body mass index, whereas only urban women displayed positive correlation of waist circumference with systolic (r = 0.183**) and diastolic (r = 0.151**) blood pressure.

Towards Efficient Wireless Body Area Network Using Two-Way Relay Cooperation

PubMed Central

Waheed, Maham; Ahmad, Rizwan; Ahmed, Waqas

2018-01-01

The fabrication of lightweight, ultra-thin, low power and intelligent body-borne sensors leads to novel advances in wireless body area networks (WBANs). Depending on the placement of the nodes, it is characterized as in/on body WBAN; thus, the channel is largely affected by body posture, clothing, muscle movement, body temperature and climatic conditions. The energy resources are limited and it is not feasible to replace the sensor’s battery frequently. In order to keep the sensor in working condition, the channel resources should be reserved. The lifetime of the sensor is very crucial and it highly depends on transmission among sensor nodes and energy consumption. The reliability and energy efficiency in WBAN applications play a vital role. In this paper, the analytical expressions for energy efficiency (EE) and packet error rate (PER) are formulated for two-way relay cooperative communication. The results depict better reliability and efficiency compared to direct and one-way relay communication. The effective performance range of direct vs. cooperative communication is separated by a threshold distance. Based on EE calculations, an optimal packet size is observed that provides maximum efficiency over a certain link length. A smart and energy efficient system is articulated that utilizes all three communication modes, namely direct, one-way relay and two-way relay, as the direct link performs better for a certain range, but the cooperative communication gives better results for increased distance in terms of EE. The efficacy of the proposed hybrid scheme is also demonstrated over a practical quasi-static channel. Furthermore, link length extension and diversity is achieved by joint network-channel (JNC) coding the cooperative link. PMID:29438278

Psychosocial Factors Are Associated With Blood Pressure Progression Among African Americans in the Jackson Heart Study

PubMed Central

Sims, Mario; Higginbotham, John C.; Crowther, Martha R.; Wyatt, Sharon B.; Musani, Solomon K.; Payne, Thomas J.; Fox, Ervin R.; Parton, Jason M.

2016-01-01

BACKGROUND Research that examines the associations of psychosocial factors with incident hypertension among African Americans (AA) is limited. Using Jackson Heart Study (JHS) data, we examined associations of negative affect and stress with incident hypertension and blood pressure (BP) progression among AA. METHODS Our sample consisted of 1,656 normotensive participants at baseline (2000–2004) (mean age 47±12; 61% women). We investigated associations of negative affect (cynical distrust, anger-in, anger-out, and depressive symptoms) and stress (perceived stress, weekly stress inventory (WSI)-event, WSI-impact, and major life events) with BP progression (an increase by one BP stage as defined by JNC VII) and incident hypertension by examination 2 (2005–2008). Poisson regression analysis was utilized to examine the prevalence ratios (PRs; 95% confidence interval (CI)) of BP tracking and incident hypertension with psychosocial factors, adjusting for baseline age, sex, socioeconomic status (SES), and hypertension risk factors. RESULTS Fifty-six percentage of the sample (922 cases) had BP progression from 2005 to 2008. After adjustment for age, sex, and SES, a high anger-out score was associated with a 20% increased risk of BP progression compared to a low anger-out score (PR 1.20; 95% CI 1.05–1.36). High depressive symptoms score was associated with BP progression in the age, sex, and SES-adjusted model (PR 1.14; 95% CI 1.00–1.30). High WSI-event scores were associated with BP progression in the fully adjusted model (PR 1.21; 95% CI 1.04–1.40). We did not observe significant associations with any of the psychosocial measures and incident hypertension. CONCLUSIONS Psychosocial factors were associated with BP progression, with the strongest evidence for number of stressful events that occurred. PMID:26964661

Self-management of hypertension using technology enabled interventions in primary care settings.

PubMed

Chandak, Aastha; Joshi, Ashish

2015-01-01

Self-management of hypertension by controlling Blood Pressure (BP) through technology-based interventions can effectively reduce the burden of high BP, which affects one out of every three adults in the United States. The primary aim of this study is to explore the role of technology enabled interventions to improve or enhance self-management among individuals with hypertension. We conducted a systematic review of the literature published between July 2008 and June 2013 on the MEDLINE database (via PubMed interface) during July 2013. The search words were "hypertension" and "primary care" in combination with each of the terms of "technology", "internet", "computer" and "cell phone". Our inclusion criteria consisted of: (a) Randomized Controlled Trials (RCTs) (b) conducted on human subjects; (c) technology-based interventions (d) to improve self-management (e) of hypertension and if the (f) final results of the study were published in the study. Our exclusion criteria included (a) management of other conditions and (b) literature reviews. The initial search resulted in 108 results. After applying the inclusion and exclusion criteria, a total of 12 studies were analyzed. Various technologies implemented in the studies included internet-based telemonitoring and education, telephone-based telemonitoring and education, internet-based education, telemedicine via videoconferencing, telehealth kiosks and automated modem device. Some studies also involved a physician intervention, in addition to patient intervention. The outcomes of proportion of subjects with BP control and change in mean SBP and DBP were better for the group of subjects who received combined physician and patient interventions. Interventions to improve BP control for self-management of hypertension should be aimed at both physicians as well as the patients. More interventions should utilize the JNC-7 guidelines and cost-effectiveness of the intervention should also be assessed.

Prevalence and risk factors of hypertension among bank employees in urban Puducherry, India.

PubMed

Ganesh Kumar, S; Deivanai Sundaram, N

2014-04-01

There is paucity of information on the prevalence of hypertension and its risk factors among bank employees at global level. To assess the prevalence and risk factors of hypertension among bank employees in Puducherry, India. A cross-sectional study was conducted on 192 (128 male and 64 female) bank employees from 12 nationalized banks in urban Puducherry, India. Blood pressure was measured and classified according to the Joint National Committee (JNC) VII criteria. Data on risk factors of hypertension, including consumption of extra salt while dining, eating high-salt food, junk food, servings of fruits and vegetables, smoking, alcohol use, physical activity, and body mass index, were obtained for each participant using a standard questionnaire. Stress level was assessed by Cohen's Perceived Stress scale. Data was analyzed by Chi-square test and multiple logistic regression analysis. The mean±SD age of the participants was 39.5±10.6 years. The prevalence of hypertension and pre-hypertension was 44.3% (95% CI: 37.2%-51.3%) and 41.1% (95% CI: 34.1%-48.1%), respectively. Of 85 participants with hypertension, 47 (55%) was known case and 38 (45%) were newly diagnosed. Multiple logistic regression analysis revealed that living in the 4th (OR: 3.13) or 6th (OR: 3.11) decade of life, consumption of extra salt (OR: 2.49), and physical activity ≥2 hours per day (OR: 0.21) were associated with hypertension among bank employees. Prevalence of hypertension is high among bank employees. There is a need for strengthening adoption of certain interventional measures in lifestyle such as reducing salt intake and promoting physical activity among this vulnerable group.

Stages of Systemic Hypertension and Blood Pressure as Correlates of Computed Tomography-Assessed Aortic Valve Calcium (From the Multi-Ethnic Study of Atherosclerosis)

PubMed Central

Linefsky, Jason; Katz, Ronit; Budoff, Matthew; Probstfield, Jeffrey; Owens, David; Takasu, Junichiro; Shavelle, David; Ouyang, Pamela; Psaty, Bruce; O’Brien, Kevin D.

2010-01-01

Hypertension has been identified as a risk factor for aortic valve calcium (AVC) but the magnitude of the risk relation with hypertension severity or whether age affects the strength of this risk association has not been studied. The relationship of hypertension severity, as defined by JNC-7 hypertension stages or blood pressure (BP), to CT-assessed AVC prevalence and severity was examined in 4,274 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) without treated hypertension. Analyses were stratified by age < or ≥ 65 years, were adjusted for common cardiovascular risk factors, and excluded those on antihypertensive medications. In age-stratified, adjusted analyses, Stage I/II hypertension was associated with prevalent AVC in those <65 but not in those ≥65 years of age [OR (95% CI): 2.31 (1.35, 3.94) vs. 1.33 (0.96, 1.85), P-interaction = 0.041]. Similarly, systolic BP and pulse pressure (PP) were more strongly associated with prevalent AVC in those <65 than those ≥65 years of age [OR (95% CI): 1.21 (1.08, 1.35) vs. 1.07 (1.01, 1.14) per 10 mmHg increase in systolic BP, Pinteraction = 0.006] and [OR (95% CI): 1.41 (1.21, 1.64) vs. 1.14 (1.05, 1.23) per 10 mmHg increase in PP]. No associations were found between either hypertension stage or BP and AVC severity. In conclusion, stage I/II hypertension, as well as higher systolic pressure and pulse pressure were associated with prevalent AVC. These risk associations were strongest in participants younger than age 65 years. PMID:21146685

Patients' blood pressure knowledge, perceptions and monitoring practices in community pharmacies.

PubMed

Lam, Jennifer Y; Guirguis, Lisa M

2010-07-01

Hypertension is a modifiable risk factor for cardiovascular disease. Despite this, patients often cannot or inaccurately estimate their risk factors. IN ORDER TO IMPROVE PHARMACIST INTERVENTIONS, WE SOUGHT TO: 1) find out patients' knowledge about blood pressure (BP) and their self-monitoring behaviors and 2) identify the relationships between these two elements. Specifically, if evaluation of BP control were related to knowledge of one's BP level and self-monitoring habits, and if knowledge of one's target and BP level varied with monitoring habits. Final year pharmacy students were trained and interviewed patients in community pharmacies as a required exercise in their pharmacy clerkship. Each student recruited a convenience sample of 5-10 patients who were on hypertension medication, and surveyed them regarding their BP targets, recent BP levels as well as monthly and home BP monitoring practices. One third of the 449 patients interviewed were able to report a blood pressure target with 26% reporting a JNC 7 recognized target. Three quarters of patients who reported a blood pressure target were able to report a blood pressure level, with 12% being at their self-reported target. Roughly two thirds of patients perceived their BP to be "about right", and slightly less than a third thought it to be "high". Sixty percent of patients monitor their BP monthly, but less than 50% of patients practice home BP monitoring. This study along with others before it point to the knowledge and self-management gaps in patients with chronic conditions. Furthermore, pharmacy students were able to use a brief intervention to screen patients during routine care. Pharmacists can help improve patient understanding and promote increased self-management through regular BP monitoring.

Impact of Computerized Decision Support on Blood Pressure Management and Control: A Randomized Controlled Trial

PubMed Central

Sequist, Thomas D.; Ayanian, John Z.; Shaykevich, Shimon; Fairchild, David G.; Orav, E. John; Bates, David W.

2008-01-01

BACKGROUND We conducted a cluster randomized controlled trial to examine the effectiveness of computerized decision support (CDS) designed to improve hypertension care and outcomes in a racially diverse sample of primary care patients. METHODS We randomized 2,027 adult patients receiving hypertension care in 14 primary care practices to either 18 months of their physicians receiving CDS for each hypertensive patient or to usual care without computerized support for the control group. We assessed prescribing of guideline-recommended drug therapy and levels of blood pressure control for patients in each group and examined if the effects of the intervention differed by patients’ race/ethnicity using interaction terms. MEASUREMENTS AND MAIN RESULTS Rates of blood pressure control were 42% at baseline and 46% at the outcome visit with no significant differences between groups. After adjustment for patients’ demographic and clinical characteristics, number of prior visits, and levels of baseline blood pressure control, there were no differences between intervention groups in the odds of outcome blood pressure control. The use of CDS to providers significantly improved Joint National Committee (JNC) guideline adherent medication prescribing compared to usual care (7% versus 5%, P < 0.001); the effects of the intervention remained after multivariable adjustment (odds ratio [OR] 1.39 [CI, 1.13–1.72]) and the effects of the intervention did not differ by patients’ race and ethnicity. CONCLUSIONS CDS improved appropriate medication prescribing with no improvement in disparities in care and overall blood pressure control. Future work focusing on improvement of these interventions and the study of other practical interventions to reduce disparities in hypertension-related outcomes is needed. PMID:18373141

Mild MPP+ exposure impairs autophagic degradation through a novel lysosomal acidity-independent mechanism.

PubMed

Miyara, Masatsugu; Kotake, Yaichiro; Tokunaga, Wataru; Sanoh, Seigo; Ohta, Shigeru

2016-10-01

Parkinson's disease (PD) is the second most common neurodegenerative disorder, but its underlying cause remains unknown. Although recent studies using PD-related neurotoxin MPP + suggest autophagy involvement in the pathogenesis of PD, the effect of MPP + on autophagic processes under mild exposure, which mimics the slow progressive nature of PD, remains largely unclear. We examined the effect of mild MPP + exposure (10 and 200 μM for 48 h), which induces a more slowly developing cell death, on autophagic processes and the mechanistic differences with acute MPP + toxicity (2.5 and 5 mM for 24 h). In SH-SY5Y cells, mild MPP + exposure predominantly inhibited autophagosome degradation, whereas acute MPP + exposure inhibited both autophagosome degradation and basal autophagy. Mild MPP + exposure reduced lysosomal hydrolase cathepsin D activity without changing lysosomal acidity, whereas acute exposure decreased lysosomal density. Lysosome biogenesis enhancers trehalose and rapamycin partially alleviated mild MPP + exposure induced impaired autophagosome degradation and cell death, but did not prevent the pathogenic response to acute MPP + exposure, suggesting irreversible lysosomal damage. We demonstrated impaired autophagic degradation by MPP + exposure and mechanistic differences between mild and acute MPP + toxicities. Mild MPP + toxicity impaired autophagosome degradation through novel lysosomal acidity-independent mechanisms. Sustained mild lysosomal damage may contribute to PD. We examined the effects of MPP + on autophagic processes under mild exposure, which mimics the slow progressive nature of Parkinson's disease, in SH-SY5Y cells. This study demonstrated impaired autophagic degradation through a reduction in lysosomal cathepsin D activity without altering lysosomal acidity by mild MPP + exposure. Mechanistic differences between acute and mild MPP + toxicity were also observed. Sustained mild damage of lysosome may be an underlying cause of Parkinson's disease. Cover Image for this issue: doi: 10.1111/jnc.13338. © 2016 International Society for Neurochemistry.

Synthesis and deposition of basement membrane proteins by primary brain capillary endothelial cells in a murine model of the blood-brain barrier.

PubMed

Thomsen, Maj Schneider; Birkelund, Svend; Burkhart, Annette; Stensballe, Allan; Moos, Torben

2017-03-01

The brain vascular basement membrane is important for both blood-brain barrier (BBB) development, stability, and barrier integrity and the contribution hereto from brain capillary endothelial cells (BCECs), pericytes, and astrocytes of the BBB is probably significant. The aim of this study was to analyse four different in vitro models of the murine BBB for expression and possible secretion of major basement membrane proteins from murine BCECs (mBCECs). mBCECs, pericytes and glial cells (mainly astrocytes and microglia) were prepared from brains of C57BL/6 mice. The mBCECs were grown as monoculture, in co-culture with pericytes or mixed glial cells, or as a triple-culture with both pericytes and mixed glial cells. The integrity of the BBB models was validated by measures of transendothelial electrical resistance (TEER) and passive permeability to mannitol. The expression of basement membrane proteins was analysed using RT-qPCR, mass spectrometry and immunocytochemistry. Co-culturing mBCECs with pericytes, mixed glial cells, or both significantly increased the TEER compared to the monoculture, and a low passive permeability was correlated with high TEER. The mBCECs expressed all major basement membrane proteins such as laminin-411, laminin-511, collagen [α1(IV)] 2 α2(IV), agrin, perlecan, and nidogen 1 and 2 in vitro. Increased expression of the laminin α5 subunit correlated with the addition of BBB-inducing factors (hydrocortisone, Ro 20-1724, and pCPT-cAMP), whereas increased expression of collagen IV α1 primarily correlated with increased levels of cAMP. In conclusion, BCECs cultured in vitro coherently form a BBB and express basement membrane proteins as a feature of maturation. Cover Image for this issue: doi: 10.1111/jnc.13789. © 2016 International Society for Neurochemistry.

Psychosocial Factors Are Associated With Blood Pressure Progression Among African Americans in the Jackson Heart Study.

PubMed

Ford, Cassandra D; Sims, Mario; Higginbotham, John C; Crowther, Martha R; Wyatt, Sharon B; Musani, Solomon K; Payne, Thomas J; Fox, Ervin R; Parton, Jason M

2016-08-01

Research that examines the associations of psychosocial factors with incident hypertension among African Americans (AA) is limited. Using Jackson Heart Study (JHS) data, we examined associations of negative affect and stress with incident hypertension and blood pressure (BP) progression among AA. Our sample consisted of 1,656 normotensive participants at baseline (2000-2004) (mean age 47±12; 61% women). We investigated associations of negative affect (cynical distrust, anger-in, anger-out, and depressive symptoms) and stress (perceived stress, weekly stress inventory (WSI)-event, WSI-impact, and major life events) with BP progression (an increase by one BP stage as defined by JNC VII) and incident hypertension by examination 2 (2005-2008). Poisson regression analysis was utilized to examine the prevalence ratios (PRs; 95% confidence interval (CI)) of BP tracking and incident hypertension with psychosocial factors, adjusting for baseline age, sex, socioeconomic status (SES), and hypertension risk factors. Fifty-six percentage of the sample (922 cases) had BP progression from 2005 to 2008. After adjustment for age, sex, and SES, a high anger-out score was associated with a 20% increased risk of BP progression compared to a low anger-out score (PR 1.20; 95% CI 1.05-1.36). High depressive symptoms score was associated with BP progression in the age, sex, and SES-adjusted model (PR 1.14; 95% CI 1.00-1.30). High WSI-event scores were associated with BP progression in the fully adjusted model (PR 1.21; 95% CI 1.04-1.40). We did not observe significant associations with any of the psychosocial measures and incident hypertension. Psychosocial factors were associated with BP progression, with the strongest evidence for number of stressful events that occurred. © American Journal of Hypertension, Ltd 2016. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Corticosterone and exogenous glucose alter blood glucose levels, neurotoxicity, and vascular toxicity produced by methamphetamine.

PubMed

Bowyer, John F; Tranter, Karen M; Sarkar, Sumit; George, Nysia I; Hanig, Joseph P; Kelly, Kimberly A; Michalovicz, Lindsay T; Miller, Diane B; O'Callaghan, James P

2017-10-01

Our previous studies have raised the possibility that altered blood glucose levels may influence and/or be predictive of methamphetamine (METH) neurotoxicity. This study evaluated the effects of exogenous glucose and corticosterone (CORT) pretreatment alone or in combination with METH on blood glucose levels and the neural and vascular toxicity produced. METH exposure consisted of four sequential injections of 5, 7.5, 10, and 10 mg/kg (2 h between injections) D-METH. The three groups given METH in combination with saline, glucose (METH+Glucose), or CORT (METH+CORT) had significantly higher glucose levels compared to the corresponding treatment groups without METH except at 3 h after the last injection. At this last time point, the METH and METH+Glucose groups had lower levels than the non-METH groups, while the METH+CORT group did not. CORT alone or glucose alone did not significantly increase blood glucose. Mortality rates for the METH+CORT (40%) and METH+Glucose (44%) groups were substantially higher than the METH (< 10%) group. Additionally, METH+CORT significantly increased neurodegeneration above the other three METH treatment groups (≈ 2.5-fold in the parietal cortex). Thus, maintaining elevated levels of glucose during METH exposure increases lethality and may exacerbate neurodegeneration. Neuroinflammation, specifically microglial activation, was associated with degenerating neurons in the parietal cortex and thalamus after METH exposure. The activated microglia in the parietal cortex were surrounding vasculature in most cases and the extent of microglial activation was exacerbated by CORT pretreatment. Our findings show that acute CORT exposure and elevated blood glucose levels can exacerbate METH-induced vascular damage, neuroinflammation, neurodegeneration and lethality. Cover Image for this issue: doi. 10.1111/jnc.13819. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

Stress-sensitivity of The Hydraulic Properties of A Fault Gouge

NASA Astrophysics Data System (ADS)

Harrington, J. F.; Horseman, S. T.; Hama, K.; Metcalfe, R.

Tono Mine is located about 350 km southwest of Tokyo and is the site of the most extensive uranium deposits in Japan. The geological setting comprises Tertiary (Mizu- nami Group) sedimentary rocks overlying Cretaceous granitic basement rocks. In as- cending order, the sedimentary rocks are the Toki Lignite-bearing Formation (con- glomerate, interbedded sandstone and mudstone), the Akeyo Formation (tuffaceous sandstone) and the Oidawara Formation (siltstone and mudstone). The Tsukiyoshi Fault cuts through this sequence and is a reverse fault, dipping to the south at 60- 70 degrees, with a throw of about 30 metres. As part of its hydrogeological studies, JNC is evaluating the impact of the fault on groundwater flow in the Tertiary sedi- ments. A sample was taken from a borehole in the NATM Drift, where the fault zone contains gouge material with two clay-bearing layers around 2 to 3 cm thick, separated by a 10 to 20 cm thick layer of unconsolidated fine sandy material. The sample was obtained using a triple-tube core barrel fitted with a split sample tube and a diamond bit. A specimen was prepared and consolidated at successive effective stress levels of 2, 6 and 12 MPa. The plot of void ratio against the logarithm of effective stress was found to be sensibly linear with a negative slope, kappa, of 0.036 rising to 0.044 at higher stress levels. The evidence suggests that the gouge is overconsolidated. Hy- draulic conductivity and specific storage were also measured at each stress level using the constant flow rate method. Hydraulic conductivity was found to be strongly stress sensitive, falling from 1.84 x 10-12 m.s-1 at 2 MPa to 7.9 x 10-14 m.s-1 at 12 MPa. Specific storage values were analysed using the critical state soil mechanics approach assuming a stress-dependent pore compressibility. Reasonable agreement was found between the theoretical curve with kappa = 0.036 and the measured values.

Low sex hormone-binding globulin is associated with hypertension: a cross-sectional study in a Swedish population

PubMed Central

2013-01-01

Background The aim of this study was to investigate the association of sex hormone-binding globulin (SHBG) and hypertension in a Swedish population. Methods The study is based on a random sample of a Swedish population of men and women aged 30–74 years (n=2,816). Total testosterone, oestradiol and SHBG were measured in 2,782 participants. Free androgen index was then calculated according to the formula FAI=100 × (Total testosterone)/SHBG. Hypertension was diagnosed according to JNC7. Results In men, but not in women, significant association between SHBG and both diastolic (diastolic blood pressure: β=−0.143 p<0.001) and systolic blood pressure (systolic blood pressure β=−0.114 p<0.001) was found. The association was still significant after adjusting for age, body mass index (BMI), homeostatic model assessment insulin resistance (HOMA-IR), triglycerides, high density lipoproteins (HDL) and C-reactive protein (CRP) (diastolic blood pressure: β=−0.113 p<0.001; systolic blood pressure β=−0.093 p=0.001). An inverse association was observed between SHBG and hypertension in both men (B=−0.024 p<0.001) and women (B=−0.022 p<0.001). The association was still significant in women older than 50 years after adjustments for age, BMI, physical activity, CRP and alcohol consumption (B=−0.014, p=0.008). Conclusion In conclusion, these results show a strong association between SHBG and blood pressure independent of major determinants of high blood pressure. This association might be addressed to direct effects of SHBG in endothelial cells through the receptor for SHBG. If this is confirmed by other observational and experimental studies, it might become a new field for the development of therapies for lowering blood pressure. PMID:23594436

[The knowledge, attitude and practice of blood pressure management from the patient's viewpoint: a qualitative study].

PubMed

Lee, Sok-Goo; Jeon, So-Youn

2008-07-01

This study adopted a qualitative method to explore the layman's beliefs and experience concerning high blood pressure and its management in order to develop a strategy to increase adherence to proper medical treatment. Semi-structured interviews that focused on personal experiences with hypertension and its management were conducted with 26 hypertensive patients. The participants were selected according to a BP above 140/90 mmHg (hypertension stage 1), based on the seventh report of the Joint National Committee on prevention, detection, evaluation and treatment of high blood pressure (JNC-VII). The interviews lasted for approximately 30 minutes (range: 20-60 minutes). The resulting questions were formulated into open-ended questions. The interview questionnaire was composed 17 items to examine non-adherence to treatment and 19 items to examine adherence to treatment. Most participants recognized that the direct cause of high blood pressure was unhealthy behavior rather than inheritance. Thus, the hypertensive patient believed they could recover their blood pressure to a normal level through removing the direct cause of hypertension (weight reduction, diet, exercise) instead of taking drugs. The reasons for these statements were that the drugs for controlling hypertension are not natural or they are artificial, and they may have side effects, and drugs are not treatment for the root cause of hypertension. Most of the hypertensive patients chose to manage their behaviors as soon as they knew their blood pressure was high. Therefore, we should not divide the subjects into two groups according to their taking drugs or not, but they should be divided into two groups according to their willingness or not to manage their condition. For developing a strategy for an individual approach to hypertension management, we need to develop a client-centered attitude and strategy. That is, we need to tailor our approach to individual cases to avoid generalizations and stereotyping when developing an adherence increasing strategy.

Endothelial-dependent flow-mediated dilation in African Americans with masked-hypertension.

PubMed

Veerabhadrappa, Praveen; Diaz, Keith M; Feairheller, Deborah L; Sturgeon, Katie M; Williamson, Sheara T; Crabbe, Deborah L; Kashem, Abul M; Brown, Michael D

2011-10-01

Office-blood pressure (BP) measurements alone overlook a significant number of individuals with masked-hypertension (office-BP: 120/80-139/89 mm Hg and 24-h ambulatory BP monitoring (ABPM) daytime ≥135/85 mm Hg or night-time ≥120/70 mm Hg). Diminished endothelial function contributes to the pathogenesis of hypertension. To better understand the pathophysiology involved in the increased cardiovascular (CV) disease risk associated with masked-hypertension, we estimated the occurrence, assessed the endothelial function, compared plasma levels of inflammatory markers, white blood cell count (WBC count), tumor necrosis factor-α (TNF-α), and high sensitivity C-reactive protein (hsCRP) and examined the possible relationship between endothelial function and inflammatory markers in apparently healthy prehypertensive (office-BP: 120/80-139/89 mm Hg) African Americans. Fifty African Americans who were sedentary, nondiabetic, nonsmoking, devoid of CV disease were recruited. Office-BP was measured according to JNC-7 guidelines to identify prehypertensives in whom ABPM was then assessed. Fasting plasma samples were assayed for inflammatory markers. Brachial artery flow-mediated dilation (FMD) at rest and during reactive hyperemia was measured in a subset of prehypertensives. Subjects in the masked-hypertension sub-group had a higher hsCRP (P = 0.04) and diminished endothelial function (P = 0.03) compared to the true-prehypertensive sub-group (office-BP: 120/80-139/89 mm Hg and ABPM: daytime <135/85 mm Hg or night-time <120/70 mm Hg). Regression analysis showed that endothelial function was inversely related to hsCRP amongst the masked-hypertensive sub-group (R(2) = 0.160; P = 0.04). Masked-hypertension was identified in 58% of African Americans which suggests that a masking phenomenon may exist in a sub-group of prehypertensives who also seem to have a diminished endothelial function that could be mediated by an elevated subclinical inflammation leading to the increased CV disease.

Combined Treatment with Amlodipine and Atorvastatin Calcium Reduces Circulating Levels of Intercellular Adhesion Molecule-1 and Tumor Necrosis Factor-α in Hypertensive Patients with Prediabetes.

PubMed

Huang, Zhouqing; Chen, Chen; Li, Sheng; Kong, Fanqi; Shan, Peiren; Huang, Weijian

2016-01-01

To assess the effect of amlodipine and atorvastatin on intercellular adhesion molecule (ICAM)-1 and tumor necrosis factor (TNF)-α expression, as endothelial function and inflammation indicators, respectively, in hypertensive patients with and without prediabetes. Forty-five consecutive patients with hypertension, diagnosed according to JNC7, were divided into two groups based on the presence (HD group, n = 23) or absence (H group, n = 22) of prediabetes, diagnosed according to 2010 ADA criteria, including impaired glucose tolerance (IGT) and fasting glucose tests. All patients simultaneously underwent 12-week treatment with daily single-pill amlodipine besylate/atorvastatin calcium combination (5/10 mg; Hisun-Pfizer Pharmaceuticals Co. Ltd). Serum isolated before and after treatment from overnight fasting blood samples was analyzed by ELISA. In the HD and H groups after vs. before 12-week amlodipine/atorvastatin treatment, there were significantly (all P < 0.01) lower levels of ICAM-1 (3.06 ± 0.34 vs. 4.07 ± 0.70 pg/ml; 3.26 ± 0.32 vs. 3.81 ± 0.60 pg/ml, respectively) and TNF-α (78.71 ± 9.19 vs. 110.94 ± 10.71 pg/ml; 80.95 ± 9.33 vs. 101.79 ± 11.72 pg/ml, respectively), with more pronounced reductions in HD vs. H group (ICAM-1Δ: 1.01 ± 0.80 vs. 0.55 ± 0.64 pg/ml, respectively, P = 0.037; TNF-αΔ: 32.23 ± 14.33 vs. 20.84 ± 14.89 pg/ml, respectively, P = 0.011), independent of the blood pressure (BP) and cholesterol level reduction. Amlodipine/atorvastatin improved endothelial function and inflammation, as reflected by lower circulating levels of ICAM-1 and TNF-α, more prominently in hypertensives with than without prediabetes. Starting statin treatment before overt diabetes in hypertensives might thus improve cardiovascular outcomes.

Trends in Prevalence of Hypertension in Brazil: A Systematic Review with Meta-Analysis

PubMed Central

Picon, Rafael V.; Fuchs, Flávio D.; Moreira, Leila B.; Riegel, Glaube; Fuchs, Sandra C.

2012-01-01

Background The prevalence of hypertension in emerging nations was scarcely described to date. In Brazil, many population-based surveys evaluated the prevalence in cities throughout the country. However, there is no population-based nationwide study of prevalence of hypertension. In this study, we estimated the prevalence of hypertension for the country and analyzed the trends for the last three decades. Methods Cross-sectional and cohort studies conducted from 1980 to 2010 were independently identified by two reviewers, without language restriction, in the PubMed, Embase, LILACS, and Scielo electronic databases. Unpublished studies were identified in the Brazilian electronic database of theses and in annals of Cardiology congresses and meetings. In total, 40 studies were selected, comprising 122,018 individuals. Results Summary estimates of prevalence by the former WHO criteria (BP≥160/95 mmHg) in the 1980’s and 1990’s were 23.6% (95% CI 17.3–31.4%) and 19.6% (16.4–23.3%) respectively. The prevalence of hypertension by the JNC criteria (BP≥140/90 mmHg) in the 1980’s, 1990’s and 2000’s were 36.1% (95% CI 28.7–44.2%), 32.9% (29.9–36.0%), and 28.7% (26.2–31.4%), respectively (P<0.001). In the 2000’s, the pooled prevalence estimates of self-reported hypertension on telephone inquiries was 20.6% (19.0–22.4%), and of self-reported hypertension in home surveys was 25.2% (23.3–27.2%). Conclusions The prevalence of hypertension in Brazil seems to have diminished 6% in the last three decades, but it still is approximately 30%. Nationwide surveys by self-reporting by telephone interviews underestimate the real prevalence. Rates of blood pressure control decreased in the same period, corresponding currently to only one quarter of individuals with hypertension. PMID:23118964

Impact of Different Normality Thresholds for 24-hour ABPM at the Primary Health Care Level.

PubMed

Grezzana, Guilherme Brasil; Moraes, David William; Stein, Airton Tetelbon; Pellanda, Lucia Campos

2017-02-01

Hypertension is an important risk factor for cardiovascular outcomes. Primary health care (PHC) physicians should be prepared to act appropriately in the prevention of cardiovascular risk factors. However, the rates of patients with control of blood pressure (BP) remain low. The impact of the reclassification of high BP by 24-hour ambulatory BP monitoring (ABPM) can lead to different medical decisions in PHC. To evaluate the agreement between the BP measured by a conventional method by PHC physicians and by 24-hour ABPM, considering different BP normal thresholds for the 24-hour ABPM according to the V Brazilian ABPM Guidelines and the European Society of Hypertension Guidelines. A cross-sectional study including 569 hypertensive patients. The BP was initially measured by the PHC physicians and, later, by 24-hour ABPM. The BP measurements were obtained independently between the two methods. The therapeutic targets for the conventional BP followed the guidelines by the Eighth Joint National Committee (JNC 8), the V ABPM Brazilian Guidelines, and the 2013 European Hypertension Guidelines. There was an accuracy of 54.8% (95% confidence interval [95%CI] 0.51 - 0.58%) for the BP measured with the conventional method when compared with the 24-hour ABPM, with a sensitivity of 85% (95%CI 80.8 - 88.6%), specificity of 31.9% (95%CI 28.7 - 34.7%), and kappa value of 0.155, when considering the European Hypertension Guidelines. When using more stringent thresholds to characterize the BP as "normal" by ABPM, the accuracy was 45% (95%CI 0.41 - 0.47%) for conventional measurement when compared with 24-hour ABPM, with a sensitivity of 86.7% (95%CI 0.81 - 0.91%), specificity of 29% (95%CI 0.26 - 0.30%), and kappa value of 0.103. The BP measurements obtained by PHC physicians showed low accuracy when compared with those obtained by 24-hour ABPM, regardless of the threshold set by the different guidelines. A hipertensão arterial sistêmica é um fator de risco importante para desfechos cardiovasculares. Médicos da atenção primária à saúde (APS) devem estar preparados para atuar adequadamente na prevenção de fatores de risco cardiovascular. No entanto, as taxas de pacientes com pressão arterial (PA) controlada continuam baixas. O impacto da reclassificação do diagnóstico de hipertensão pela utilização da monitorização ambulatorial da PA (MAPA) de 24 horas pode levar a diferentes decisões médicas na APS. Avaliar a concordância entre as PAs medidas por método convencional por médicos da APS e por MAPA de 24 horas, considerando diferentes limiares de normalidade para a MAPA de 24 horas de acordo com as recomendações da V Diretriz Brasileira de MAPA e da Diretriz da Sociedade Europeia de Hipertensão. Estudo transversal com 569 pacientes hipertensos. A PA foi medida inicialmente por médicos da APS e, posteriormente, pela MAPA de 24 horas. As medidas foram obtidas de forma independente entre os dois métodos. Os alvos terapêuticos para a PA convencional seguiram as orientações do Eighth Joint National Committee (JNC 8), das V Diretrizes Brasileiras de MAPA e das Diretrizes Europeias de Hipertensão de 2013. Foi observada uma acurácia de 54,8% (intervalo de confiança de 95% [IC95%] 0,51 - 0,58%) para a PA aferida de forma convencional quando comparada à obtida com a MAPA de 24 horas, além de uma sensibilidade de 85% (IC95% 80,8 - 88,6%), especificidade de 31,9% (IC95% 28,7 - 34,7%) e kappa de 0,155, quando consideradas as Diretrizes Europeias de Hipertensão. Quando utilizados limiares mais rígidos para caracterizar a PA como "normal" pela MAPA, foi identificada uma acurácia de 45% (IC95% 0,41 - 0,47%) pela medida convencional quando comparada à obtida pela MAPA de 24 horas, além de uma sensibilidade de 86,7% (IC95% 0,81 - 0,91%), especificidade de 29% (IC95% 0,26 - 0,30%) e kappa de 0,103. As medidas de PA avaliadas pelos médicos da APS apresentaram baixa acurácia quando comparadas às medidas pela MAPA de 24 horas, independente do limiar utilizado pelas diferentes diretrizes.

Functional identification of activity-regulated, high-affinity glutamine transport in hippocampal neurons inhibited by riluzole.

PubMed

Erickson, Jeffrey D

2017-07-01

Glutamine (Gln) is considered the preferred precursor for the neurotransmitter pool of glutamate (Glu), the major excitatory transmitter in the mammalian CNS. Here, an activity-regulated, high-affinity Gln transport system is described in developing and mature neuron-enriched hippocampal cultures that is potently inhibited by riluzole (IC 50 1.3 ± 0.5 μM), an anti-glutamatergic drug, and is blocked by low concentrations of 2-(methylamino)isobutyrate (MeAIB), a system A transport inhibitor. K + -stimulated MeAIB transport displays an affinity (K m ) for MeAIB of 37 ± 1.2 μM, saturates at ~ 200 μM, is dependent on extracellular Ca 2+ , and is blocked by inhibition of voltage-gated Ca 2+ channels. Spontaneous MeAIB transport is also dependent on extracellullar Ca 2+ and voltage-gated calcium channels, but is also blocked by the Na + channel blocker tetrodotoxin, by Glu receptor antagonists, and by GABA indicating its dependence on intact neural circuits driven by endogenous glutamatergic activity. The transport of MeAIB itself does not rely on Ca 2+ , but on Na + ions, and is pH sensitive. Activity-regulated, riluzole-sensitive spontaneous and K + -stimulated transport is minimal at 7-8 days in vitro, coordinately induced during the next 2 weeks and is maximally expressed by days in vitro > 20; the known period for maturation of the Glu/Gln cycle and regulated pre-synaptic Glu release. Competition analyses with various amino acids indicate that Gln is the most likely physiological substrate. Activity-regulated Gln/MeAIB transport is not observed in astrocytes. The functional identification of activity-regulated, high-affinity, riluzole-sensitive Gln/MeAIB transport in hippocampal neurons may have important ramifications in the neurobiology of activity-stimulated pre-synaptic Glu release, the Glu/Gln cycle between astrocytes and neurons, and neuronal Glu-induced excitotoxicity. Cover Image for this issue: doi: 10.1111/jnc.13805. © 2017 International Society for Neurochemistry.

Uncontrolled Hypertension and Its Determinants in Patients with Concomitant Type 2 Diabetes Mellitus (T2DM) in Rural South Africa.

PubMed

Adeniyi, Oladele Vincent; Yogeswaran, Parimalaranie; Longo-Mbenza, Benjamin; Ter Goon, Daniel

2016-01-01

Paucity of data on the prevalence, treatment and control of hypertension in individuals living with type 2 diabetes mellitus (T2DM) in the rural communities of South Africa may undermine efforts to reduce the morbidity and mortality associated with cardiovascular diseases. This study examines the socio-demographic and clinical determinants of uncontrolled hypertension among individuals living with T2DM in the rural communities of Mthatha, South Africa. This cross-sectional study involved a serially selected sample of 265 individuals living with T2DM and hypertension at Mthatha General Hospital, Mthatha. Uncontrolled hypertension was defined as systolic blood pressure greater than or equal to 140 mmHg and diastolic blood pressure greater than or equal to 90mmHg in accordance with the Eight Joint National Committee Report (JNC 8) (2014). We performed univariate and multivariate logistic regression analyses to identify the significant determinants of uncontrolled hypertension. Of the total participants (n = 265), the prevalence of uncontrolled hypertension was 75.5% (n = 200). In univariate analysis of all participants, male gender (p = 0.029), age≥65 years (p = 0.016), unemployed status (p<0.0001), excessive alcohol intake (p = 0.005) and consumption of western-type diet (p<0.0001) were positively associated with uncontrolled hypertension. In multivariate logistic regression (LR method) analysis, unemployed status (p<0.0001), excessive alcohol intake (p = 0.007) and consumption of western-type diet (p<0.0001) were independently and significantly associated with uncontrolled hypertension. There is significant association between increasing number and classes of anti-hypertensive drugs and uncontrolled hypertension (p = 0.05 and 0.02, respectively). Prevalence of uncontrolled hypertension was high in individuals with concomitant hypertension and T2DM in the study population. Male sex, aging, clinic inertia, unemployed status and nutritional transitions are the most important determinants of uncontrolled hypertension in T2DM in Mthatha, South Africa. Treatment to blood pressure targets, though feasible in our setting, would require concerted efforts by addressing these determinants and clinic inertia.

Muscle biopsies from human muscle diseases with myopathic pathology reveal common alterations in mitochondrial function.

PubMed

Sunitha, Balaraju; Gayathri, Narayanappa; Kumar, Manish; Keshava Prasad, Thottethodi Subrahmanya; Nalini, Atchayaram; Padmanabhan, Balasundaram; Srinivas Bharath, Muchukunte Mukunda

2016-07-01

Muscle diseases are clinically and genetically heterogeneous and manifest as dystrophic, inflammatory and myopathic pathologies, among others. Our previous study on the cardiotoxin mouse model of myodegeneration and inflammation linked muscle pathology with mitochondrial damage and oxidative stress. In this study, we investigated whether human muscle diseases display mitochondrial changes. Muscle biopsies from muscle disease patients, represented by dysferlinopathy (dysfy) (dystrophic pathology; n = 43), polymyositis (PM) (inflammatory pathology; n = 24), and distal myopathy with rimmed vacuoles (DMRV) (distal myopathy; n = 31) were analyzed. Mitochondrial damage (ragged blue and COX-deficient fibers) was revealed in dysfy, PM, and DMRV cases by enzyme histochemistry (SDH and COX-SDH), electron microscopy (vacuolation and altered cristae) and biochemical assays (significantly increased ADP/ATP ratio). Proteomic analysis of muscle mitochondria from all three muscle diseases by isobaric tag for relative and absolute quantitation labeling and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis demonstrated down-regulation of electron transport chain (ETC) complex subunits, assembly factors and Krebs cycle enzymes. Interestingly, 80 of the under-expressed proteins were common among the three pathologies. Assay of ETC and Krebs cycle enzyme activities validated the MS data. Mitochondrial proteins from muscle pathologies also displayed higher tryptophan (Trp) oxidation and the same was corroborated in the cardiotoxin model. Molecular modeling predicted Trp oxidation to alter the local structure of mitochondrial proteins. Our data highlight mitochondrial alterations in muscle pathologies, represented by morphological changes, altered mitochondrial proteome and protein oxidation, thereby establishing the role of mitochondrial damage in human muscle diseases. We investigated whether human muscle diseases display mitochondrial changes. Muscle biopsies from dysferlinopathy (Dysfy), polymyositis (PM), and distal myopathy with rimmed vacuoles (DMRV) displayed morphological and biochemical evidences of mitochondrial dysfunction. Proteomic analysis revealed down-regulation of electron transport chain (ETC) subunits, assembly factors, and tricarboxylic acid (TCA) cycle enzymes, with 80 proteins common among the three pathologies. Mitochondrial proteins from muscle pathologies also displayed higher Trp oxidation that could alter the local structure. Cover image for this issue: doi: 10.1111/jnc.13324. © 2016 International Society for Neurochemistry.

[Prevalence and associated risk factors of arterial hypertension in Sobremonte and Ojo de Agua Departments in Cordoba State].

PubMed

Pedraza, Antonio; Camino Willhuber, Gastón; Chaile, Iván

2008-01-01

Arterial Hypertension (AH) is a disease with multiple risk factors (RF), and it is one of the most important risk factor for cardiovascular diseases. The objective of this study was to determine the prevalence of AH in Sobremonte area and its correlation to other risk factors. The study was done in an special programme called "Solidarity in Health" (SIH) supported by the College of Medicine at the National University of Córdoba, which provided primary care to residents of Cachi Yaco (Sobremonte Department). It is an small village near Santiago del Estero province located in 226 km from Córdoba city. They went to the city and they examined the patients at the the "French and Berutti" school for nine consecutive years (2000-2008). Sobremonte area is the poorest deparment in the province of Córdoba and it has the highest rate of lowest socio-economic development, and a very deficient health care system.. The only hospital providing primary care is in San Francisco del Chañar, and the access is not free. The study involved the determination of the arterial pressure (AP) according to the seventh "JNC"criteria, body mass index (BMI), levels of alcohol consumption, exercise, salt consumption, diabetes and smoking in all the patients. Additionally, three water samples from different representative zones were collected and tested for sodium concentration. 471 patients were included. The incidence of AH was 43.5% of the patients. (51% men and 36% women). Higher incidence of AH was found in patients between 50 and 59 years old. There was a stadistical difference in the BMI, diabetes, and alcohol consumption between healthy patients and patients with AH. There was not any correlation between AH and exercise. We found higher levels of sodium in the water of this area and it was between 13-35 higher than in C6rdoba city and it was correlated with AH. We conclude that the increased sodium consumption is one of the most important risk factor of AH in this population.

Effects of acute blood pressure elevation on biochemical-metabolic parameters in individuals with hypertensive crisis.

PubMed

Andrade, Days Oliveira; Santos, Sara Patrícia O; Pinhel, Marcela Augusta S; Valente, Flávia Mariana; Giannini, Marcela Cavichiolo; Gregório, Michele Lima; De Godoy, Moacir Fernandes; Souza, Dorotéia Rossi S; Vilela-Martin, José Fernando

2017-01-01

Hypertensive crisis is a common clinical situation that presents a high rate of morbidity and mortality and it is characterized by symptomatic rise of blood pressure (BP), systolic (SBP) ≥ 180 mmHg and/or diastolic (DBP) ≥ 120 mmHg. It is classified as emergency (HE) or hypertensive urgency (HU). There is no description of laboratory findings in patients who present acute BP elevation. Thus, this study had the objective to assess the biochemical-metabolic parameters of patients with HC. We studied 74 normotensive individuals (NT), 74 controlled hypertensive patients (ContrHT), 50 subjects with HU, and 78 with HE for evaluating biochemical-metabolic parameters. HE occurs in older individuals and more frequently in those with known hypertension. More patients with HE had dyslipidemia than those with HU (58% vs. 38%). The diastolic BP and heart rate were higher in the HE group (120 mmHg and 87 bpm) compared to ContrHT (71 mmHg and 71 bpm; p < 0.0001) and NT groups (75 mmHg and 68 bpm; p < 0.0001). Glycemia was higher in HE vs. NT and ContrHT (p < 0.05). HDL cholesterol was lower in HE than NT (p = 0.0088). Potassium was lower in HE vs. NT, ContrHT and HU groups (p < 0.05). Creatinine was higher in the HC group vs. NT and ContrHT (p < 0.05). The GFR was significantly lower in HE group vs. HU, ContrHT and NT (p < 0.001). In conclusion, individuals with HC show biochemical alterations when compared to ContrHT and NT. Acute BP elevations are associated with hyperglycemia, dyslipidemia, and higher potassium and creatinine levels and lower renal function. Abbreviations BMI = body mass index BP = blood pressure CH = hypertensive crisis ContrHT = controlled hypertensive DBP = diastolic blood pressure GFR = glomerular filtration rate HbA1c = glycated hemoglobin HDLc = high-density lipoprotein cholesterol HE = hypertensive emergency HPLC = high-performance liquid chromatography HR = heart rate HU = hypertensive urgency JNC 7 = VII Joint National Committee on the Detection, Evaluation, and Treatment of High Blood Pressure LDLc = low-density lipoprotein cholesterol MDRD = Modification of Diet in Renal Disease NT = normotensive RASB = renin-angiotensin system blockers SBP = systolic blood pressure TC = total cholesterol TG = triglycerides.

Prise en charge des hypertendus dans la ville de Cotonou (Bénin) en 2011: connaissances attitudes et pratiques des médecins généralistes

PubMed Central

Houenassi, Martin Dèdonougbo; David, Dokoui; Codjo, Léopold Houétondji; Attinsounon, Angelo Cossi; Alassani, Adebayo; Ahoui, Séraphin; Dovonou, Albert Comlan; Adoukonou, Thierry Armel; Dohou, Serge Hugues Mahougnon; Wanvoegbe, Armand; Agbodande, Anthelme

2016-01-01

Summary But: Ce travail vise à évaluer les connaissances, attitudes et pratiques des médecins généralistes sur la prise en charge de l’hypertension artérielle à Cotonou. Méthodes: L’étude était transversale et descriptive basée sur une enquête multicentrique du 1er Mai 2011 au 31 Juillet 2011. Un recrutement de tous les médecins généralistes, volontaires exerçant dans les centres de santé privés, publics et confessionnels de la ville de Cotonou, ayant autorisé l’étude, a été fait. Le 7ème rapport de Joint National Committee (JNC7) a été utilisé comme référentiel pour l’évaluation de la prise en charge des hypertendus. Un auto-questionnaire adressé aux généralistes, testé et validé, a été utilisé pour recueillir ces données. Résultats: Au total, 41 médecins généralistes dans huit établissements sanitaires ont été inclus. Près de la moitié des généralistes (48.8%) ne connaissaient pas la définition de l’HTA. Seulement 25 généralistes (61.0%) pouvaient décrire les conditions de mesure de la pression artérielle. Dix généralistes (24.4%) étaient incapables de lister la moitié des examens du bilan minimum de l’hypertension artérielle (HTA). La majorité (92.7%) ne connaissait pas la notion de risque cardiovasculaire global. L’objectif tensionnel (TA ≤ 140/90 mmHg) n’était connu que par 18 (43.9%) médecins. Les mesures hygiéno-diététiques seules (82.9%) et la monothérapie seule (70.7%) étaient les modalités thérapeutiques les plus prescrites. Les classes pharmacologiques antihypertensives prescrites étaient surtout les inhibiteurs calciques (82.9%), les inhibiteurs de l’enzyme de conversion (53.7%) et les diurétiques (36.6%). Les généralistes référaient les hypertendus aux cardiologues principalement pour non-maitrise du chiffres tensionnels (63,4%) et l’apparition de complications aigues (56.1%). Conclusion: Les connaissances des généralistes sur la prise en charge de l’HTA étaient insuffisantes et leurs attitudes et pratiques ne respectaient pas les recommandations internationales. PMID:27841915

Nuclear Data Needs for Generation IV Nuclear Energy Systems

NASA Astrophysics Data System (ADS)

Rullhusen, Peter

2006-04-01

Nuclear data needs for generation IV systems. Future of nuclear energy and the role of nuclear data / P. Finck. Nuclear data needs for generation IV nuclear energy systems-summary of U.S. workshop / T. A. Taiwo, H. S. Khalil. Nuclear data needs for the assessment of gen. IV systems / G. Rimpault. Nuclear data needs for generation IV-lessons from benchmarks / S. C. van der Marck, A. Hogenbirk, M. C. Duijvestijn. Core design issues of the supercritical water fast reactor / M. Mori ... [et al.]. GFR core neutronics studies at CEA / J. C. Bosq ... [et al]. Comparative study on different phonon frequency spectra of graphite in GCR / Young-Sik Cho ... [et al.]. Innovative fuel types for minor actinides transmutation / D. Haas, A. Fernandez, J. Somers. The importance of nuclear data in modeling and designing generation IV fast reactors / K. D. Weaver. The GIF and Mexico-"everything is possible" / C. Arrenondo Sánchez -- Benmarks, sensitivity calculations, uncertainties. Sensitivity of advanced reactor and fuel cycle performance parameters to nuclear data uncertainties / G. Aliberti ... [et al.]. Sensitivity and uncertainty study for thermal molten salt reactors / A. Biduad ... [et al.]. Integral reactor physics benchmarks- The International Criticality Safety Benchmark Evaluation Project (ICSBEP) and the International Reactor Physics Experiment Evaluation Project (IRPHEP) / J. B. Briggs, D. W. Nigg, E. Sartori. Computer model of an error propagation through micro-campaign of fast neutron gas cooled nuclear reactor / E. Ivanov. Combining differential and integral experiments on [symbol] for reducing uncertainties in nuclear data applications / T. Kawano ... [et al.]. Sensitivity of activation cross sections of the Hafnium, Tanatalum and Tungsten stable isotopes to nuclear reaction mechanisms / V. Avrigeanu ... [et al.]. Generating covariance data with nuclear models / A. J. Koning. Sensitivity of Candu-SCWR reactors physics calculations to nuclear data files / K. S. Kozier, G. R. Dyck. The lead cooled fast reactor benchmark BREST-300: analysis with sensitivity method / V. Smirnov ... [et al.]. Sensitivity analysis of neutron cross-sections considered for design and safety studies of LFR and SFR generation IV systems / K. Tucek, J. Carlsson, H. Wider -- Experiments. INL capabilities for nuclear data measurements using the Argonne intense pulsed neutron source facility / J. D. Cole ... [et al.]. Cross-section measurements in the fast neutron energy range / A. Plompen. Recent measurements of neutron capture cross sections for minor actinides by a JNC and Kyoto University Group / H. Harada ... [et al.]. Determination of minor actinides fission cross sections by means of transfer reactions / M. Aiche ... [et al.] -- Evaluated data libraries. Nuclear data services from the NEA / H. Henriksson, Y. Rugama. Nuclear databases for energy applications: an IAEA perspective / R. Capote Noy, A. L. Nichols, A. Trkov. Nuclear data evaluation for generation IV / G. Noguère ... [et al.]. Improved evaluations of neutron-induced reactions on americium isotopes / P. Talou ... [et al.]. Using improved ENDF-based nuclear data for candu reactor calculations / J. Prodea. A comparative study on the graphite-moderated reactors using different evaluated nuclear data / Do Heon Kim ... [et al.].

Retraction Statement: Anti-inflammatory properties of tianeptine on lipopolysaccharide-induced changes in microglial cells involve toll-like receptor-related pathways.

PubMed

2017-09-01

'Anti-inflammatory properties of tianeptine on lipopolysaccharide-induced changes in microglial cells involve toll-like receptor-related pathways' by Slusarczyk, J., Trojan, E., Glombik, K., Piotrowska, A., Budziszewska, B., Kubera, M., Popiolek-Barczyk, K., Lason, W., Mika, J. and Basta-Kaim, A. The above article from the Journal of Neurochemistry published on 14 February 2016 on Wiley Online Library ( www.onlinelibrary.com), and in Volume 136, pp. 958-970, is being retracted by agreement between the corresponding author Agnieszka Basta-Kaim, the Journal's Editor-in-Chief Jörg Schulz, and John Wiley & Sons Ltd. The Editorial Office was alerted by a science journalist that the same Western Blot lane had been used to represent two different proteins. The Western Blot signal of iNOS in Fig. 4a was supposedly identical to the Western Blot signal of phospho-JNK in Fig. 6b. The corresponding author stated that "on the final step of figure 6 preparation the first author made, by mistake, an incorrect attachment of representative p-JNK blots." A corrected Fig. 6b is enclosed below. The second concern reaching the Editorial Office was that the same Western Blot signal appeared to have been used to represent two different experimental conditions: the iNOS control signal (-/- LPS/TIA Fig. 4a) appears as a horizontal and vertical mirror image of the last signal in this line (+/10 LPS/TIA Fig. 4a). The raw membrane which was used to produce Fig. 4a is enclosed on the next page and highlights the steps that were undertaken during figure preparation. Although the initial concern was not proven, concerns remained regarding the question how an inadvertent flipping of the first Western blot lane could happen. A corrected Fig. 4a prepared by the corresponding author from the raw image of iNOS western blot depicted above, without flipped first lane, is presented below: Although the corresponding author provided a large amount of evidence to explain disparities in the presentation of Western Blot images, due to the number of inconsistencies that were revealed during review of the provided evidence and the inability to confirm the nature of the steps that led to them, it was felt that the above mentioned Western Blot images presented in this publication were not reliable, even if the conclusions may still be valid. The first author would like to apologize to the readers, reviewers and editors of Journal of Neurochemistry for the errors. Reference Slusarczyk J., Trojan E., Glombik K., Piotrowska A., Budziszewska B., Kubera M., Popiolek-Barczyk K., Lason W., Mika J. and Basta-Kaim A. (2016) Anti-inflammatory properties of tianeptine on lipopolysaccharide-induced changes in microglial cells involve toll-like receptor-related pathways. J. Neurochem. 136, 958-970. https://doi.org/10.1111/jnc.13452. © 2017 International Society for Neurochemistry.

Pre-Hypertension among Young Adults (20-30 Years) in Coastal Villages of Udupi District in Southern India: An Alarming Scenario.

PubMed

Kini, Sanjay; Kamath, Veena G; Kulkarni, Muralidhar M; Kamath, Asha; Shivalli, Siddharudha

2016-01-01

According to Joint National Committee-7 (JNC-7) guidelines, a systolic blood pressure (SBP) of 120 to 139 mm Hg and/or diastolic blood pressure (DBP) of 80 to 89 mm Hg is considered as pre-hypertension. Existing evidence suggest that the cardiovascular morbidities are increasing among pre-hypertensive individuals compared to normal. To assess the magnitude and factors associated with pre-hypertension among young adults (20-30 years) in coastal villages of Udupi Taluk (an area of land with a city or town that serves as its administrative centre and usually a number of villages), Udupi District, Karnataka state, India. Community based cross sectional study. 6 (out of total 14) coastal villages of Udupi Taluk, Karnataka state, India. 1,152 young adults (age group: 20-30 years) selected by stratified random sampling in 6 coastal villages of Udupi Taluk, Karnataka state, India. A semi structured pre-tested questionnaire was used to elicit the details on socio-demographic variables, dietary habits, tobacco use, alcohol consumption, physical activity, family history of hypertension and stress levels. Anthropometric measurements and blood pressure were recorded according to standard protocols. Serum cholesterol was measured in a sub sample of the study population. Multivariate logistic regression was applied to identify the independent correlates of pre-hypertension among young adults (20-30 years). Prevalence, Odds ratio (OR) and adjusted (adj) OR for pre-hypertension among young adults (20-30 years). The prevalence of pre-hypertension in the study population was 45.2% (95%CI: 42.4-48). Multivariate logistic regression analysis revealed that age group of 25-30 years (adj OR: 4.25, 95% CI: 2.99-6.05), white collared (adj OR: 2.29, 95% CI: 1.08-4.85) and skilled occupation (adj OR: 3.24, 95% CI: 1.64-6.42), students (adj OR: 2.46, 95% CI: 1.22-4.95), using refined cooking oil (adj OR: 0.53, 95% CI: 0.29-0.95), extra salt in meals (adj OR: 2.46, 95% CI: 1.52-3.99), salty food items (adj OR: 6.99, 95% CI: 3.63-13.48), pre-obese (adj OR: 1.66, 95% CI: 1.03-2.67) and obese (adj OR: 9.16, 95% CI: 2.54, 36.4) were the significant correlates of pre-hypertension. In the study population, prevalence of pre-hypertension among young adults (20-30 years) was high (45.2%). Biological (age 25-30 years, pre-obesity and obesity) and behavioral (sedentary occupation, intake of extra salt in meals/salty food and not using refined cooking oil) factors were associated with pre-hypertension. Study emphasizes the need of community based screening of pre-hypertension under National Rural Health Mission. It also provides apt information for the evidence based designing of interventions for lifestyle modifications among high risk young adults in the study area.

Preface

NASA Astrophysics Data System (ADS)

2003-09-01

MEM03: The Second International Workshop on Mechano-Electromagnetic Properties of Composite Superconductors (Kyoto, Japan, 3–5 March 2003) Superconductivity is on course to be widely applied in various advanced technologies including: (1) magnetically levitated vehicles (MAGLEV), international thermonuclear experimental reactors (ITER), electric generators, high energy accelerator and magnetic resonance imaging (MRI) using metallic composite superconductors; (2) cable, fault-current-limiters (FCL), transformers, flywheels and motors by using oxide composite superconductors; (3) high field NMR and other sophisticated devices by combining both metallic and oxide superconductors. In order to create a real market for these advanced technologies using superconductivity, it is absolutely essential to develop superconducting wires/tapes with better performance. The development of accompanying assessment technologies is therefore indispensable for their R&D. Some important properties are related to the mechanical properties of the conductors. It is well known that degraded superconducting and mechanical properties (during fabrication as well as under operation) can cause serious problems, because the critical current depends sensitively on bending and tensile stresses, electromagnetic force, and mechanical and thermal cycling. Therefore he assessment of mechanical properties and the effect of strain on transport properties is crucial for improving and developing high performance superconducting devices. It is now very timely to have a meeting in order to discuss common scientific problems systematically and comprehensively. The Second International Workshop on Mechano-Electromagnetic Properties of Composite Superconductors, MEM03, was held in Kyoto, Japan, 3–5 March 2003, mainly to discuss the fundamentals of the following topics. • Electromagnetic properties: change of critical current, RRR and ac loss due to external forces like bending, compressive and tensile stresses, electromagnetic force, and mechanical and thermal cycling. • Mechanical properties: tensile and compressive properties, fatigue characteristics and fracture behaviour. • Thermal properties: thermal conductivity, thermal dilatation and thermal strain. • Modelling: prediction of critical current and mechanical properties of composite superconductors through statistical analysis, finite element analysis, etc. • Test methods: international cooperative research work to establish test methods for assessing mechano-electromagnetic properties based on the activity of VAMAS/TWA-16. This discussion took place with respect to three types of composites: • MFC (multifilamentary composite): BSCCO, MgB2, Nb-Ti, Nb3Sn and Nb3Al. • CCC (coated conductor composite): YBCO and ReBCO. • BCC (bulk crystal composite): YBCO and ReBCO. More than 55 researchers attended the MEM03 workshop, coming from eight different countries. A total of 42 papers were presented. In this special issue of Superconductor Science and Technology selected papers have been included that are concerned with the comprehensive scientific research subjects mentioned above. The aim of this issue is to provide a snapshot of some of the current state-of-the-art research and to promote further research into the mechano-electromagnetic properties of composite superconductors. The workshop was organized under the activities of NEDO technology quest and VAMAS/TWA-16. We wish to thank the following for their contribution to the success of the workshop: NEDO Super-ACE project, AFOSR, AOARD and IEC/TC90-JNC. Guest Editors: Kozo Osamura Hitoshi Wada Arman Nyilas Damian Hampshire

Period1 gates the circadian modulation of memory-relevant signaling in mouse hippocampus by regulating the nuclear shuttling of the CREB kinase pP90RSK.

PubMed

Rawashdeh, Oliver; Jilg, Antje; Maronde, Erik; Fahrenkrug, Jan; Stehle, Jörg H

2016-09-01

Memory performance varies over a 24-h day/night cycle. While the detailed underlying mechanisms are yet unknown, recent evidence suggests that in the mouse hippocampus, rhythmic phosphorylation of mitogen-activated protein kinase (MAPK) and cyclic adenosine monophosphate response element-binding protein (CREB) are central to the circadian (~ 24 h) regulation of learning and memory. We recently identified the clock protein PERIOD1 (PER1) as a vehicle that translates information encoding time of day to hippocampal plasticity. We here elaborate how PER1 may gate the sensitivity of memory-relevant hippocampal signaling pathways. We found that in wild-type mice (WT), spatial learning triggers CREB phosphorylation only during the daytime, and that this effect depends on the presence of PER1. The time-of-day-dependent induction of CREB phosphorylation can be reproduced pharmacologically in acute hippocampal slices prepared from WT mice, but is absent in preparations made from Per1-knockout (Per1(-/-) ) mice. We showed that the PER1-dependent CREB phosphorylation is regulated downstream of MAPK. Stimulation of WT hippocampal neurons triggered the co-translocation of PER1 and the CREB kinase pP90RSK (pMAPK-activated ribosomal S6 kinase) into the nucleus. In hippocampal neurons from Per1(-/-) mice, however, pP90RSK remained perinuclear. A co-immunoprecipitation assay confirmed a high-affinity interaction between PER1 and pP90RSK. Knocking down endogenous PER1 in hippocampal cells inhibited adenylyl cyclase-dependent CREB activation. Taken together, the PER1-dependent modulation of cytoplasmic-to-nuclear signaling in the murine hippocampus provides a molecular explanation for how the circadian system potentially shapes a temporal framework for daytime-dependent memory performance, and adds a novel facet to the versatility of the clock gene protein PER1. We provide evidence that the circadian clock gene Period1 (Per1) regulates CREB phosphorylation in the mouse hippocampus, sculpturing time-of-day-dependent memory formation. This molecular mechanism constitutes the functional link between circadian rhythms and learning efficiency. In hippocampal neurons of wild-type mice, pP90RSK translocates into the nucleus upon stimulation with forskolin (left), whereas in Period1-knockout (Per1(-/-) ) mice (right) the kinase is trapped at the nuclear periphery, unable to efficiently phosphorylate nuclear CREB. Consequently, the presence of PER1 in hippocampal neurons is a prerequisite for the time-of-day-dependent phosphorylation of CREB, as it regulates the shuttling of pP90RSK into the nucleus. Representative immunofluorescence images show a temporal difference in phosphorylated cAMP response element-binding protein (pCREB; green color) levels in all regions of the dorsal hippocampus between a wild-type C3H mouse (WT; left) and a Period1-knockout (Per1(-/-) ; right) mouse. Images were taken 2 h after lights on, thus, when fluctuating levels of pCREB peak in WT mouse hippocampus. Insets show a representative hippocampal neuron, in response to activating cAMP signaling, stained for the neuronal marker NeuN (red), the nuclear marker DAPI (blue) and the activated CREB kinase pP90RSK (green). The image was taken 2 h after light onset (at the peak of the endogenous CREB phosphorylation that fluctuates with time of day). Magnification: 100X, inset 400X. Read the Editorial Highlight for this article on page 650. Cover image for this issue: doi: 10.1111/jnc.13332. © 2016 International Society for Neurochemistry.