bluuebunny/crossref_metadata_2025 huggingface dataset:
Volume-Related Measurement Error by Three-Dimensional Ultrasound with a Rotational Multiplanar Technique
Authors: Smeets N.A.C. , Winkens B. , Oei S.G.
Published: October 2012

Background: The goal of this study was to calculate the accuracy of three-dimensional volume measurements with the rotational multiplanar technique VOCAL (Volume Organ Computer-aided AnaLysis). Methods: An ultrasound phantom with 13 objects (volume 10.2–40.5 cm3) was created. After data acquisition, the volumes of the objects were measured with the VOCAL technique. Results: A linear mixed model analysis showed a significant linear (B = –0.008, 95% CI –0.014, –0.002, p = 0.005) and a significant quadratic trend (B = 0.0001, 95% CI 0.000004, 0.0002, p = 0.040). The absolute error increases significantly with the increasing volume of interest with 0.044 cm3 for each cm3 rise of the volume of interest. The actual volume increased from an initial value of 10 cm3 to values of 20, 30 and 40 cm3, resulting in a decrease in the mean estimated percentage error from 15.4 to 10.6%, 8.0% and 7.5%. Conclusion: The results of this study showed that volume measurements with three-dimensional ultrasound and the VOCAL software can be used for volume measurements in vivo. However, it is important to assess the measurement error and to consider these error values when interpreting the results in daily practice.
Role of Pelvic Floor Muscle Exercises in the Prevention of Stress Urinary Incontinence during Pregnancy and the Postpartum Period
Authors: Kocaöz Semra , Eroğlu Kafiye , Sivaslıoğlu Ahmet Akın
Published: October 2012

Objective: The aim of this study was to determine the role of pelvic floor muscle exercises (PFME) in the prevention of stress urinary incontinence (SUI) during pregnancy and the postpartum period. Methods: A total of 102 women was included in the study. Data, collected through forms, included characteristics of the women, follow-up data during the pregnancy and postpartum period and a three-day urinary diary. Both groups were evaluated in terms of SUI at the 14th–20th, 28th and 32nd weeks of gestation and at 12 weeks postpartum. Results: As shown by the pad test, SUI developed in 5.8, 17.3 and 1.9% of the subjects in the intervention group at the 28th and 32nd gestational week and the 12th postpartum week, respectively. The relevant ratios in the control group were 30, 48 and 18%, respectively. A statistically significant difference was found between the intervention and control groups in terms of SUI development at the 28th and 32nd weeks of gestation and the 12th postpartum week (p < 0.05). Conclusion: PFME are effective for prevention of SUI development during pregnancy and in the postpartum period. Health care providers are therefore recommended to provide education and counseling to pregnant women about SUI prevention.
Activation of TRPV4 Strengthens the Tight-Junction Barrier in Human Epidermal Keratinocytes
Authors: Akazawa Y. , Yuki T. , Yoshida H. , Sugiyama Y. , Inoue S.
Published: October 2012

The transient receptor potential cation channel, subfamily V (TRPV), is expressed in the epidermis and considered to be a sensor of extrinsic stimuli such as temperature and other physical or chemical factors. In this study, we examined whether or not the activation of TRPVs by their agonists alters the epidermal tight junction (TJ) function in cultured human epidermal keratinocytes. Reverse transcription-polymerase chain reaction (RT-PCR) analyses showed that mRNA for TRPV1, 3 and 4 were expressed in differentiated keratinocytes in which TJs had formed. Stimulation of the keratinocytes with a TRPV4 agonist (4α-phorbol 12, 13-didecanoate, 4α-PDD) strengthened the TJ-associated barrier, analyzed by means of transepithelial electric resistance measurements and flux measurements of the paracellular tracer. Stimulation with TRPV1 and TRPV3 agonists did not have the same result. Simultaneously, the 4α-PDD-stimulated keratinocytes showed an upregulation of TJ structural proteins, occludin and claudin-4, and TJ regulatory factors, phospho-atypical PKCζ/ι. It was also observed that the amounts of occludin and phospho-atypical PKCζ/ι complex were higher in 4α-PDD stimulated keratinocytes. In conclusion, we demonstrated that the activation of TRPV4 strengthened the TJ-associated barrier of epidermal cells. It was also suggested that the upregulation of TJ structural proteins and/or the posttranslational modification of TJ structural proteins by phospho-atypical PKCζ/ι are responsible for the enhancement of TJ function. Our study supports the hypothesis that TJs change their function in response to a change in the external environment sensed through TRPVs.
Relationship between the Expression of the Extracellular Matrix Genes SPARC, SPP1, FN1, ITGA5 and ITGAV and Clinicopathological Parameters of Tumor Progression and Colorectal Cancer Dissemination
Authors: Viana Luciano de Souza , Affonso Jr. Renato José , Silva Sandra Regina Morini , Denadai Marcos Vinicius Araujo , Matos Delcio , Salinas de Souza Carolina , Waisberg Jaques
Published: October 2012

Objective: To evaluate the relationship between the expression of the extracellular matrix (ECM) genes SPARC, SPP1, FN1, ITGA5 and ITGAV and the histopathologic parameters of neoplastic progression and colorectal carcinoma (CRC) dissemination. Methods: A retrospective study was conducted in 114 patients with stage I–IV CRC who underwent primary tumor resection. Quantitative real-time PCR and immunohistochemistry (IHC) assays were performed in samples obtained from the primary tumors. The correlation between the expression of these markers and the expression of p53, Bcl-2, Ki67, epidermal growth factor receptor (EGFR) and vascular endothelial growth factor was assessed with the Spearman coefficient (r). Results: The ITGAV gene was found to be significantly amplified in tumors with positive perineural invasion (p = 0.028). Expression of the SPARC, SPP1, FN1, ITGA5 and ITGAV genes did not correlate with TNM staging. A direct relationship between ITGAV and EGFR expression (r = 0.774; p < 0.001) was observed by IHC. Conclusions: ECM gene expression did not correlate with classical prognostic factors for CRC, but overexpression of the ITGAV gene and protein was correlated with an increased risk of perineural invasion. The relationship between ITGAV and EGFR expression suggests the possibility of crosstalk in this signal pathway.
Urinary miR-21, miR-29, and miR-93: Novel Biomarkers of Fibrosis
Authors: Wang Gang , Kwan Bonnie Ching-Ha , Lai Fernand Mac-Moune , Chow Kai-Ming , Li Philip Kam-Tao , Szeto Cheuk-Chun
Published: October 2012

Background: MicroRNAs (miRNAs) play important roles in the progression of renal fibrosis. We studied the urinary levels of miR-21, miR-29 family and miR-93, which are downstream mediators of the transforming growth factor-β1 (TGF-β1), in patients with immunoglobulin A (IgA) nephropathy. Methods: We studied the urinary miRNA levels of 43 IgA nephropathy patients and 13 healthy controls. Results: The IgA nephropathy group had significantly lower urinary miR-29b and miR-29c, but higher miR-93 levels than controls. Proteinuria significantly correlated with urinary levels of miR-29b (r = –0.388, p = 0.003) and miR-29c (r = –0.409, p = 0.002). Glomerular filtration rate significantly correlated with urinary levels of miR-21 (r = 0.338, p = 0.028), miR-29b (r = 0.333, p = 0.031) and miR-29c (r = 0.304, p = 0.050). Urinary miR-93 level significantly correlated with glomerular scarring (r = –0.392, p = 0.010). Urinary miRNA level of SMAD3, but not TGF-β1, correlated with urinary miR-21 (r = 0.624, p < 0.001), miR-29b (r = 0.566, p < 0.001), miR-29c (r = 0.619, p < 0.001) and miR-93 (r = 0.332, p = 0.032). Conclusions: Urinary miR-29b and miR-29c levels correlated with proteinuria and renal function, while urinary miR-93 level correlated with glomerular scarring. More importantly, urinary levels of these miRNA targets significantly correlated with urinary SMAD3 level. Our results suggest that these miRNA targets are regulated by the TGF-β1/SMAD3 pathway and they may play important roles in the development of progressive renal fibrosis in IgA nephropathy.
RAS-Mediated Adaptive Mechanisms in Cardiovascular Tissues: Confounding Factors of RAS Blockade Therapy and Alternative Approaches
Authors: Gul Rukhsana , Ramdas Maya , Mandavia Chirag H. , Sowers James R. , Pulakat Lakshmi
Published: October 2012

Since the classic experiments by Tigerstedt and Bergman that established the role of renin in hypertension a century ago, aggressive efforts have been launched to effectively block the renin-angiotensin system (RAS). Blockade of RAS is advocated at multiple levels by direct renin inhibitor, angiotensin-converting enzyme inhibitor and/or angiotensin II type 1 receptor blocker, or aldosterone inhibitor (spironolactone), and has now become part of the standard of care to control hypertension and related metabolic diseases including diabetes. However, recent lessons learned from randomized clinical trials question the wisdom of blocking RAS at multiple levels. In this context, it is highly pertinent that components of RAS are evolutionarily conserved, and novel physiological/adaptive/protective roles for renin and angiotensin-converting enzyme are currently emerging. Angiotensin II, the classical RAS effector peptide responsible for hypertension, hypertrophy, fluid retention and fibrosis, manifests its cardiovascular protective effect when it activates the angiotensin II type 2 receptor. Additionally, angiotensin-converting enzyme 2 and the angiotensin II metabolite Ang-(1–7) that acts through the Mas proto-oncogene constitute the cardiovascular and renal protective branch of RAS. It is conceivable that modulating this vasodilative/anti-inflammatory branch of RAS by activation of the RAS components that constitute this branch may offer a safer long-term treatment strategy to balance RAS activity and achieve homeostasis compared to chronic multilevel RAS inhibition.
Association between Kidney Function and Telomere Length: The Heart and Soul Study
Authors: Bansal Nisha , Whooley Mary A. , Regan Mathilda , McCulloch Charles E. , Ix Joachim H. , Epel Elissa , Blackburn Elizabeth , Lin Jue , Hsu Chi-yuan
Published: October 2012

Background: Telomere attrition is a novel risk factor for cardiovascular disease. Studies of telomere length in relation to kidney function are limited. We explored the association of kidney function with telomere length and telomere shortening. Methods: The Heart and Soul Study is a longitudinal study of patients with stable coronary heart disease. Measures of baseline kidney function included: serum creatinine, creatinine-derived estimated glomerular filtration rate (eGFRCKD-EPI), 24-hour urine measured creatinine clearance, cystatin C, cystatin C-derived estimated glomerular filtration rate (eGFRcys) and urine albumin to creatinine ratio. Telomere length was measured from peripheral blood leukocytes at baseline (n = 954) and 5 years later (n = 608). Linear regression models were used to test the association of kidney function with (i) baseline telomere length and (ii) change in telomere length over 5 years. Results: At baseline, mean eGFRCKD-EPI was 72.6 (±21.5) ml/min/1.73 m2, eGFRcys was 71.0 (±23.1) ml/min/1.73 m2 and ACR was 8.6 (±12.3) mg/g. Only lower baseline eGFRCKD-EPI was associated with shorter baseline telomere length (9.1 (95% CI 1.2–16.9) fewer base pairs for every 5 ml/min/1.73 m2 lower eGFRCKD-EPI). Lower baseline eGFRCKD-EPI (and all other measures of kidney function) predicted more rapid telomere shortening (10.8 (95% CI 4.3–17.3) decrease in base pairs over 5 years for every 5 ml/min/1.73 m2 lower eGFRCKD-EPI). After adjustment for age, these associations were no longer statistically significant. Conclusions: In patients with coronary heart disease, reduced kidney function is associated with (i) shorter baseline telomere length and (ii) more rapid telomere shortening over 5 years; however, these associations are entirely explained by older age.
Effect of Dialyzed Saliva on Human Enamel Demineralization
Authors: Martins C. , Castro G.F. , Siqueira M.F. , Xiao Y. , Yamaguti P.M. , Siqueira W.L.
Published: October 2012

Background: Saliva is supersaturated with respect to calcium and phosphate ions. Salivary ions may well play a role in the subsequent adsorption of proteins and consequently in the formation of the acquired enamel pellicle. Among several biological functions, the enamel pellicle forms a selectively permeable barrier that regulates demineralization processes. Aim: The aim of this study was to evaluate the importance of salivary proteins when adsorbed on enamel surface and the resultant protective effect against demineralization without the presence of salivary ions. Methods: Enamel surfaces were coated with whole saliva, parotid saliva, dialyzed whole saliva or dialyzed parotid saliva (molecular weight cutoff 1 kDa). Adsorption was allowed to proceed for a period of 2 h. Enamel specimens were then washed with deionized water and immersed into a demineralization solution of pH 4.5 for 12 days. This solution was used to measure the amount of calcium and phosphate released from enamel specimens after the demineralization period. Results: All coated specimen groups showed a significantly higher protection than those not coated with any type of saliva. In addition, undialyzed saliva (whole saliva and parotid saliva) was more effective in protecting the enamel against demineralization than dialyzed saliva. Conclusion: The present investigation indicates that the ionic composition of saliva can amplify the demineralization protection effect by reducing acid-induced enamel demineralization. Moreover, a protective effect of salivary proteins without presence of ions was demonstrated in this study.
Methods for the Evaluation of the Protective Efficacy of Sunscreen Products
Authors: Vergou T. , Patzelt A. , Schanzer S. , Meinke M.C. , Weigmann H.-J. , Thiede G. , Sterry W. , Lademann J. , Darvin M.E.
Published: October 2012

The objective of the present investigation was to examine the utilization of optical and spectroscopic methods for the noninvasive characterization of Anthelios XL Fluide Extreme (SPF 50+), an exemplary sunscreen, concerning its homogeneity of distribution on the skin, its spectroscopic properties and its overall protective efficacy. The homogeneity of the distribution of the sunscreen on the skin was investigated with a multiphoton tomography microscope. Additionally, the sum transmission spectrum was determined using tape stripping and spectroscopic measurements. The results revealed a very homogeneous distribution of the sunscreen on the skin surface and also in the deep furrows. The sum transmission spectrum reflects a high protective efficacy of the sunscreen in both the UVA and UVB ranges. The sunscreen Anthelios XL Fluide Extreme (SPF 50+) generates a comfortable feeling on the skin and can be easily distributed. The presented optical methods have been shown to be suitable to investigate the overall protective efficacy of sunscreen products objectively, noninvasively and quickly.
Average versus Highest Intraocular Pressure Analyses in Glaucoma Clinical Trials
Authors: DeMill D.L. , Wirostko Barbara M. , Nelson Lindsay A. , Stewart Jeanette A. , Stewart William C.
Published: October 2012

Purpose: To evaluate methods which account for both eyes as a single, independent variable in glaucoma clinical trials. Methods: A review of clinical trial articles published between January 1995 and April 2011 evaluating currently used topical glaucoma medications. Results: This analysis included 17 articles with 36 treatment arms of which 14 were prostaglandins, 13 β-blockers, 6 topical carbonic anhydrase inhibitors and 3 α-agonists. Twenty-four articles used average intraocular pressure (IOP) analysis, 12 used the highest IOP analysis and none utilized the randomized eye method. At untreated baseline, there was a difference in the IOP between average IOP and highest baseline IOP analyses at 8 a.m. (p = 0.001) and for the diurnal curve (p = 0.02) as well as specifically for β-blockers (p = 0.002) at 8 a.m. and β-blockers for the diurnal curve (p = 0.01). Conclusions: This study suggests that the highest IOP analysis method generally provides slightly higher IOPs at baseline than the average IOP analysis method.
Influence of Parental Overweight on the Association of Birth Weight and Fat Distribution Later in Childhood
Authors: Adegboye Amanda R.A. , Andersen Lars B. , Wedderkopp Niels , Heitmann Berit L.
Published: October 2012

Objective: To examine whether the association between birth weight and fat distribution in childhood is modified by parental overweight. Methods: Cross-sectional study of 728 Danish children aged 8–10 and 14–16 years. The main outcomes were waist circumference, waist-to-height ratio, subscapular skinfold, and subscapular-to-triceps skinfold ratio. Analyses were stratified by parental overweight status (none vs. ≥1 overweight parent) for each dependent variable, expressed as z-scores. Results: Birth weight z-score was negatively associated with waist circumference (β –0.08 SD; 95% CI –0.15, –0.02), waist-to-height ratio (β –0.15 SD; 95% CI –0.22, –0.07), and subscapular-to-triceps ratio (β –0.28 SD; 95% CI –0.44, –0.12) after adjustment for sex, age, puberty, preterm birth, BMI, height, socio-economic status, mother’s age at delivery, parity, breastfeeding, energy intake, and aerobic fitness in the group with ≥1 overweight parent. Birth weight was negatively associated with subscapular skinfold in groups with (β –0.16 SD; 95% CI –0.24, –0.06) and without overweight parents (β –0.09 SD; 95% CI –0.16, –0.02), but the magnitude of the association was greater in the former group. Conclusion: The association between birth weight and fat distribution seems to be influenced by parental overweight. Lower birth weights are associated with central adiposity among offspring of overweight parents.
Efficacy and Safety of Metformin for Treatment of Overweight and Obesity in Adolescents: An Updated Systematic Review and Meta-Analysis
Authors: Bouza Carmen , López-Cuadrado Teresa , Gutierrez-Torres Luisa Fernanda , Amate JoséMaria
Published: October 2012

Objective: To assess the efficacy and safety of using metformin in overweight and obese adolescents without related morbidity. Methods: We conducted a systematic review and meta-analysis of randomized clinical trials published until June 2011, comparing metformin to placebo or other interventions. Our primary variables were baseline BMI changes and development of adverse effects. Results: Nine studies (498 participants, mean age 14.2 years; mean BMI 36.4 kg/m2) met the inclusion criteria. In all but one study, metformin was combined with lifestyle modification and was compared to placebo combined with changes in lifestyle. Analysis showed that metformin reduced mean BMI by 1.42 kg/m2 (95% CI –2.18, 0.66), fasting insulin by 9.9 µU/ml (95% CI –13.8, –6.06) and the HOMA index by –1.78 (95% CI –3.32, –0.23). No changes in any other parameter were observed. No statistical differences were found in the rate of adverse events (33% metformin, 32% placebo).The withdrawal rates due to side effects in the metformin and placebo groups were 2.7% and 2.5%, respectively. Conclusions: The available evidence indicates that, in the short term, administration of metformin in addition to lifestyle modification is relatively effective for reducing BMI and hyperinsulinemia among obese adolescents without related morbidity, and displays an acceptable safety pattern. Nevertheless, its long-term impact is unknown.
The Local Implementation of a Chronic Disease Management Model for Childhood Overweight and Obesity
Authors: Brink-Melis Willy J. , Derksen Elze R.E. , Westerman Marjan J. , Renders Carry M. , Seidell Jacob C. , Visscher Tommy L.S.
Published: October 2012

Background: The aim of this study is to determine opportunities and barriers regarding the management of overweight and obese children in daily practice, and to show the value of using focus groups when developing an action plan for childhood overweight management in a local context. Methods: Seven focus groups and four semi-structured interviews were conducted with 29 professionals from nine different care disciplines and 7 parents of overweight and obese children aged 4–19 years. Results: After thorough analysis of the focus groups, issues concerning finding the most appropriate care and realising a long-term weight management in daily practice have become clear. Some examples of these issues are: lack of awareness, reluctance to discuss and refer, mutual cooperation, contradictory advice and expectations of treatment and lack of effective support strategies. Conclusion: Focus groups deliver important information on local issues that are important for the development and implementation of a childhood overweight management action plan. And, besides delivering necessary information, focus groups lead to an increased awareness and willingness to improve childhood overweight management in a local context.
Resting Energy Expenditure in Normal-Weight and Overweight/Obese Subjects Was Similar Despite Elevated Sympathovagal Balance
Authors: Dal Ugur , Erdogan A.Taner , Cureoglu Asligul , Beydagi Huseyin
Published: October 2012

Objective: Alterations in the autonomic nervous system (ANS) may cause impairment in the metabolic processes that can lead to weight gain. The purpose of this study was to determine the difference between the resting energy expenditure (REE) and the resting ANS activity in overweight/obese and normal-weight healthy subjects. Method: Group 1 consisted of 18 subjects with BMI > 25 kg/m2, and 20 subjects with BMI ranging from 20 to 25 kg/m2 formed group 2. Measurements of low-frequency (LF) and high-frequency (HF) power components expressed in normalized units (LFnu, HFnu) and LF/HF ratio were assessed for analysis of heart rate variability, and simultaneously REE measurement was performed. Results: The mean LFnu (27.2% increased) and the LF/HF were higher and the mean HFnu was lower (29.9% decreased) in group 1 than in group 2 (p < 0.01). Although a statistical difference was observed in REE between groups, REE per kilogram corrected for fat-free mass (REEFFMcorr) was 21.47 ± 2.92 kcal/day/kg in group 1, and 21.56 ± 1.90 kcal/day/kg in group 2, and this difference was not statistically significant (p > 0.05). Conclusion: We concluded that REEFFMcorr in overweight/obese and normal-weight subjects were similar despite elevated sympathovagal balance in overweight/obese individuals, and REEFFMcorr should be used to avoid misestimating the REE in obese and normal-weight subjects.
Adipocyte Deficiency of Angiotensinogen Prevents Obesity-Induced Hypertension in Male Mice
Authors: Yiannikouris Frederique , Gupte Manisha , Putnam Kelly , Thatcher Sean , Charnigo Richard , Rateri Debra L. , Daugherty Alan , Cassis Lisa A.
Published: October 2012

Previous studies demonstrated that diet-induced obesity increased plasma angiotensin II concentrations and elevated systolic blood pressures in male mice. Adipocytes express angiotensinogen and secrete angiotensin peptides. We hypothesize that adipocyte-derived angiotensin II mediates obesity-induced increases in systolic blood pressure in male high fat-fed C57BL/6 mice. Systolic blood pressure was measured by radiotelemetry during week 16 of low-fat or high-fat feeding in
Agt

fl/fl

and adipocyte angiotensinogen-deficient mice (
Agt

aP2

). Adipocyte angiotensinogen deficiency had no effect on diet-induced obesity. Basal 24-hour systolic blood pressure was not different in low fat-fed
Agt

fl/fl

compared with
Agt

aP2

mice (124±3 versus 128±3 mm Hg, respectively). In
Agt

fl/fl

mice, high-fat feeding significantly increased systolic blood pressure (24 hours; 134±2 mm Hg;
P
<0.05). In contrast, high fat-fed
Agt

aP2

mice did not exhibit an increase in systolic blood pressure (126±2 mm Hg). Plasma angiotensin II concentrations were increased by high-fat feeding in
Agt

fl/fl

mice (low fat, 32±14; high fat, 219±58 pg/mL;
P
<0.05). In contrast, high fat-fed
Agt

aP2

mice did not exhibit elevated plasma angiotensin II concentrations (high fat, 18±7 pg/mL). Similarly, adipose tissue concentrations of angiotensin II were significantly decreased in low fat- and high fat-fed
Agt

aP2

mice compared with controls. In conclusion, adipocyte angiotensinogen deficiency prevented high fat-induced elevations in plasma angiotensin II concentrations and systolic blood pressure. These results suggest that adipose tissue serves as a major source of angiotensin II in the development of obesity hypertension.
Modulation of Bulbospinal Rostral Ventral Lateral Medulla Neurons by Hypoxia/Hypercapnia but Not Medullary Respiratory Activity
Authors: Boychuk Carie R. , Woerman Amanda L. , Mendelowitz David
Published: October 2012

Although sympathetic vasomotor discharge has respiratory modulation, the site(s) responsible for this cardiorespiratory interaction is unknown. One likely source for this coupling is the rostral ventral lateral medulla (RVLM), where presympathetic neurons originate in close apposition to respiratory neurons. The current study tested the hypothesis that RVLM bulbospinal neurons are modulated by medullary respiratory network activity using whole-cell patch-clamp electrophysiological recordings of RVLM neurons while simultaneously recording fictive respiratory bursting activity from the hypoglossal rootlet. Additionally, we examined whether challenges to cardiorespiratory function, mainly hypoxia/hypercapnia, alter the activity of bulbospinal neurons and, secondarily, whether changes in synaptic input mediate these responses. Surprisingly, our results indicate that inspiratory-related activity did not modulate glutamatergic, γ-aminobutyric acid-ergic, or glycinergic synaptic events or spontaneous action potential firing in these RVLM neurons. However, hypoxia/hypercapnia reversibly decreased the frequency of γ-aminobutyric acid and glycine inhibitory postsynaptic currents. Glycinergic inhibitory postsynaptic current frequency was depressed from the fifth through the 10th minute, whereas the depression of γ-aminobutyric acid-ergic events became significant only at the 10th minute of hypoxia/hypercapnia. On the basis of spontaneous firing activity, there were 2 populations of RVLM bulbospinal neurons. The firing frequency of low-discharging RVLM neurons was facilitated by hypoxia/hypercapnia, and this increase depended on reduced inhibitory neurotransmission. The firing frequency in RVLM neurons with high-discharge rates was inhibited, independent of synaptic input, by hypoxia/hypercapnia. This article demonstrates that sympathetic-respiratory coupling is not active in the neonatal brain stem slice, and reductions in inhibitory neurotransmission to low spontaneously active bulbospinal RVLM neurons are responsible for hypoxia/hypercapnia-elicited increases in activity.
Peroxisome Proliferator-Activated Receptor-γ Ameliorates Pulmonary Arterial Hypertension by Inhibiting 5-Hydroxytryptamine 2B Receptor
Authors: Liu Yahan , Tian Xiao Yu , Mao Guangmei , Fang Xi , Fung Man Lung , Shyy John Y.-J. , Huang Yu , Wang Nanping
Published: October 2012

An elevated plasma level of 5-hydroxytryptamine (5-HT) or upregulation of 5-HT receptor signaling or both is implicated in vascular contraction and remodeling in pulmonary arterial hypertension (PAH). Recently, peroxisome proliferator-activated receptor-γ (PPARγ) agonists have been shown to ameliorate PAH. However, their effects on the 5-HT-induced contraction of pulmonary arteries remain unknown. Here, we examined the role of PPARγ in inhibiting 5-HT2B receptor (5-HT2BR) to ameliorate PAH. Pulmonary arteries from PAH rats induced by monocrotaline or chronic hypoxia showed an enhanced vasoconstriction in response to BW723C86, a specific agonist for 5-HT2BR. Expression of 5-HT2BR was also increased in pulmonary arteries from the PAH rats, accompanied by vascular remodeling and right ventricular hypertrophy. Treatment with the PPARγ agonist rosiglitazone in vivo reversed the expression and the vasocontractive effect of 5-HT2BR as well as the thickening of pulmonary arteries. In pulmonary artery smooth muscle cells, 5-HT induced the gene expression of 5-HT2BR, which was inhibited by rosiglitazone, pioglitazone, or adenovirus-mediated overexpression of constitutively activated PPARγ. The pharmacological effect of PPARγ was through the suppression of the 5-HT-induced activator protein-1 activity. These results demonstrated the beneficial effect of PPARγ on 5-HT2BR-mediated vasocontraction, providing a new mechanism for the potential use of PPARγ agonists in PAH.
Hyperphosphorylation of Na-K-2Cl Cotransporter in Thick Ascending Limbs of Dahl Salt-Sensitive Rats
Authors: Ares Gustavo R. , Haque Mohammed Z. , Delpire Eric , Ortiz Pablo A.
Published: October 2012

Salt-sensitive hypertension involves a renal defect preventing the kidney from eliminating excess NaCl. The thick ascending limb of Henle loop reabsorbs ≈30% of filtered NaCl via the apical Na-K-2Cl cotransporter (NKCC2). Higher NKCC2 activity and Cl reabsorption have been reported in the thick ascending limbs from Dahl salt-sensitive rats (DSS) fed normal salt. NKCC2 activity is primarily regulated by protein trafficking and phosphorylation at Thr
96
/Thr
101
via STE20- and SPS1-related proline and alanine-rich kinases and oxidative stress-responsive kinase 1. However, the mechanism for enhanced NKCC2 activity in DSS is unclear. We hypothesized that DSS exhibit enhanced NKCC2 trafficking and higher NKCC2 phosphorylation compared with Dahl salt-resistant rats on normal salt diet. We measured steady state surface NKCC2 expression and phosphorylation at Thr
96
and Thr
101
by surface biotinylation and Western blot. In DSS, the surface:total NKCC2 ratio was enhanced by 25% compared with Dahl salt-resistant rats (
P
<0.05) despite lower NKCC2 expression. Total NKCC2 phosphorylation at Thr
96
and Thr
101
was enhanced ≈5-fold in DSS thick ascending limbs. Moreover, total STE20- and SPS1-related proline and alanine-rich kinases expression, kidney-specific STE20- and SPS1-related proline and alanine-rich kinases, and oxidative stress-responsive kinase 1 were not different between strains, although STE20- and SPS1-related proline and alanine-rich kinases/oxidative stress-responsive kinase 1 phosphorylation was enhanced by 60% (
P
<0.05) in DSS rats, suggesting increased activity. We concluded that phosphorylation of NKCC2 Thr
96
and Thr
101
and surface:total NKCC2 ratio are enhanced in DSS rats. These differences in NKCC2 may be, in part, responsible for higher NKCC2 activity and abnormally enhanced thick ascending limb NaCl reabsorption in DSS rats.
Cytochrome P450 1B1 Gene Disruption Minimizes Deoxycorticosterone Acetate-Salt–Induced Hypertension and Associated Cardiac Dysfunction and Renal Damage in Mice
Authors: Jennings Brett L. , Estes Anne M. , Anderson Larry J. , Fang Xiao R. , Yaghini Fariborz A. , Fan Zheng , Gonzalez Frank J. , Campbell William B. , Malik Kafait U.
Published: October 2012

Previously, we showed that the cytochrome P450 1B1 inhibitor 2,3′,4,5′-tetramethoxystilbene reversed deoxycorticosterone acetate (DOCA)-salt–induced hypertension and minimized endothelial and renal dysfunction in the rat. This study was conducted to test the hypothesis that cytochrome P450 1B1 contributes to cardiac dysfunction, and renal damage and inflammation associated with DOCA-salt–induced hypertension, via increased production of reactive oxygen species and modulation of neurohumoral factors and signaling molecules. DOCA-salt increased systolic blood pressure, cardiac and renal cytochrome P450 1B1 activity, and plasma levels of catecholamines, vasopressin, and endothelin-1 in wild-type (
Cyp1b1

+/+

) mice that were minimized in
Cyp1b1

−/−

mice. Cardiac function, assessed by echocardiography, showed that DOCA-salt increased the thickness of the left ventricular posterior and anterior walls during diastole, the left ventricular internal diameter, and end-diastolic and end-systolic volume in
Cyp1b1

+/+

but not in
Cyp1b1

−/−

mice; stroke volume was not altered in either genotype. DOCA-salt increased renal vascular resistance and caused vascular hypertrophy and renal fibrosis, increased renal infiltration of macrophages and T lymphocytes, caused proteinuria, increased cardiac and renal nicotinamide adenine dinucleotide phosphate-oxidase activity, caused production of reactive oxygen species, and increased activities of extracellular signal-regulated kinase 1/2, p38 mitogen-activated protein kinase, and cellular-Src; these were all reduced in DOCA-salt–treated
Cyp1b1

−/−

mice. Renal and cardiac levels of eicosanoids were not altered in either genotype of mice. These data suggest that, in DOCA-salt hypertension in mice, cytochrome P450 1B1 plays a pivotal role in cardiovascular dysfunction, renal damage, and inflammation, and increased levels of catecholamines, vasopressin, and endothelin-1, consequent to generation of reactive oxygen species and activation of extracellular signal-regulated kinase 1/2, p38 mitogen-activated protein kinase, and cellular-Src independent of eicosanoids.
Cardiomyocyte Mineralocorticoid Receptors Are Essential for Deoxycorticosterone/Salt-Mediated Inflammation and Cardiac Fibrosis
Authors: Rickard Amanda J. , Morgan James , Bienvenu Laura A. , Fletcher Elizabeth K. , Cranston Greg A. , Shen Jimmy Z. , Reichelt Melissa E. , Delbridge Lea M. , Young Morag J.
Published: October 2012

Because the role of mineralocorticoid receptors in specific cell types in cardiac remodeling remains unknown, we have compared cardiac responses with deoxycorticosterone/salt in cardiomyocyte mineralocorticoid receptor-null (MyoMRKO) and wild-type (WT) mice at 8 days and 8 weeks. No differences in cardiac function between untreated WT and MyoMRKO mice were found, whereas profibrotic markers were reduced in MyoMRKO hearts at baseline. At 8 days, MyoMRKO showed monocyte/macrophage recruitment equivalent to WT mice in response to deoxycorticosterone/salt but a suppression of markers of fibrosis compared with WT. At 8 weeks, MyoMRKO mice showed no deoxycorticosterone/salt-induced increase in inflammatory cell infiltration and collagen deposition or in proinflammatory gene expression. Although some profibrotic markers were equivalently increased in both genotypes, MyoMRKO mice also showed increased baseline levels of mRNA and protein for the transforming growth factor-β/connective tissue growth factor inhibitor decorin compared with WT that was accompanied by higher levels of matrix metalloproteinase 2/matrix metalloproteinase 9 activity. These data point to a direct role for cardiomyocyte mineralocorticoid receptor in both deoxycorticosterone/salt-induced tissue inflammation and remodeling and suggest potential mechanisms for the cardioprotective effects of selective mineralocorticoid receptor blockade in cardiomyocytes that may involve regulation of matrix metalloproteinase 2/matrix metalloproteinase 9 activity and the transforming growth factor-β-connective tissue growth factor profibrotic pathway.
Buoyancy-Driven Interannual Sea Level Changes in the Tropical South Atlantic
Authors: Piecuch Christopher G. , Ponte Rui M.
Published: October 2012

Linear models of dynamical ocean adjustment to wind field changes, local atmospheric driving, and eastern boundary forcing are often invoked to explain observed patterns of interannual regional sea level variability. While skillful in some regions, these processes alone cannot explain low levels of interannual sea level variability observed in the tropical Atlantic. In this study, through a set of modeling approaches, interannual sea level changes in the tropical South Atlantic are attributed and the dynamical influence of buoyancy forcing is elucidated. Similar to recent findings in the southeast tropical Pacific, sea level patterns in the tropical South Atlantic (as estimated from a data-constrained ocean general circulation model) are found to result from the action of both surface wind and buoyancy forcing; in addition to static local effects, the buoyancy-driven changes comprise important nonlocal ocean dynamical processes. It is shown that the buoyancy-driven sea level changes can be understood within the framework of a linear first baroclinic mode Rossby wave model forced by atmospheric fields and variability along the eastern boundary. To lowest order, the linear model framework also reproduces qualitative patterns of basinwide compensation between wind- and buoyancy-driven sea level changes, which are mostly tied to the anticorrelation of both surface and boundary forcing. Results suggest that the ocean’s dynamical adjustment to buoyancy forcing exerts an important influence on interannual sea level changes across all tropical oceans.
Calibration and Quality Assurance of Flux Observations from a Small Research Aircraft*
Authors: Vellinga Olaf S. , Dobosy Ronald J. , Dumas Edward J. , Gioli Beniamino , Elbers Jan A. , Hutjes Ronald W. A.
Published: October 2012

Small environmental research aircraft (ERA) are becoming more common for detailed studies of air–surface interactions. The Sky Arrow 650 ERA, used by multiple groups, is designed to minimize the complexity of high-precision airborne turbulent wind measurement. Its relative wind probe, of a nine-port design, is furthermore used with several other airplanes. This paper gives an overview of 1) calibration of the model that converts the probe’s raw measurements to meteorological quantities; 2) quality control and assurance (QC–QA) in postprocessing of these quantities to compute fluxes; and 3) sensitivity of fluxes to errors in calibration parameters. The model, an adapted version of standard models of potential flow and aerodynamic upwash, is calibrated using an integrated method to derive a globally optimum set of parameters from in-flight maneuvers. Methods of QC–QA from the tower flux community are adopted for use with airborne flux data to provide more objective selection criteria for large datasets. Last, measurements taken from a standard operational flight are used to show fluxes to be most sensitive to calibration parameters that directly affect the vertical wind component. In another test with the same data, varying all calibration parameters simultaneously by ±10% of their optimum values, the model computes a response in the fluxes smaller than 10%, though a larger response may occur if only a subset of parameters is perturbed. A MATLAB toolbox has been developed that facilitates the procedures presented here.
The Role of Convectively Coupled Atmospheric Kelvin Waves on African Easterly Wave Activity
Authors: Ventrice Michael J. , Thorncroft Chris D.
Published: October 2012

The role of convectively coupled atmospheric Kelvin waves (CCKWs) on African easterly wave (AEW) activity is explored over tropical Africa during boreal summer. Examination of the pre-Alberto AEW in 2000 highlights the observation that the convective trigger for the initiation of the AEW was generated by a strong CCKW and that the subsequent intensification of the AEW at the West African coast was associated with a second CCKW. Composite analysis shows that, generally, AEW activity increases during and after the passage of the convectively active phase of strong CCKWs. The increase in AEW activity is consistent with convective triggering at the leading edge of the convective phase of the CCKW. This convective triggering occurs in a region where the background low-level easterly vertical wind shear is increased by the CCKW. As the AEW propagates westward through the convectively active phase of the CCKW, it can develop in an environment favorable for convection. It is also shown that this phase of the CCKW is characterized by enhanced meridional vorticity gradients in the core of the African easterly jet suggesting that enhanced mixed barotropic–baroclinic growth may also be responsible for enhanced AEW activity there.
The Causal Logic of Critical Junctures
Authors: Soifer Hillel David
Published: October 2012

Despite the fact that critical junctures are frequently deployed in historical analyses, we lack an explicit causal logic for them. This article proposes a distinction between permissive and productive conditions in critical junctures. Permissive conditions are necessary conditions that mark the loosening of constraints on agency or contingency and thus provide the temporal bounds on critical junctures. Productive conditions, which can take various logical forms, act within the context of these permissive conditions to produce divergence. I develop these concepts in detail and use classic analyses that apply the concept to show the implications of this new framework for the scope conditions, case selection, and theoretical completeness of historical analysis, as well as for broader issues in historical analysis such as the relationships between crisis and outcome, and between stability and change.
Sports Hernia in National Hockey League Players
Authors: Jakoi Andre , O’Neill Craig , Damsgaard Christopher , Fehring Keith , Tom James
Published: October 2012

Background:

Athletic pubalgia is a complex injury that results in loss of play in competitive athletes, especially hockey players. The number of reported sports hernias has been increasing, and the importance of their management is vital. There are no studies reporting whether athletes can return to play at preinjury levels.

Purpose:

The focus of this study was to evaluate the productivity of professional hockey players before an established athletic pubalgia diagnosis contrasted with the productivity after sports hernia repair.

Study Design:

Cohort study; Level of evidence, 3.

Methods:

Professional National Hockey League (NHL) players who were reported to have a sports hernia and who underwent surgery from 2001 to 2008 were identified. Statistics were gathered on the players’ previous 2 full seasons and compared with the statistics 2 full seasons after surgery. Data concerning games played, goals, average time on ice, time of productivity, and assists were gathered. Players were divided into 3 groups: group A incorporated all players, group B were players with 6 or fewer seasons of play, and group C consisted of players with 7 or more seasons of play. A control group was chosen to compare player deterioration or improvement over a career; each player selected for the study had a corresponding control player with the same tenure in his career and position during the same years.

Results:

Forty-three hockey players were identified to have had sports hernia repairs from 2001 to 2008; ultimately, 80% would return to play 2 or more full seasons. Group A had statistically significant decreases in games played, goals scored, and assists. Versus the control group, the decreases in games played and assists were supported. Statistical analysis showed significant decreases in games played, goals scored, assists, and average time on ice the following 2 seasons in group C, which was also seen in comparison with the control group. Group B (16 players) showed only statistical significance in games played versus the control group.

Conclusion:

Players who undergo sports hernia surgeries return to play and often perform similar to their presurgery level. Players with over 7 full seasons return but with significant decreases in their overall performance levels. Less veteran players were able to return to play without any statistical decrease in performance and are likely the best candidates for repair once incurring injury.
Effects of T-2 toxin on testosterone biosynthesis in mouse Leydig cells
Authors: Yang Jianying , Zhang Yongfa , Jing Aihua , Ma Kaiwang , Gong Qiang , Qin Cuili
Published: October 2012

Objective:

To investigate the effects of T-2 toxin on testosterone biosynthesis in mouse Leydig cells.

Methods:

Leydig cells isolated from clean and healthy Kunming male mice, whose concentration was adjusted to 5 × 105/mL and the purity identified by the modified 3β-hydroxysteroid dehydrogenase staining method, were used to establish a primary Leydig cell culture model. Blank control group (treated with 0 ng/mL human chorionic gonadotropin (hCG) and 0 mol/L T-2 toxin), inductive control group (treated with 10 ng/mL hCG and 0 mol/L T-2 toxin), low-dose T-2-toxin-exposure group (treated with 10 ng/mL hCG and 10−9 mol/L T-2 toxin), middle-dose T-2 toxin-exposure group (treated with 10 ng/mL hCG and 10−8 mol/L T-2 toxin) and high-dose T-2-toxin-exposure group (treated with 10 ng/mL hCG and 10−7 mol/L T-2 toxin) were designed. The testosterone level was measured after 24 h incubation.

Results:

After 24 h culture in liquid medium containing serum, the fresh isolated Leydig cells grew well and the purity exceeded 90%. By inducing 10 ng/mL hCG, the testosterone level of Leydig cells increased significantly and the difference compared with the blank control was of statistical sense. Compared with the inductive control group, the testosterone level of Leydig cells decreased, and the difference was of statistical sense in all T-2-toxin-exposure groups. Furthermore, the decrease was due to the increase in the dosage of T-2 toxin.

Conclusions:

T-2 toxin can directly decrease the testosterone biosynthesis in the primary Leydig cells derived from the mouse testis.
Parent Support Services for Families of Children With Emotional Disturbances Served in Elementary School Special Education Settings
Authors: Duchnowski Albert J. , Kutash Krista , Green Amy L. , Ferron John M. , Wagner Mary , Vengrofski Bonnie
Published: October 2012

Using data from the Special Education Elementary Longitudinal Study, we describe parent involvement and support activities in schools educating a nationally representative sample of students with emotional disturbances (EDs). We describe the extent to which programs aimed at encouraging family involvement are offered by schools and received by families and their relationship to child, family, and school characteristics. Student-level information was obtained from students, teachers, and parents, whereas school-level information was obtained from school administrators. Although schools attended by 71% of the students reported offering at least one type of family involvement activity, teachers reported only 17% of families of children with ED received a parent support service. Compared with families who did not receive support services, those who did were more involved in their school, and their children received more services in the community and had higher achievement levels. The need and potential methods for increasing parent engagement are discussed.
Designing Effective Tier 2 Reading Instruction in Early Elementary Grades With Limited Resources
Authors: Johnson Evelyn S. , Boyd Lisa
Published: October 2012

Within a response to intervention framework, Tier 2 is commonly conceptualized as a supplemental, 30-minute intervention that is provided in addition to the core instructional program. Given the resource constraints that many schools face, this type of model might not be feasible. However, in the light of data that suggest a need for a well-designed, targeted intervention system, schools need to do something. This article describes one school’s approach to data evaluation and Tier 2 implementation for struggling first grade readers. Working within resource constraints, the school was able to realize positive outcomes for its struggling readers by adhering to effective instructional principles, responding to data, and challenging the conventional wisdom of core plus supplement.