Colorectal cancer metastasis: the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation.

PURPOSE: To assess the usefulness of combining hyperthermia with a DNA repair inhibitor (double-strand break bait [Dbait]) and its potential application to radiofrequency ablation (RFA) in a preclinical model of human colorectal cancer. MATERIALS AND METHODS: The local ethics committee of animal experimentation approved all investigations. First, the relevance was assessed by studying the survival of four human colorectal adenocarcinoma cell cultures after 1 hour of hyperthermia at 41°C or 43°C with or without Dbait. Human colon adenocarcinoma cells (HT-29) were grafted subcutaneously into nude mice (n = 111). When tumors reached approximately 500 mm(3), mice were treated with Dbait alone (n = 20), sublethal RFA (n = 21), three different Dbait schemes and sublethal RFA (n = 52), or a sham treatment (n = 18). RFA was performed to ablate the tumor center alone. To elucidate antitumor mechanisms, 39 mice were sacrificed for blinded pathologic analysis, including assessment of DNA damage, cell proliferation, and tumor necrosis. Others were monitored for tumor growth and survival. Analyses of variance and log-rank tests were used to evaluate differences. RESULTS: When associated with mild hyperthermia, Dbait induced cytotoxicity in all tested colon cancer cell lines. Sublethal RFA or Dbait treatment alone moderately improved survival (median, 40 days vs 28 days for control; P = .0005) but combination treatment significantly improved survival (median, 84 days vs 40 days for RFA alone, P = .0004), with approximately half of the animals showing complete tumor responses. Pathologic studies showed that the Dbait and RFA combination strongly enhances DNA damage and coagulation areas in tumors. CONCLUSION: Combining Dbait with RFA sensitizes the tumor periphery to mild hyperthermia and increases RFA antitumor efficacy.

Uncontrolled Intersection report

By October 1, 2014, the county engineer of each county shall provide a report to the department of transportation identifying all locations in the county where two different roads or highways having speed limits of 55 miles per hour or greater intersect but are not controlled by an official traffic-control signal or by official traffic-control devices that direct traffic approaching from every direction to stop or yield before entering the intersection. On or before December 31, 2014, the department shall file a report with the legislative services agency detailing the number of locations of the intersections identified in the county engineers’ reports.

Prevalence and time course of acute mountain sickness in older children and adolescents after rapid ascent to 3450 meters

OBJECTIVE: Acute mountain sickness is a frequent and debilitating complication of high-altitude exposure, but there is little information on the prevalence and time course of acute mountain sickness in children and adolescents after rapid ascent by mechanical transportation to 3500 m, an altitude at which major tourist destinations are located throughout the world. METHODS: We performed serial assessments of acute mountain sickness (Lake Louise scores) in 48 healthy nonacclimatized children and adolescents (mean +/- SD age: 13.7 +/- 0.3 years; 20 girls and 28 boys), with no previous high-altitude experience, 6, 18, and 42 hours after arrival at the Jungfraujoch high-altitude research station (3450 m), which was reached through a 2.5-hour train ascent. RESULTS: We found that the overall prevalence of acute mountain sickness during the first 3 days at high altitude was 37.5%. Rates were similar for the 2 genders and decreased progressively during the stay (25% at 6 hours, 21% at 18 hours, and 8% at 42 hours). None of the subjects needed to be evacuated to lower altitude. Five subjects needed symptomatic treatment and responded well. CONCLUSION: After rapid ascent to high altitude, the prevalence of acute mountain sickness in children and adolescents was relatively low; the clinical manifestations were benign and resolved rapidly. These findings suggest that, for the majority of healthy nonacclimatized children and adolescents, travel to 3500 m is safe and pharmacologic prophylaxis for acute mountain sickness is not needed.

Gènere i sexoafectivitat segons els adolescents dels usuaris dels centres oberts de la ciutat de Girona

L’objectiu d’aquest treball és conèixer la percepció que tenen els adolescents usuaris dels centres oberts de la ciutat de Girona sobre la sexualitat, l’afectivitat, quins rols de gènere se’n deriven i quines creences els sustenten. El disseny del treball ha estat qualitatiu, observacional, grups de discussió. Pel que fa als subjectes i al mètode, la població seleccionada ha estat de 33 adolescents i joves d’edats compreses entre els 12 i els 22 anys, usuaris de quatre centres oberts de Girona: el centre obert de Taialà, el Centre Obert de Font de la Pólvora (Onyar), el Centre Obert de Santa Eugènia i el Centre Obert del Barri Vell. Es van dur a terme grups de discussió d’una hora de duració sense descans amb d’entre 6 i 8 persones a partir d’un guió format per diversos mites i frases en relació a diversos temes (El festeig, la virginitat, la curiositat pel cos i per la sexualitat, els anticonceptius i les principals fonts d’informació) sobre les que havien de dir si estaven d’acord o no i qui creien que les deia (si un noi o una noia). Sobre els resultats del treball cal dir que s’ha observat la persistència d’algunes creences del model del amor romàntic en relació al rols de gènere com la definició de la dona vinculada a papers de cura i prevenció, una dona que té accés a la sexualitat però segueix estan catalogada per la vivència d’aquesta essent una persona “respectable” o una “puta”, que pren un rol més actiu en la iniciativa però no el l’assertivitat en les relacions; i un home, més impulsiu i sexual. En relació als comportaments sexuals destacar l’embaràs no desitjat com la principal preocupació de les relacions i el desconeixement/confusió entre els mètodes anticonceptius i de barrera disponibles a la xarxa de salut. Apareix la pornografia com a model emergent de relacions sexuals i models de relació entre homes i dones, en contraposició a altres fonts de informació i consulta tradicionals com els amics que segueixen essent la més significativa, la família, els serveis socials i educatius, i Internet. Com a conclusió cal dir que queda palesa la necessitat de incorporar una perspectiva de gènere en la formació curricular dels joves i el fet de seguir replantejant les millors estratègies d’intervenció per una concepció integradora de la sexualitat

Epidemiology of Masked and White-Coat Hypertension: The Family-Based SKIPOGH Study.

OBJECTIVE: We investigated factors associated with masked and white-coat hypertension in a Swiss population-based sample. METHODS: The Swiss Kidney Project on Genes in Hypertension is a family-based cross-sectional study. Office and 24-hour ambulatory blood pressure were measured using validated devices. Masked hypertension was defined as office blood pressure<140/90 mmHg and daytime ambulatory blood pressure≥135/85 mmHg. White-coat hypertension was defined as office blood pressure≥140/90 mmHg and daytime ambulatory blood pressure<135/85 mmHg. Mixed-effect logistic regression was used to examine the relationship of masked and white-coat hypertension with associated factors, while taking familial correlations into account. High-normal office blood pressure was defined as systolic/diastolic blood pressure within the 130-139/85-89 mmHg range. RESULTS: Among the 652 participants included in this analysis, 51% were female. Mean age (±SD) was 48 (±18) years. The proportion of participants with masked and white coat hypertension was respectively 15.8% and 2.6%. Masked hypertension was associated with age (odds ratio (OR) = 1.02, p = 0.012), high-normal office blood pressure (OR = 6.68, p<0.001), and obesity (OR = 3.63, p = 0.001). White-coat hypertension was significantly associated with age (OR = 1.07, p<0.001) but not with education, family history of hypertension, or physical activity. CONCLUSIONS: Our findings suggest that physicians should consider ambulatory blood pressure monitoring for older individuals with high-normal office blood pressure and/or who are obese.

Consommation d'aliments riches en calcium dans la population adulte de Suisse romande et du Tessin. [Consumption of calcium-rich food in the adult population of French-speaking Switzerland and of Tessin].

Food intake high in calcium content is important in the development of skeleton and the prevention of osteoporosis. From a public health perspective, it is therefore important to know the dietary calcium intake of a population. Two population surveys in the French and Italian parts of Switzerland (MONICA, 1988-1989, and Geneva, 1991), were combined to study nutritional habits related to calcium intake. A random population sample, aged 35 et 65 years, answered to a 24 hour recall questionnaire, either self-administered (MONICA, cantons of Vaud, Fribourg and Tessin, N = 2734) or by phone (canton of Geneva, N = 475). In the 4 cantons, for the previous day, 60% of participants ate dairy products, particularly whole milk and cheese. They drunk 3-4 dl/day of milk. A significant proportion (10%) of french and italian speaking Swiss did not consume any food high in calcium content. In Geneva, the mean daily calcium intake was 656 mg in men and 489 mg in women. In conclusion 1) eating habits related to calcium intake are similar across cantons; 2) women consume dairy products more frequently than men, but in smaller quantities; 3) about 60% of men and 80% of women do not get the daily amount of calcium recommended for the prevention of osteoporosis.

Early effects of intravitreal triamcinolone on macular edema: mechanistic implication.

PURPOSE: To evaluate the early effects of intravitreal triamcinolone acetonide (TA) on cystoid macular edema associated with retinal vein occlusion and diabetic retinopathy. DESIGN: Prospective, interventional, small case series. PARTICIPANTS: Four patients with cystoid macular edema resulting from retinal vein occlusion or diabetic retinopathy of more than 4 months' duration and evaluated as suitable for treatment with intravitreous injection of TA. METHODS: After ophthalmic examination, including visual acuity assessment, intraocular pressure (IOP) measurement, and optical coherence tomography (OCT) analysis, the patients received a single intravitreal injection of 4 mg TA. After the injection, consecutive visual acuity assessment, IOP measurement, and OCT analysis were performed after 1 hour, 6 hours, 1 week, and 2 weeks. MAIN OUTCOME MEASURE: Optical coherence tomography assessment of macular thickness. RESULTS: Macular thickness and edema initially were reduced as early as 1 hour after TA injection. A further continuous decrease was observed during the 2 weeks after treatment. CONCLUSIONS: This rapid effect of intravitreal TA is interpreted to indicate that nongenomic effects on retinal or retinal pigment epithelial cell membranes, or both, may be responsible for this phenomenon. Identifications of these mechanisms may help design alternative, more specific drugs for the treatment of macular edema.

Basil conservation affected by cropping season, harvest time and storage period

Fresh basil (Ocimum basilicum L.) is used in food, phytotherapic industry, and in traditional therapeutic, due to its essential oil content and composition. Nevertheless basil can not be kept for long periods after harvest and its quality can be reduced. This work aimed to assess the influence of the season and harvest time in the postharvest conservation of basil stored for different periods. Basil was harvested at 8 am and 4 pm both in August/1999 and January/2000. Cuttings were conditioned in PVC packages and stored for 3, 6, and 9 days. During storage, chlorophyll content, essential oil content and composition were determined as well as microbiological analyses were carried out. Harvest season and the days of storage influenced the final content of essential oil. There was a linear decrease in the content of essential oil, in the chlorophyll content and in the number of mold and yeast colonies during storage. There was no effect of cropping season or harvest hour on essential oil composition, but the eugenol and linalool content increased during storage. Coliforms were under 0.3 MPN g-1 and the number of Staphylococcus aureus was under 1.0x10² UFC g-1.

Aliskiren monotherapy does not cause paradoxical blood pressure rises: meta-analysis of data from 8 clinical trials.

Angiotensin receptor blockers, angiotensin-converting enzyme inhibitors, and diuretics all cause reactive rises in plasma renin concentration, but particularly high levels have been reported with aliskiren. This prompted speculation that blockade of plasma renin activity with aliskiren could be overwhelmed, leading to paradoxical increases in blood pressure. This meta-analysis of data from 4877 patients from 8 randomized, double-blind, placebo- and/or active-controlled trials examined this hypothesis. The analysis focused on the incidence of paradoxical blood pressure increases above predefined thresholds, after > or =4 weeks of treatment with 300 mg of aliskiren, angiotensin receptor blockers (300 mg of irbesartan, 100 mg of losartan, or 320 mg of valsartan), 10 mg of ramipril, 25 mg of hydrochlorothiazide, or placebo. There were no significant differences in the frequency of increases in systolic (>10 mm Hg; P=0.30) or diastolic (>5 mm Hg; P=0.65) pressure among those treated with aliskiren (3.9% and 3.1%, respectively), angiotensin receptor blockers (4.0% and 3.7%), ramipril (5.7% and 2.6%), or hydrochlorothiazide (4.4% and 2.7%). Increases in blood pressure were considerably more frequent in the placebo group (12.6% and 11.4%; P<0.001). None of the 536 patients with plasma renin activity data who received 300 mg of aliskiren exhibited an increase in systolic pressure >10 mm Hg that was associated with an increase in plasma renin activity >0.1 ng/mL per hour. In conclusion, the incidence of blood pressure increases with aliskiren was similar to that during treatment with other antihypertensive drugs. Blood pressure rises on aliskiren treatment were not associated with increases in plasma renin activity. This meta-analysis found no evidence that aliskiren uniquely causes paradoxical rises in blood pressure.

Teaching Motivational Interviewing to Medical Students to Improve Behavior Change Counseling Skills - Results of a Pilot Test

BACKGROUND: Patient behavior accounts for half or more of the variance in health, disease, mortality and treatment outcome and costs. Counseling using motivational interviewing (MI) effectively improves the substance use and medical compliance behavior of patients. Medical training should include substantial focus on this key issue of health promotion. The objective of the study is to test the efficacy of teaching MI to medical students. METHODS: Thirteen fourth-year medical students volunteered to participate. Seven days before and after an 8-hour interactive MI training workshop, each student performed a video-recorded interview with two standardized patients: a 60 year-old alcohol dependent female consulting a primary care physician for the first time about fatigue and depression symptoms; and a 50 year-old male cigarette smoker hospitalized for myocardial infarction. All 52 videos (13 students×2 interviews before and after training) were independently coded by two blinded clinicians using the Motivational Interviewing Training Integrity (MITI, 3.0). MITI scores consist of global spirit (Evocation, Collaboration, Autonomy/Support), global Empathy and Direction, and behavior count summary scores (% Open questions, Reflection to question ratio, % Complex reflections, % MI-adherent behaviors). A "beginning proficiency" threshold (BPT) is defined for each of these 9 scores. The proportion of students reaching BPT before and after training was compared using McNemar exact tests. Inter-rater reliability was evaluated by comparing double coding, and test-retest analyses were conducted on a sub-sample of 10 consecutive interviews by each coder. Weighted Kappas were used for global rating scales and intra-class correlations (ICC) were computed for behavior count summary scores. RESULTS: The percent of counselors reaching BPT before and after MI training increased significantly for Evocation (15% to 65%, p<.001), Collaboration (27% to 77%, p=.001), Autonomy/Support (15% to 54%, p=.006), and % Open questions (4% to 38%, p=.004). Proportions increased, but were not statistically significant for Empathy (38% to 58%, p=.18), Reflection to question ratio (0% to 15%, p=.12), % Complex reflection (35% to 54%, p=.23), and % MI-adherent behaviors (8% to 15%, p=.69). There was virtually no change for the Direction scale (92% to 88%, p=1.00). The reliability analyses produced mixed results. Weighted kappas for inter-rater reliability ranged from .14 for Direction to .51 for Collaboration, and from .27 for Direction to .80 for Empathy for test-retest. ICCs ranged from .20 for Complex reflections to .89 for Open questions (inter-rater), and from .67 for Complex reflections to .99 for Reflection to question ratio (test-retest). CONCLUSION: This pilot study indicates that a single 8-hour training in motivational interviewing for voluntary fourth-year medical students results in significant improvement of some MI skills. A larger sample of randomly selected medical students observed over longer periods should be studied to test if MI training generalizes to medical students. Inter-rater reliability and test-retest findings indicate a need for caution when interpreting the present results, as well as for more intensive training to help appropriately capture more dimensions of the process in future studies.

Heritability of blood pressure in the swiss population: the family-based skipogh study

Objective: Blood pressure is known to aggregate in families. Yet, heritability estimates are population-specific and no Swiss data have been published so far. Moreover, little is known on the heritability of the white-coat effect. We investigated the heritability of various blood pressure (BP) traits in a Swiss population-based sample. Methods: SKIPOGH (Swiss Kidney Project on Genes in Hypertension) is a family-based multi-centre (Lausanne, Bern, Geneva) cross-sectional study that examines the role of genes in determining BP levels. Office and 24-hour ambulatory BP were measured using validated devices (A&D UM-101 and Diasys Integra). We estimated the heritability of systolic BP (SBP), diastolic BP (DBP), heart rate (HR), pulse pressure (PP), proportional white-coat effect (i.e. [office BP-mean ambulatory daytime BP]/mean ambulatory daytime BP), and nocturnal BP dipping (difference between mean ambulatory daytime and night-time BP) using a maximum likelihood method implemented in the SAGE software. Analyses were adjusted for age, sex, body mass index (BMI), and study centre. Analyses involving PP were additionally adjusted for DBP. Results: The 517 men and 579 women included in this analysis had a mean (}SD) age of 46.8 (17.8) and 47.8 (17.1) years and a mean BMI of 26.0 (4.2) and 24.2 (4.6) kg/m2, respectively. Heritability estimates (}SE) for office SBP, DBP, HR, and PP were 0.20}0.07, 0.20}0.07, 0.39}0.08, and 0.16}0.07 (all P<0.01). Heritability estimates for 24-hour ambulatory SBP, DBP, HR, and PP were, respectively, 0.39}0.07, 0.30}.08, 0.19}0.09, and 0.25}0.08 (all P<0.05). The heritability of the white-coat effect was 0.29}0.07 for SBP and 0.31}0.07 for DBP (both P<0.001). The heritability of nocturnal BP dipping was 0.15}0.08 for SBP and 0.22}0.07 for DBP (both P<0.05). Conclusions: We found that the white-coat effect is significantly heritable. Our findings show that BP traits are moderately heritable in a multi-centric study in Switzerland, in line with previous population-based studies, justifying the ongoing search for genetic determinants in this field.

Highway Work Zone Capacity Estimation Using Field Data from Kansas, TPF-5(081), 2015

Although extensive research has been conducted on urban freeway capacity estimation methods, minimal research has been carried out for rural highway sections, especially sections within work zones. This study attempted to fill that void for rural highways in Kansas, by estimating capacity of rural highway work zones in Kansas. Six work zone locations were selected for data collection and further analysis. An average of six days’ worth of field data was collected, from mid-October 2013 to late November 2013, at each of these work zone sites. Two capacity estimation methods were utilized, including the Maximum Observed 15-minute Flow Rate Method and the Platooning Method divided into 15-minute intervals. The Maximum Observed 15-minute Flow Rate Method provided an average capacity of 1469 passenger cars per hour per lane (pcphpl) with a standard deviation of 141 pcphpl, while the Platooning Method provided a maximum average capacity of 1195 pcphpl and a standard deviation of 28 pcphpl. Based on observed data and analysis carried out in this study, the suggested maximum capacity can be considered as 1500 pcphpl when designing work zones for rural highways in Kansas. This proposed standard value of rural highway work zone capacity could be utilized by engineers and planners so that they can effectively mitigate congestion at or near work zones that would have otherwise occurred due to construction/maintenance.

Haemodynamic role of vasopressin released during Finnish sauna.

The effect of vasopressin released during Finnish sauna on blood pressure, heart rate and skin blood flow was investigated in 12 healthy volunteers. Exposure to the hot air decrease body weight by 0.6 to 1.25 kg (mean = 0.8 kg, P less than 0.001). One hour after the end of the sauna sessions, plasma vasopressin was higher (1.7 +/- 0.2 pg/ml, P less than 0.01 mean +/- SEM) than before the sauna (1.0 +/- 0.1 pg/ml). No simultaneous change in plasma osmolality, plasma renin activity, plasma norepinephrine, epinephrine, cortisol, aldosterone, beta-endorphin and metenkephalin levels was observed. Despite the slight sauna-induced elevation in circulating vasopressin, intravenous injection of the specific vascular vasopressin antagonist d(CH2)5Tyr(Me)AVP (5 micrograms/kg) 1 h after the sauna had no effect on blood pressure, heart rate or skin blood flow. These data suggest that vasopressin released into the circulation during a sauna session reaches concentrations which are not high enough to interfere directly with vascular tone.

A novel cyclosporin a aqueous formulation for dry eye treatment: in vitro and in vivo evaluation.

PURPOSE: The aim of the present study was the in vitro and in vivo evaluation of a novel aqueous formulation based on polymeric micelles for the topical delivery of cyclosporine A for dry eye treatment. METHODS: In vitro experiments were carried out on primary rabbit corneal cells, which were characterized by immunocytochemistry using fluorescein-labeled lectin I/isolectin B4 for the endothelial cells and mouse monoclonal antibody to cytokeratin 3+12 for the epithelial ones. Living cells were incubated for 1 hour or 24 hours with a fluorescently labeled micelle formulation and analyzed by fluorescence microscopy. In vivo evaluations were done by Schirmer test, osmolarity measurement, CyA kinetics in tears, and CyA ocular distribution after topical instillation. A 0.05% CyA micelle formulation was compared to a marketed emulsion (Restasis). RESULTS: The in vitro experiments showed the internalization of micelles in the living cells. The Schirmer test and osmolarity measurements demonstrated that micelles did not alter the ocular surface properties. The evaluation of the tear fluid gave similar CyA kinetics values: AUC = 2339 ± 1032 min*μg/mL and 2321 ± 881.63; Cmax = 478 ± 111 μg/mL and 451 ± 74; half-life = 36 ± 9 min and 28 ± 9 for the micelle formulation and Restasis, respectively. The ocular distribution investigation revealed that the novel formulation delivered 1540 ± 400 ng CyA/g tissue to the cornea. CONCLUSIONS: The micelle formulation delivered active CyA into the cornea without evident negative influence on the ocular surface properties. This formulation could be applied for immune-related ocular surface diseases.

Evaluation of the PAVEDEX Road Survey System in Iowa, HR-547, 1990

The Iowa Department of Transportation (DOT) evaluated the PAS I Road Survey System from PAVEDEX, Inc. of Spokane, Washington. This system uses video photograph to identify and quantify pavement cracking and patching distresses. Comparisons were made to procedures currently used in the State. Interstate highway, county roads and city streets, and two shoulder sections were evaluated. Variables included travel speeds, surface type and texture, and traffic control conditions. Repeatability and distress identification were excellent on rigid pavements. Differences in distress identification and the effect of surface textures in the flexible test sections limited the repeatability and correlation of data to that of the Iowa DOT method. Cost data indicates that PAVEDEX is capable of providing comparable results with improved accuracy at a reasonable cost, but in excess of that experienced currently by the Iowa DOT. PAVEDEX is capable of providing network level pavement condition data at highway speeds and analysis of the data to identify 1/8-inch cracks at approximately 2-3 lane miles per hour with manual evaluation. Photo-logging capability is also included in the unit.