Cutoffs for white-coat and masked blood pressure effects: an ambulatory blood pressure monitoring study.

The values used to define white-coat and masked blood pressure (BP) effects are usually arbitrary. This study aimed at investigating the accuracy of various cutoffs based on the differences (ΔBP) between office BP (OBP) and 24h-ambulatory BP monitoring (ABPM) to identify white-coat (WCH) and masked (MH) hypertension, which are phenotypes coupled with adverse prognosis. This cross-sectional study included 11,350 [Derivation cohort; 45% men, mean age = 55.1 ± 14.1 years, OBP = 132.1 ± 17.6/83.9 ± 12.5 mmHg, 24 h-ABPM = 121.6 ± 11.4/76.1 ± 9.6 mmHg, 25% using antihypertensive medications (AH)] and 7220 (Validation cohort; 46% men, mean age = 58.6 ± 15.1 years, OBP = 136.8 ± 18.7/87.6 ± 13.0 mmHg, 24 h-ABPM = 125.5 ± 12.6/77.7 ± 10.3 mmHg; 32% using AH) unique individuals who underwent 24 h-ABPM. We compared the sensitivity, specificity, positive and negative predictive values and area under the curve (AUC) of diverse ΔBP cutoffs to detect WCH (ΔsystolicBP/ΔdiastolicBP = 28/17, 20/15, 20/10, 16/11, 15/9, 14/9 mmHg and ΔsystolicBP = 13 and 10 mmHg) and MH (ΔsystolicBP/ΔdiastolicBP = -14/-9, -5/-2, -3/-1, -1/-1, 0/0, 2/2 mmHg and ΔsystolicBP = -5 and -3mmHg). The 20/15 mmHg cutoff showed the best AUC (0.804, 95%CI = 0.794-0.814) to detect WCH, while the 2/2 mmHg cutoff showed the highest AUC (0.741, 95%CI = 0.728-0.754) to detect MH in the Derivation cohort. Both cutoffs also had the best accuracy to detect WCH (0.767, 95%CI = 0.754-0.780) and MH (0.767, 95%CI = 0.750-0.784) in the Validation cohort. In secondary analyses, these cutoffs had the best accuracy to detect individuals with higher and lower office-than-ABPM grades in both cohorts. In conclusion, the 20/15 and 2/2 mmHg ΔBP cutoffs had the best accuracy to detect hypertensive patients with WCH and MH, respectively, and can serve as indicators of marked white-coat and masked BP effects derived from 24 h-ABPM.

AT1 receptors modulate ethanol-induced loss of anticontractile effect of perivascular adipose tissue.

Ethanol consumption activates renin-angiotensin-aldosterone system (RAAS), which plays a major role in the pro-contractile and hypertensive effects linked to ethanol. We hypothesized that ethanol consumption induces loss of the anticontractile effect of perivascular adipose tissue (PVAT)through RAAS-mediated mechanisms. We examined the contribution of angiotensin II type 1 receptors (AT1R) to ethanol-induced PVAT dysfunction. With this purpose, male Wistar Hannover rats were treated with ethanol 20 % (in volume ratio) and/or losartan (antagonist of AT1R; 10 mg/kg/day, gavage) for 9 weeks. Losartan prevented the increase in blood pressure and the loss of the anticontractile effect of PVAT induced by ethanol consumption. PVAT dysfunction occurred after 3 and 9 weeks of treatment with ethanol in an endothelium-dependent manner. Blockade of AT1R prevented ethanol-induced reduction of adiponectin levels in PVAT from ethanol-treated rats. Functional assays revealed that ethanol impaired the anticontractile effect of PVAT-derived angiotensin (1-7) and endothelial nitric oxide (NO). In conclusion, AT1R are implicated in ethanol-induced loss of the anticontractile effect of PVAT. In PVAT, AT1R activation decreases the production of adiponectin, a PVAT-derived factor that promotes vasorelaxation in an endothelium-dependent manner. In the endothelium, AT1R favors the production of superoxide (O2•-) leading to a reduction in NO bioavailability. These responses impair the vasodilator action induced by PVAT-derived angiotensin (1-7), which occurs via Mas receptors located in endothelial cells. Ethanol-induced PVAT dysfunction favors vascular hypercontractility, a response that could contribute to the hypertensive state associated with ethanol consumption.

Pendular mechanism determinants and elastic energy usage during walking of obese and non-obese children.

The mechanical and metabolic responses of walking by obese children are not yet well understood. The objectives of this study were (1) to compare the pendular mechanism (recovery, phase shift by α and ß values, and ratio between forward and vertical mechanical work), the maximum possible elastic energy usage and the bilateral coordination during walking between non-obese and obese children, and (2) to verify if the bilateral coordination could contribute to understanding the pendular mechanism and elastic energy usage in these populations. Nine obese (six female, 8.7 ± 0.5 years, 1.38 ± 0.04 m, 44.4 ± 6.3 kg and 24.1 ± 3.50 kg/m2 ) and eight non-obese (four female, 7.4 ± 0.5 years, 1.31 ± 0.08 m, 26.6 ± 2.1 kg and 16.4 ± 1.40 kg/m2 ) children were analysed during walking on a treadmill at five speeds: 1, 2, 3, 4 and 5 km/h. The results indicated that although the mechanical energy response of the centre of mass during walking is similar between obese and non-obese children, the obese children showed a lower pendulum-like mechanism and greater elastic energy usage during level walking. Therefore, obese children seem to use more elastic energy during walking compared to non-obese children, which may be related to their apparent higher positive work production during the double support phase. Finally, bilateral coordination presented high values at slow speeds in both groups and requires further attention due to its association with falls. NEW FINDINGS: What is the central question of this study? Are there any differences of the pendular and elastic mechanisms and bilateral coordination during walking between non-obese and obese children? What is the main finding and its importance? To our knowledge, this study is the first to analyse the mechanical energy usage and the bilateral coordination of obese and non-obese children during walking. Obese children had a lower pendular recovery mechanism and used more elastic energy compared to non-obese children. The bilateral coordination was higher at slow speeds in both groups and requires further attention due to its association with falls.

Effect of age and speed on the step-to-step transition strategies in children.

The development and acquisition of mature walking in children is multifactorial, depending among others on foot interaction with the ground, body dynamics and the knowledge of the 'rules' stemming from the gravity field. Indeed, each step the velocity of the centre of mass must be redirected upwards. This redirection may be initiated by the trailing leg, propulsing forward and upward the body before foot contact, or later by the loading limb after the contact with the ground. While it has been suggested that mature walking develops slowly from first independent steps to about 7 years of age, it is still unknown how children acquire the appropriate loading and propulsion forces during the step-to-step transition. To answer that question, twenty-four children (from 3 to 12 years old) and twelve young adults (from 20 to 27 years old) walked on force platforms at different walking speed. The ground reaction forces under each foot were recorded and the vertical velocity of the centre of mass of the body was computed. With decreasing age and increasing velocity (or Froude number), the occurrence of unanticipated transition is higher, related to a different ratio between the vertical support of the front and back leg. The different transition strategy observed in children indicates that body weight transfer from one limb to the other is not fully mature at 12 years old.

Process mining for healthcare: Characteristics and challenges.

Process mining techniques can be used to analyse business processes using the data logged during their execution. These techniques are leveraged in a wide range of domains, including healthcare, where it focuses mainly on the analysis of diagnostic, treatment, and organisational processes. Despite the huge amount of data generated in hospitals by staff and machinery involved in healthcare processes, there is no evidence of a systematic uptake of process mining beyond targeted case studies in a research context. When developing and using process mining in healthcare, distinguishing characteristics of healthcare processes such as their variability and patient-centred focus require targeted attention. Against this background, the Process-Oriented Data Science in Healthcare Alliance has been established to propagate the research and application of techniques targeting the data-driven improvement of healthcare processes. This paper, an initiative of the alliance, presents the distinguishing characteristics of the healthcare domain that need to be considered to successfully use process mining, as well as open challenges that need to be addressed by the community in the future.

Inhibition of inducible nitric oxide synthase protects against the deleterious effects of sub-lethal sepsis and ethanol in the cardiorenal system.

We tested the hypothesis that ethanol would aggravate the deleterious effects of sub-lethal cecal ligation and puncture (SL-CLP) sepsis in the cardiorenal system and that inhibition of inducible nitric oxide synthase (iNOS) would prevent such response. Male C57BL/6 mice were treated with ethanol for 12 weeks. One hour before SL-CLP surgery, mice were treated with N6-(1-iminoethyl)-lysine (L-NIL, 5 mg/kg, i.p.), a selective inhibitor of iNOS. A second dose of L-NIL was administered 24 h after SL-CLP surgery. Mice were killed 48 h post surgery and the blood, the renal cortex, and the left ventricle (LV) were collected for biochemical analysis. L-NIL attenuated the increase in serum creatinine levels induced by ethanol, but not by SL-CLP. Ethanol, but not SL-CLP, increased creatine kinase (CK)-MB activity and L-NIL did not prevent this response. In the renal cortex, L-NIL prevented the redox imbalance induced by ethanol and SL-CLP. Inhibition of iNOS also decreased lipoperoxidation induced by ethanol and SL-CLP in the LV. L-NIL prevented the increase of pro-inflammatory cytokines and reactive oxygen species induced by ethanol and (or) SL-CLP in the cardiorenal system, suggesting that iNOS modulated some of the molecular mechanisms that underlie the deleterious effects of both conditions in the cardiorenal system.

Mechanical work as a (key) determinant of energy cost in human locomotion: recent findings and future directions.

NEW FINDINGS: What is the topic of this review? This narrative review explores past and recent findings on the mechanical determinants of energy cost during human locomotion, obtained by using a mechanical approach based on König's theorem (Fenn's approach). What advances does it highlight? Developments in analytical methods and their applications allow a better understanding of the mechanical-bioenergetic interaction. Recent advances include the determination of 'frictional' internal work; the association between tendon work and apparent efficiency; a better understanding of the role of energy recovery and internal work in pathological gait (amputees, stroke and obesity); and a comprehensive analysis of human locomotion in (simulated) low gravity conditions. ABSTRACT: During locomotion, muscles use metabolic energy to produce mechanical work (in a more or less efficient way), and energetics and mechanics can be considered as two sides of the same coin, the latter being investigated to understand the former. A mechanical approach based on König's theorem (Fenn's approach) has proved to be a useful tool to elucidate the determinants of the energy cost of locomotion (e.g., the pendulum-like model of walking and the bouncing model of running) and has resulted in many advances in this field. During the past 60 years, this approach has been refined and applied to explore the determinants of energy cost and efficiency in a variety of conditions (e.g., low gravity, unsteady speed). This narrative review aims to summarize current knowledge of the role that mechanical work has played in our understanding of energy cost to date, and to underline how recent developments in analytical methods and their applications in specific locomotion modalities (on a gradient, at low gravity and in unsteady conditions) and in pathological gaits (asymmetric gait pathologies, obese subjects and in the elderly) could continue to push this understanding further. The recent in vivo quantification of new aspects that should be included in the assessment of mechanical work (e.g., frictional internal work and elastic contribution) deserves future research that would improve our knowledge of the mechanical-bioenergetic interaction during human locomotion, as well as in sport science and space exploration.

Nebivolol Prevents Up-Regulation of Nox2/NADPH Oxidase and Lipoperoxidation in the Early Stages of Ethanol-Induced Cardiac Toxicity.

Changes in redox state are described in the early stages of ethanol-induced cardiac toxicity. Here, we evaluated whether nebivolol would abrogate ethanol-induced redox imbalance in the heart. Male Wistar rats were treated with a solution of ethanol (20% v/v) for 3 weeks. Treatment with nebivolol (10 mg/kg/day; p.o. gavage) prevented the increase of both superoxide (O2•-) and thiobarbituric acid reactive substances (TBARS) in the left ventricle of rats chronically treated with ethanol. Neither ethanol nor nebivolol affected the expression of Nox4, p47phox, or Rac-1. Nebivolol prevented ethanol-induced increase of Nox2 expression in the left ventricle. Superoxide dismutase (SOD) activity as well as the concentration of reduced glutathione (GSH) was not altered by ethanol or nebivolol. Augmented catalase activity was detected in the left ventricle of both ethanol- and nebivolol-treated rats. Treatment with nebivolol, but not ethanol increased eNOS expression in the left ventricle. No changes in the activity of matrix metalloproteinase (MMP)2 or in the expressions of MMP2, MMP9, and tissue inhibitor metalloproteinase (TIMP)1 were detected after treatment with ethanol or nebivolol. However, ethanol increased the expression of TIMP2, and this response was prevented by nebivolol. Our results provided novel insights into the mechanisms underlying the early stages of the cardiac injury induced by ethanol consumption. We demonstrated that Nox2/NADPH oxidase-derived ROS play a role in ethanol-induced lipoperoxidation and that this response was prevented by nebivolol. In addition, we provided evidence that MMPs are not activated in the early stages of ethanol-induced cardiac toxicity.

Ethanol and cyclophosphamide induce similar nephrotoxic effects: possible role for Nox4 and superoxide.

We tested the hypothesis that ethanol consumption would aggravate the renal damage induced by cyclophosphamide (CYP). Male C57BL/6 J mice from control (n = 8) and CYP (n = 12) groups had free access to filtered water and standard rodent chow for 12 weeks. Then, 24 h before euthanasia mice received an intraperitoneal injection of saline or CYP (300 mg/kg). Mice from ethanol (n = 8) and CYP + ethanol (n = 12) groups had free access to increasing doses of ethanol for 12 weeks. Twenty-four hours before euthanasia, mice from ethanol and CYP + ethanol groups received an intraperitoneal injection of saline or CYP, respectively. Ethanol, CYP, or the association of both drugs augmented serum levels of creatinine and increased the levels of superoxide ([Formula: see text]) generation and thiobarbituric acid reactive substances in the renal cortex. Upregulation of Nox4 and increased activity of superoxide dismutase were detected in the renal cortex of mice treated with ethanol, CYP, or the combination of these drugs; however, these molecular alterations induced by CYP were not potentiated by ethanol consumption. Our findings revealed that chronic ethanol consumption had no potentiating effect on the nephrotoxic effects displayed by CYP. It is possible that the combination of these drugs showed no synergistic effect because they share the same molecular mechanisms of renal toxicity.

Acute restraint stress increases blood pressure and oxidative stress in the cardiorenal system of rats: a role for AT1 receptors.

We evaluate whether acute restraint stress may affect the oxidative state of the cardiorenal system and the possible contribution of angiotensin II/AT1 receptors in such response. Male Wistar rats were restrained for 60 min within wire mesh chambers. Some rats were treated with losartan (selective AT1 receptor antagonist, 10 mg/kg, p.o., gavage) 30 min before being stressed. Biochemical analyses were conducted after the 60-min period of restraint. Treatment with losartan prevented the increase in mean arterial pressure (MAP), but not heart rate (HR) induced by acute stress. Phenylephrine-induced contraction of endothelium-intact aortas was not affected by acute stress. Losartan prevented the increase in both superoxide anion (O2•-) and hydrogen peroxide (H2O2) levels induced by acute stress in the aorta and renal cortex. Similarly, the augmented activity of superoxide dismutase (SOD) induced by acute stress in the aorta and renal cortex was prevented by losartan. Enhanced levels of O2•- and thiobarbituric acid reactive species (TBARS) were detected in the left ventricle (LV) of stressed rats, but losartan did not prevent these responses. Similarly, losartan did not inhibited stress-induced decrease in the concentration of nitrate/nitrite (NOx) and H2O2 in the left ventricle. Stress increased ROS generation and affected the enzymatic antioxidant system in the cardiorenal system. In addition to its well-known cardiovascular changes during acute stress, angiotensin II also induces ROS generation in the cardiorenal system in a tissue-specific manner. The increase in oxidative stress mediated by angiotensin II/AT1 receptors could be one mechanism by which acute stress predisposes to cardiorenal dysfunctions.

Influence of a slow-start on overall performance and running kinematics during 6-h ultramarathon races.

The aim of this study was to describe the pacing during a 6-h ultramarathon (race 1) and to investigate whether a slow-start affects performance, running kinematic changes, ratings of perceived exertion (RPE) and fatigue (ROF) (race 2). After a critical speed test, participants completed two 6-h ultramarathons. Race 1 (n = 16) was self-paced, whereas in race 2 (n = 10), athletes performed the initial 36 min at speeds 18% below the mean speed of the initial 36 min of race 1. In race 1, participants adopted an inverse sigmoid pacing. Contact times increased after 1 h, and flight times decreased after 30 min (all P ≤ .009); stride length reduced after 1 h 30 min (all P = .022), and stride frequency did not change. Despite the lower speeds during the first 10% of race 2, and higher speeds at 50% and 90%, performance remained unchanged (57.5 ± 10.2 vs. 56.3 ± 8.5 km; P = .298). However, RPE and ROF were lowered for most of race 2 duration (all P < .001). For the comparison of kinematic variables between races, data were normalised by absolute running speed at each time point from 1 h onwards. No differences were found for any of the kinematic variables. In conclusion, decreasing initial speed minimises RPE and ROF, but does not necessarily affect performance. In addition, running kinematic changes do not seem to be affected by pacing manipulation.

Differences in negative predictive value of prostate MRI based in men with suspected or known cancer.

OBJECTIVE: To compare the negative predictive value (NPV) of multiparametric MRI for Gleason score (GS) ≥ 3+4 cancer and evaluate predictors of these tumors in men with suspected disease and under active surveillance (AS). MATERIALS AND METHODS: This retrospective study included 38 men with suspected prostate cancer and 38 under AS with scans assigned PI-RADS v2 scores 1 or 2 between May 2016 and September 2017. Biopsy results were no cancer, GS = 3+3, or GS ≥ 3+4. Pre-MRI PSA, gland volume, and PSA density were recorded. Chi-square, equality of proportions, and logistic regressions were used to analyze the data. RESULTS: Intermediate to high-grade cancer was found in 12.8% (95% CI = 2.3-23.3) and 35.9% (95% CI = 20.8-50.9) of men with suspected cancer, and under AS (p = 0.02), respectively. The NPV for GS ≥ 3+4 were 87.2% (suspected cancer; 76.7-97.7) and 64.1% (AS; 49.0-79.2). In neither group PSA significantly predicted cancer grade (p = 0.75 and 0.63). Although it did not reach conventional statistical significance, PSA density was a good predictor of cancer grade in men with suspected disease (p = 0.06), but not under AS (p = 0.62). CONCLUSION: The NPV of multiparametric MRI for GS ≥ 3+4 is higher in men with suspected prostate cancer than in men under AS. PSA density ≤ 0.15 improved the prediction of intermediate to high-grade disease in patients without known cancer.

OBJETIVO: Comparar o valor preditivo negativo (VPN) da RM multiparamétrica da próstata para o diagnóstico de tumores escore de Gleason (EG) ≥ 3+4 e avaliar os preditores desses tumores em homens com suspeita de doença e nos sob vigilância ativa (VA). MATERIAIS E MÉTODOS: Este estudo retrospectivo incluiu 38 homens com suspeita de câncer de próstata e 38 em VA com RM, aos quais foram atribuídos escores PI-RADS v2 1 ou 2 entre maio de 2016 e setembro de 2017. Os resultados da biópsia foram ausência de câncer, câncer EG = 3+3 ou câncer EG ≥ 3+4. PSA pré-RM, volume da glândula e densidade de PSA foram anotados. Qui-quadrado, igualdade de proporções e regressões logísticas foram utilizados para analisar os dados. RESULTADOS: Câncer de grau intermediário a alto grau foi encontrado em 12,8% (IC 95% = 2,3­23,3) e 35,9% (IC 95% = 20,8­50,9) dos homens com suspeita de câncer e nos sob VA (p = 0,02), respectivamente. O VPN para GS ≥ 3+4 foi 87,2% (suspeita de câncer; IC 95% = 76,7­97,7) e 64,1% (VA; IC 95% = 49,0­79,2). Em nenhum dos grupos o PSA previu significativamente o grau de câncer (p = 0,75 e 0,63. Embora não tenha alcançado o limiar de significância estatística usual, a densidade de PSA foi um bom preditor de grau de câncer em homens com suspeita de doença (p = 0,06), mas não sob VA (p = 0,62). CONCLUSÃO: O VPN da RM multiparamétrica para GS ≥ 3+4 é maior em homens com suspeita de câncer de próstata do que em homens sob VA. Uma densidade de PSA ≤ 0,15 melhorou a previsão de doença de grau intermediário a alto grau em pacientes sem diagnóstico prévio de câncer.

Differences in negative predictive value of prostate MRI based in men with suspected or known cancer / Diferenças no valor preditivo negativo da ressonância magnética da próstata baseada em homens com câncer suspeito ou conhecido

Abstract Objective: To compare the negative predictive value (NPV) of multiparametric MRI for Gleason score (GS) ≥ 3+4 cancer and evaluate predictors of these tumors in men with suspected disease and under active surveillance (AS). Materials and Methods: This retrospective study included 38 men with suspected prostate cancer and 38 under AS with scans assigned PI-RADS v2 scores 1 or 2 between May 2016 and September 2017. Biopsy results were no cancer, GS = 3+3, or GS ≥ 3+4. Pre-MRI PSA, gland volume, and PSA density were recorded. Chi-square, equality of proportions, and logistic regressions were used to analyze the data. Results: Intermediate to high-grade cancer was found in 12.8% (95% CI = 2.3-23.3) and 35.9% (95% CI = 20.8-50.9) of men with suspected cancer, and under AS (p = 0.02), respectively. The NPV for GS ≥ 3+4 were 87.2% (suspected cancer; 76.7-97.7) and 64.1% (AS; 49.0-79.2). In neither group PSA significantly predicted cancer grade (p = 0.75 and 0.63). Although it did not reach conventional statistical significance, PSA density was a good predictor of cancer grade in men with suspected disease (p = 0.06), but not under AS (p = 0.62). Conclusion: The NPV of multiparametric MRI for GS ≥ 3+4 is higher in men with suspected prostate cancer than in men under AS. PSA density ≤ 0.15 improved the prediction of intermediate to high-grade disease in patients without known cancer.

Resumo Objetivo: Comparar o valor preditivo negativo (VPN) da RM multiparamétrica da próstata para o diagnóstico de tumores escore de Gleason (EG) ≥ 3+4 e avaliar os preditores desses tumores em homens com suspeita de doença e nos sob vigilância ativa (VA). Materiais e Métodos: Este estudo retrospectivo incluiu 38 homens com suspeita de câncer de próstata e 38 em VA com RM, aos quais foram atribuídos escores PI-RADS v2 1 ou 2 entre maio de 2016 e setembro de 2017. Os resultados da biópsia foram ausência de câncer, câncer EG = 3+3 ou câncer EG ≥ 3+4. PSA pré-RM, volume da glândula e densidade de PSA foram anotados. Qui-quadrado, igualdade de proporções e regressões logísticas foram utilizados para analisar os dados. Resultados: Câncer de grau intermediário a alto grau foi encontrado em 12,8% (IC 95% = 2,3-23,3) e 35,9% (IC 95% = 20,8-50,9) dos homens com suspeita de câncer e nos sob VA (p = 0,02), respectivamente. O VPN para GS ≥ 3+4 foi 87,2% (suspeita de câncer; IC 95% = 76,7-97,7) e 64,1% (VA; IC 95% = 49,0-79,2). Em nenhum dos grupos o PSA previu significativamente o grau de câncer (p = 0,75 e 0,63. Embora não tenha alcançado o limiar de significância estatística usual, a densidade de PSA foi um bom preditor de grau de câncer em homens com suspeita de doença (p = 0,06), mas não sob VA (p = 0,62). Conclusão: O VPN da RM multiparamétrica para GS ≥ 3+4 é maior em homens com suspeita de câncer de próstata do que em homens sob VA. Uma densidade de PSA ≤ 0,15 melhorou a previsão de doença de grau intermediário a alto grau em pacientes sem diagnóstico prévio de câncer.

Chronic ethanol consumption induces micturition dysfunction and alters the oxidative state of the urinary bladder.

Oxidative stress is pointed out as a major mechanism by which ethanol induces functional and structural changes in distinctive tissues. We evaluated whether ethanol consumption would increase oxidative stress and cause micturition dysfunction. Male C57BL/6J mice were treated with 20% ethanol (v/v) for 10 weeks. Our findings showed that chronic ethanol consumption reduced micturition spots and urinary volume in conscious mice, whereas in anaesthetized animals cystometric analysis revealed reduced basal pressure and increased capacity, threshold pressure, and maximum voiding. Treatment with ethanol reduced the contraction induced by carbachol in isolated bladders. Chronic ethanol consumption increased the levels of oxidant molecules and thiobarbituric acid reactive species in the mouse bladder. Upregulation of Nox2 was detected in the bladder of ethanol-treated mice. Increased activity of both superoxide dismutase and catalase were detected in the mouse bladder after treatment with ethanol. Conversely, decreased levels of reduced glutathione were detected in the bladder of ethanol-treated mice. The present study first demonstrated that chronic ethanol consumption induced micturition dysfunction and that this response was accompanied by increased levels of oxidant molecules in the mousebladder. These findings suggest that ethanol consumption is a risk factor for vesical dysfunction.

Discharge Instruction Comprehension and Adherence Errors: Interrelationship Between Plan Complexity and Parent Health Literacy.

OBJECTIVE: To examine associations between parent health literacy, discharge plan complexity, and parent comprehension of and adherence to inpatient discharge instructions. STUDY DESIGN: This was a prospective cohort study of English/Spanish-speaking parents (n = 165) of children ≤12 years discharged on ≥1 daily medication from an urban, public hospital. Outcome variables were parent comprehension (survey) of and adherence (survey, in-person dosing assessment, chart review) to discharge instructions. Predictor variables included low parent health literacy (Newest Vital Sign score 0-3) and plan complexity. Generalized estimating equations were used to account for the assessment of multiple types of comprehension and adherence errors for each subject, adjusting for ethnicity, language, child age, length of stay, and chronic disease status. Similar analyses were performed to assess for mediation and moderation. RESULTS: Error rates were highest for comprehension of medication side effects (50%), adherence to medication dose (34%), and return precaution (78%) instructions. Comprehension errors were associated with adherence errors (aOR, 8.7; 95% CI, 5.9-12.9). Discharge plan complexity was associated with comprehension (aOR, 7.0; 95% CI, 5.4-9.1) and adherence (aOR, 5.5; 95% CI, 4.0-7.6) errors. Low health literacy was indirectly associated with adherence errors through comprehension errors. The association between plan complexity and comprehension errors was greater in parents with low (aOR, 8.3; 95% CI, 6.2-11.2) compared with adequate (aOR, 3.8; 95% CI, 2.2-6.5) health literacy (interaction term P = .004). CONCLUSIONS: Parent health literacy and discharge plan complexity play key roles in comprehension and adherence errors. Future work will focus on the development of health literacy-informed interventions to promote discharge plan comprehension.

Association of calcified carotid artery plaque in panoramic images and diagonal earlobe crease.

OBJECTIVES:: Brazilians who are free of traditional atherogenic risk factors frequently suffer myocardial infarctions (MI). Calcified carotid artery plaque (CCAP) on panoramic images (PIs) has been shown to be a validated "risk indicator" of future MIs. The diagonal earlobe crease (DELC) is likewise a validated "risk indicator" of future MI. We sought to determine the prevalence of DELC+ among patients having CCAP+ on their PIs. METHODS:: In a masked cross-sectional study, three dentists evaluated PIs of patients (N = 481) over age 55 for presence of CCAP+. Among the CCAP+ cohort, the presence of DELC+ was determined by two additional dentists masked to the presence of CCAP+ on PIs. A control group (CCAP-) comprised of individuals with PIs devoid of plaque was similarly evaluated for evidence of DELC+. RESULTS:: A mixed-gender group (8.6%) of patients (N = 41; mean age 67.5 ± 6.8) evidenced CCAP+ on their PIs and approximately 88% of these individuals (N = 36) had concomitant DELC+. Among members of the control group (N = 41), 17 patients were DELC+. Our results demonstrated that among the full mixed-gender cohort (N = 82), the association between CCAP+ and DELC+ was statistically significant (p = 0.0001). However, when adjusting for gender, only the CCAP+ men were significantly (p = 0.00011) more likely to evidence DELC+ on clinical examination. CONCLUSIONS:: Males with atherosclerosis of their carotid arteries as evidenced by PIs displaying calcified atheromas are significantly more likely to evidence a DELC+ than those without an imaged atheroma.

Biochemical and milk-clotting properties and mapping of catalytic subsites of an extracellular aspartic peptidase from basidiomycete fungus Phanerochaete chrysosporium.

For a long time, proteolytic enzymes have been employed as key tools of industrial processes, especially in the dairy industry. In the present work, we used Phanerochaete chrysosporium for biochemical characterization and analysis of catalytic specificity of an aspartic peptidase. Our results revealed an aspartic peptidase with molecular mass ∼38kDa, maximal activity at pH 4.5 and 50°C, and stability above 80% in the pH range of 3-8 and temperature up to 55°C for 1h. In a milk-clotting assay, this peptidase showed maximal milk clotting activity at 60-65°C and maintenance of enzymatic activity above 80% in the presence of 20mM CaCl2. In a specificity assay, we observed stronger restriction of catalysis at the S1 subsite, with a preference for lysine, arginine, leucine, tyrosine, and phenylalanine residues. The restricted proteolysis and milk-clotting potential are attractive properties for the use in cheese production.