Development and sensory test of a dairy product with ACE inhibitory and antioxidant peptides produced at a pilot plant scale.

A scale-up process was carried out to obtain potent bioactive peptides from whey protein through a simple hydrolysis process. The scale-up was satisfactory, with results similar to those obtained at lab scale: a fraction of peptides < 1 kDa with ACE inhibitory activity of 18.44 ± 2.47 µg/mL, a DPPH value of 69.40 ± 0.44%, and an ORAC value of 3.37 ± 0.03 µmol TE/mg protein. The peptide sequences responsible for the ACE inhibitory activity were also similar to those identified at lab scale: PM, LL, LF, HFKG and PT. The hydrolysate was used as a functional ingredient in a low-fat yoghurt. The consumer sensory taste panel found no significant difference (p > 0.05) between the bitterness of the control and the functional yoghurt, and about 50% of consumers would buy it. The hydrolysate maintained its bioactivities for 4 months at -20 °C (after thawing and pasteurisation), and for 1 week in yoghurt at 4 °C.

Optimisation of bovine ß-lactoglobulin hydrolysis using cardosins from dried flowers of Cynara cardunculus.

Bovine whey protein was hydrolysed using cardosins A and B purified from dried flowers of Cynara cardunculus by combining diafiltration, anion-exchange chromatography and ultrafiltration. The proteolysis experiments were performed using different whey protein concentrations and enzyme/substrate (E/S) ratios. Complete hydrolysis of the main whey proteins, ß-Lactoglobulin (ß-Lg) and α-lactalbumin (α-La), was achieved after 4 h, at E/S ratios of 1/150 U/mg, regardless the initial protein concentration. In previous reports, the authors suggested that cardosins could not hydrolyse ß-lactoblogulin. However, our promising results open up new possibilities to further explore the action of cardosins on whey proteins for the production of bioactive peptides.

Effectiveness of proteolytic enzymes to remove gluten residues and feasibility of incorporating them into cleaning products for industrial purposes.

The development of protocols for efficient gluten elimination is one of the most critical aspects of any allergen management strategy in the industry. The suitability of different proteolytic enzymes to be included in a cleaning formulation that allows the effective elimination of gluten residues was studied. Alcalase (ALC), neutrase (NEUT) and flavourzyme (FLAV) were selected from in silico analysis. The presence of 1% (v/v) of linear alkylbenzene sulphonate (LAS), a common anionic detergent, improved the gluten solubility, which may favour its elimination. Chromatographic analysis showed that the three enzymes studied were able to hydrolyse gluten in the presence of LAS. The highest percentage of short peptides (< 5 kDa) was achieved with ALC, what increases the probability of reducing the gluten antigenicity. Besides, in the presence of ALC and detergent LAS have detected the lowest levels of gluten with ELISA kits. So, effective amounts of ALC and LAS were added to a cleaning formulation, where its proteolytic activity was maintained above 90% after 37 days at 4 °C and 25 °C (under dark). Preliminary validation of the effectiveness enzymatic cleaning formulation to hydrolyse gluten was performed in a ready-to-eat/frozen food company, in which previous episodes of cross-contamination with gluten have been detected. The gluten content decreased to values below 0.125 µg/100 cm2 when the cleaning formulation was tested on different surfaces with different cleaning protocols, demonstrating the high suitability of the enzymatic cleaning formulation developed.

One-step chromatographic method to purify α-lactalbumin from whey for nanotube synthesis purposes.

A one-step anion-exchange chromatography method (NaCl gradient elution on a DEAE Sepharose™ Fast Flow gel column) was developed to purify α-lactalbumin (α-LA) from whey protein isolate. α-LA nearly 100% pure (based on the total protein content) was obtained with a yield of about 39%. Besides pure α-LA, which was the main objective of this work, highly pure ß-lactoglobulin was also obtained with a yield of about 59%. The high purity of the obtained α-LA samples allowed its use to synthesise protein nanotubes with excellent gelation properties for their use as food thickeners and bioactive carriers. The samples' purity degree obtained (based on the total protein content) was critical in the formation of proper nanotubes instead of random aggregates, which produced opaque and weak gels, less useful for food applications.

Tratamiento quirúrgico conservador en paciente monorrenal con esclerosis tuberosa y angiomiolipoma complicado: presentación de caso y revisión bibliográfica / Conservative surgical treatment in monorrenal patient with sclerosis and complicated tuberous angiomyolipom: case report and literature review

Los angiomiolipomas renales son formaciones renales que se presentan de forma aislada o asociadas con otras patologías como esclerosis tuberosa o enfermedad de Von Hippel Lindau. Los angiomiolipomas renales se pueden presentar clínicamente con un shock hipovolémico por lesión de uno de sus vasos o con dolor abdominal por efecto masa debido a su tamaño. La resolución de los angiomiolipomas puede ser de manera programada o de urgencia, siendo las vías elegidas la nefrectomía parcial o la embolización arterial selectiva, dependiendo siempre de los recursos que se tengan y la experiencia del equipo quirúrgico.

Renal angiomyolipomas are kidney formations presented in isolation or associated with other diseases such as tuberous sclerosis or Von Hippel Lindau disease. Renal angiomyolipoma may present clinically with hypovolemic shock due to injury of one of its vessels or with abdominal pain due to mass effect because of its size. Angiomyolipomas can be resolved on scheduled basis or emergency, where the chosen ways are partial nephrectomy or selective arterial embolization, always depending on the resources you count on and the experience of the surgical team.

Influence of pH on viscoelastic properties of heat-induced gels obtained with a ß-Lactoglobulin fraction isolated from bovine milk whey hydrolysates.

A ß-Lactoglobulin fraction (r-ßLg) was isolated from whey hydrolysates produced with cardosins from Cynara cardunculus. The impact of the hydrolysis process on the r-ßLg structure and the rheological properties of heat-induced gels obtained thereafter were studied at different pH values. Differences were observed between r-ßLg and commercial ß-Lg used as control. Higher values for the fluorescence emission intensity and red shifts of the emission wavelength of r-ßLg suggested changes in its tertiary structure and more solvent-exposed tryptophan residues. Circular dichroism spectra also supported these evidences indicating that hydrolysis yielded an intermediate (non-native) ß-Lg state. The thermal history of r-ßLg through the new adopted conformation improved the microstructure of the gels at acidic pH. So, a new microstructure with better rheological characteristics (higher conformational flexibility and lower rigidity) and greater water holding ability was founded for r-ßLg gel. These results were reflected in the microstructural analysis by scanning electron microscopy.

Structural and thermo-rheological analysis of solutions and gels of a ß-lactoglobulin fraction isolated from bovine whey.

A ß-Lactoglobulin fraction (r-ßLg) was isolated from milk whey hydrolysates produced with cardosins from Cynara cardunculus. The impact of the technological process on the r-ßLg structure and how in turn this determined its heat-induced gelation was investigated. Results were analysed taking pure ß-Lg (p-ßLg) as control sample. The process induced changes in the r-ßLg native conformation causing exposure of hydrophobic groups, lower thermal stability and also, shorter thermal treatments needed to give rise to non-native and aggregated species. At pH 3.2, r-ßLg and p-ßLg solutions exhibited two gelation steps, with the advantage that r-ßLg protein may form stable gels at lower temperature than p-ßLg. At pH 7.2, a specific thermo-viscoelastic stability to 73 °C was found, which corresponded to the gel point in both protein solutions. The difference was that while for p-ßLg solution in sol state δ<45° (solid-like), however for r-ßLg solution δ>45° (fluid-like).

Liberal alcohol legislation: does it amplify the effects among Swiss men of person-related risk factors on heavy alcohol use?

AIM: To estimate the statistical interactions between alcohol policy strength and the person-related risk factors of sensation-seeking, antisocial personality disorder and attention-deficit/hyperactivity disorder related to heavy alcohol use. DESIGN: Cross-sectional survey. SETTING: Young Swiss men living within 21 jurisdictions across Switzerland. PARTICIPANTS: A total of 5701 Swiss men (mean age 20 years) participating in the Cohort Study on Substance Use Risk Factors (C-SURF). MEASUREMENTS: Outcome measures were alcohol use disorder (AUD) as defined in the DSM-5 and risky single-occasion drinking (RSOD). Independent variables were sensation-seeking, antisocial personality disorder (ASPD), attention-deficit/hyperactivity disorder (ADHD) and an index of alcohol policy strength. FINDINGS: Alcohol policy strength was protective against RSOD [odds ratio (OR) = 0.91 (0.84-0.99)], while sensation-seeking and ASPD were risk factors for both RSOD [OR = 1.90 (1.77-2.04); OR = 1.69 (1.44-1.97)] and AUD [OR = 1.58 (1.47-1.71); OR = 2.69 (2.30-3.14)] and ADHD was a risk factor for AUD [OR = 1.08 (1.06-1.10)]. Significant interactions between alcohol policy strength and sensation-seeking were identified for RSOD [OR = 1.06 (1.01-1.12)] and AUD [OR = 1.06 (1.01-1.12)], as well as between alcohol policy strength and ASPD for both RSOD [OR = 1.17 (1.03-1.31)] and AUD [OR = 1.15 (1.02-1.29)]. These interactions indicated that the protective effects of alcohol policy strength on RSOD and AUD were lost in men with high levels of sensation-seeking or an ASPD. No interactions were detected between alcohol policy strength and ADHD. CONCLUSION: Stronger alcohol legislation protects against heavy alcohol use in young Swiss men, but this protective effect is lost in individuals with high levels of sensation-seeking or having an antisocial personality disorder.

Temporal Patterns of Alcohol Consumption and Alcohol-Related Road Accidents in Young Swiss Men: Seasonal, Weekday and Public Holiday Effects.

AIMS: To assess seasonal, weekday, and public holiday effects on alcohol-related road accidents and drinking diaries among young Swiss men. METHODS: Federal road accident data (35,485 accidents) from Switzerland and drinking diary data from a large cohort of young Swiss men (11,930 subjects) were analysed for temporal effects by calendar week, weekday and public holiday (Christmas, New Years, National Day). Alcohol-related accidents were analysed using rate ratios for observed versus expected numbers of accidents and proportions of alcohol-related accidents relative to the total number. Drinking diaries were analysed for the proportion of drinkers, median number of drinks consumed, and the 90th percentile's number of drinks consumed. RESULTS: Several parallel peaks were identified in alcohol-related accidents and drinking diaries. These included increases on Fridays and Saturdays, with Saturday drinking extending until early Sunday morning, an increase during the summer on workdays but not weekends, an increase at the end of the year, and increases on public holidays and the evening before. CONCLUSIONS: Our results suggest specific time-windows that are associated with increases in drinking and alcohol-related harm. Established prevention measures should be enforced during these time-windows to reduce associated peaks.

The impact of frailty in older patients with non-ischaemic cardiomyopathy after implantation of cardiac resynchronization therapy defibrillator.

AIMS: Frailty status impacts the prognosis in older patients with heart disease. However, frailty status impact is unknown in patients with non-ischaemic cardiomyopathy after cardiac resynchronization therapy (CRT). METHODS AND RESULTS: Functional measures of baseline frailty and clinical data were collected for all patients with non-ischaemic cardiomyopathy before CRT defibrillator (CRT-D) implantation. The level of frailty was assessed using the Fried and Walston definition. Cox proportional hazard regression models were used to examine the association between baseline frailty and decompensated heart failure (HF) at the 12 months follow-up. The cohort study consisted of 102 patients with a mean age of 73 ± 4 years, 53% of which were male patients. Twenty-nine patients (28%) were classified as frail before CRT-D implantation. Twenty-seven patients experienced decompensated HF after CRT-D implantation at the 12-month follow-up. In the non-frail group, 12 of 73 patients (16.4%) experienced episodes of decompensated HF. In contrast, 15 of 29 (55.6%) frail patients experienced higher proportions of decompensated HF (P < 0.001). Patients who were frail (hazard ratio 4.55, 95% confidence interval 1.726-12.013) were at increased risk for the decompensated HF (P for trend = 0.002) compared with those who were not frail. CONCLUSION: Frailty is a strong predictor of adverse post-implantation outcome in patients with non-ischaemic cardiomyopathy undergoing CRT-D.

A reliability study on brain activation during active and passive arm movements supported by an MRI-compatible robot.

In neurorehabilitation, longitudinal assessment of arm movement related brain function in patients with motor disability is challenging due to variability in task performance. MRI-compatible robots monitor and control task performance, yielding more reliable evaluation of brain function over time. The main goals of the present study were first to define the brain network activated while performing active and passive elbow movements with an MRI-compatible arm robot (MaRIA) in healthy subjects, and second to test the reproducibility of this activation over time. For the fMRI analysis two models were compared. In model 1 movement onset and duration were included, whereas in model 2 force and range of motion were added to the analysis. Reliability of brain activation was tested with several statistical approaches applied on individual and group activation maps and on summary statistics. The activated network included mainly the primary motor cortex, primary and secondary somatosensory cortex, superior and inferior parietal cortex, medial and lateral premotor regions, and subcortical structures. Reliability analyses revealed robust activation for active movements with both fMRI models and all the statistical methods used. Imposed passive movements also elicited mainly robust brain activation for individual and group activation maps, and reliability was improved by including additional force and range of motion using model 2. These findings demonstrate that the use of robotic devices, such as MaRIA, can be useful to reliably assess arm movement related brain activation in longitudinal studies and may contribute in studies evaluating therapies and brain plasticity following injury in the nervous system.

Prevalence of and associated factors for adult attention deficit hyperactivity disorder in young Swiss men.

OBJECTIVE: The present study aimed to measure the prevalence of adult attention deficit hyperactivity disorder (ADHD) in a large, representative sample of young Swiss men and to assess factors associated with this disorder. METHODS: Our sample consisted of 5656 Swiss men (mean age 20 years) who participated in the Cohort Study on Substance Use Risk Factors (C-SURF). ADHD was assessed with the World Health Organization (WHO) adult ADHD Self Report Screener (ASRS). Logistic regression analyses were conducted to assess the association between ADHD and several socio-demographic, clinical and familial factors. RESULTS: The prevalence of ADHD was 4.0%, being higher in older and French-speaking conscripts. A higher prevalence also was identified among men whose mothers had completed primary or high school/university and those with a family history of alcohol or psychiatric problems. Additionally, adults with ADHD demonstrated impairment in their professional life, as well as considerable mental health impairment. CONCLUSION: Our results demonstrate that ADHD is common among young Swiss men. The impairments in function and mental health we observed highlight the need for further support and interventions to reduce burden in affected individuals. Interventions that incorporate the whole family also seem crucial.

Crossmodal representation of a functional robotic hand arises after extensive training in healthy participants.

The way in which humans represent their own bodies is critical in guiding their interactions with the environment. To achieve successful body-space interactions, the body representation is strictly connected with that of the space immediately surrounding it through efficient visuo-tactile crossmodal integration. Such a body-space integrated representation is not fixed, but can be dynamically modulated by the use of external tools. Our study aims to explore the effect of using a complex tool, namely a functional prosthesis, on crossmodal visuo-tactile spatial interactions in healthy participants. By using the crossmodal visuo-tactile congruency paradigm, we found that prolonged training with a mechanical hand capable of distal hand movements and providing sensory feedback induces a pattern of interference, which is not observed after a brief training, between visual stimuli close to the prosthesis and touches on the body. These results suggest that after extensive, but not short, training the functional prosthesis acquires a visuo-tactile crossmodal representation akin to real limbs. This finding adds to previous evidence for the embodiment of functional prostheses in amputees, and shows that their use may also improve the crossmodal combination of somatosensory feedback delivered by the prosthesis with visual stimuli in the space around it, thus effectively augmenting the patients' visuomotor abilities.

Enhanced activation of motor execution networks using action observation combined with imagination of lower limb movements.

The combination of first-person observation and motor imagery, i.e. first-person observation of limbs with online motor imagination, is commonly used in interactive 3D computer gaming and in some movie scenes. These scenarios are designed to induce a cognitive process in which a subject imagines himself/herself acting as the agent in the displayed movement situation. Despite the ubiquity of this type of interaction and its therapeutic potential, its relationship to passive observation and imitation during observation has not been directly studied using an interactive paradigm. In the present study we show activation resulting from observation, coupled with online imagination and with online imitation of a goal-directed lower limb movement using functional MRI (fMRI) in a mixed block/event-related design. Healthy volunteers viewed a video (first-person perspective) of a foot kicking a ball. They were instructed to observe-only the action (O), observe and simultaneously imagine performing the action (O-MI), or imitate the action (O-IMIT). We found that when O-MI was compared to O, activation was enhanced in the ventralpremotor cortex bilaterally, left inferior parietal lobule and left insula. The O-MI and O-IMIT conditions shared many activation foci in motor relevant areas as confirmed by conjunction analysis. These results show that (i) combining observation with motor imagery (O-MI) enhances activation compared to observation-only (O) in the relevant foot motor network and in regions responsible for attention, for control of goal-directed movements and for the awareness of causing an action, and (ii) it is possible to extensively activate the motor execution network using O-MI, even in the absence of overt movement. Our results may have implications for the development of novel virtual reality interactions for neurorehabilitation interventions and other applications involving training of motor tasks.

Modeling the angiotensin-converting enzyme inhibitory activity of peptide mixtures obtained from cheese whey hydrolysates using concentration-response curves.

Three mathematical models, two logistic models (previously published in previous works) and one mechanistic, developed in this work and based on Michaelis-Menten kinetics, were compared to select the most adequate model in describing the angiotensin-converting enzyme (ACE)-inhibitory activity of bioactive peptide mixtures obtained from cheese whey protein. The significance of both the model and its parameters as well as the value of the regression coefficient was used as criteria to select the most adequate model for obtaining the IC(50) values corresponding to each bioactive peptides mixture. The best results were obtained with the Michaelis-Menten-based model because it provided the best fits and in addition the values for its parameters were always significant. As parameters of this model have a physical meaning, it could be used for inhibition-testing experiments in the development of novel bioactive peptides. The results obtained indicated that the peptide mixture derived from the neutrase hydrolysis exhibited strong ACE inhibition activity. The main active peptides were short, with molecular masses below 1 kDa (IC(50) = 40.37 ± 2.66 µg/mL) and represent 38% of the initial protein content in the hydrolysate.

fMRI assessment of upper extremity related brain activation with an MRI-compatible manipulandum.

PURPOSE: Longitudinal studies to evaluate the effect of rehabilitative therapies require an objective, reproducible and quantitative means for testing function in vivo. An fMRI assessment tool for upper extremity related brain activation using an MRI-compatible manipulandum was developed and tested for use in neurorehabilitation research. METHODS: Fifteen healthy, right-handed subjects participated in two fMRI sessions, which were three to four weeks apart. A block design paradigm, composed of three conditions of subject-passive movement, subject-active movement and rest, was employed for the fMRI recordings. During the rest condition, subjects simply held the device handle without applying any force or movement. The same type of auditory and visual instructions were given in all the three conditions, guiding the subjects to perform the motor tasks interactively with the MRI-compatible arm manipulandum. The tasks were controlled across the fMRI sessions. The subjects' brain activation was recorded by fMRI, and their behavioral performance was recorded by the manipulandum. The brain network activated by the subjects' interaction with the manipulandum was identified, and the reproducibility and reliability of the obtained activation were determined. RESULTS: All subjects completed the trial protocol. Two subjects were excluded from analysis due to head motion artifacts. All passive movements were performed well. Four out of the total 780 active movements were missed by two subjects. Brain activation was found in the contralateral sensorimotor cortex, secondary somatosensory cortex and non-primary motor cortex as well as in subcortical areas in the thalamus, basal ganglia and the cerebellum. These activations were consistent across the two fMRI sessions. CONCLUSION: The MRI-compatible manipulandum elicited robust and reproducible brain activations in healthy subjects during the subject-active and subject-passive upper extremity motor tasks with a block design paradigm. This system is promising for many applications in neurorehabilitation research and may be useful for longitudinal studies.

Historia de la técnica y saber científico / The history of scientific technique and knowledge

El presente artículo describa las distintas etapas de constitución del isntrumento técnico en occidente. Se analizan sumariamente cuatro formas de conceptualización de la técnica en distintas etapas históricas (antiguedad clásica, siglo XVII, siglo XIX y siglo XX), situando en cada caso el lugar que ésta ocupaba en relación al modo de conocimiento propio de cada uno. Dicho estudio de la técnica y su relación con el saber científico, desde la perspectiva histórica, resulta relevante para pensar la incidencia de la tecnología en la clínica odontológica y las consecuencias que ésta acarrea en la relación odontólogo-paciente. Se trata de un esquema inicial para abordar las problemáticas del binomio técnica-clínica en la práctica odontológica, en lo que hace a los criterios de intervención terapéutica