Simulation and optimization of reconstructive surgery procedures on human skin.

The complex procedures involved in the reconstructive surgery of human skin to minimize post-operative scarring are here modeled by means of an automated computational tool. A finite strain no-compression membrane model accounting for the tendency to develop wrinkling regions in the skin is presented. The constitutive behavior of the material is then described by a suitable hyperelastic incompressible potential. Transpositions of skin flaps during surgery procedures are here computationally described by a general mapping technique of the internal boundary corresponding to surgery cut. The archetypal reconstructive surgery of a Z-plasty, where a rotational transposition of the resulting triangular flaps is involved, is considered in details, along with multiple Z-plasty and rhombic flap transposition. The results are discussed in terms of optimal deformation parameters, related to stress/strain localization, displacement discontinuities and wrinkling.

Fluid-solid interaction in the rate-dependent failure of brain tissue and biomimicking gels.

Brain tissue is a heterogeneous material, constituted by a soft matrix filled with cerebrospinal fluid. The interactions between, and the complexity of each of these components are responsible for the non-linear rate-dependent behaviour that characterises what is one of the most complex tissue in nature. Here, we investigate the influence of the cutting rate on the fracture properties of brain, through wire cutting experiments. We also present a computational model for the rate-dependent behaviour of fracture propagation in soft materials, which comprises the effects of fluid interaction through a poro-hyperelastic formulation. The method is developed in the framework of finite strain continuum mechanics, implemented in a commercial finite element code, and applied to the case of an edge-crack remotely loaded by a controlled displacement. Experimental and numerical results both show a toughening effect with increasing rates, which is linked to the energy dissipated by the fluid-solid interactions in the region surrounding the crack tip.

Relation between heart beat fluctuations and cyclic alternating pattern during sleep in insomnia patients.

Insomnia is a condition that affects the nervous and muscular system. Thirty percent of the population between 18 and 60 years suffers from insomnia. The effects of this disorder involve problems such as poor school or job performance and traffic accidents. In addition, patients with insomnia present changes in the cardiac function during sleep. Furthermore, the structure of electroencephalographic A-phases, which builds up the Cyclic Alternating Pattern during sleep, is related to the insomnia events. Therefore, the relationship between these brain activations (A-phases) and the autonomic nervous system would be of interest, revealing the interplay of central and autonomic activity during insomnia. With this goal, a study of the relationship between A-phases and heart rate fluctuations is presented. Polysomnography recording of five healthy subjects, five sleep misperception patients and five patients with psychophysiological insomnia were used in the study. Detrended Fluctuation Analysis (DFA) was used in order to evaluate the heart rate dynamics and this was correlated with the number of A-phases. The results suggest that pathological patients present changes in the dynamics of the heart rate. This is reflected in the modification of A-phases dynamics, which seems to modify of heart rate dynamics.

On separability of A-phases during the cyclic alternating pattern.

A statistical analysis of the separability of EEG A-phases, with respect to basal activity, is presented in this study. A-phases are short central events that build up the Cyclic Alternating Pattern (CAP) during sleep. The CAP is a brain phenomenon which is thought to be related to the construction, destruction and instability of sleep stages dynamics. From the EEG signals, segments obtained around the onset and offset of the A-phases were used to evaluate the separability between A-phases and basal sleep stage oscillations. In addition, a classifier was trained to separate the different A-phase types (A1, A2 and A3). Temporal, energy and complexity measures were used as descriptors for the classifier. The results show a percentage of separation between onset and preceding basal oscillations higher than 85 % for all A-phases types. For Offset separation from following baseline, the accuracy is higher than 80 % but specificity is around 75%. Concerning to A-phase type separation, A1-phase and A3-phase are well separated with accuracy higher than 80, while A1 and A2-phases show a separation lower than 50%. These results encourage the design of automatic classifiers for Onset detection and for separating among A-phases type A1 and A3. On the other hand, the A-phase Offsets present a smooth transition towards the basal sleep stage oscillations, and A2-phases are very similar to A1-phases, suggesting that a high uncertainty may exist during CAP annotation.

Characterization of the autonomic system during the cyclic alternating pattern of sleep.

Evaluation of the RR variability was carried out during the Cyclic Alternating Pattern (CAP) in sleep. CAP is a central phenomenon formed by short events called A-phases that break basal electroencephalogram (EEG) oscillations of the sleep stages. A-phases are classified in three types (A1, A2 and A3) based on the EEG desynchronization during A-phase. However, the relation of A-phases with other systems, such as cardiovascular system, is unclear and a deep analysis is required. For the study, six patients with Nocturnal Front Lobe Epilepsy (NFLE) and other six healthy controls patients underwent whole night polysomnographic recordings with CAP and hypnogram annotations. Amplitude reduction and time delay of the RR intervals minimum with respect to A-phases onset were computed. In addition, the same process was computed over randomly chosen RR interval segments during the NREM sleep for further comparison. The results suggest that the onset of the A-phases is correlated with a significative increase of the heart rate that peaks at around 4s after the Aphase onset, independently of the A-phase subtype.

Insomnia types and sleep microstructure dynamics.

This work aims to investigate sleep microstructure as expressed by Cyclic Alternating Pattern (CAP), and its possible alterations in pathological sleep. Three groups, of 10 subjects each, are considered: a) normal sleep, b) psychophysiological insomnia, and c) sleep misperception. One night sleep PSG and sleep macro- micro structure annotations were available per subject. The statistical properties and the dynamics of CAP events are in focus. Multiscale and non-linear methods are presented for the analysis of the microstructure event time series, applied for each type of CAP events, and their combination. The results suggest that a) both types of insomnia present CAP differences from normal sleep related to hyperarousal, b) sleep misperception presents more extensive differences from normal, potentially reflecting multiple sleep mechanisms, c) there are differences between the two types of insomnia as regard to the intertwining of events of different subtypes. The analysis constitutes a contribution towards new markers for the quantitative characterization of insomnia, and its subtypes.

Nonlinear analysis of the change points between A and B phases during the Cyclic Alternating Pattern under normal sleep.

This study analyzes the nonlinear properties of the EEG at transition points of the sequences that build the Cyclic Alternating Pattern (CAP). CAP is a sleep phenomenon built up by consecutive sequences of activations and non-activations observed during the sleep time. The sleep condition can be evaluated from the patterns formed by these sequences. Eleven recordings from healthy and good sleepers were included in this study. We investigated the complexity properties of the signal at the onset and offset of the activations. The results show that EEG signals present significant differences (p<0.05) between activations and non-activations in the Sample Entropy and Tsallis Entropy indices. These indices could be useful in the development of automatic methods for detecting the onset and offset of the activations, leading to significant savings of the physician's time by simplifying the manual inspection task.

A novel method to assist the detection of the Cyclic Alternating Pattern (CAP).

This study proposes a novel method to assist the detection of the components that build up the Cyclic Alternating Pattern (CAP). CAP is a sleep phenomenon formed by consecutive sequences of activations (A1, A2, A3) and non-activations during nonREM sleep. The main importance of CAP evaluation is the possibility of defining the sleep process more accurately. Ten recordings from healthy and good sleepers were included in this study. The method is based on inferential statistics to define the initial and ending points of the CAP components based only on an initialization point given by the expert. The results show concordance up to 95% for A1, 85% for A2 and 60% for A3, together with an overestimation of 1.5 s in A1, 1.3 s in A2 and 0 s in A3. The total CAP rate presents a total underestimation of 7 min. Those results suggest that the method is able to accurately detect the initial and ending points of the activations, and may be helpful for the physicians by reducing the time dedicated to the manual inspection task.

Predicting EEG complexity from sleep macro and microstructure.

This work investigates the relation between the complexity of electroencephalography (EEG) signal, as measured by fractal dimension (FD), and normal sleep structure in terms of its macrostructure and microstructure. Sleep features are defined, encoding sleep stage and cyclic alternating pattern (CAP) related information, both in short and long term. The relevance of each sleep feature to the EEG FD is investigated, and the most informative ones are depicted. In order to quantitatively assess the relation between sleep characteristics and EEG dynamics, a modeling approach is proposed which employs subsets of the sleep macrostructure and microstructure features as input variables and predicts EEG FD based on these features of sleep micro/macrostructure. Different sleep feature sets are investigated along with linear and nonlinear models. Findings suggest that the EEG FD time series is best predicted by a nonlinear support vector machine (SVM) model, employing both sleep stage/transitions and CAP features at different time scales depending on the EEG activation subtype. This combination of features suggests that short-term and long-term history of macro and micro sleep events interact in a complex manner toward generating the dynamics of sleep.

Sleep bruxism and sleep arousal: an experimental challenge to assess the role of cyclic alternating pattern.

Rhythmic masticatory muscle activity (RMMA) is the characteristic electromyographic pattern of sleep bruxism (SB), a sleep-related motor disorder associated with sleep arousal. Sleep arousals are generally organised in a clustered mode known as the cyclic alternating pattern (CAP). CAP is the expression of sleep instability between sleep maintaining processes (phase A1) and stronger arousal processes (phases A2 and A3). This study aimed to investigate the role of sleep instability on RMMA/SB occurrence by analysing CAP and electroencephalographic (EEG) activities. The analysis was performed on the sleep recordings of 8 SB subjects and 8 controls who received sensory stimulations during sleep. Baseline and experimental nights were compared for sleep variables, CAP, and EEG spectral analyses using repeated measure ANOVAs. Overall, no differences in sleep variables and EEG spectra were found between SB subjects and controls. However, SB subjects had higher sleep instability (more phase A3) than controls (P= 0·05). The frequency of phase A3 was higher in the pre-REM sleep periods (P < 0·001), where peaks in RMMA/SB activity were also observed (P = 0·05). When sleep instability was experimentally increased by sensory stimuli, both groups showed an enhancement in EEG theta and alpha power (P = 0·04 and 0·02, respectively) and significant increases in sleep arousal and all CAP variables. No change in RMMA/SB index was found within either groups (RMMA/SB occurred in all SB subjects and only one control during the experimental night). These findings suggest that CAP phase A3 may act as a permissive window rather than a generator of RMMA/SB activity in predisposed individuals.

Assessment of the EEG complexity during activations from sleep.

The present study quantitatively analyzes the EEG characteristics during activations (Act) that occur during NREM sleep, and constitute elements of sleep microstructure (i.e. the Cyclic Alternating Pattern). The fractal dimension (FD) and the sample entropy (SampEn) measures were used to study the different sleep stages and the Act that build up the sleep structure. Polysomnographic recordings from 10 good sleepers were analyzed. The complexity indexes of the Act were compared with the non-activation (NAct) periods during non-REM sleep. In addition, complexity measures among the different Act subtypes (A1, A2 and A3) were analyzed. A3 presented a quite similar complexity independently of the sleep stage, while A1 and A2 showed higher complexity in light sleep than during deep sleep. The current results suggest that Act present a hierarchic complexity between subtypes A3 (higher), A2 (intermediate) and A1 (lower) in all sleep stages.

CAP sleep in insomnia: new methodological aspects for sleep microstructure analysis.

This work aims to propose new methodologies for the quantitative characterization of insomnia. Sleep microstructure, as expressed by Cyclic Alternatic pattern (CAP) sleep, is studied and differences between normal sleepers and insomniacs are investigated. The dynamic in the structure of CAP activation events is studied by use of wavelet analysis and the content of events, i.e. EEG dynamics, is studied in terms of complexity analysis. Both in structure and content, features exhibiting statistically significant differences are proposed, opening new perspectives for the understanding and the quantitative characterization of sleep and its disorders.

EEG complexity during sleep: on the effect of micro and macro sleep structure.

This work investigates the relation between EEG complexity measures, in particular Fractal Dimension and Sample Entropy, and sleep structure, in terms of both macrostructure, i.e. sleep stages, and microstructure, i.e. phase A activation of CAP sleep. Activation phases are compared with the non-activation periods of non-REM sleep. The study suggests that complexity features can serve as consistent descriptors of sleep dynamics and can potentially assist in the classification of sleep stages.

Evaluation of milk enzymes and electrolytes, plasma metabolites, and oxidative status in twin cows milked in an automatic milking system or twice daily in a conventional milking parlor.

The aim of this paper was to evaluate the effects of automatic milking (AM) on milk enzymes and minerals related to mammary epithelial integrity in comparison with twice-daily conventional milking (CM). One cow from each of 6 pairs of twins was assigned to be milked with AM or with CM throughout first lactation. Milk production was recorded and milk samples were collected at 4, 11, 18, 25, 32, and 39 wk of lactation (WOL) to determine fat and protein content, somatic cell count, pH, plasminogen (pl) and plasmin (Pl) activities, Na, K, and Cl. Body condition score was monitored; blood samples were collected to determine energy-related metabolites in the first third of lactation (14 WOL), and plasma oxidative status throughout lactation. Overall mean and standard deviation of milking frequency (MF) in AM were 2.69 and 0.88, respectively. Milk production, fat and protein contents, and somatic cell count did not differ between milking systems. The pl and pl+Pl activities were lesser in AM than in CM. Milk pH was greater in AM than in CM. Milk Na, K, Na/K ratio, and Cl did not differ across the whole lactation. Milk pH had a positive correlation with milk Pl activity (r = 0.41), Na (r = 0.37), and Cl (r = 0.40) concentration, and negative correlation with the log(10) of pl/Pl ratio (r = -0.47). The milk Na/K ratio had a positive correlation (r = 0.55) with milk Pl activity. Milking system (MS) did not seem to affect mammary epithelial permeability. The differences in enzymatic (proteolytic) activity due to the MS, probably related to daily MF, lead one to suppose that the quality of the protein fraction for the cheese-making process was preserved better with AM than with CM, even if differences in pH might negatively interfere. No difference was detected in BCS, and in plasma concentration of triglycerides and nonesterified fatty acids, whereas plasma cholesterol concentration during the first 10 WOL was lesser in AM than CM. Oxidative status, measured by plasma reactive oxygen metabolites and thiol groups, did not differ between MS throughout the whole lactation. These results suggest that early lactation of AM primiparous cows may give rise to crucial situations: for milk production, when a low MF may impair further mammary cell proliferation; for milk quality, if an irregular MF, with prolonged milking intervals, leads to an increased milk pH with increased conversion of pl to Pl.

Effects of zolpidem on cyclic alternating pattern, an objective marker of sleep instability, in Japanese patients with psychophysiological insomnia: a randomized crossover comparative study with placebo.

OBJECTIVE: A placebo-controlled randomized crossover study to investigate the effects of zolpidem on sleep stability in Japanese insomniac patients was performed using the cyclic alternating pattern (CAP) rate, a polysomnographic marker that reflects sleep instability. METHODS: Seventeen patients (5 M and 12 F, mean age: 40.4+/-13.6 years) who met the International Classification of Sleep Disorders (ICSD) criteria for psychophysiological insomnia were evaluated. During the first period, patients were administered the placebo on the first night, followed by either zolpidem or the placebo on the second night (treatment night). The second crossover period was conducted after a minimum 3-day observation. Improvement in the overnight CAP rate was the primary endpoint. Secondary endpoints included the CAP variables, conventional sleep variables, EEG arousals, subjective evaluation of sleep quality (measured by means of a visual analogue scale and the St. Mary's Hospital Sleep Questionnaire), and drug safety. RESULTS: Zolpidem significantly decreased the overnight CAP rate values (57.6 vs. 39.0%, p=0.009) and improved "sleep depth" (p=0.044) and "sleep quality" (p=0.023) subjective questionnaire scores. Zolpidem also significantly improved VAS (p=0.036). The amount of time spent in sleep stages 3+4 was significantly increased by zolpidem without affecting the amounts of stage 2 and rapid eye movement (REM) sleep. Significant negative correlations were found when the sleep quality score was matched to the CAP rate (p=0.022). No serious adverse events occurred during the study. DISCUSSION: In Japanese patients with psychophysiological insomnia, zolpidem increased sleep stability by significantly improving the overnight CAP rate. Zolpidem also improved sleep depth and sleep quality, both subjectively and objectively.

Source of cell injected is a critical factors for short and long engraftment in xeno-transplantation.

This study aims to investigate engraftment of human cord blood and foetal bone marrow stem cells after in utero transplantation via the intracoelomic route in the sheep. Here, we performed transplantation in 14 single and 1 twin sheep foetuses at 40-47 days of development, using a novel schedule for injection. (i) Single injection of CD34(+) human cord blood stem cells via the coelomic route (from 10 to 50 x 10(4)) in seven single foetuses. (ii) Single injection of CD34(+) foetal bone marrow stem cells via the intracoelomic route with further numbers of cells (20 x 10(5) and 8 x 10(5), respectively) in three single and in one twin foetuses. (iii) Double fractioned injection (20-30 x 10(6)) via the coelomic route and 20 x 10(6) postnatally, intravenously, shortly after birth of CD3-depleted cord blood stem cells in four single foetuses. In the first group, three single foetuses showed human/sheep chimaerism at 1, 8 and 14 months after birth. In the second group, the twin foetuses showed human/sheep chimaerism at 1 month after birth. In the third group, only two out of four single foetuses that underwent transplantation showed chimaerism at 1 month. While foetal bone marrow stem cells showed good short-term engraftment (1 month after birth), cord blood stem cells were able to persist longer in the ovine recipients (at 1, 8 and 14 months after birth).

The effects of subterranean clover phytoestrogens on sheep growth, reproduction and carcass characteristics.

The aim of the present study was to evaluate the effect of a prolonged administration of phytoestrogens on sheep growth rate, female reproductive response, lamb carcass conformation and meat quality. To investigate these effects, two groups of Comisana sheep (24 females and 20 males, initial average live weights of 25.0 and 29.9kg, respectively) were fed on subterranean clover (SC, phytoestrogen content=0.8mg/g of DM) and Italian ryegrass (C, non-oestrogenic control diet) for about one year. Feedstuffs were offered ad libitum and supplemented with maize grain and sunflower meal to maintain an adequate and similar energy and protein intake. The results demonstrated that the prolonged administration of the selected subterranean clover cultivars, with low formononetin content (lower than 10% of total isoflavones on dry basis), did not affect ewe reproduction but induced a significant improvement in animal weigh gain and, in males, good carcass and meat characteristics.

The challenge of chronic insomnia: is non-nightly hypnotic treatment a feasible alternative?

The adverse effects of insomnia on health and quality of life are matters receiving increasing attention. Yet, surveys have consistently shown that most people suffering from insomnia do not seek medical help, perhaps, in part, because of a concern of becoming dependent on hypnotic medication. The treatment of chronic insomnia poses a particular dilemma in that continuous hypnotic treatment is restricted in many countries to a maximum of 4 weeks, and behavioural treatment is not readily available. Non-nightly hypnotic treatment of chronic insomnia offers a promising alternative option for the many patients whose symptoms do not necessitate nightly drug intake, allaying fears of psychological dependence on medication and respecting regulatory constraints on hypnotic use while providing patients with adequate symptom relief. The practical feasibility and efficacy of this approach has been demonstrated with zolpidem using various treatment regimens and study designs. So far, six clinical trials have been completed on over 4000 patients. Published results show effective treatment of insomnia without any evidence of either adverse event associated with a discontinuous regimen or increased hypnotic use over the treatment period.

Fertility rate evaluation by laparoscopic approach in the experimental animal.

PURPOSE OF INVESTIGATION: The aim of the present study was to evaluate the effect of laparoscopic insemination (LAP) and natural mating (NM) on fertility rate in experimental animal (Ovis Aries Comisana) during the month of June. METHODS: For the experiment, 97 ewes were used. Laparoscopic insemination was performed with the frozen semen of three different Romanov rams: Laparoscopic insemination I (n = 24); Laparoscopic insemination 2 (n = 26); and laparoscopic insemination 3 (n = 28), and natural mating was performed with two different Ovis Aries Comisana rams with proven fertility: Natural mating I (n = 10); Natural mating 2 (n = 9). Estrus was synchronized with fluorogestone acetate impregnated intravaginal sponges (40 mg, 14 days). Pregnant mare serum gonadotrophin (Folligon, Intervet International) at a dose of 400 UI was given intramuscularly at sponge removal. Artificial insemination was carried out 60 hours after the removal of the sponges in the laparoscopic insemination groups. RESULTS: The mean pregnancy rate at ecographic diagnosis performed at about 36 days from sponge removal for the laparoscopic insemination and natural mating groups were respectively, 62.8% and 78.9% with no significant difference. CONCLUSION: The mean fertility rates for the LAP and NM groups were 56.0 and 73.4, respectively, with no significant difference.