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1.
Neurosci Lett ; 821: 137625, 2024 Jan 31.
Article in English | MEDLINE | ID: mdl-38185203

ABSTRACT

Risk is the probability of an adverse event. The proneness to take a risk and the risk taking behavior differ among the general population. Hypnotizability is a stable psychophysiological trait expressing the individual proneness to modify perception, memory and behavior following specific suggestions also in the ordinary state of consciousness. Some hypnotizability-related neurophysiological and behavioral correlates suggest that hypnotizability level, measured by standard scales classifying individuals as low (lows), medium (mediums) and high hypnotizable (highs) subjects, can be related to risk propensity and risk-taking. To study whether hypnotizability modulates risk propensity and behavior, we recruited healthy participants, classified through the Standford Hypnotic Susceptibility scale, form A, and compared lows' (n = 33), mediums' (n = 19) and highs'(n = 15) experiential and behavioral risk perception and propensity variables through the Domain-specific risk-taking scale and the Balloon Analogue Risk Task. MANOVA results indicated that different hypnotizability levels are not associated with different risky behavior and experience, except for higher expected financial benefits from risky behavior in lows. However, hypnotizability-related risk profiles were identified through correlational analyses. In fact, highs exhibited a negative association between risk perception and propensity to risk-taking, whereas mediums and lows displayed a positive association between risk propensity and expected benefit. In conclusion, the highs' profile indicates a more automatic behavior with respect to mediums and lows.


Subject(s)
Hypnosis , Risk-Taking , Humans , Hypnosis/methods
2.
NPJ Syst Biol Appl ; 10(1): 3, 2024 Jan 06.
Article in English | MEDLINE | ID: mdl-38184707

ABSTRACT

Experimental studies have shown that chromatin modifiers have a critical effect on cellular reprogramming, i.e., the conversion of differentiated cells to pluripotent stem cells. Here, we develop a model of the OCT4 gene regulatory network that includes genes expressing chromatin modifiers TET1 and JMJD2, and the chromatin modification circuit on which these modifiers act. We employ this model to compare three reprogramming approaches that have been considered in the literature with respect to reprogramming efficiency and latency variability. These approaches are overexpression of OCT4 alone, overexpression of OCT4 with TET1, and overexpression of OCT4 with JMJD2. Our results show more efficient and less variable reprogramming when also JMJD2 and TET1 are overexpressed, consistent with previous experimental data. Nevertheless, TET1 overexpression can lead to more efficient reprogramming compared to JMJD2 overexpression. This is the case when the recruitment of DNA methylation by H3K9me3 is weak and the methyl-CpG-binding domain (MBD) proteins are sufficiently scarce such that they do not hamper TET1 binding to methylated DNA. The model that we developed provides a mechanistic understanding of existing experimental results and is also a tool for designing optimized reprogramming approaches that combine overexpression of cell-fate specific transcription factors (TFs) with targeted recruitment of epigenetic modifiers.


Subject(s)
Cellular Reprogramming , Gene Regulatory Networks , Cellular Reprogramming/genetics , Cell Differentiation/genetics , Gene Regulatory Networks/genetics , Chromatin , Epigenesis, Genetic/genetics
3.
Rheumatology (Oxford) ; 63(4): 1076-1083, 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-37432350

ABSTRACT

OBJECTIVES: In a cross-sectional study, we explored possible differences in sleep parameters between SLE patients and age- and gender-matched healthy controls through actigraphic and self-reported measures. Furthermore, we aimed to identify possible predictors of such disturbances in the patient cohort. METHODS: Participants' sociodemographic data and sleep parameters were collected. Sleep parameters were evaluated through the Pittsburgh Sleep Quality Index, the Insomnia Severity Index and 7-day actigraphic monitoring. The 10-item Perceived Stress Scale was used to investigate stress. Disease activity and daily glucocorticoid dose were assessed in SLE patients. Possible predictors of the SLE group were explored through two binomial logistic models. Within the SLE group, possible predictors of sleep parameters were tested estimating multiple linear regression models. RESULTS: A total of 40 SLE patients and 33 controls were included in the study. The SLE group showed worse sleep maintenance actigraphic parameters (i.e. sleep efficiency and wake after sleep onset), higher total sleep time and higher perceived stress. Within the SLE cohort, the daily glucocorticoids dose was associated with an impairment in sleep maintenance despite no reduction in sleep duration, typical of normal sleep duration insomnia, whereas perceived stress was associated with short sleep duration insomnia. CONCLUSION: Compared with healthy controls, SLE patients showed worse sleep quality and greater perceived stress severity. As glucocorticoids and perceived stress are associated with different types of insomnia in these patients, a multidimensional approach to both sleep characterization and therapy might be preferred.


Subject(s)
Lupus Erythematosus, Systemic , Psychological Tests , Sleep Initiation and Maintenance Disorders , Humans , Self Report , Sleep Initiation and Maintenance Disorders/etiology , Sleep Initiation and Maintenance Disorders/complications , Cross-Sectional Studies , Sleep , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/drug therapy
4.
Sci Adv ; 9(48): eadg8495, 2023 12.
Article in English | MEDLINE | ID: mdl-38019912

ABSTRACT

Reprogramming human fibroblasts to induced pluripotent stem cells (iPSCs) is inefficient, with heterogeneity among transcription factor (TF) trajectories driving divergent cell states. Nevertheless, the impact of TF dynamics on reprogramming efficiency remains uncharted. We develop a system that accurately reports OCT4 protein levels in live cells and use it to reveal the trajectories of OCT4 in successful reprogramming. Our system comprises a synthetic genetic circuit that leverages noise to generate a wide range of OCT4 trajectories and a microRNA targeting endogenous OCT4 to set total cellular OCT4 protein levels. By fusing OCT4 to a fluorescent protein, we are able to track OCT4 trajectories with clonal resolution via live-cell imaging. We discover that a supraphysiological, stable OCT4 level is required, but not sufficient, for efficient iPSC colony formation. Our synthetic genetic circuit design and high-throughput live-imaging pipeline are generalizable for investigating TF dynamics for other cell fate programming applications.


Subject(s)
Cellular Reprogramming , Induced Pluripotent Stem Cells , Humans , Cell Differentiation/genetics , Cells, Cultured , Cellular Reprogramming/genetics , Fibroblasts/metabolism , Induced Pluripotent Stem Cells/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism
5.
J Psychiatr Res ; 165: 96-104, 2023 09.
Article in English | MEDLINE | ID: mdl-37487294

ABSTRACT

The present study evaluates the effect of exogenous melatonin (exo-MEL) on sleep and circadian parameters in patients with bipolar disorder (BD) and delayed sleep-wake phase disorder (DSWPD). BD euthymic patients (n = 83, mean age = 45.13 ± 13.68, males 56%) were evaluated for chronotype (reduced Morningness-Eveningness Questionnaire [rMEQ]), sleep quality (Pittsburgh Sleep Quality Index), sleep and circadian parameters (actigraphic monitoring). Patients that fulfilled criteria for DSWPD (n = 25) were treated for three months with exo-MEL 2 mg administered approximately 4 h before the sleep onset time (SOT) actigraphically-determined at baseline. Sleep and circadian parameters at baseline (T0) and after the exo-MEL treatment (T1) were compared using paired Wilcoxon test. In patients that completed the treatment (n = 19), the rMEQ score increased between T0 (median = 8.0 [IQR = 7.0, 11.0]) and T1 (median = 13.5 [IQR = 9.3, 15.0], p-value = 0.006), the SOT was advanced between T0 (median = 00:55 [IQR = 00:25, 01:39] and T1 (median = 00:09 [IQR = 23:41, 01:04], p-value = 0.039), the sleep efficiency and total sleep time increased (T0: median = 84.4 [IQR = 81.3, 89.4]; T1 (median = 90.3 [IQR = 85.5, 92.9] %, p-value = 0.01, and T0: median = 7.20 [IQR = 6.15, 8.15]; T1: median = 7.7 [IQR = 7.0, 9.3] hours, p-value = 0.04, respectively). These results indicate that in BD with comorbid DSWPD, the self-reported chronotype, the sleep onset time, and sleep efficiency and duration were modified after a personalized treatment with exo-MEL, suggesting its potential efficacy in improving sleep patterns in BD. The absence of proper control groups and of treatment randomization constitute limitations of our study and further randomized controlled trials are required to confirm our results.


Subject(s)
Bipolar Disorder , Melatonin , Male , Humans , Adult , Middle Aged , Melatonin/pharmacology , Melatonin/therapeutic use , Bipolar Disorder/complications , Bipolar Disorder/drug therapy , Sleep , Circadian Rhythm , Comorbidity
6.
bioRxiv ; 2023 Mar 01.
Article in English | MEDLINE | ID: mdl-36909486

ABSTRACT

In the last decade, several experimental studies have shown how chromatin modifications (histone modifications and DNA methylation) and their effect on DNA compaction have a critical effect on cellular reprogramming, i.e., the conversion of differentiated cells to a pluripotent state. In this paper, we compare three reprogramming approaches that have been considered in the literature: (a) prefixed overexpression of transcription factors (TFs) alone (Oct4), (b) prefixed overexpression of Oct4 and DNA methylation "eraser" TET, and (c) prefixed overexpression of Oct4 and H3K9me3 eraser JMJD2. To this end, we develop a model of the pluritpotency gene regulatory network, that includes, for each gene, a circuit recently published encapsulating the main interactions among chromatin modifications and their effect on gene expression. We then conduct a computational study to evaluate, for each reprogramming approach, latency and variability. Our results show a faster and less stochastic reprogramming process when also eraser enzymes are overexpressed, consistent with previous experimental data. However, TET overexpression leads to a faster and more efficient reprogramming compared to JMJD2 overexpression when the recruitment of DNA methylation by H3K9me3 is weak and the MBD protein level is sufficiently low such that it does not hamper TET binding to methylated DNA. The model developed here provides a mechanistic understanding of the outcomes of former experimental studies and is also a tool for the development of optimized reprogramming approaches that combine TF overexpression with modifiers of chromatin state.

7.
CNS Spectr ; 28(6): 726-738, 2023 12.
Article in English | MEDLINE | ID: mdl-36942635

ABSTRACT

OBJECTIVE: Although the association between chronotype and mood disorders has been consistently reported, conversely, attempts to measure the association between chronotype and anxiety symptoms have generated inconsistent results. We aimed at evaluating whether chronotype (assessed through subjective and objective measures) is associated with lifetime mood and panic-agoraphobic spectrum symptoms in healthy controls (HCs) and in patients with bipolar disorder (BD). METHODS: Overall, 173 subjects, patients with BD in euthymic phase (n = 76) and HC (n = 97), were evaluated through the reduced Morningness-Eveningness Questionnaire (rMEQ), actigraphy monitoring and mood and panic-agoraphobic spectrum self-report (MOODS-SR and PAS-SR). The discrepancy between objective (actigraphic-based) versus subjective (rMEQ-based) circadian typology was estimated through the Circadian Classification Discrepancy Index (CCDI). RESULTS: rMEQ-based evening chronotype (ET) was associated with higher scores in MOODS-SR depressive and rhythmicity and vegetative functions domains in HC and BD.Both ET and morning chronotypes (MT) were associated with higher PAS-SR scores in BD only. Actigraphic-based MT was associated with higher MOODS-SR depressive scores in HC. Likewise, the discrepancy between actigraphic-based and rMEQ-based circadian typology was associated with depressive symptoms in HC only. CONCLUSION: Self-reported ET was consistently associated with mood symptoms, while associations with panic-agoraphobic symptoms only emerged in BD and involved both extreme chronotypes. The discrepancy between the preferred circadian typology (rMEQ-based) and the actual one (actigraphic-based) could contribute to depressive symptoms in HC. These results pave the way for interventional studies targeting circadian typology in an attempt to prevent or treat mental health disorders.


Subject(s)
Bipolar Disorder , Humans , Bipolar Disorder/complications , Bipolar Disorder/psychology , Chronotype , Mood Disorders , Anxiety , Affect , Surveys and Questionnaires , Circadian Rhythm , Sleep
8.
Bull Math Biol ; 85(5): 39, 2023 03 31.
Article in English | MEDLINE | ID: mdl-37000280

ABSTRACT

Continuous-time Markov chains are frequently used as stochastic models for chemical reaction networks, especially in the growing field of systems biology. A fundamental problem for these Stochastic Chemical Reaction Networks (SCRNs) is to understand the dependence of the stochastic behavior of these systems on the chemical reaction rate parameters. Towards solving this problem, in this paper we develop theoretical tools called comparison theorems that provide stochastic ordering results for SCRNs. These theorems give sufficient conditions for monotonic dependence on parameters in these network models, which allow us to obtain, under suitable conditions, information about transient and steady-state behavior. These theorems exploit structural properties of SCRNs, beyond those of general continuous-time Markov chains. Furthermore, we derive two theorems to compare stationary distributions and mean first passage times for SCRNs with different parameter values, or with the same parameters and different initial conditions. These tools are developed for SCRNs taking values in a generic (finite or countably infinite) state space and can also be applied for non-mass-action kinetics models. When propensity functions are bounded, our method of proof gives an explicit method for coupling two comparable SCRNs, which can be used to simultaneously simulate their sample paths in a comparable manner. We illustrate our results with applications to models of enzymatic kinetics and epigenetic regulation by chromatin modifications.


Subject(s)
Algorithms , Mathematical Concepts , Stochastic Processes , Epigenesis, Genetic , Models, Biological , Markov Chains , Kinetics
9.
bioRxiv ; 2023 Jan 25.
Article in English | MEDLINE | ID: mdl-36747813

ABSTRACT

Reprogramming human fibroblasts to induced pluripotent stem cells (iPSCs) is inefficient, with heterogeneity among transcription factor (TF) trajectories driving divergent cell states. Nevertheless, the impact of TF dynamics on reprogramming efficiency remains uncharted. Here, we identify the successful reprogramming trajectories of the core pluripotency TF, OCT4, and design a genetic controller that enforces such trajectories with high precision. By combining a genetic circuit that generates a wide range of OCT4 trajectories with live-cell imaging, we track OCT4 trajectories with clonal resolution and find that a distinct constant OCT4 trajectory is required for colony formation. We then develop a synthetic genetic circuit that yields a tight OCT4 distribution around the identified trajectory and outperforms in terms of reprogramming efficiency other circuits that less accurately regulate OCT4. Our synthetic biology approach is generalizable for identifying and enforcing TF dynamics for cell fate programming applications.

10.
J Biol Rhythms ; 38(2): 185-196, 2023 04.
Article in English | MEDLINE | ID: mdl-36680409

ABSTRACT

Adolescents' conflict between circadian rhythm and early school start time is more pronounced in evening chronotypes, who tend to reduce sleep duration during school days compensating during the free days by oversleeping (i.e., social jetlag). Cumulative weekly sleep debt may impair sport performance, which relies on physical and cognitive skills modulated by sleep. We hypothesized that chronotype predicts sport performance, and that it may interact with the day of the week. Moreover, given the role sleep plays in motor memory consolidation, we tested the hypothesis that school attendance, and the related chronic sleep deprivation, might be detrimental for participants in a training phase. Ninety-three adolescent male basketball players performed multiple free throw sessions (n = 7880) during both the school and holiday periods. Chronotype and its interaction with the day of the week significantly predicted shooting accuracy when attending school, but not on holidays. Evening types' performance gradually decreased from Monday to Friday. Participants with a more unstable performance (i.e., who did not complete the acquisition of the free throw motor scheme) worsened their accuracy when attending school. Our results suggest that the impact of chronotype and day of the week on sport performance is related to the presence of an externally imposed sleep/wake schedule and is consistent with evening types' increased likelihood of experiencing social jetlag. Possibly due to early school start time, attending school worsened the performance of participants in a training phase. Further investigations are required to assess whether reducing the mismatch between biological and social clocks might improve sport performance, along with other aspects of adolescents' life.


Subject(s)
Basketball , Circadian Rhythm , Humans , Male , Adolescent , Chronotype , Sleep , Jet Lag Syndrome , Schools , Surveys and Questionnaires
11.
Curr Neuropharmacol ; 21(4): 951-987, 2023.
Article in English | MEDLINE | ID: mdl-35176989

ABSTRACT

The use of exogenous melatonin (exo-MEL) as a sleep-promoting drug has been under extensive debate due to the lack of consistency of its described effects. In this study, we conduct a systematic and comprehensive review of the literature on the chronobiotic, sleep-inducing, and overall sleep-promoting properties of exo-MEL. To this aim, we first describe the possible pharmacological mechanisms involved in the sleep-promoting properties and then report the corresponding effects of exo-MEL administration on clinical outcomes in: a) healthy subjects, b) circadian rhythm sleep disorders, c) primary insomnia. Timing of administration and doses of exo-MEL received particular attention in this work. The exo-MEL pharmacological effects are hereby interpreted in view of changes in the physiological properties and rhythmicity of endogenous melatonin. Finally, we discuss some translational implications for the personalized use of exo-MEL in the clinical practice.


Subject(s)
Melatonin , Humans , Melatonin/pharmacology , Melatonin/therapeutic use , Circadian Rhythm , Sleep/physiology
12.
Scand J Med Sci Sports ; 33(4): 503-511, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36403189

ABSTRACT

The study aims to investigate the association between different sleep management strategies and the final ranking during a one-night sailing race. A large sample of 190 teams participating in the overnight sailing regatta (151 Miglia) were included in the study. The experimental design consisted of two surveys, administered one before the start of the race and the other after the arrival. The questionnaires provided general information on the sailboat, its crew, and the strategy adopted to manage sleep during the race. In this one-night regatta, the self-management of sleep/wake timing emerged as the most successful strategy. Among participants who adopted a shift-based racing strategy, a short night shift duration (i.e., 2 h) significantly predicted a better placement. These findings confirmed the relevance of sleep management in sport performance and provided new insights into the most suitable sleep management strategy during a relatively short offshore regatta. The conclusions might apply also to similar continuous-cycle activities. Further investigations are needed to explore best sleep management strategy in team regattas of longer duration.


Subject(s)
Sports , Work Schedule Tolerance , Humans , Sleep , Surveys and Questionnaires , Circadian Rhythm
13.
Nat Sci Sleep ; 14: 941-956, 2022.
Article in English | MEDLINE | ID: mdl-35611177

ABSTRACT

Purpose: A large portion of the adult population is thought to suffer from obstructive sleep apnoea syndrome (OSAS), a sleep-related breathing disorder associated with increased morbidity and mortality. International guidelines include the polysomnography and the cardiorespiratory monitoring (CRM) as diagnostic tools for OSAS, but they are unfit for a large-scale screening, given their invasiveness, high cost and lengthy process of scoring. Current screening methods are based on self-reported questionnaires that suffer from lack of objectivity. On the contrary, commercial smartbands are wearable devices capable of collecting accelerometric and photoplethysmographic data in a user-friendly and objective way. We questioned whether machine-learning (ML) classifiers trained on data collected through these wearable devices would help predict OSAS severity. Patients and Methods: Each of the patients (n = 78, mean age ± SD: 57.2 ± 12.9 years; 30 females) underwent CRM and concurrently wore a commercial wrist smartband. CRM's traces were scored, and OSAS severity was reported as apnoea hypopnoea index (AHI). We trained three pairs of classifiers to make the following prediction: AHI <5 vs AHI ≥5, AHI <15 vs AHI ≥15, and AHI <30 vs AHI ≥30. Results: According to the Matthews correlation coefficient (MCC), the proposed algorithms reached an overall good correlation with the ground truth (CRM) for AHI <5 vs AHI ≥5 (MCC: 0.4) and AHI <30 vs AHI ≥30 (MCC: 0.3) classifications. AHI <5 vs AHI ≥5 and AHI <30 vs AHI ≥30 classifiers' sensitivity, specificity, positive predictive values (PPV), negative predictive values (NPV) and diagnostic odds ratio (DOR) are comparable with the STOP-Bang questionnaire, an established OSAS screening tool. Conclusion: Machine learning algorithms showed an overall good performance. Unlike questionnaires, these are based on objectively collected data. Furthermore, these commercial devices are widely distributed in the general population. The aforementioned advantages of machine-learning algorithms applied to smartbands' data over questionnaires lead to the conclusion that they could serve a population-scale screening for OSAS.

14.
PLoS Comput Biol ; 18(4): e1009961, 2022 04.
Article in English | MEDLINE | ID: mdl-35385468

ABSTRACT

Epigenetic cell memory allows distinct gene expression patterns to persist in different cell types despite a common genotype. Although different patterns can be maintained by the concerted action of transcription factors (TFs), it was proposed that long-term persistence hinges on chromatin state. Here, we study how the dynamics of chromatin state affect memory, and focus on a biologically motivated circuit motif, among histones and DNA modifications, that mediates the action of TFs on gene expression. Memory arises from time-scale separation among three circuit's constituent processes: basal erasure, auto and cross-catalysis, and recruited erasure of modifications. When the two latter processes are sufficiently faster than the former, the circuit exhibits bistability and hysteresis, allowing active and repressed gene states to coexist and persist after TF stimulus removal. The duration of memory is stochastic with a mean value that increases as time-scale separation increases, but more so for the repressed state. This asymmetry stems from the cross-catalysis between repressive histone modifications and DNA methylation and is enhanced by the relatively slower decay rate of the latter. Nevertheless, TF-mediated positive autoregulation can rebalance this asymmetry and even confers robustness of active states to repressive stimuli. More generally, by wiring positively autoregulated chromatin modification circuits under time scale separation, long-term distinct gene expression patterns arise, which are also robust to failure in the regulatory links.


Subject(s)
Chromatin , Histones , Chromatin/genetics , Epigenesis, Genetic/genetics , Epigenomics , Histone Code , Histones/genetics , Histones/metabolism
15.
J Sleep Res ; 30(6): e13346, 2021 12.
Article in English | MEDLINE | ID: mdl-33837981

ABSTRACT

Consumer "Smartbands" can collect physiological parameters, such as heart rate (HR), continuously across the sleep-wake cycle. Nevertheless, the quality of HR data detected by such devices and their place in the research and clinical field is debatable, as they are rarely rigorously validated. The objective of the present study was to investigate the reliability of pulse photoplethysmographic detection by the Fitbit ChargeHR™ (FBCHR, Fitbit Inc.) in a natural setting of continuous recording across vigilance states. To fulfil this aim, concurrent portable polysomnographic (pPSG) and the Fitbit's photoplethysmographic data were collected from a group of 25 healthy young adults, for ≥12 hr. The pPSG-derived HR was automatically computed and visually verified for each 1-min epoch, while the FBCHR HR measurements were downloaded from the application programming interface provided by the manufacturer. The FBCHR was generally accurate in estimating the HR, with a mean (SD) difference of -0.66 (0.04) beats/min (bpm) versus the pPSG-derived HR reference, and an overall Pearson's correlation coefficient (r) of 0.93 (average per participant r = 0.85 ± 0.11), regardless of vigilance state. The correlation coefficients were larger during all sleep phases (rapid eye movement, r = 0.9662; N1, r = 0.9918; N2, r = 0.9793; N3, r = 0.9849) than in wakefulness (r = 0.8432). Moreover, the correlation coefficient was lower for HRs of >100 bpm (r = 0.374) than for HRs of <100 bpm (r = 0.84). Consistently, Bland-Altman analysis supports the overall higher accuracy in the detection of HR during sleep. The relatively high accuracy of FBCHR pulse rate detection during sleep makes this device suitable for sleep-related research applications in healthy participants, under free-living conditions.


Subject(s)
Fitness Trackers , Sleep , Heart Rate , Humans , Polysomnography , Reproducibility of Results , Young Adult
16.
Proc Am Control Conf ; 2019: 5089-5096, 2019 Jul.
Article in English | MEDLINE | ID: mdl-32103851

ABSTRACT

Cellular reprogramming is traditionally accomplished through an open loop (OL) control approach, wherein key transcription factors (TFs) are injected in cells to steer the state of the pluripotency (PL) gene regulatory network (GRN), as encoded by TFs concentrations, to the pluripotent state. Due to the OL nature of this approach, the concentration of TFs cannot be accurately controlled. Recently, a closed loop (CL) feedback control strategy was proposed to overcome this problem with promising theoretical results. However, previous analyses of the controller were based on deterministic models. It is well known that cellular systems are characterized by substantial stochasticity, especially when molecules are in low copy number as it is the case in reprogramming problems wherein the gene copy number is usually one or two. Hence, in this paper, we analyze the Chemical Master Equation (CME) for the reaction model of the PL GRN with and without the feedback controller. We computationally and analytically investigate the performance of the controller in biologically relevant parameter regimes where stochastic effects dictate system dynamics. Our results indicate that the feedback control approach still ensures reprogramming even when both the PL GRN and the controller are stochastic.

17.
J Asthma ; 41(4): 419-31, 2004 Jun.
Article in English | MEDLINE | ID: mdl-15281328

ABSTRACT

OBJECTIVE: This study on attachment in children with recurrent asthmatic bronchitis and their mothers addresses three issues. The first aim was to test whether children affected by recurrent asthmatic bronchitis more often display an insecure pattern of attachment in comparison with healthy children. The second aim was to verify whether the distribution of adult attachment representations in the mothers of children affected by recurrent asthmatic bronchitis is different from the one shown by the mothers of the healthy comparison group. The third aim was to investigate intergenerational transmission of attachment. METHODS: Sixty Italian children, aged between 2 and 5 years, and their mothers participated in the study. The Adult Attachment Interview and the Attachment Q-Sort were used to assess, respectively, the security of mothers' attachment representations and of mother-child attachment. RESULTS: Children affected by recurrent asthmatic bronchitis appeared to be less secure in comparison with healthy children. Their mothers showed a higher percentage of insecure attachment representations. Finally, the intergenerational transmission of attachment was not influenced by the preclinical condition of the children. CONCLUSIONS: We propose a model of genetic and social transmission of insecure attachments in families struggling with asthma.


Subject(s)
Asthma/psychology , Mother-Child Relations , Object Attachment , Adult , Child, Preschool , Female , Humans , Male , Models, Psychological , Recurrence
18.
Rev Assoc Med Bras (1992) ; 49(1): 35-9, 2003.
Article in Portuguese | MEDLINE | ID: mdl-12724810

ABSTRACT

OBJECTIVE: To evaluate the presence of immune complexes and the phagocytes by polymorphonuclear neutrophils in patients with systemic lupus erythematosus, with and without disease activity. METHODS: The peripheral blood of 55 subjects was analyzed. Ten of those subjects had disease activity, 15 had not disease activity, and 30 were healthy. We used radial immune diffusion to detect immune complexes. The phagocytic function was estimated by the ingestion of zymosan by polymorphonuclear neutrophils. RESULTS: In this study we found the presence of immune complexes formatted of IgM, IgG, IgA, and complement component C3 and C4 in LES patients. The arithmetic average of zymosan particles ingested by the neutrophils incubated with homologous human serum and autologous human serum was significantly decreased (p<0.05) in the LES activity patients when we compare with the group without activity, and the control group. CONCLUSION: We conclude that there are immune complexes in the LES patients with and without disease activity, and there is a reduction in the digestive step of the phagocytes by polymorphonuclear neutrophils in patients with disease activity. The conclusions of the present study are according with the pathogenesis of the disease and with the high mortality in these patients.


Subject(s)
Antigen-Antibody Complex/immunology , Lupus Erythematosus, Systemic/immunology , Neutrophils/immunology , Phagocytosis , Adult , Antibodies, Antinuclear/blood , Antibodies, Antinuclear/immunology , Case-Control Studies , Female , Humans , Immunodiffusion , Immunoglobulins/analysis , Lupus Erythematosus, Systemic/blood , Male , Middle Aged , Zymosan/analysis
19.
Rev. Assoc. Med. Bras. (1992) ; 49(1): 35-39, jan.-mar. 2003. tab, graf
Article in Portuguese | LILACS | ID: lil-332711

ABSTRACT

OBJETIVO: Avaliar a presença de imunocomplexos e a atividade fagocitária de polimorfonucleares neutrofílicos em pacientes com Lúpus Eritematoso Sistêmico (LES) com e sem sinais e sintomas de atividade da doença. MÉTODOS: Analisou-se o sangue periférico de 55 indivíduos, sendo 10 pacientes com forma ativa da doença, 15 fora de atividade e 30 indivíduos sadios. Foi utilizada imunodifusäo radial para identificaçäo de imunocomplexos e estudada a etapa de ingestäo da fagocitose por neutrófilos com partículas de zimosan. RESULTADOS: Observou-se a presença de crioprecipitado constituído por IgM, IgG, IgA, componentes C3 e C4 do complemento nos pacientes com LES. As médias aritméticas da ingestäo por neutrófilos de partículas de zimosan incubado com soro homólogo e zimosan incubado com soro autólogo mostraram uma diminuiçäo significativa (p<0.05) para os pacientes com LES em atividade quando comparadas as de pacientes com LES fora atividade e de indivíduos sadios. CONCLUSÄO: Concluímos haver presença de imunocomplexos nos pacientes com LES em atividade e fora de atividade e uma diminuiçäo da fagocitose por neutrófilos no grupo de pacientes com LES em atividade. As conclusöes do presente estudo säo coerentes com a patogênese da doença e com a alta mortalidade por infecções nesses pacientes


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Antigen-Antibody Complex , Lupus Erythematosus, Systemic , Neutrophils , Phagocytosis , Antibodies, Antinuclear , Case-Control Studies , Immunodiffusion , Immunoglobulins , Lupus Erythematosus, Systemic , Zymosan
20.
J. bras. med ; 81(5/6): 48-50, nov.-dez. 2001. tab, graf
Article in Portuguese | LILACS | ID: lil-304992

ABSTRACT

O objetivo deste trabalho foi a avaliação da resposta imunológica em pacientes hospitalizados por mais de 30 dias. Analisou-se o sangue periférico de 50 indivíduos - 25 hospitalizados por mais de 30 dias, imobilizados por fraturas, sem necessidade de procedimentos cirúrgicos e 25 sadios. Realizou-se: contagem de linfócitos totais, linfócitos T e B, fagocitose de partículas de zymosan por monócitos, teste do NBT, dosagens de imunoglobulinas séricas e dosagens de C3 e C4. O principal resultado encontrado foi a diminuição do teste do notroblue tetrazolium em pacientes hospitalizados, indicando uma redução na etapa da digestão da fagocitose por polimorfonucleares neutrofílicos. Provavelmente as alterações encontradas predisponham estes pacientes à infecção hospitalar, cuja agente mais freqüente é o Staphylococcus aureus


Subject(s)
Humans , Antibody Formation/physiology , Immunity, Cellular , Cross Infection/prevention & control , Cross Infection/transmission , Length of Stay , Staphylococcal Infections , Staphylococcus aureus
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