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ABSTRACT IMPACT: Human exhaled breath is rich in metabolomic content that represents pulmonary function and gas exchange with blood, which can provide insights into an individual’s state of health. OBJECTIVES/GOALS: Human exhaled breath is rich in metabolomic content that represents pulmonary function and gas exchange with blood. It contains a mixture of compounds that offer insight into an individual’s state of health. Here, we present two novel non-invasive breath sampling devices for use in basic medical practice. METHODS/STUDY POPULATION: The two breath samplers have a disposable mouthpiece, a set of inhale and exhale one-way flap valves to allow condensation of exhaled breath only, and a saliva filter. The housing is constructed out of Teflon®, a chemically inert material to reduce chemical absorbance. The first device condenses exhaled breath into a frozen condensate using dry ice pellets and the other is a miniaturized design that liquifies exhaled breath on a condenser surface with micropatterned features on a cooling plate. Both designs have individual strategic and analytical advantages: frozen exhaled breath condensate (EBC) has high retention of analytes and sample volume; EBC collected in liquid phase offers facilitated sample collection and device portability. RESULTS/ANTICIPATED RESULTS: We investigated if breath aerosol size distribution affects the types or abundances of metabolites. We modified the geometry of the first device to redirect aerosol trajectories based on size. The trapping of larger aerosols increases with filter length, thus altering the aerosol size distribution although no significant changes in the metabolite profiles were found. With the miniaturized device, metabolite abundances were measured in a small cohort of healthy control and mild asthmatic subjects. Differences among subjects were found, as well as main differences between control and asthmatic groups. All analyses of EBC were performed with liquid chromatography - mass spectrometry. Inflammatory suppression found in asthmatic subjects can be explained by prescribed daily use of inhaled corticosteroids. DISCUSSION/SIGNIFICANCE OF FINDINGS: Breath collection devices can be used in intensive care units, outpatient clinics, workplaces, and at home. EBC analysis has been used to monitor asthma and chronic obstructive pulmonary disease. It can be applied to infectious respiratory diseases (e.g. influenza, COVID-19) and for monitoring environmental and occupational chemical exposures.
Epilepsy surgery has progressed significantly in the last 150 years. Functional brain maps allowed for the localization of epileptogenic lesions based on seizure patterns, allowing surgeons like McEwan and Horsely to treat epilepsy surgically. Berger’s electroencephalogram marked the first modality directly identifying epileptic abnormalities. Penfield and Jasper collaborated, as neurosurgeon and neurologist, to use EEG for surgery. Meanwhile, Wada developed the amobarbital test, improving the protection of language and memory. Talairach and Bancaud pioneered invasive monitoring of deep brain activity with stereoelectroencephalography before the computer age made CT and MRI possible. Looking forward, AI and robotics hold promise for further improving outcomes.
The mechanics of extreme intensity events in the buffer and logarithmic layers of a turbulent channel at $Re_\tau =2000$ is investigated. The 99.9th percentile of the most intense events in the dissipation of turbulent kinetic energy is analysed by means of conditional space–time proper orthogonal decomposition. The computed spatio-temporal modes are coherent in space and over the considered time frame, and optimally capture the energy of the ensemble. The most energetic mode with transverse symmetric structure describes a turbulent burst event. The underlying mechanism is a varicose instability which generates localized extrema in the dissipation and production of turbulent kinetic energy and drives the formation of a hairpin vortex. The most energetic anti-symmetric mode is related to a sinuous-type instability that is situated in the shear layer between two very-large-scale streaks. Statistical results show the energy in the symmetric mode to exceed that in the anti-symmetric mode by a near constant factor for the considered wall distances. Both mechanisms occur throughout the range of wall distances in an effectively self-similar manner that is consistent with the attached-eddy hypothesis. By analogy with transitional flows, the results suggest that the events are induced by an exponential growth mechanism.
Studies have long observed the bidirectional nature of mother–infant relationships. While behavioral studies have shown that mothers high in social avoidance tendencies can influence the development of these traits in their offspring, the neurophysiological mechanisms underlying this phenomenon, and the role that the infants play, are not well understood. Here we acquired frontal electroencephalogram asymmetry (FA) data simultaneously in 40 mother–infant dyads (Mage mother = 31.6 years; Mage infant = 9 months). Using an actor–partner interdependence model, we examined whether mother (or infant) resting-state FA predicted infant (or mother) FA during two subsequent emotion-eliciting conditions (happy and fear). Maternal social approach versus avoidance traits were assessed as moderators to examine the impact of maternal characteristics on these mother–infant FA relations. In dyads led by mothers with high social avoidance/low social approach characteristics, maternal resting-state FA predicted infant FA during both emotion-eliciting conditions. We did not observe any effects of infant FA on mothers. Therefore, we speculate that individual differences in FA patterns might be a putative brain mechanism through which socially avoidant mothers transfer affective/behavioral information to their infants.
Effects of stresses associated with extremely preterm birth may be biologically “recorded” in the genomes of individuals born preterm via changes in DNA methylation (DNAm) patterns. Genome-wide DNAm profiles were examined in buccal epithelial cells from 45 adults born at extremely low birth weight (ELBW; ≤1000 g) in the oldest known cohort of prospectively followed ELBW survivors (Mage = 32.35 years, 17 male), and 47 normal birth weight (NBW; ≥2500 g) control adults (Mage = 32.43 years, 20 male). Sex differences in DNAm profiles were found in both birth weight groups, but they were greatly enhanced in the ELBW group (77,895 loci) versus the NBW group (3,424 loci), suggesting synergistic effects of extreme prenatal adversity and sex on adult DNAm profiles. In men, DNAm profiles differed by birth weight group at 1,354 loci on 694 unique genes. Only two loci on two genes distinguished between ELBW and NBW women. Gene ontology (GO) and network analyses indicated that loci differentiating between ELBW and NBW men were abundant in genes within biological pathways related to neuronal development, synaptic transportation, metabolic regulation, and cellular regulation. Findings suggest increased sensitivity of males to long-term epigenetic effects of extremely preterm birth. Group differences are discussed in relation to particular gene functions.
The impact of a collapsing gas bubble above rigid, notched walls is considered. Such surface crevices and imperfections often function as bubble nucleation sites, and thus have a direct relation to cavitation-induced erosion and damage structures. A generic configuration is investigated numerically using a second-order accurate compressible multi-component flow solver in a two-dimensional axisymmetric coordinate system. Results show that the crevice geometry has a significant effect on the collapse dynamics, jet formation, subsequent wave dynamics and interactions. The wall-pressure distribution associated with erosion potential is a direct consequence of development and intensity of these flow phenomena.
This study examined the link between two biological markers of stress vulnerability at 22–26 years of age and telomere length at 30–35 among extremely low birth weight (ELBW; <1000 g) survivors and normal birth weight (NBW; >2500 g) control participants. Sixteen ELBW and 22 NBW participants provided baseline afternoon salivary cortisol samples and resting frontal electroencephalogram (EEG) alpha asymmetry data at 22–26 years. Buccal cells were assayed for telomere length at 30–35 years. Analyses controlled for sex, postnatal steroid exposure, childhood socioeconomic status, time of cortisol sample collection, and body mass index at 22–26 years. Salivary cortisol and frontal asymmetry at age 22–26 independently predicted telomere length at age 30–35, such that relatively higher cortisol and greater relative right frontal asymmetry at rest predicted telomere shortening among NBW controls, but not among ELBW survivors. However, similar associations were not noted in ELBW survivors, suggesting that ELBW survivors may have different mechanisms of stress coping as a result of their early-life exposures. These findings offer preliminary evidence in support of the role of stress in the genesis of cellular senescence at least among those born at NBW, but that these links may differ in those born preterm.
Purpose of this study was to assess subjective well-being in schizophrenia inpatients and to find variables predictive for response and remission of subjective well-being.
The subjective well-being under neuroleptic treatment scale (SWN-K) was used in 232 schizophrenia patients within a naturalistic multicenter trial. Early response was defined as a SWN-K total score improvement of 20% and by at least 10 points within the first 2 treatment weeks, response as an improvement in SWN-K total score of at least 20% and by at least 10 points from admission to discharge and remission in subjective well-being as a total score of more or equal to 80 points at discharge. Logistic regression and CART analyses were used to determine valid predictors of subjective well-being outcome.
Twenty-nine percent of the patients were detected to be SWN-K early responders, 40% fulfilled criteria for response in subjective well-being and 66% fulfilled criteria for remission concerning subjective well-being. Among the investigated predictors, SWN-K early improvement and the educational status were significantly associated with SWN-K response. The SWN-K total score at baseline showed a significant negative predictive value for response. Baseline SWN-K total score, PANSS global subscore, and side effects as well as the educational status were found to be significantly predictive for remission.
Depressive symptoms should be radically treated and side effects closely monitored to improve the patient's subjective well-being. The important influence of subjective well-being on overall treatment outcome could be underlined.
This guidance paper from the European Psychiatric Association (EPA) aims to provide evidence-based recommendations on early intervention in clinical high risk (CHR) states of psychosis, assessed according to the EPA guidance on early detection. The recommendations were derived from a meta-analysis of current empirical evidence on the efficacy of psychological and pharmacological interventions in CHR samples. Eligible studies had to investigate conversion rate and/or functioning as a treatment outcome in CHR patients defined by the ultra-high risk and/or basic symptom criteria. Besides analyses on treatment effects on conversion rate and functional outcome, age and type of intervention were examined as potential moderators. Based on data from 15 studies (n = 1394), early intervention generally produced significantly reduced conversion rates at 6- to 48-month follow-up compared to control conditions. However, early intervention failed to achieve significantly greater functional improvements because both early intervention and control conditions produced similar positive effects. With regard to the type of intervention, both psychological and pharmacological interventions produced significant effects on conversion rates, but not on functional outcome relative to the control conditions. Early intervention in youth samples was generally less effective than in predominantly adult samples. Seven evidence-based recommendations for early intervention in CHR samples could have been formulated, although more studies are needed to investigate the specificity of treatment effects and potential age effects in order to tailor interventions to the individual treatment needs and risk status.
Data about quality of life (QoL) are important to estimate the impact of diseases on functioning and well-being. The present study was designed to assess the association of different aspects of panic disorder (PD) with QoL and to examine the relationship between QoL and symptomatic outcome following brief cognitive-behavioral group therapy (CBGT).
The sample consisted of 55 consecutively recruited outpatients suffering from PD who underwent CBGT. QoL was assessed by the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) at baseline, post-treatment and six months follow-up. SF-36 baseline scores were compared with normative data obtained from a large German population sample.
Agoraphobia, disability, and worries about health were significantly associated with decreased QoL, whereas frequency, severity and duration of panic attacks were not. Treatment responders showed significantly better QoL than non-responders. PD symptom reduction following CBGT was associated with considerable improvement in emotional and physical aspects of QoL. However, the vitality subscale of the SF-36 remained largely unchanged over time.
Our results are encouraging for cognitive-behavior therapists who treat patients suffering from PD in groups, since decrease of PD symptoms appears to be associated with considerable improvements in QoL. Nevertheless, additional interventions designed to target specific aspects of QoL, in particular vitality, may be useful to enhance patients’ well-being.
The aim of this guidance paper of the European Psychiatric Association is to provide evidence-based recommendations on the early detection of a clinical high risk (CHR) for psychosis in patients with mental problems. To this aim, we conducted a meta-analysis of studies reporting on conversion rates to psychosis in non-overlapping samples meeting any at least any one of the main CHR criteria: ultra-high risk (UHR) and/or basic symptoms criteria. Further, effects of potential moderators (different UHR criteria definitions, single UHR criteria and age) on conversion rates were examined. Conversion rates in the identified 42 samples with altogether more than 4000 CHR patients who had mainly been identified by UHR criteria and/or the basic symptom criterion ‘cognitive disturbances’ (COGDIS) showed considerable heterogeneity. While UHR criteria and COGDIS were related to similar conversion rates until 2-year follow-up, conversion rates of COGDIS were significantly higher thereafter. Differences in onset and frequency requirements of symptomatic UHR criteria or in their different consideration of functional decline, substance use and co-morbidity did not seem to impact on conversion rates. The ‘genetic risk and functional decline’ UHR criterion was rarely met and only showed an insignificant pooled sample effect. However, age significantly affected UHR conversion rates with lower rates in children and adolescents. Although more research into potential sources of heterogeneity in conversion rates is needed to facilitate improvement of CHR criteria, six evidence-based recommendations for an early detection of psychosis were developed as a basis for the EPA guidance on early intervention in CHR states.
To examine the predictive validity of early improvement in a naturalistic sample of inpatients and to identify the criterion that best defines early improvement.
Two hundred and forty-seven inpatients who fulfilled ICD-10 criteria for schizophrenia were assessed with the Positive And Negative Syndrome Scale (PANSS) at admission and at biweekly intervals until discharge from hospital. Remission was defined according to the recently proposed consensus criteria, response as a reduction of at least 40% in the PANNS total score from admission to discharge.
Receiver operating characteristic (ROC) analyses showed that early improvement (reduction of the PANSS total score within the first 2 weeks of treatment) predicts remission (AUC = 0.659) and response (AUC = 0.737) at discharge. A 20% reduction in the PANSS total score within the first 2 weeks was the most accurate cut-off for the prediction of remission (total accuracy: 65%; sensitivity: 53%; specificity: 76%), and a 30% reduction the most accurate cut-off for the prediction of response (total accuracy: 76%; sensitivity: 47%; specificity: 90%).
The findings of clinical drug trials that early improvement is a predictor of subsequent treatment response were replicated in a naturalistic sample. Further studies should examine whether patients without early improvement benefit from an early change of antipsychotic medication.
People with eating disorders (ED) are at high risk for suicidal behavior. Among different ED, anorexia nervosa (AN) has the highest rates of completed suicide whereas suicide attempt rates are similar or lower than in bulimia nervosa (BN). Attempted suicide is a key predictor of completed suicide, thus this mismatch is intriguing. We sought to explore whether the clinical characteristics of suicidal acts differ between suicide attempters with AN, BN or without an ED.
Case-control study in cohort of suicide attempters (n = 1563). Forty-four patients with AN and 71 with BN were compared with 235 non-ED attempters matched for sex, age and education, using interview measures of suicidal intent and severity.
AN patients were more likely to have made a serious attempt (OR = 3.4, 95% CI 1.4–7.9), with a higher expectation of dying (OR = 3.7, 95% CI 1.1–13.5), and an increased risk of lethality (OR = 3.4, 95% CI 1.2–9.6). BN patients did not differ from the control group.
There are distinct features of suicide attempts in AN. This may explain the higher suicide rates in AN. Deaths from suicide in AN may not be the result simply of their greater physical frailty.
Even though most than a hundred years have passed since we know Alzheimer's disease today it's considered as the human's frightful flagellum. While most of mental disease seem to be losing its evilness, the neurocognitives disorders caused by Alzheimer's disease, far from attenuating has duplicated it's appearance every each five years. And its symptoms are still being more depriving.
So, in opposition to the rest of the illness that affect the nervous system and the psychic apparatus, which due to the new treatment has been attenuated the clinical forms’ Alzheimer. With its severe pronostic and the illness evolution, haven’t been soften.
Our intention is firstly, share some concepts to consider Alzheimer's disease as a cruel illness that can reache all the elderly people around the world.
Secondly, to analyze the different forms of presentation than can mask a clinical state. Which many times could end-up in dementia. And will soon destroy the whole psychic apparatus of a person.
Present our study group in the three institutional medical centers, with ambulatory patients, who consult about a cognitive disease. We describe the evolution trough time, taking into account the pharmacological treatments.
The importance of the early detection of memory disorder, as one of the first signs of alarm which give us the opportunity to intervene therapeutically in on time.
We can recognize the Mild Cognitive Disorder as a clue which reveal a first therapeutic instance probably in efficacy in this cruel evolution towards dementia.
To evaluate the efficacy of galantamine-paroxetine association in patients with Mild Cognitive Disorder and Depression. So there is a possible relation between the deficit in executive and cognitive cerebral function and depression or relation between the serotonin system and cholinergic system in relation with disease comorbidity cognitive-depression.
To evaluate the therapeutic response in patients with comorbility between Mild Cognitive Disorder and Depression in treatment with Galantamine (acetylcholinesterase inhibitor) with Escitalopram (Selective serotonin reuptake inhibitors) and the two drugs associated.
A group of 705 patients with symptoms of Mild Cognitive Disorder and Depression (DSM IV-TR criteria) were separated in 3 groups of 235 patients. Each group received different treatment in an 12 months period:
Group 1: Galantamine 16 mg/day.
Group 2: Escitalopram 10 mg/day.
Group 3: both drugs, same dose.
The therapeutic response evaluated in Hamilton Scale for Depression (HAM-D), Montgomery and Äsberg Depression Rating Scale (M.A.D.R.S.), Mini Mental State Examination (M.M.S.E.) and Global Clinical Impression (G.C.I.) scores during 12 months. In the third group who received the two drugs associated, had much better response than the others and “brain enhancer”.
The group who received the association of the cholinergic agent Galantamine with antidepressant (SSRIs) Escitalopram had a relevant satisfactory therapeutic response: the best result, so there is a possible relation between the deficit in cholinergic systems and depression. Could be cerebral cholinergic systems deficit a generator of Depressive Disorder?
Some studies have shown that alexithymic patients respond poorly to pharmacotherapy and that alexithymia may have a negative impact on the naturalistic course of psychiatric illnesses. The view that alexithymic patients are also less responsive to psychotherapy is often described in the literature, but few empirical studies have examined this issue, with inconsistent results.
We conducted two prospective studies (pre/post/follow-up) with patients with panic disorder and obsessive-compulsive disorder, to evaluate alexithymia as a potential predictor of the outcome of cognitive-behavioral therapy (CBT) including exposure response management. A further aim was to examine the absolute and relative stability of alexithymia.
Regression analyses revealed that alexithymia, as measured with the 20-item Toronto Alexithymia Scale, was related neither to the post-treatment nor to the follow-up outcome. The repeated measures ANOVA showed a significant decrease of alexithymia over time, even after controlling for depression. The high test-retest correlations of alexithymia total and factor scores indicated relative stability of this construct, suggesting that it is a stable personality trait rather than a state-dependent phenomenon in these patients.
The results are encouraging for cognitive-behavior therapists working with alexithymic patients with panic disorder and obsessive-compulsive disorder, since the CBT outcome of these patients does not appear to be negatively affected by alexithymia. Furthermore, some alexithymic characteristics may decrease during CBT, even when the therapy program is not specifically directed to alexithymia. Future controlled studies should examine whether these improvements of alexithymia are due to psychotherapeutic interventions, in particular exposure therapy.
To evaluate the efficacy of galantamine in patients with Mild Cognitive Impairment. So there is a possible benefit in the deficit in executive and cognitive cerebral function (cholinergic system) with treatment with Galantamine.
Galantamine is a reversible, competitive cholinesterasa inhibitor that also allosterically modulates nicotine acetylcholine receptors. Inhibition of acetylcholinesterase, the enzyme responsible for hydrolisis of acetylcholine at the cholinergic cognitive impairment. To evaluate the efficacy, safety and tolerability of galantamine in long-term in Mild Cognitive Disorder.
A multicenter, open label, prospective, observational study enrolled 1028 patients, more 55 years old with Mild Neurocognitive Disorder (DSM IV criteria), during 30 months of treatment with galantamine 16 mg./day. Assessments included the MMSE, CDR, ADAS-GOG, FAQ, GCI, Trail making test, Global Deterioration Scale, and UKU scale of Adverse Effects.
A total 1028 outpatients were treated with 16 mg./day galantamine during 30 months, the therapeutic response evaluated with CDR, MMSE and the tests and scales of function cognitive measuring, GCI and UKU scale of adverse effects, comparing the baseline to final scores.
Mild Cognitive Disorder is being examined, so there aren’t enought treatment for this. A long-term treatment (30 months) galantamine improves cognition and global function, behavioural symptoms and the general state well being of patients with MCD. With incidence of adverse effects not significant and a very good profile of safety, the final results of the study suggest that galantamine may be particularly appropiate in the Mild Cognitive Disorder.
Population: Outpatient with aged more of 65 years. Diagnosis: DSM-IV criteria for chronic primary insomnia; Treatment: Single-dose zolpidem extended-release 12.5 mg (n = 128) or placebo (n = 127), self-administered every night.
Patient's Global Impression (PGI) and Clinical Global Impression-Improvement (CGI-I) were assessed every 4 weeks up to six month. Patient Morning Questionnaire (PMQ), recorded daily, assessed subjective sleep measures-sleep onset latency (SOL), total sleep time (TST), number of awakenings (NAW), wake time after sleep onset (WASO), and quality of sleep (QOS)-and next-day functioning. Zolpidem extended-release also was statistically significantly superior to placebo at every time point for PGI (Items 1–4) and CGI-I (P < 0.0001, rank score), TST, WASO, QOS (P < 0.0001), and SOL (P < or = 0.0014); NAW (Months 2–6; P < 0.0001). Sustained improvement (P < 0.0001, all time points) was observed in morning sleepiness and ability to concentrate (P = 0.0014, month 6) with zolpidem extended-release compared with placebo. Most frequent adverse events for zolpidem extended-release were headache, anxiety and somnolence to the morning. No rebound effect was observed during the first 3 nights of discontinuation.
These findings establish the efficacy of dosing of zolpidem extended-release 12.5 mg for up to 6 months. Treatment provided sustained and significant improvements in sleep onset and maintenance and also improved next-day concentration and morning sleepiness.