[Risk Assessment of Acute Exacerbation in COPD Patients in the Context of Pulmonary Follow-Up Rehabilitation Based on the Prevalence and Severity of Comorbidities]. / Risikoabschätzung einer akuten Exazerbation bei COPD-Patienten im Rahmen einer pneumologischen Anschluss-Rehabilitation anhand der Prävalenz und Schwergradausprägung von Komorbiditäten.

INTRODUCTION: Acute COPD exacerbations (AECOPD) in the context of pulmonary rehabilitation (PR) are frequent and dangerous complications and, in addition to impairing quality of life, lead to an interruption of PR and jeopardize PR success. In this study, a correlation between the health status and an increased risk of AECOPD is described. The question arises whether the Charlson Comorbidity Index (CCI) or the Cumulative Illness Rating Scale (CIRS) are suitable for the preventive detection of COPD patients at risk for exacerbation in PR. PATIENTS AND METHODS: In a retrospective study, data of COPD patients who underwent PR in 2018 were analyzed with the CCI as the primary endpoint. All data were taken from the Phoenix Clinical Information System, and COPD exacerbations were recorded. The 44 patients (22 with and 22 without exacerbation during PR) required according to the sample size planning were randomly recruited from this pool of patients (using a random list for each group). CCI and CIRS were determined for all the cases included in the two groups. The primary endpoint (CCI) was evaluated by group comparison of the arithmetic means and Welch test. This was supported by further statistical measures of position and dispersion (median, quartile, standard deviation).In addition, the optimal cut-off point for discrimination in AECOPD and non-AECOPD patients was obtained via Receiver Operating Characteristic (ROC) analysis for both the CCI and the CIRS. RESULTS: Out of 244 COPD patients who underwent PR for an average of 21 days, 59 (24 %) suffered AECOPD that required treatment during PR. The 22 patients with AECOPD had a mean CCI of 6.77 (SD: 1.97) and the 22 patients without AECOPD had a mean CCI of 4.32 (SD: 1.17). This difference of -2.45 was statistically significant at a level of significance of 5 % (p < 0.001; 95 % CI: [-3.45; -1.46]). The ROC analysis led to 6 as the optimal cut-off point for the CCI, with 81.8 % sensitivity for determining an AECOPD and 86.4 % specificity with an area under the curve (AUC) value of 0.87. The optimal cut-off point for CIRS was 19 with a sensitivity of 50 %, a specificity of 77.2 % and an AUC of 0.65. CONCLUSION: COPD patients with acute exacerbation during PR have a higher CCI. The CCI allows the risk of AECOPD to be assessed with high sensitivity and specificity in participants with COPD in an inpatient PR program.

Effectiveness of daily rinsing of alfalfa sprouts with aqueous chlorine dioxide and ozonated water on the growth of Listeria monocytogenes during sprouting.

Alfalfa sprouts have been implicated in multiple foodborne disease outbreaks. This study evaluated the growth of Listeria monocytogenes during sprouting of alfalfa seeds and the effectiveness of daily chlorine dioxide & ozone rinsing in controlling the growth. Alfalfa seeds inoculated with L. monocytogenes were sprouted for 5 days (25°C) with a daily aqueous ClO2 (3 ppm, 10 min) or ozone water (2 ppm, 5 min) rinse. Neither treatment significantly reduced the growth of L. monocytogenes on sprouting alfalfa seeds. The initial level of L. monocytogenes was 3·44 ± 0·27, which increased to c. 7·0 log CFU per g following 3 days of sprouting. There was no significant difference in the bacterial population between the treatment schemes. Bacterial distribution in roots (7·63 ± 0·511 log CFU per g), stems (7·51 ± 0·511 log CFU per g) and leaves (7·41 ± 0·511 log CFU per g) were similar after 5 days. Spent sanitizers had significantly lower levels of bacterial populations compared to the spent distilled water control. The results indicated that sprouting process provides a favourable condition for the growth of L. monocytogenes and the sanitizer treatment alone may not be able to reduce food safety risks. SIGNIFICANCE AND IMPACT OF THE STUDY: Sprouts are high-risk foods. Consumption of raw sprouts is frequently associated with foodborne disease outbreaks. Optimum sprouting procedure involves soaking seeds in water followed by daily water rinsing to maintain a moist environment that is also favourable for the growth of pathogenic micro-organisms. The present study emphasized the potential food safety risks during sprouting and the effect of applying daily sanitizer rinsing in the place of water rinsing to reduce those risks. The finding of this study may be useful in the development of pre-harvest and post-harvest risk management strategies.

[Skin-to-skin during caesarean section: Assessment of professional practices]. / Le peau à peau du nouveau-né en cours de césarienne : une étude d'évaluation des pratiques professionnelles.

BACKGROUND: Considering its benefits, immediate skin-to-skin should be applied irrespective of the way of delivery. While it is increasingly applied in case of vaginal delivery, it remains difficult to implement in case of caesarean section. OBJECTIVE: To estimate the degree of implementation of skin-to-skin in case of caesarean section. METHODS: Survey in immediate postpartum with a continuous series of patients having given birth by caesarean - whether scheduled or not - in a level 3 hospital systematically realizing skin-to-skin in case of vaginal delivery. The patients were included if the caesarean section had been realized between 16/11/17 and 28/11/17. RESULTS: Thirty-five women gave birth by caesarean section during the period of study, among which 26 were planned (74%). The emergency levels were varied: 18 had a green code (51%), 12 an orange code (34%) and 5 a red code (14%). Forty-six percent of the newborn children were placed skin-to-skin. The frequency of skin-to-skin was closely linked to the planned character of the caesarean section (89 vs. 31%, P=0.005), as well as its color code (green 72%, orange 25%, red 0%). In case of impossibility to realize skin-to-skin in the course of the caesarean, the reasons were mainly related to the maternal state (63%) (malaise, bleeding, pain). In this situation, skin-to-skin was proposed to the spouse in 83% of cases and realized in recovery room with the mother in 82% of the cases. CONCLUSION: Skin-to-skin is feasible during caesarean section, regardless of the color code of the procedure.

Regulatory Considerations for the Clinical and Research Use of Transcranial Direct Current Stimulation (tDCS): review and recommendations from an expert panel.

The field of transcranial electrical stimulation (tES) has experienced significant growth in the past 15 years. One of the tES techniques leading this increased interest is transcranial direct current stimulation (tDCS). Significant research efforts have been devoted to determining the clinical potential of tDCS in humans. Despite the promising results obtained with tDCS in basic and clinical neuroscience, further progress has been impeded by a lack of clarity on international regulatory pathways. We therefore convened a group of research and clinician experts on tDCS to review the research and clinical use of tDCS. In this report, we review the regulatory status of tDCS, and we summarize the results according to research, off-label and compassionate use of tDCS in the following countries: Australia, Brazil, France, Germany, India, Iran, Italy, Portugal, South Korea, Taiwan and United States. Research use, off label treatment and compassionate use of tDCS are employed in most of the countries reviewed in this study. It is critical that a global or local effort is organized to pursue definite evidence to either approve and regulate or restrict the use of tDCS in clinical practice on the basis of adequate randomized controlled treatment trials.

A rate-based transcutaneous CO2 sensor for noninvasive respiration monitoring.

The pain and risk of infection associated with invasive blood sampling for blood gas measurements necessitate the search for reliable noninvasive techniques. In this work we developed a novel rate-based noninvasive method for a safe and fast assessment of respiratory status. A small sampler was built to collect the gases diffusing out of the skin. It was connected to a CO2 sensor through gas-impermeable tubing. During a measurement, the CO2 initially present in the sampler was first removed by purging it with nitrogen. The gases in the system were then recirculated between the sampler and the CO2 sensor, and the CO2 diffusion rate into the sampler was measured. Because the measurement is based on the initial transcutaneous diffusion rate, reaching mass transfer equilibrium and heating the skin is no longer required, thus, making it much faster and safer than traditional method. A series of designed experiments were performed to analyze the effect of the measurement parameters such as sampler size, measurement location, subject positions, and movement. After the factor analysis tests, the prototype was sent to a level IV NICU for clinical trial. The results show that the measured initial rate of increase in CO2 partial pressure is linearly correlated with the corresponding arterial blood gas measurements. The new approach can be used as a trending tool, making frequent blood sampling unnecessary for respiratory status monitoring.

Localizing acute stroke-related EEG changes: assessing the effects of spatial undersampling.

Because of its sensitivity to metabolic and ionic disturbances related to ischemia, the EEG can be a potentially useful tool for acute stroke detection and for monitoring affected tissue. However, the clinical use of the EEG in detecting stroke is determined in part by how accurately the spatial information is characterized. The purpose of the current study was to determine the effects of spatial undersampling on the distribution and interpretation of the stroke-related topographic EEG. Using a 128-channel sensor montage, EEG was recorded from six stroke patients acutely (between 8 and 36 hours) after symptom onset. The EEG was submitted to a spectral analysis and was compared with patient symptoms and MRI and computed tomographic findings. To determine loss of spatial and clinical information resulting from spatial undersampling, the average-referenced data from the original 128-channel recording montage were subsampled into 64-, 32-, and 19-channel arrays. Furthermore, the analytical findings were compared with a board-certified electroencephalographer's review of the raw EEG using a conventional clinical montage. As predicted, the results showed that accurate description of stroke-related topographic EEG changes is dependent on adequate spatial sampling density. Accurate description of the spatial distribution of the stroke-related EEG was achieved only with the 64- and 128-channel EEG. As the recording density decreases to 32 channels, the distribution of the scalp EEG spectra is distorted, potentially resulting in mislocalization of the affected region. Results of the clinical review by an expert electroencephalographer corroborated the quantitative analyses, and the results also demonstrated the shortcomings of the conventional 10-20 recording density for capturing focal EEG abnormalities in several cases. The EEG provides useful information about the localization of acute cerebral ischemia, but recording densities of 64 channels or higher are required for accurate spatial characterization of focal stroke-related EEG changes.

Regulating action: alternating activation of midline frontal and motor cortical networks.

OBJECTIVES: Focal electrical fields recorded over the midline prefrontal cortex have been found to index rapid evaluative decisions, including the recognition of having made an error in a speeded response task. The nature of these electrical fields and how they are related to cortical areas involved in response execution remains to be clarified. METHODS: As subjects performed a speeded response task the EEG was recorded with a 128-channel sensor array. By filtering out the large slow waves of the event-related potential, we found that the error-related negativity (Ne/ERN) arises from a midline frontal oscillation that alternates with oscillations over lateral sensorimotor cortex. Electrical source analyses were used to determine the brain sources involved in the generation of these oscillations. RESULTS: The results show that the midline and lateral oscillations have a period of about 200 ms (theta), and they are present for both correct and error responses. When an error is made, the midline error oscillation is recruited strongly, and it becomes correlated with the motor oscillation. Source analyses localized the midline error oscillation to centromedial frontal cortex and the lateral oscillation to sensorimotor cortices. CONCLUSIONS: Because of the similarity between the midline oscillation observed in the present study and frontal midline theta, the nature of the Ne/ERN may be clarified by the frontal midline theta literature. The correlation between the midline and sensorimotor oscillations suggests a possible mechanism for how midline frontal evaluative and monitoring networks contribute to action regulation.

Scalp electrode impedance, infection risk, and EEG data quality.

OBJECTIVES: Breaking the skin when applying scalp electroencephalographic (EEG) electrodes creates the risk of infection from blood-born pathogens such as HIV, Hepatitis-C, and Creutzfeldt-Jacob Disease. Modern engineering principles suggest that excellent EEG signals can be collected with high scalp impedance ( approximately 40 kOmega) without scalp abrasion. The present study was designed to evaluate the effect of electrode-scalp impedance on EEG data quality. METHODS: The first section of the paper reviews electrophysiological recording with modern high input-impedance differential amplifiers and subject isolation, and explains how scalp-electrode impedance influences EEG signal amplitude and power line noise. The second section of the paper presents an experimental study of EEG data quality as a function of scalp-electrode impedance for the standard frequency bands in EEG and event-related potential (ERP) recordings and for 60 Hz noise. RESULTS: There was no significant amplitude change in any EEG frequency bands as scalp-electrode impedance increased from less than 10 kOmega (abraded skin) to 40 kOmega (intact skin). 60 Hz was nearly independent of impedance mismatch, suggesting that capacitively coupled noise appearing differentially across mismatched electrode impedances did not contribute substantially to the observed 60 Hz noise levels. CONCLUSIONS: With modern high input-impedance amplifiers and accurate digital filters for power line noise, high-quality EEG can be recorded without skin abrasion.

Cognitive and emotional influences in anterior cingulate cortex.

Anterior cingulate cortex (ACC) is a part of the brain's limbic system. Classically, this region has been related to affect, on the basis of lesion studies in humans and in animals. In the late 1980s, neuroimaging research indicated that ACC was active in many studies of cognition. The findings from EEG studies of a focal area of negativity in scalp electrodes following an error response led to the idea that ACC might be the brain's error detection and correction device. In this article, these various findings are reviewed in relation to the idea that ACC is a part of a circuit involved in a form of attention that serves to regulate both cognitive and emotional processing. Neuroimaging studies showing that separate areas of ACC are involved in cognition and emotion are discussed and related to results showing that the error negativity is influenced by affect and motivation. In addition, the development of the emotional and cognitive roles of ACC are discussed, and how the success of this regulation in controlling responses might be correlated with cingulate size. Finally, some theories are considered about how the different subdivisions of ACC might interact with other cortical structures as a part of the circuits involved in the regulation of mental and emotional activity.

Medial frontal cortex in action monitoring.

Effective behavior requires continuous action monitoring. Electrophysiological studies in both monkeys and humans have shown activity in the medial frontal cortex that reflects dynamic control and monitoring of behavioral acts. In humans, the centromedial frontal cortex shows an electrical response within 100 msec of an error, the error-related negativity (ERN). The ERN occurs only when subjects are aware of making an error, suggesting that a critical factor may be self-monitoring of the action process. In the present study, we examined late responses in a deadline reaction time task, in which the subject becomes increasingly aware of making an error as the response becomes increasingly late. We found evidence of response conflict before errors defined by late responses but not before errors defined by incorrect responses. The results also show a linear increase in the amplitude of the ERN with increasingly late responses. These data suggest that frontal networks provide dynamic representations that monitor and evaluate the unfolding action plan.

Mood and spatial memory: emotion and right hemisphere contribution to spatial cognition.

Depressed persons show an impairment of spatial cognition that may reflect the influence of affective arousal on right hemisphere cognition. We examined normal university students to determine whether individual differences in mood and arousal levels would be related to performance on a spatial memory task. Right-hemisphere specialization for this spatial memory task was confirmed by a left field advantage for the targets and this field asymmetry was enhanced as task difficulty was increased. Event-related brain potentials (ERPs), assessed with a 64-channel sensor array, showed a processing negativity contralateral to the target in the P300 interval (300-500 ms after the target appeared). This effect increased as task difficulty was increased. A stronger posterior negativity for good (rather than bad) targets may suggest that attention was allocated toward the good locations. A suggestion of right hemisphere sensitivity to mood in this normal sample was a tendency for the subjects high in Negative Arousal not to show the normal right hemisphere (left field) superiority for the spatial memory task. Interestingly, a medial frontal lobe negativity was elicited in the ERPs by the bad targets, perhaps paralleling the error-related negativity observed in other paradigms. This medial frontal negativity was also seen in response to the feedback stimulus for the bad targets. Motivation may be important to this frontal effect: It was enhanced for subjects describing themselves as high in either positive or negative affective arousal during the task.

Tracking the time course of object categorization using event-related potentials.

Object categorization processes were investigated by measuring event-related potentials while subjects categorized objects at the superordinate (e.g. animal), basic (e.g. dog) and subordinate (e.g. beagle) levels of abstraction. An enhanced negative deflection (N1) was found at posterior recording sites for subordinate level categorizations compared with basic level categorizations and was interpreted as a marker of increased visual analysis. In contrast, superordinate level categorizations produced a larger frontal negativity relative to basic level categorizations and were interpreted as an indicator of increased semantic processing. These results suggest a neurophysiological basis for the separate cognitive processes responsible for subordinate and superordinate object categorizations.

Ultrasound-modulated twin-fluid atomization of a liquid jet.

A resonant liquid capillary wave theory which extends Taylor's dispersion relation to include the sheltering effect of liquid surface inclination caused by air flow is presented. The resulting dispersion curves are compared to new experimental results of how drop-size and size distributions vary with surface tension and air velocity in both airblast and ultrasound-modulated twin-fluid atomization of liquids with a constant kinematic viscosity of 2 cSt. Good agreements between the theoretical predictions of relative growth rates of the capillary waves and the experimental results of drop-size and size distributions led to the conclusion that Taylor-mode breakup of capillary waves plays a very important role in twin-fluid (airblast) atomization of a liquid jet. Thus, the ultrasound-modulated twin-fluid atomization not only verifies the capillary wave mechanism but also provides a means for controlling the drop-size and size distributions in twin-fluid atomization, which has a variety of applications in fuel combustion, spray drying, and spray coating.

P-TEFb kinase is required for HIV Tat transcriptional activation in vivo and in vitro.

To identify novel inhibitors of transcriptional activation by the HIV Tat protein, we used a combination of in vitro and in vivo Tat-dependent transcription assays to screen >100,000 compounds. All compounds identified blocked Tat-dependent stimulation of transcriptional elongation. Analysis of a panel of structurally diverse inhibitors indicated that their target is the human homolog of Drosophila positive transcription elongation factor b (P-TEFb). Loss of Tat transactivation in extracts depleted of the kinase subunit of human P-TEFb, PITALRE, was reversed by addition of partially purified human P-TEFb. Transfection experiments with wild-type or kinase knockout PITALRE demonstrated that P-TEFb is required for Tat function. Our results suggest that P-TEFb represents an attractive target for the development of novel HIV therapeutics.

Binding of SP1 to the immediate-early protein-responsive element of the human cytomegalovirus DNA polymerase promoter.

Human cytomegalovirus (HCMV), a member of the herpesvirus family of DNA viruses, encodes two major immediate-early (IE) transcription factors, IE72 and IE86, that are important for regulated expression of the viral genome. The purpose of this study was to identify the host cellular components required for regulation of the HCMV DNA polymerase promoter (UL54) by HCMV IE proteins. Extensive mutagenesis defined a DNA element located between -54 and -43 relative to the transcription start site that was required for both basal transcriptional activity and transactivation by viral IE proteins. A single copy of the UL54 -54/-43 sequence enhanced the responsiveness of a heterologous minimal promoter to HCMV IE proteins. Fractionation of extracts prepared from uninfected cells led to the isolation of two cellular proteins with apparent molecular masses of 95 and 105 kDa that bound specifically to the UL54 -54/-43 element. Biochemical and immunochemical analyses identified this protein as the transcription factor SP1. Although initial inspection of the UL54 -54/-43 sequence did not predict an SP1 binding site, subsequent analyses indicated that it is indeed a nonconsensus GC box. We propose that SP1 is required to direct basal levels of promoter activity and that SP1-regulated transcription complexes allow the entry of HCMV IE proteins into the transcription cycle.

Emotional expectancy: brain electrical activity associated with an emotional bias in interpreting life events.

University students in either an optimistic or pessimistic mood state read brief stories of daily life events as event-related brain potentials were collected during the final word of each story. For subjects in a pessimistic mood, a bias to expect negative outcomes was seen as an N400/P300 effect over posterior scalp regions. For subjects in an optimistic mood, a differentiation between good and bad outcomes was also observed, but it was specific to medial frontal areas. Analysis of single-trial P300 latencies suggested that semantically incongruent and mood-incongruent outcome words resulted in increased median latency of the late positive complex (LPC) and resulted in increased variability of LPC latency across trials.

Inhibition of the association of RNA polymerase II with the preinitiation complex by a viral transcriptional repressor.

Transcriptional repression is an important component of regulatory networks that govern gene expression. In this report, we have characterized the mechanisms by which the immediate early protein 2 (IE2 or IE86), a master transcriptional regulator of human cytomegalovirus, down-regulates its own expression. In vitro transcription and DNA binding experiments demonstrate that IE2 blocks specifically the association of RNA polymerase II with the preinitiation complex. Although, to our knowledge, this is the first report to describe a eukaryotic transcriptional repressor that selectively impedes RNA polymerase II recruitment, we present data that suggest that this type of repression might be widely used in the control of transcription by RNA polymerase II.

Social and emotional self-regulation.

In humans, frontal lesions result in deficits of social and emotional behavior that are often surprising in the presence of intact language and other cognitive skills. The connections between the motivation and memory functions of limbic cortex and the motor planning functions of frontal neocortex must be fundamental to meeting the daily challenges of self-regulation. The connectional architecture of limbic and neocortical networks suggests a model of function. The densely interconnected paralimbic cortices may serve to maintain a global motivational context within which specific actions are articulated and sequenced within frontal neocortical networks. The paralimbic networks represent the visceral and kinesthetic information that is integral to the representation of the bodily self. In a general sense, the implicit self-representation within paralimbic networks may shape the significance of perceptions and the motivational context for developing actions. The network architecture of the frontal lobe reflects the dual limbic origins of frontal cortex, in the dorsal archicortical and ventral paleocortical structures. In this paper, we speculated that these two limbic-cortical pathways apply different motivational biases to direct the frontal lobe representation of working memory. The dorsal limbic mechanisms projecting through the cingulate gyrus may be influenced by hedonic evaluations, social attachments, and they may initiate a mode of motor control that is holistic and impulsive. In contrast, the ventral limbic pathway from the amygdala to orbital frontal cortex may implement a tight, restricted mode of motor control that reflects adaptive constraints of self-preservation. In the human brain, hemispheric specialization appears to have led to asymmetric elaborations of the dorsal and ventral pathways. Understanding the inherent asymmetries of corticolimbic architecture may be important in interpreting the increasing evidence that the left and right frontal lobes contribute differently to normal and pathological forms of self-regulation.

Efficient induction of fibrosarcomas by v-jun requires mutations in the DNA binding region and the transactivation domain.

v-jun is the transforming gene of ASV 17, a retrovirus isolated from a spontaneous chicken fibrosarcoma. There are three mutations in the viral Jun protein (v-Jun) as compared to its cellular progenitor c-Jun: a deletion in the transactivation domain (called delta) and two amino acid substitutions in and near the DNA binding region. The effect of each of these mutations on fibrosarcoma development is described. All three mutations contribute towards tumor formation, and their cumulative effect makes v-Jun more tumorigenic compared to Jun proteins that carry only one or two of the mutations. Viruses rescued from tumors induced by c-Jun carrying the two amino acid substitutions in the DNA binding region have increased transforming and tumorigenic potential. These increases are probably due to further mutations that result in the expression of a rearranged Jun protein. Taken together the results show that the evolution of the c-Jun oncoprotein to an efficient carcinogen requires mutations in the transactivation and DNA binding regions.