Immunocytochemical detection of milk proteins in tracheal aspirates of ventilated infants: a pilot study

In this study, we evaluated immunocytochemical staining for milk proteins (alpha-lactalbumin and beta-lactoglobulin) in tracheal aspirates of mechanically ventilated infants, and assessed whether this staining technique supported a clinical diagnosis of aspiration in infants receiving orogastric feedings. All newborns requiring mechanical ventilation in the neonatal intensive care unit of a major tertiary care hospital were potential subjects for this study. Tracheal aspirates were obtained prior to the introduction of enteral feeding and at various time points thereafter in newborns requiring mechanical ventilation. Cells were obtained and processed for immunocytochemical staining of alpha-lactalbumin and beta-lactoglobulin. In total, 88 specimens recovered from 34 infants were adequate for staining. Alveolar macrophages recovered from most of the infants who were never fed (true negative controls) did not display immunoreactivity for milk proteins: 4/34 or 12% of infants' aspirates demonstrated presence of milk proteins before enteral feeding was commenced. Tracheal aspirates obtained from 12 infants after introduction of enteral feedings appeared to support clinical and radiological findings suggestive of aspiration events, with positive immunostaining on several occasions. These observations support our work in a murine model and demonstrate that immunocytochemical staining of tracheal aspirates for milk proteins may enhance the ability to diagnose pulmonary aspiration. Further studies are needed to define the clinical significance of our findings and the effects of single and repeated aspiration events on respiratory status.     

Serum glutathione-S-transferase and glutathione reductase activity in head and neck cancer patients

Glutathione, an antioxidant plays an important role in phase-II detoxification of carcinogens. The levels of reduced glutathione are maintained by glutathione-depleting as well as replenishing enzymes such as glutathione-s-transferase (GST) and glutathione reductase (GR), respectively. Pre and post treatment changes in GST and GR activities in head and neck cancer patients were analysed. Serum GST and GR were analysed from untreated head and neck cancer patients (PT) (n=146), controls with habit of tobacco (VHT) (n=25) as well as without (no) habit of tobacco (NHT) (n=25) and patients with oral precancerous conditions (OPC) (n=50). The cancer patients were followed-up after initiation of anticancer therapy. Follow-up blood samples were collected. Serum GST and GR activities were estimated by highly sensitive and specific spectrophotometric methods. Untreated cancer patients showed elevated mean serum GST and GR activities as compared to NHT. Patients with OPC had declined mean GST activity as compared to WHT and untreated cancer patients. Paired t-test revealed that complete responders (CR) showed significantly elevated GST levels and declined GR activities (p < 0.001) as compared to those in PT. No correlation was found between stage of the disease and GST, GR activity. Paired t-test showed significant decreased in GR activity in nonresponders (NR) treated with radiotherapy (p=0.01). The study suggested that analysis of glutathione and glutathione-depleting enzymes can be helpful for treatment monitoring of head and neck cancer patients.     

Preoperative predictors of choledocholithiasis in patients presenting with acute calculous cholecystitis

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Distinct electrophysiological signatures of task-unrelated and dynamic thoughts

Humans spend much of their lives engaging with their internal train of thoughts. Traditionally, research focused on whether or not these thoughts are related to ongoing tasks, and has identified reliable and distinct behavioral and neural correlates of task-unrelated and task-related thought. A recent theoretical framework highlighted a different aspect of thinking—how it dynamically moves between topics. However, the neural correlates of such thought dynamics are unknown. The current study aimed to determine the electrophysiological signatures of these dynamics by recording electroencephalogram (EEG) while participants performed an attention task and periodically answered thought-sampling questions about whether their thoughts were 1) task-unrelated, 2) freely moving, 3) deliberately constrained, and 4) automatically constrained. We examined three EEG measures across different time windows as a function of each thought type: stimulus-evoked P3 event-related potentials and non–stimulus-evoked alpha power and variability. Parietal P3 was larger for task-related relative to task-unrelated thoughts, whereas frontal P3 was increased for deliberately constrained compared with unconstrained thoughts. Frontal electrodes showed enhanced alpha power for freely moving thoughts relative to non-freely moving thoughts. Alpha-power variability was increased for task-unrelated, freely moving, and unconstrained thoughts. Our findings indicate distinct electrophysiological patterns associated with task-unrelated and dynamic thoughts, suggesting these neural measures capture the heterogeneity of our ongoing thoughts.

Cognitive neuroscience has reached a consensus that the brain is not idle at rest (1). This rings intuitively true: When left alone, our minds rarely stay still. Moreover, recent evidence suggests that rest is not a homogeneous state (2), nor is the brain truly “at rest” as it fluctuates across time and contexts (3–6). This too is intuitive: What is striking is not just that we move from thought to thought unprompted but also the diverse ways that trains of thought unfold over time. Sometimes, our thoughts freely wander between topics. You might remember this morning’s run, then imagine gardening, then think about the dinner you’ll cook tonight. Other times, we deliberately constrain our thoughts and work diligently toward a goal. In a quiet moment, you might methodically contemplate the results of your latest experiment. Still other times, our thoughts get stuck on an affectively salient topic, from which it is difficult to break free. You might worry, over and over, about your niece who is going through major surgery next week.Research has traditionally examined the internal train of thought in the context of mind wandering. This field has expanded at such a rapid pace that some have dubbed this the “era of the wandering mind” (7). To date, the vast majority of mind-wandering research has focused on the static content of individual thoughts. In particular, mind-wandering studies have primarily focused on task-unrelated thought (8)—that is, thoughts that are unrelated to an ongoing, typically externally oriented, task (8–10). In the laboratory, subjects’ thoughts are often unrelated to the experimental task (9). Task-unrelated thought is also frequent in everyday life (11), as when a student becomes distracted during a lecture or while driving.Recent theories are less task-centric and instead focus on the dynamics of mind wandering—that is, how internal trains of thoughts unfold over time (12–17). In particular, the “dynamic framework” of spontaneous thought distinguishes three subtypes within the train of thoughts: 1) deliberately constrained, 2) automatically constrained, and 3) freely moving thoughts (12, 14). Constraints on the train of thoughts serve to focus internal attention on a topic for extended periods of time. For example, deliberately constrained thoughts occur when a person actively directs her thoughts to goal-relevant information (e.g., when you contemplate your latest experiment). This type of constraint is implemented through cognitive control. Automatically constrained thoughts focus on affectively or personally salient information that is difficult to disengage from (e.g., when you worry about your niece who will have surgery). This type of constraint is automatic in nature and thought to operate largely outside of cognitive control. In contrast, freely moving thoughts occur when both of these constraints are weak, allowing the mind to wander with no overarching purpose and direction (e.g., when your thoughts drift from a movie, to gardening, to dinner). Notably, the dynamic framework purports that these three subtypes of thoughts are independent of task relatedness. In other words, task-related and task-unrelated thoughts can both be deliberately constrained, automatically constrained, or freely moving. See SI Appendix for further details about the relationship between dynamic categories.Empirical research on the dynamics of thought is in its infancy. Behavioral research has focused on contrasting task-unrelated thoughts with the other three subtypes of thoughts, with a particular emphasis on freely moving thoughts. These findings suggest that self-reported freely moving and task-unrelated thoughts have distinct behavioral markers. For example, studies of mind wandering in everyday life found that self-reports of freely moving and task-unrelated thought fluctuate at different rates throughout the day (11). Consistent with predictions of the dynamic framework, these studies reported that task-unrelated and freely moving thoughts are only modestly correlated (r < 0.3) and they occurred independent of each other (8, 11). Specifically, although task-related thoughts are often deliberately constrained and task-unrelated thoughts sometimes move freely, the dynamic framework predicts that this is not always the case. In fact, task-related thoughts can move freely (e.g., when a graphic designer freely associate ideas for her new website design) or be automatically constrained (e.g., when someone obsesses over a problem at work). Task-unrelated thoughts can be deliberately or automatically constrained (e.g., when you construct a grocery list or worry about your niece’s surgery during a lecture). The only two empirical studies to date have focused explicitly on freely moving thought (8, 11). Although this provides some initial evidence that task-unrelated thought is different from dynamic thoughts, no studies have assessed the neural correlates of dynamic thought types. The identification of different electrophysiological signatures of these thought types would thus provide important validation that these categories reflect distinct entities.In the current study, we examined the electrophysiological signatures of the four types of thought by recording an electroencephalogram (EEG) while participants performed an attention task. Participants occasionally answered thought-sampling questions about the nature of their thoughts throughout the task. Thought sampling is the standard method in mind-wandering research: Participants are randomly interrupted as they perform a laboratory task and answer questions about their immediately preceding thoughts (9, 10). In line with previous studies, we ask the standard question about whether participants’ thoughts were task-unrelated (see ref. 8 for a review). In addition, we asked whether subjects’ trains of thought were freely moving, deliberately constrained, and automatically constrained.We used electroencephalography because this method has the temporal resolution necessary to capture the transient changes in neural activity corresponding to our trains of thoughts, including stimulus-evoked, task-dependent activity and stimulus-independent, intrinsic activity. We first examined event-related potentials (ERPs), which index the electrophysiological response evoked by task-relevant stimuli. Previous research suggests that task-unrelated thought attenuates the magnitude of ERP components associated with sensory (18–20) and cognitive (21–24) processing of task-relevant stimuli. ERPs therefore provide an electrophysiological signature of when a participant has disengaged from task-relevant stimuli. We predicted that task-unrelated thoughts would be associated with a reduced P3 ERP component.To index stimulus-independent, intrinsic neural activity, we examined spectral power in the alpha band (8 to 14 Hz) during a time window after the offset of ERPs, which is unlikely to be impacted by stimulus-evoked responses. This segregation of the poststimulus time window allowed us to disentangle stimulus-evoked, task-dependent responses captured by ERP components in the earlier window and stimulus-independent activity likely associated with the subject’s ongoing thoughts as captured by alpha power in the later time window (as illustrated in Fig. 1). Alpha-power increases recorded over posterior sites have been associated with internal attention (23, 25) as well as spontaneous brain activity recorded at rest that is not elicited by external stimuli (26, 27). In contrast, frontal alpha has been linked to creative, divergent thinking (28, 29). Accordingly, we hypothesized that task-unrelated thoughts would be associated with enhanced posterior alpha power, whereas freely moving thoughts would be associated with increased frontal alpha power. Given that our dynamic thought-sampling questions address variability within the train of thought over time, we examined the neural correlates of these thought dynamics by capturing momentary changes in alpha power (i.e., alpha-power variability) over the same ERP-free time window. We predicted that freely moving thought would be associated with increased alpha-power variability, whereas constrained thought would show reduced alpha-power variability.Open in a separate windowFig. 1.EEG measures across the poststimulus time window. We examined three EEG measures. Stimulus-evoked activity as captured by P3 ERP components was examined during the 0- to 0.6-s poststimulus time window. Alpha power and variability index intrinsic neural activity not impacted by an external stimulus examined after the offset of P3s during the 0.6- to 1.8-s poststimulus time window.     

Estimation of absolute left ventricular volume from gated radionuclide ventriculograms. A method using phase image assisted automated edge detection and two-dimensional echocardiography

Twenty-four patients underwent gated cardiac blood pool (GBP) imaging, two-dimensional echocardiography (2-D echo), and single-plane contrast ventriculography (within 24 hours). Variable left ventricular (LV) regions of interest on GBP images were identified by an automated threshold radial search. To avoid excluding LV counts we indexed the search threshold to the threshold identified by a phase image generated by Fourier analysis. LV depth calculated by 2-D echo was used for attenuation correction of LV counts. LV end-diastolic volume (EDV) and end-systolic volume (ESV) were calculated by dividing attenuation, background and deadtime corrected LV count rates by the background corrected count rate/ml of venous blood drawn during the study. Correlations between radionuclide and contrast volumes were good (EDV + ESV r = 0.97, EDV r = 0.94, ESV r = 0.95). Regression lines were close to the lines of identity. This method, in which GBP imaging and automated LV edge finding are complemented by 2-D echo for count attenuation correction, demonstrated reliable and reproducible noninvasive estimates of absolute LV volume.     

Sequence dependence of hydrogen exchange kinetics in DNA duplexes at the individual base pair level in solution.

The kinetics for hydrogen exchange at individual base pairs in self-complementary deoxydodecanucleotide duplexes have been estimated from NMR saturation recovery measurements on the resolved imino protons as a function of temperature. The imino protons of dA . dT base pairs in the center of the fully alternating d(C-G-C-G-T-A-T-A-C-G-C-G) duplex exchange a factor of 2- to 3-fold faster than the corresponding protons at the same positions in the partially alternating d(C-G-C-G-A-A-T-T-C-G-C-G) duplex. These exchange parameters are a direct measure of the rate constants for transient opening of individual dA . dT base pairs in the dodecanucleotide duplexes and demonstrate faster opening kinetics for the "TATA" box region compared to the related "AATT" segment.     

"Stem cell" origin of the hematopoietic defect in dyskeratosis congenita

We have used the long-term bone marrow culture (LTBMC) system to analyze hematopoiesis in three patients with dyskeratosis congenita (DC), two of whom had aplastic anemia, and the third had a normal blood count (apart from mild macrocytosis) and normal BM cellularity. Hematopoiesis was severely defective in all three patients, as measured by a low incidence of colony-forming cells and a low level of hematopoiesis in LTBMC. The function of the marrow stroma was normal in its ability to support the growth of hematopoietic progenitors from normal marrows seeded onto them in all three cases, but the generation of hematopoietic progenitors from patients marrow cells inoculated onto normal stromas was reduced, thus suggesting the defect to be of stem cell origin. The parents and unaffected brother of one of the families have also been studied in LTBMC and all showed normal hematopoietic and stromal cell function. From this study we speculate that there are some similarities between DC and the defect in the W/Wv mouse.     

The Blue Cross Blue Shield of Michigan Cardiovascular Consortium (BMC2) collaborative quality improvement initiative in percutaneous coronary interventions

The past decade has been characterized by increased scrutiny of outcomes of surgical and percutaneous coronary interventions (PCIs). This increased scrutiny has led to the development of regional, state, and national databases for outcome assessment and for public reporting. This report describes the initial development of a regional, collaborative, cardiovascular consortium and the progress made so far by this collaborative group. In 1997, a group of hospitals in the state Michigan agreed to create a regional collaborative consortium for the development of a quality improvement program in interventional cardiology. The project included the creation of a comprehensive database of PCIs to be used for risk assessment, feedback on absolute and risk-adjusted outcomes, and sharing of information. To date, information from nearly 20,000 PCIs have been collected. A risk prediction tool for death in the hospital and additional risk prediction tools for other outcomes have been developed from the data collected, and are currently used by the participating centers for risk assessment and for quality improvement. As the project enters into year 5, the participating centers are deeply engaged in the quality improvement phase, and expansion to a total of 17 hospitals with active PCI programs is in process. In conclusion, the Blue Cross Blue Shield of Michigan Cardiovascular Consortium is an example of a regional collaborative effort to assess and improve quality of care and outcomes that overcome the barriers of traditional market and academic competition.     

Effect of Lowering the Dialysate Temperature in Chronic Hemodialysis: A Systematic Review and Meta-Analysis

Background and objectives

Lowering the dialysate temperature may improve outcomes for patients undergoing chronic hemodialysis. We reviewed the reported benefits and harms of lower temperature dialysis.

Design, setting, participants, & measurements

We searched the Cochrane Central Register, OVID MEDLINE, EMBASE, and Pubmed until April 15, 2015. We reviewed the reference lists of relevant reviews, registered trials, and relevant conference proceedings. We included all randomized, controlled trials that evaluated the effect of reduced temperature dialysis versus standard temperature dialysis in adult patients receiving chronic hemodialysis. We followed the Grading of Recommendations Assessment, Development and Evaluation approach to assess confidence in the estimates of effect (i.e., the quality of evidence). We conducted meta-analyses using random effects models.

Results

Twenty-six trials were included, consisting of a total of 484 patients. Compared with standard temperature dialysis, reduced temperature dialysis significantly reduced the rate of intradialytic hypotension by 70% (95% confidence interval, 49% to 89%) and significantly increased intradialytic mean arterial pressure by 12 mmHg (95% confidence interval, 8 to 16 mmHg). Symptoms of discomfort occurred 2.95 (95% confidence interval, 0.88 to 9.82) times more often with reduced temperature compared with standard temperature dialysis. The effect on dialysis adequacy was not significantly different, with a Kt/V mean difference of −0.05 (95% confidence interval, −0.09 to 0.01). Small sample sizes, loss to follow-up, and a lack of appropriate blinding in some trials reduced confidence in the estimates of effect. None of the trials reported long-term outcomes.

Conclusions

In patients receiving chronic hemodialysis, reduced temperature dialysis may reduce the rate of intradialytic hypotension and increase intradialytic mean arterial pressure. High–quality, large, multicenter, randomized trials are needed to determine whether reduced temperature dialysis affects patient mortality and major adverse cardiovascular events.