Search

Over recent years, a number of enhanced recovery programs have appeared in first, adult colorectal surgery, and subsequently many other adult surgical specialties. Increasing interest in this approach to perioperative management in children culminated in the recent development of the first enhanced recovery pathway for pediatric intestinal surgery, endorsed by Enhanced Recovery after Surgery Society (ERAS®). In parallel, there has been increasing interest in the refinement of perioperative management of selected pediatric cardiac surgical patients, invariably referred to as "fast track" management. Initiatives have largely focused on duration of postoperative ventilation rather than on a much wider range of perioperative interventions to optimize recovery and ensure timely discharge after surgery. In our institution, a "Level 1" pediatric cardiac surgical center, we assembled a multidisciplinary team to design a comprehensive enhanced recovery pathway, based on ERAS® methodology, for selected cardiac surgical patients. After a lengthy period of planning, staff education, and preparation, we implemented the pathway at the end of November 2019.We conducted a prospective audit of the perioperative management and outcomes of the first 88 patients managed according to this enhanced recovery pathway over a 25-month period in our institution.The mean age of the patients was 5.8 years (range 0.5-17.9), and the mean weight was 22.4 kg (range 6.6-57.2). Sixty-eight of the 88 patients were cardiopulmonary bypass cases. A total of 54% of patients received all four defined intraoperative anesthetic interventions (intravenous paracetamol, non-steroidal anti-inflammatory drug, antiemetic if aged more than 4 years, and use of a local anesthetic technique). A total of 89% of patients met the target extubation time of 6 h after administration of protamine. Median postoperative intensive care unit length of stay was 23.5 h (range 15.2-89.5). When compared to a historic control group, this represented a 22% reduction in median intensive care unit stay, although the total hospital length of stay remained unchanged. A total of 83% of patients met the target hospital discharge target of the fifth postoperative day.These preliminary results suggest that enhanced recovery pathway implementation for selected pediatric cardiac surgical patients is feasible, with acceptable outcomes. They suggest areas for further development and the potential for wider implementation.

Aims:\ud The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials.\ud \ud Methods and Results:\ud Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure

Background Mexican children are characterized by a high-starch intake diet and high prevalence of obesity. Objectives To investigate the association of AMY1A/AMY2A copy numbers (CNs) and AMY1/AMY2 serum enzymatic activity with childhood obesity in up to 427 and 337 Mexican cases and controls. Methods Anthropometric and dietary starch intake data were collected. CN of AMY1A/AMY2A and AMY1/AMY2 serum enzymatic activity were determined using droplet digital PCR (ddPCR) and enzymatic colorimetry, respectively. An individual participant level data meta-analysis of association between AMY1A CNVs and obesity was also performed. Results A positive association between AMY1A/AMY2A CNs and their corresponding AMY1/AMY2 serum enzyme activity was observed in children with normal weight and obesity. The serum enzyme activity of AMY1 and AMY2 was negatively associated with childhood obesity risk, and the association was restricted to kids eating medium/high amount of starch (Pinteraction = .004). While no association between AMY1A and AMY2A CNs and childhood obesity was observed in our sample, we confirmed a significant association between AMY1A CN and obesity in a meta-analysis of 3100 Mexican children. Conclusions Our data suggest that genetically determined salivary and pancreatic amylase activity can increase/decrease the risk of obesity in Mexican children, this effect being blunted by a low-starch diet.

Osteopontin (OPN), a senescence‐associated secretory phenotype factor, is increased in patients with nonalcoholic fatty liver disease (NAFLD). Cellular senescence has been associated with age‐dependent hepatosteatosis. Thus, we investigated the role of OPN in the age‐related hepatosteatosis. For this, human serum samples, animal models of aging, and cell lines in which senescence was induced were used. Metabolic fluxes, lipid, and protein concentration were determined. Among individuals with a normal liver, we observed a positive correlation between serum OPN levels and increasing age. This correlation with age, however, was absent in patients with NAFLD. In wild‐type (WT) mice, serum and liver OPN were increased at 10 months old (m) along with liver p53 levels and remained elevated at 20m. Markers of liver senescence increased in association with synthesis and concentration of triglycerides (TG) in 10m OPN‐deficient (KO) hepatocytes when compared to WT hepatocytes. These changes in senescence and lipid metabolism in 10m OPN‐KO mice liver were associated with the decrease of 78 kDa glucose‐regulated protein (GRP78), induction of ER stress, and the increase in fatty acid synthase and CD36 levels. OPN deficiency in senescent cells also diminished GRP78, the accumulation of intracellular TG, and the increase in CD36 levels. In 20m mice, OPN loss led to increased liver fibrosis. Finally, we showed that OPN expression in vitro and in vivo was regulated by p53. In conclusion, OPN deficiency leads to earlier cellular senescence, ER stress, and TG accumulation during aging. The p53‐OPN axis is required to inhibit the onset of age‐related hepatosteatosis., OPN is a protective factor required to preserve liver health during aging. As OPN‐deficient mice become older, increased levels of senescence, ER stress, hepatosteatosis, DNA damage, fibrosis, and inflammation appear.

Objectives To report the initial clinical experience with a novel atrial septal defect (ASD) closure device, the GORE® CARDIOFORM ASD Occluder (GCO). Background Transcatheter closure has become the treatment of choice for secundum ASD. A wide range of occluder devices are available, but concern has been raised about the risk of cardiac erosion associated with rigid devices and future access to the left atrium Methods Retrospective chart review of patients treated with the GCO at three Canadian centers. Primary outcomes were procedural success and residual shunting at follow-up, as well as 30-day major adverse events. Secondary outcomes included new onset atrial arrhythmias, wire frame fractures (WFF), and all cause mortality. Clinical, echocardiographic, procedural data, and follow-up outcome variables were collected in each participating hospital. Results Between February and December 2015, 26 patients (5 children and 21 adults) underwent transcatheter ASD closure with the GCO and were included in the study cohort. Procedural success was achieved in 22 of 26 patients (85%) and no major procedural complications were observed. Two patients (8%) presented new onset atrial tachyarrhythmia during early follow-up (0–30 days). Follow-up echocardiography (median of 119 days [IQR: 92–146]) demonstrated no residual shunt in all implanted patients. After a median clinical follow-up of 174 days (IQR: 135–239), one patient died of an unrelated cause, there were no documented major adverse cardiovascular events. Fluoroscopic imaging of the device was performed in 20 patients (91%), and WFF was noted in five cases. No clinical consequence or device dysfunction was observed in these patients. Conclusions In this first-in-man multicenter study, the GCO was safe and effective for ASD closure, with no major adverse events or residual shunt at follow-up. © 2017 Wiley Periodicals, Inc.

Elevated stratopauses are typically associated with prolonged disturbed conditions in the northern hemisphere polar winter. MIPAS and MLS observed a short-lived and highly zonally asymmetric strato...

Background and Objective Transcranial laser stimulation of the brain with near‐infrared light is a novel form of non‐invasive photobiomodulation or low‐level laser therapy (LLLT) that has shown therapeutic potential in a variety of neurological and psychological conditions. Understanding of its neurophysiological effects is essential for mechanistic study and treatment evaluation. This study investigated how transcranial laser stimulation influences cerebral hemodynamics and oxygenation in the human brain in vivo using functional near‐infrared spectroscopy (fNIRS). Materials and Methods Two separate experiments were conducted in which 1,064‐nm laser stimulation was administered at (1) the center and (2) the right side of the forehead, respectively. The laser emitted at a power of 3.4 W and in an area of 13.6 cm2, corresponding to 0.25 W/cm2 irradiance. Stimulation duration was 10 minutes. Nine healthy male and female human participants of any ethnic background, in an age range of 18–40 years old were included in each experiment. Results In both experiments, transcranial laser stimulation induced an increase of oxygenated hemoglobin concentration (Δ[HbO2]) and a decrease of deoxygenated hemoglobin concentration (Δ[Hb]) in both cerebral hemispheres. Improvements in cerebral oxygenation were indicated by a significant increase of differential hemoglobin concentration (Δ[HbD] = Δ[HbO2] − Δ[Hb]). These effects increased in a dose‐dependent manner over time during laser stimulation (10 minutes) and persisted after laser stimulation (6 minutes). The total hemoglobin concentration (Δ[HbT] = Δ[HbO2] + Δ[Hb]) remained nearly unchanged in most cases. Conclusion Near‐infrared laser stimulation applied to the forehead can transcranially improve cerebral oxygenation in healthy humans. Lasers Surg. Med. 48:343–349, 2016. © 2016 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.

Transcranial infrared laser stimulation is a new non-invasive form of low-level light therapy that may have a wide range of neuropsychological applications. It entails using low-power and high-energy-density infrared light from lasers to increase metabolic energy. Preclinical work showed that this intervention can increase cortical metabolic energy, thereby improving frontal cortex-based memory function in rats. Barrett and Gonzalez-Lima (2013, Neuroscience, 230, 13) discovered that transcranial laser stimulation can enhance sustained attention and short-term memory in humans. We extend this line of work to executive function. Specifically, we ask whether transcranial laser stimulation enhances performance in the Wisconsin Card Sorting Task that is considered the gold standard of executive function and is compromised in normal ageing and a number of neuropsychological disorders. We used a laser of a specific wavelength (1,064 nm) that photostimulates cytochrome oxidase - the enzyme catalysing oxygen consumption for metabolic energy production. Increased cytochrome oxidase activity is considered the primary mechanism of action of this intervention. Participants who received laser treatment made fewer errors and showed improved set-shifting ability relative to placebo controls. These results suggest that transcranial laser stimulation improves executive function and may have exciting potential for treating or preventing deficits resulting from neuropsychological disorders or normal ageing.

RationaleFibrotic interstitial lung disease (ILD) is among the top indications for patients undergoing lung transplantation worldwide. While our group and others have demonstrated a role for monocy...

Behavioral function lost in mammals (including humans) after peripheral nerve severance is slowly (weeks to years) and often poorly restored by 1-2-mm/day, nonspecifically directed outgrowths from proximal axonal stumps. To survive, proximal stumps must quickly repair (seal) plasmalemmal damage. We report that, after complete cut- or crush-severance of rat sciatic nerves, morphological continuity, action potential conduction, and behavioral functions can be consistently (>98% of trials), rapidly (minutes to days), dramatically (70-85% recovery), and chronically restored and some Wallerian degeneration prevented. We assess axoplasmic and axolemmal continuity by intra-axonal dye diffusion and action potential conduction across the lesion site and amount of behavioral recovery by Sciatic Functional Index and Foot Fault tests. We apply well-specified sequences of solutions containing FDA-approved chemicals. First, severed axonal ends are opened and resealing is prevented by hypotonic Ca²⁺-free saline containing antioxidants (especially methylene blue) that inhibit plasmalemmal sealing in sciatic nerves in vivo, ex vivo, and in rat B104 hippocampal cells in vitro. Second, a hypotonic solution of polyethylene glycol (PEG) is applied to open closely apposed (by microsutures, if cut) axonal ends to induce their membranes to flow rapidly into each other (PEG-fusion), consistent with data showing that PEG rapidly seals (PEG-seals) transected neurites of B104 cells, independently of any known endogenous sealing mechanism. Third, Ca²⁺-containing isotonic saline is applied to induce sealing of any remaining plasmalemmal holes by Ca²⁺-induced accumulation and fusion of vesicles. These and other data suggest that PEG-sealing is neuroprotective, and our PEG-fusion protocols that repair cut- and crush-severed rat nerves might rapidly translate to clinical procedures.

Purpose:- Disparity sensitivity may be explained by interocular positional differences of the receptive fields (RF) of visual cortical cells or by interocular shifts of the On and Off RF subregions. Since this latter model assumes shifts are orthogonal to the orientation of the RF, cells with disparity sensitivity should be oriented. The objective of the present study is to test this assumption.Methods:- Single unit recordings were performed in areas V1 and V2 of two Macaca mulatta. For assessing disparity sensitivity, we generated dynamic random dot stereograms. A stereofigure was flashed over the cell RF with different horizontal disparities. To assess orientation sensitivity we used a flashing bar with eight orientations, in several positions over the cell RF in a pseudorandom manner.Results:- We found no relationship between sensitivity to horizontal disparity and orientation preference in V1 and V2 cells.Conclusions:- Our data indicate that horizontal disparity sensitivity and orientation preference are unrelated properties. This favors the notion that sensitivity to horizontal disparity is mostly based on RF interocular horizontal positional differences. © 2010 The Authors. Ophthalmic and Physiological Optics © 2010 The College of Optometrists.

Transgenic mouse models of Alzheimer's disease (AD) show some characteristic features of the disease, and we aim to further bridge the gap between studies of humans with AD, those at risk, and these murine models by providing shared markers of disease which could be used to track progression and assess future interventions. Brain imaging measurements may prove useful in this regard. We previously found that the homozygous PDAPP mouse model of AD showed significant declines in glucose uptake with age in posterior cingulate cortex (PCC), an area homologous to the human posterior cingulate, which shows significant declines in AD and in those at risk for AD. To further evaluate this potential biomarker and its correlation across age, we used fluorodeoxyglucose (FDG) autoradiography at two ages (2 and 12 months) in wildtype, heterozygous, and homozygous PDAPP mice. We found significant posterior cingulate fluorodeoxyglucose uptake declines again in homozygous PDAPP mice, but at both ages assessed. There was a strong effect of gene dose; homozygous mice showed larger and earlier effects. These results, in conjunction with our previous analyses, indicate a nonlinear progression stemming from synergistic effects of the overexpressed mutant gene, both developmental and pathological. The posterior cingulate is preferentially vulnerable to both effects of transgene in the PDAPP mouse, and both are independent of amyloid deposition.

We are able to judge the direction of movement and orientation of objects because they have contrast-defined edges. However, we are also able to perceive the orientation and direction of movement of stereobars made of random dot stereograms in the absence of contrast-defined edges. We recorded 207 disparity-sensitive cells from visual areas V1 and V2 of two Macaca mulatta monkeys while performing an attentive fixation task. Luminance defined bars and random-dot stereo-defined bars were used to assess direction and orientation selectivity of these cells. Orientation and direction preference for luminance bars and for stereobars showed a statistically significant relationship (r=0.83, P

The associative inhibitory control of behaviour is a major component of Pavlovian learning theory, but little is known about its functional neuroanatomy. The associative effects of differential inhibition of conditioned behaviour were investigated by mapping learning-related changes in brain activity of the rat with fluorodeoxyglucose autoradiography. Of interest was how a tone is processed in auditory and extra-auditory systems of the rat brain under similar behavioural, but different associative conditions. Conditioned emotional suppression to drink was used to assess training, and summation tests were used to verify that the tone became an inhibitor of conditioned behaviour. In the Inhibitor group, presentations of a tone stimulus alone were intermixed with presentations of a light stimulus followed by footshock. In the Pseudorandom group, the same numbers of tone, light and footshock presentations were used, but they were presented in a pseudorandom fashion. After training, fluorodeoxyglucose uptake was measured during tone presentations. Behavioural responding to the tone was similar during fluorodeoxyglucose uptake in the two groups, yet associative effects were found in brain activity. In the auditory system, the tone produced reduced fluorodeoxyglucose uptake in major relay nuclei (cochlear nucleus and inferior colliculus) in the Inhibitor group relative to the Pseudorandom group. The tone inhibitor produced similar decreases in the septohippocampal system and the retrosplenial cortex. In contrast, the tone inhibitor produced activity increases in somatosensory and reticulocerebellar systems. The findings provide the first detailed map of neural regions involved in the learned associations controlling differential inhibition of conditioned behaviour.

Binocular disparities are crucial for building an accurate three-dimensional representation of the peripersonal environment in a viewer-centred frame of reference. Previous studies have shown that visual cells of the medial superior temporal cortex (MST) have large receptive fields and that they are sensitive to disparities present in large surfaces. By using a reverse cross-correlation technique in this study we tested 175 disparity-sensitive units recorded from MST in the awake Macaca mulatta monkey to determine if these large receptive fields are homogeneous in terms of disparity sensitivity. We found that the receptive fields of 50 cells (50 out of 175, 29%) showed subregions with specific disparity sensitivity. These subregions presented eccentricities from 0.8 to 22.3 degrees and their sizes varied from 1.6 to 15.3 degrees 2. This particular receptive field organization represents a suitable mechanism for encoding the location of small objects within our peripersonal space.

The CXCR3 chemokine receptor, expressed on activated T lymphocytes, is seen within the central nervous system (CNS) in inflammatory conditions where a T-cell response is prominent. However, the distribution of CXCR3 in parenchymal CNS cells is unknown. Using a monoclonal antibody against CXCR3 and post-mortem tissue of patients with and without CNS pathology, we have determined its expression pattern. CXCR3 was found in subpopulations of cells morphologically consistent with astrocytes, particularly reactive astrocytes, and in cerebellar Purkinje cells. It was also detected in arterial endothelial and smooth muscle cells, particularly in areas associated with atherosclerotic plaques. CXCR3-positive astrocytes were particularly prominent in the CNS of HIV-positive patients, in patients with Multiple Sclerosis (MS), in ischaemic infarcts and in astrocytic neoplasms. Immunofluorescence studies of mixed adult primary glial cultures and fetal glial cultures also showed expression of CXCR3 in astrocytes. CXCR3 mRNA was detected in Purkinje cells by in situ hybridization with a CXCR3-specific probe. Thus, the predominant expression of CXCR3 in reactive astrocytes may indicate that it plays a role in the development of reactive gliosis in a variety of infectious, inflammatory, vascular and neoplastic processes in the CNS. The relationship between CXCR3 expression in astrocytes to its expression in Purkinje cells, endothelial cells and smooth muscle cells is yet to be determined.

Greater persistence in extinction is observed following inconsistent reward compared to that observed following consistent reward, an effect termed the partial reinforcement extinction effect (PREE). We report three experiments in which the extinction rates of random partially reinforced (PRF) or continuously reinforced (CRF) infant rat pups were compared to the extinction rate of pups trained with an alternative and regular schedule of partial reinforcement, known as patterned single alternation (PSA). In PSA, subjects learn to alternate speed of responding in anticipation of the regular alternation of reward and nonreward trials in the straight alley runway. In Experiment 1, 17-day-old PSA subjects showed CRF-like extinction rates; whereas in Experiment 2, in which extinction was initiated early in training prior to the onset of the PSA discrimination, PSA subjects showed prolonged, PRF-like extinction curves. In contrast, 12-day-old pups in Experiment 3 showed no reward-schedule-related differences in extinction, despite differences in behavior during acquisition. These results prompt a modification of Amsel's (1962) model of discrimination learning, and suggest the existence of a dissociation between different types of reward-related expectancies in the younger subjects.

Purpose The study was carried out to describe the indocyanine green angiographic findings in isolated primary retinal arterial macroaneurysms and their contribution to the diagnosis of this condition. Methods Fluorescein and indocyanine green angiography examination techniques were used to study isolated primary retinal arterial macroaneurysms in 8 consecutive patients with retinal or preretinal haemorrhage over a period of 12 months. Results The fluorescein angiography examination showed the macroaneurysm in four cases; pulsatility was not observed in any case. Indocyanine green angiography disclosed the macroaneurysm in six cases; pulsatility was observed in two cases. Conclusion Indocyanine green angiography allows better visualization of arterial macroaneurisms in the first examination and therefore facilitates the diagnosis, follow-up and laser treatment of this vascular abnormality.

The microalga Phaeodactylum tricornutum was grown in a concentric tube airlift photobioreactor. A maximum specific growth rate of 0. 023 h-1 was obtained using a superficial gas velocity around 0.055 m/s. Lower or higher gas flow rates limited the culture performance. To establish if the observed limitation was due to CO2 or to the photosynthetically active irradiance, characteristic times for mixing, mass transfer and CO2 consumption, and the photon flux absorbed by the culture were analyzed. The CO2-gradients in the culture were shown to be responsible for the limitation during the exponential growth phase, and both CO2 and light irradiance were limiting in the linear growth phase. The decrease in specific growth rate relative to the maximum was found to be related to the specific gas-liquid interfacial area, the length scale of the microeddies and the shear rate. Copyright 1998 John Wiley & Sons, Inc.

The effects of excitatory classical conditioning on cytochrome oxidase activity in the central auditory system were investigated using quantitative histochemistry. Rats in the conditioned group were trained with consistent pairings of a compound conditional stimulus (a tone and a light) with a mild footshock, to elicit conditioned suppression of drinking. Rats in the pseudorandom group were exposed to pseudorandom presentations of the same tone, light and shock stimuli without consistent pairings. Untrained rats in a naive group did not receive presentations of the experimental stimuli. The findings demonstrated that auditory fear conditioning modifies the metabolic neuronal responses of the auditory system, supporting the hypothesis that sensory neurons are responsive to behavioural stimulus properties acquired by learning. There was a clear distinction between thalamocortical and lower divisions of the auditory system based on the differences in metabolic activity evoked by classical conditioning, which lead to an overt learned behavioural response versus pseudorandom stimulus presentations, which lead to behavioural habituation. Increases in cytochrome oxidase activity indicated that tone processing is enhanced during associative conditioning at upper auditory structures (medial geniculate nucleus and secondary auditory cortices). In contrast, metabolic activation of lower auditory structures (cochlear nuclei and inferior colliculus) in response to the pseudorandom presentation of the experimental stimuli suggest that these areas may be activated during habituation to tone stimuli. Together these findings show that mapping the metabolic activity of cytochrome oxidase with quantitative histochemistry can be successfully used to map regional long-lasting effects of learning on brain systems.

The extent to which variation within and between the sexes can be assigned to genes vs. environment is problematic, because, in most vertebrates, males and females differ genetically. However, factors other than sex chromosomes and the consequent sex-typical gonadal hormone secretions may play important roles in the differentiation of the neural mechanisms underlying individual and sex differences in aggressive and sexual behavior. The leopard gecko, like many oviparous reptiles, lacks sex chromosomes. Instead, gonadal sex is determined by temperature during embryogenesis, with low and high incubation temperatures producing females and intermediate temperatures producing mixed sex ratios. In essence, this allows for the study of individual and sex differences without the confounding variable of genetically determined gender. Experiments have shown that the temperature experienced during incubation plays a critical role in establishing the adult morphological, endocrinological, and behavioral phenotype. In this experiment, the independent effects of incubation temperature and gonadal sex on the morphology and metabolic capacity of specific brain nuclei were determined. Both individual and sex differences in the volume of the preoptic area and ventromedial nucleus of the hypothalamus are determined primarily by incubation temperature, not by gonadal sex. However, incubation temperature and gonadal sex are both important in determining the metabolic capacity in the anterior hypothalamus, external amygdala, dorsal lateral nucleus of the hypothalamus, dorsal lateral nucleus of the thalamus, dorsal ventricular ridge, habenula, lateral hypothalamus, nucleus rotundus, nucleus sphericus, periventricular nucleus of the hypothalamus, preoptic area, periventricular nucleus of the preoptic area, septum, striatum, torus semicircularis, and ventromedial nucleus of the hypothalamus. This is the first demonstration in a vertebrate that factors other than gonadal sex hormones, which arise from the individual’s genetic constitution, can affect the sexual differentiation of the brain. J. Comp. Neurol. 380:409‐421, 1997. r 1997 Wiley-Liss, Inc. Indexing terms: reptile; differentiation; steroid hormones; oxidative metabolism; sexual dimorphism

Magnetization transfer imaging (MT) and localized proton spectroscopy (1H-MRS) were utilized in the evaluation of lesions (high signal abnormalities on T2-weighted images) and normal-appearing white matter (NAWM) in multiple sclerosis (MS). Eleven patients with a clinical diagnosis of MS were independently evaluated with both 1H-MRS and MT. The magnetization transfer ratio (MTR) of lesions was compared with the relative concentration of N-acetyl-aspartate (NAA) and a composite peak at 2.1 to 2.6 ppm termed "marker peaks." The MTR of white matter lesions in the MS patients was markedly decreased (6-34%; normal approximately 42%), and correlated well with increase in the marker peaks region (0.94-3.89). There was no correlation between the relative concentration of NAA and MTR. Increased resonance peaks in the 2.1 to 2.6 ppm range and marked decreases in MTR may be a relatively specific indicators of demyelination.

Autoradiography with 14C-2-deoxyglucose was used to determine brain metabolic activity during the quiet period that follows after daily exploratory experiences in new complex environments. Eight 1-month-old, male Tryon rats were selected from two litters. Pairs of littermates matched by body weight were assigned to one of two conditions: rats housed individually in small home cages as the “impoverished condition,” or rats exposed twice daily to changing and complex environments of two large cages with inanimate objects and conspecifics as the “enriched condition.” After 4 days, rats were injected with 2-deoxyglucose, placed individually in a home cage and left undisturbed for 90 min until sacrificed. The brains of “enriched” rats were heavier than their “impoverished” littermates, and showed a global trend for metabolic enhancement. They also showed significantly greater amounts of 2-deoxyglucose in occipital cortex (27%), hippocampal subiculum (36%), and nucleus accumbens (40%).©1994 John Wiley & Sons, Inc.

If learning is an emergent property of interacting brain regions, understanding it requires a network analysis of the patterns of interaction between brain regions. Brain mapping techniques have the potential of providing information about functional interactions within entire neural systems, but computational methods are needed to make sense of the complex interactions that take place in the brain. This review paper illustrates, with examples from auditory learning studies, the application of a computational method that quantifies the interactions among neural regions in terms of networks, and what is gained from this approach. The method is Structural Equation Modeling, and it computes network interactions by combining anatomical circuitry with the covariation in the activity between auditory structures. Activity was assessed by fluorodeoxyglucose uptake, and the functional strengths of auditory pathways were quantified by computing path coefficients representing the strength of the functional influence through each anatomical path. Changes in these values were used as indices of how learned information was processed and modified within the auditory system. Structural models of the auditory system revealed the patterns of network interactions related to habituation to a sound, as well as the patterns related to the opposite learned associative properties of the same sound. They illustrated how the functional interactions among parallel auditory neural pathways were modified as a result of auditory learning. This analysis supports the hypothesis that auditory learning is an emergent network property, distributed among connected brain regions showing specific patterns of interaction. ©1994 Wiley-Liss, Inc.

The effect of the 5 calmodulin (CaM) antagonists trifluoperazine (TFP). compound 48/80, N-(6-aminohexyl)-naphthalenesulfonamtde (W-5), N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), and calmidazolium on auxin-dependent medium acidification was investigated in abraded segments of Avena sativa L. cv. Victory I. Buffering capacity, Asn content, and changes in pH of bathing solutions were measured in the presence of these inhibitors. When coleoptiles were treated with TFP or compound 48/80, the Asn content and the buffering capacity increased, thus suggesting that plasma membrane permeability was modified. On the contrary. the effect of calmidazolium, W-5. and W-7 on Asn release and buffering capacity was rather low; only small effects being observable at the highest concentration employed. Calmidazolium and W-7 strongly inhibited auxin-dependent medium acidification. W-5 did not affect medium acidification. The specificity of these CaM antagonists and their effects on medium acidification are discussed. The data adduced is consistent with the working hypothesis which postulates an essential role for the Ca2+-CaM system on auxin-dependent medium acidification.

Due to the separation of the eyes, temporal retinal disparities are created during binocular stimulation and they have been proposed to be the basis of several stereo-visual effects. This paper studies the sensitivity of cortical neurons from area V1 to interocular temporal delay in the awake monkey (Macaca mulatta). Forty-four cells were included in this study. Temporal delay sensitivity was observed in 59% of them. About half of these temporal-delay-sensitive cells were also sensitive to the stimulation sequence of the eyes. The cells that preferred one eye to be stimulated first were termed asymmetrical (46%); those which were not sensitive to the eye sequence of stimulation were termed symmetrical (54%). No clear differences were observed in the distribution of delay-sensitive cells according to their eye dominance. Fifty-six percent of balanced cells and 65% of unbalanced cells were sensitive to interocular delay. These data underline the importance of temporal cues for depth perception.

Suzuki cross-coupling reactions of an unprecedented array of unactivated primary and secondary alkyl halides (including challenging alkyl chlorides) can be accomplished through the use of nickel/amino alcohol-based catalysts. Both the nickel precatalyst and the amino alcohols (prolinol or trans-2-aminocyclohexanol) are commercially available and air-stable. In view of the remarkable diversity of amino alcohols that are readily accessible, this discovery may open the door to the rapid development of versatile catalysts for a wide range of cross-coupling processes.

Summary: We instituted two thanatology seminars for medical students and residents which emphasized feelings more than objective data. The seminars began with students filling out a death certificate on themselves. Eighty-four per cent predicted that their own probable cause of death would be from an acute illness. Discussion and reflection on this experience helped them realize how difficult it would be to deal with a chronic illness. By answering a question about what they were most grateful for, they became aware that they valued family and friends most highly. We believe that this experience legitimized feelings which form the basis of empathy.

We describe a multiplexed TFT array for the temperature controlled thermal cycling required for DNA amplification. LTPS is an ideal technology to enable the accurate and uniform temperature profiles required for assays used in a range of medical conditions as it enables high parallelism at low cost for rapid diagnosis. We will present the application background, the design, fabrication and testing of our LTPS thermal cycler.

Granulex is an aerosolized spray (Dow B. Hickman Pharmaceuticals, Sugar Land, TX 77487) that contains trypsin, Peru balsam, and castor oil. It has been available for many years as a topical spray for the treatment of decubitus ulcers. We used Granulex to promote tissue healing of a necrotic ulcer of the oral mucosa in a patient with advanced oropharyngeal squamous cell carcinoma.