Esophageal contractions, bolus transit and perception of transit after swallows of liquid and solid boluses in normal subjects

CONTEXT: Esophageal dysphagia is the sensation that the ingested material has a slow transit or blockage in its normal passage to the stomach. It is not always associated with motility or transit alterations. OBJECTIVES: To evaluate in normal volunteers the possibility of perception of bolus transit through the esophagus after swallows of liquid and solid boluses, the differences in esophageal contraction and transit with these boluses, and the association of transit perception with alteration of esophageal contraction and/or transit. METHODS: The investigation included 11 asymptomatic volunteers, 4 men and 7 women aged 19-58 years. The subjects were evaluated in the sitting position. They performed swallows of the same volume of liquid (isotonic drink) and solid (macaroni) boluses in a random order and in duplicate. After each swallow they were asked about the sensation of bolus passage through the esophagus. Contractions and transit were evaluated simultaneously by solid state manometry and impedance. RESULTS: Perception of bolus transit occurred only with the solid bolus. The amplitude and area under the curve of contractions were higher with swallows of the solid bolus than with swallows of the liquid bolus. The difference was more evident in swallows with no perception of transit (n = 12) than in swallows with perception (n = 10). The total bolus transit time was longer for the solid bolus than for the liquid bolus only with swallows followed by no perception of transit. CONCLUSION: The results suggest that the perception of esophageal transit may be the consequence of inadequate adaptation of esophageal transit and contraction to the characteristics of the swallowed bolus.

BDNF gene polymorphism, cognition and symptom severity in a Brazilian population-based sample of first-episode psychosis subjects

OBJECTIVE: To investigate the influence of brain-derived neurotrophic factor (BDNF) gene variations on cognitive performance and clinical symptomatology in first-episode psychosis (FEP). METHODS: We performed BDNF val66met variant genotyping, cognitive testing (verbal fluency and digit spans) and assessments of symptom severity (as assessed with the PANSS) in a population-based sample of FEP patients (77 with schizophreniform psychosis and 53 with affective psychoses) and 191 neighboring healthy controls. RESULTS: There was no difference in the proportion of Met allele carriers between FEP patients and controls, and no significant influence of BDNF genotype on cognitive test scores in either of the psychosis groups. A decreased severity of negative symptoms was found in FEP subjects that carried a Met allele, and this finding reached significance for the subgroup with affective psychoses (p < 0.01, ANOVA). CONCLUSIONS: These results suggest that, in FEP, the BDNF gene Val66Met polymorphism does not exert a pervasive influence on cognitive functioning but may modulate the severity of negative symptoms.

Hearing in the mind's ear: A PET investigation of musical imagery and perception

Neuropsychological studies have suggested that imagery processes may be mediated by neuronal mechanisms similar to those used in perception. To test this hypothesis, and to explore the neural basis for song imagery, 12 normal subjects were scanned using the water bolus method to measure cerebral blood flow (CBF) during the performance of three tasks. In the control condition subjects saw pairs of words on each trial and judged which word was longer. In the perceptual condition subjects also viewed pairs of words, this time drawn from a familiar song; simultaneously they heard the corresponding song, and their task was to judge the change in pitch of the two cued words within the song. In the imagery condition, subjects performed precisely the same judgment as in the perceptual condition, but with no auditory input. Thus, to perform the imagery task correctly an internal auditory representation must be accessed. Paired-image subtraction of the resulting pattern of CBF, together with matched MRI for anatomical localization, revealed that both perceptual and imagery. tasks produced similar patterns of CBF changes, as compared to the control condition, in keeping with the hypothesis. More specifically, both perceiving and imagining songs are associated with bilateral neuronal activity in the secondary auditory cortices, suggesting that processes within these regions underlie the phenomenological impression of imagined sounds. Other CBF foci elicited in both tasks include areas in the left and right frontal lobes and in the left parietal lobe, as well as the supplementary motor area. This latter region implicates covert vocalization as one component of musical imagery. Direct comparison of imagery and perceptual tasks revealed CBF increases in the inferior frontal polar cortex and right thalamus. We speculate that this network of regions may be specifically associated with retrieval and/or generation of auditory information from memory.

Practice and perception--a nationwide survey of therapy habits in sepsis

OBJECTIVE: To simultaneously determine perceived vs. practiced adherence to recommended interventions for the treatment of severe sepsis or septic shock. DESIGN: One-day cross-sectional survey. SETTING: Representative sample of German intensive care units stratified by hospital size. PATIENTS: Adult patients with severe sepsis or septic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Practice recommendations were selected by German Sepsis Competence Network (SepNet) investigators. External intensivists visited intensive care units randomly chosen and asked the responsible intensive care unit director how often these recommendations were used. Responses "always" and "frequently" were combined to depict perceived adherence. Thereafter patient files were audited. Three hundred sixty-six patients on 214 intensive care units fulfilled the criteria and received full support. One hundred fifty-two patients had acute lung injury or acute respiratory distress syndrome. Low-tidal volume ventilation < or = 6 mL/kg/predicted body weight was documented in 2.6% of these patients. A total of 17.1% patients had tidal volume between 6 and 8 mL/kg predicted body weight and 80.3% > 8 mL/kg predicted body weight. Mean tidal volume was 10.0 +/- 2.4 mL/kg predicted body weight. Perceived adherence to low-tidal volume ventilation was 79.9%. Euglycemia (4.4-6.1 mmol/L) was documented in 6.2% of 355 patients. A total of 33.8% of patients had blood glucose levels < or = 8.3 mmol/L and 66.2% were hyperglycemic (blood glucose > 8.3 mmol/L). Among 207 patients receiving insulin therapy, 1.9% were euglycemic, 20.8% had blood glucose levels < or = 8.3 mmol/L, and 1.0% were hypoglycemic. Overall, mean maximal glucose level was 10.0 +/- 3.6 mmol/L. Perceived adherence to strict glycemic control was 65.9%. Although perceived adherence to recommendations was higher in academic and larger hospitals, actual practice was not significantly influenced by hospital size or university affiliation. CONCLUSIONS: This representative survey shows that current therapy of severe sepsis in German intensive care units complies poorly with practice recommendations. Intensive care unit directors perceive adherence to be higher than it actually is. Implementation strategies involving all intensive care unit staff are needed to overcome this gap between current evidence-based knowledge, practice, and perception.

Physician perceptions of risk regarding mood disorders and pharmacological management during pregnancy: What is current practice?

Mood disorders are the most common form of mental illness and one of the leading causes of morbidity worldwide. Major depressive disorder and bipolar disorder have a lifetime prevalence of 16.2% and 4.4%, respectively. Women comprise a substantial proportion of this population, and an estimated 500,000 pregnancies each year involve women with a psychiatric condition. Management with psychotropic medications is considered standard of care for most patients with mood disorders. However, many of these medications are known human teratogens. Because pregnant women with mood disorders face a high risk of relapse if unmanaged, the obstetrician faces a unique challenge in providing the best care to both mother and baby. It has been suggested that many obstetricians overestimate the teratogenic risks associated with psychotropic medications, while concurrently underestimating the risks associated with unmanaged mood disorders. This may be due a knowledge gap regarding the most current teratogen information, and lack of official management guidelines. Therefore, the purpose of this study is to determine the current knowledge base of obstetricians regarding the teratogenic effects of common psychotropic medications, as wells as to capture current management practices for pregnant women with mood disorders. A total of 117 Texas obstetricians responded to a survey regarding teratogen knowledge and management practice. It was common for respondents to encounter women who disclose both having a mood disorder and taking a psychotropic medication during pregnancy. Many respondents did not utilize up-to-date drug counseling resources, and were unaware of or over-estimated the teratogenic risks of common medications used to treat mood disorders. Finally, many respondents reported wanting to refer pregnant patients with mood disorders to psychiatrists for co-management, but are reportedly restricted in doing so due to accessibility or insurance issues. This study demonstrates that there is a knowledge gap among obstetricians regarding the teratogenicity of common psychotropic medications utilized to manage a patient population they frequently encounter. Further, obstetricians have vastly different risk perceptions of these medications, resulting in various management approaches and recommendations. Future research should focus on establishing standard practice guidelines, as well as better accessibility to psychiatric services for pregnant women.

Change Detection Memory in Rhesus Monkeys and Humans

Visual short-term memory (VSTM) is the storage of visual information over a brief time period (usually a few seconds or less). Over the past decade, the most popular task for studying VSTM in humans has been the change detection task. In this task, subjects must remember several visual items per trial in order to identify a change following a brief delay interval. Results from change detection tasks have shown that VSTM is limited; humans are only able to accurately hold a few visual items in mind over a brief delay. However, there has been much debate in regard to the structure or cause of these limitations. The two most popular conceptualizations of VSTM limitations in recent years have been the fixed-capacity model and the continuous-resource model. The fixed-capacity model proposes a discrete limit on the total number of visual items that can be stored in VSTM. The continuous-resource model proposes a continuous-resource that can be allocated among many visual items in VSTM, with noise in item memory increasing as the number of items to be remembered increases. While VSTM is far from being completely understood in humans, even less is known about VSTM in non-human animals, including the rhesus monkey (Macaca mulatta). Given that rhesus monkeys are the premier medical model for humans, it is important to understand their VSTM if they are to contribute to understanding human memory. The primary goals of this study were to train and test rhesus monkeys and humans in change detection in order to directly compare VSTM between the two species and explore the possibility that direct species comparison might shed light on the fixed-capacity vs. continuous-resource models of VSTM. The comparative results suggest qualitatively similar VSTM for the two species through converging evidence supporting the continuous-resource model and thereby establish rhesus monkeys as a good system for exploring neurophysiological correlates of VSTM.

Latrepirdine improves cognition and arrests progression of neuropathology in an Alzheimer's mouse model

Latrepirdine (Dimebon) is a pro-neurogenic, antihistaminic compound that has yielded mixed results in clinical trials of mild to moderate Alzheimer's disease, with a dramatically positive outcome in a Russian clinical trial that was unconfirmed in a replication trial in the United States. We sought to determine whether latrepirdine (LAT)-stimulated amyloid precursor protein (APP) catabolism is at least partially attributable to regulation of macroautophagy, a highly conserved protein catabolism pathway that is known to be impaired in brains of patients with Alzheimer's disease (AD). We utilized several mammalian cellular models to determine whether LAT regulates mammalian target of rapamycin (mTOR) and Atg5-dependent autophagy. Male TgCRND8 mice were chronically administered LAT prior to behavior analysis in the cued and contextual fear conditioning paradigm, as well as immunohistological and biochemical analysis of AD-related neuropathology. Treatment of cultured mammalian cells with LAT led to enhanced mTOR- and Atg5-dependent autophagy. Latrepirdine treatment of TgCRND8 transgenic mice was associated with improved learning behavior and with a reduction in accumulation of Aβ42 and α-synuclein. We conclude that LAT possesses pro-autophagic properties in addition to the previously reported pro-neurogenic properties, both of which are potentially relevant to the treatment and/or prevention of neurodegenerative diseases. We suggest that elucidation of the molecular mechanism(s) underlying LAT effects on neurogenesis, autophagy and behavior might warranty the further study of LAT as a potentially viable lead compound that might yield more consistent clinical benefit following the optimization of its pro-neurogenic, pro-autophagic and/or pro-cognitive activities.