Behavioral deficits during early stages of aging in Caenorhabditis elegans result from locomotory deficits possibly linked to muscle frailty

Many behavioral responses require the coordination of sensory inputs with motor outputs. Aging is associated with progressive declines in both motor function and muscle structure. However, the consequences of age-related motor deficits on behavior have not been clearly defined. Here, we examined the effects of aging on behavior in the nematode, Caenorhabditis elegans. As animals aged, mild locomotory deficits appeared that were sufficient to impair behavioral responses to sensory cues. In contrast, sensory ability appeared well maintained during aging. Age-related behavioral declines were delayed in animals with mutations in the daf-2/insulin-like pathway governing longevity. A decline in muscle tissue integrity was correlated with the onset of age-related behavioral deficits, although significant muscle deterioration was not. Treatment with a muscarinic agonist significantly improved locomotory behavior in aged animals, indicating that improved neuromuscular signaling may be one strategy for reducing the severity of age-related behavioral impairments.     

Effect of Choline Supplementation on Neurological,Cognitive, and Behavioral Outcomes in Offspring Arising from Alcohol Exposure During Development: A Quantitative Systematic Review of Clinical and Preclinical Studies

Prenatal alcohol exposure results in cognitive, behavioral, and neurological deficits in offspring. There is an urgent need for safe and effective treatments to overcome these effects. Maternal choline supplementation has been identified as a potential intervention. Our objective was to review preclinical and clinical studies using choline supplementation in known cases of fetal alcohol exposure to determine its effectiveness in ameliorating deficits in offspring. A systematic search of 6 electronic databases was conducted and studies selected by reviewing titles/abstracts against specific inclusion/exclusion criteria. Study characteristics, population demographics, alcohol exposure, and intervention methods were tabulated, and quality of reporting was assessed. Data on cognitive, behavioral, and neurological outcomes were extracted and tabulated. Quantitative analysis was performed to determine treatment effects for individual study outcomes. A total of 189 studies were retrieved following duplicate removal. Of these, 22 studies (2 randomized controlled trials, 2 prospective cohort studies, and 18 preclinical studies) met the full inclusion/exclusion criteria. Choline interventions were administered at different times relative to alcohol exposure, impacting on their success to prevent deficits for specific outcomes. Only 1 clinical study showed significant improvements in information processing in 6‐month‐old infants from mothers treated with choline during pregnancy. Preclinical studies showed significant amelioration of deficits due to prenatal alcohol exposure across a wide variety of outcomes, including epigenetic/molecular changes, gross motor, memory, and executive function. This review suggests that choline supplementation has the potential to ameliorate specific behavioral, neurological, and cognitive deficits in offspring caused by fetal alcohol exposure, at least in preclinical studies. As only 1 clinical study has shown benefit, we recommend more clinical trials be undertaken to assess the effectiveness of choline in preventing deficits across a wider range of cognitive domains in children.     

Chronic melatonin treatment and its precursor L‐tryptophan improve the monoaminergic neurotransmission and related behavior in the aged rat brain

Abstract: Melatonin has an important role in the aging process as a potential drug to relieve oxidative damage, a likely cause of age‐associated brain dysfunction. As age advances, the nocturnal production of melatonin decreases potentially causing physiological alterations. The present experiments were performed to study in vivo the effects of exogenously administered melatonin chronically on monoaminergic central neurotransmitters serotonin (5‐HT), dopamine (DA) and norepinephrine (NE) and behavioral tests in old rats. The accumulation of 5‐hydroxy‐tryptophan (5‐HTP) and L‐3,4‐dihydroxyphenylalanine (DOPA) after decarboxylase inhibition was used as a measure of the rate of tryptophan and tyrosine hydroxylation in rat brain. Also neurotransmitters 5‐HT, DA and NE and some metabolites were quantified by HPLC. In control rats, an age‐related decline was observed in neurochemical parameters. However, chronic administration of melatonin (1 mg/kg/day, diluted in drinking water, 4 wk) significantly reversed the age‐induced deficits in all the monoaminergic neurotransmitters studied. Also, neurochemical parameters were analyzed after administration of melatonin biosynthesis precursor L‐tryptophan (240 mg/kg/day, i.p., at night for 4 wk) revealing similar improvement effects to those induced by melatonin. Behavioral data corresponded well with the neurochemical findings since spatial memory test in radial‐maze and motor coordination in rota‐rod were significantly improved after chronic melatonin treatment. In conclusion, these in vivo findings suggest that melatonin and L‐tryptophan treatments exert a long‐term effect on the 5‐HT, DA and NE neurotransmission by enhancing monoamine synthesis in aged rats, which might improve the age‐dependent deficits in cognition and motor coordination.     

Ontogeny of the Enhanced Fetal‐Ethanol‐Induced Behavioral and Neurophysiologic Olfactory Response to Ethanol Odor

Background: Studies report a fundamental relationship between chemosensory function and the responsiveness to ethanol, its component orosensory qualities, and its odor as a consequence of fetal ethanol exposure. Regarding odor, fetal exposed rats display enhanced olfactory neural and behavioral responses to ethanol odor at postnatal (P) day 15. Although these consequences are absent in adults (P90), the behavioral effect has been shown to persist into adolescence (P37). Given the developmental timing of these observations, we explored the decay in the response to ethanol odor by examining ages between P37 and young adulthood. Moreover, we sought to determine whether the P15 neurophysiologic effect persists, at least, to P40. Methods: Behavioral and olfactory epithelial (OE) responses of fetal ethanol exposed and control rats were tested at P40, P50, P60, or P70. Whole‐body plethysmography was used to quantify each animal’s innate behavioral response to ethanol odor. We then mapped the odorant‐induced activity across the OE in response to different odorants, including ethanol, using optical recording methods. Results: Relative to controls, ethanol exposed animals showed an enhanced behavioral response to ethanol odor that, while significant at each age, decreased in magnitude. These results, in conjunction with previous findings, permitted the development of an ontologic odor response model of fetal exposure. The fitted model exemplifies that odor‐mediated effects exist at birth, peak in adolescence and then decline, becoming absent by P90. There was no evidence of an effect on the odor response of the OE at any age tested. Conclusions: Fetal exposure yields an enhanced behavioral response to ethanol odor that peaks in adolescence and wanes through young adulthood. This occurs absent an enhanced response of the OE. This latter finding suggests that by P40 the OE returns to an ethanol “neutral” status and that central mechanisms, such as ethanol‐induced alterations in olfactory bulb circuitry, underlie the enhanced behavioral response. Our study provides a more comprehensive understanding of the ontogeny of fetal‐ethanol‐induced olfactory functional plasticity and the behavioral response to ethanol odor.     

Long‐term oral administration of melatonin improves spatial learning and memory and protects against cholinergic degeneration in middle‐aged Ts65Dn mice,a model of Down syndrome

Ts65Dn mice (TS), the most commonly used model of Down syndrome (DS), exhibit phenotypic characteristics of this condition. Both TS mice and DS individuals present cognitive disturbances, age‐related cholinergic degeneration, and increased brain expression of β‐amyloid precursor protein (AβPP). These neurodegenerative processes may contribute to the progressive cognitive decline observed in DS. Melatonin is a pineal indoleamine that has been reported to reduce neurodegenerative processes and improve cognitive deficits in various animal models. In this study, we evaluated the potentially beneficial effects of long‐term melatonin treatment on the cognitive deficits, cholinergic degeneration, and enhanced AβPP and β‐amyloid levels of TS mice. Melatonin was administered for 5 months to 5‐ to 6‐month‐old TS and control (CO) mice. Melatonin treatment improved spatial learning and memory and increased the number of choline acetyltransferase (ChAT)‐positive cells in the medial septum of both TS and CO mice. However, melatonin treatment did not significantly reduce AβPP or β‐amyloid levels in the cortex or the hippocampus of TS mice. Melatonin administration did reduce anxiety in TS mice without inducing sensorimotor alterations, indicating that prolonged treatment with this indoleamine is devoid of noncognitive behavioral side effects (e.g., motor coordination, sensorimotor abilities, or spontaneous activity). Our results suggest that melatonin administration might improve the cognitive abilities of both TS and CO mice, at least partially, by reducing the age‐related degeneration of basal forebrain cholinergic neurons. Thus, chronic melatonin supplementation may be an effective treatment for delaying the age‐related progression of cognitive deterioration found in DS.     

Behavioral economic analysis of cue‐elicited craving for alcohol

Aims Craving as a motivational determinant of drug use remains controversial because of ambiguous empirical findings. A behavioral economic approach may clarify the nature of craving, theorizing that subjective craving functionally reflects an acute increase in a drug's value. The current study tested this hypothesis via a multidimensional assessment of alcohol demand over the course of an alcohol cue reactivity procedure. Design One‐way within‐subjects design. Setting Human laboratory environment. Participants Heavy drinkers (n = 92) underwent exposures to neutral (water) cues followed by personalized alcohol cues. Assessments Participants were assessed for craving, alcohol demand, affect, and salivation following each exposure. Findings Alcohol versus neutral cues significantly increased craving and multiple behavioral economic measures of the relative value of alcohol, including alcohol consumption under conditions of zero cost (intensity), maximum expenditure on alcohol (O_max), persistence in drinking to higher prices (breakpoint) and proportionate price insensitivity (normalized P_max). Craving was significantly correlated with demand measures at levels ranging from 0.21–0.43. Conclusions These findings support the potential utility of a behavioral economic approach to understanding the role of environmental stimuli in alcohol‐related decision making. Specifically, they suggest that the behavioral economic indices of demand may provide complementary motivational information that is related to though not entirely redundant with measures of subjective craving.     

The “First Hit” Toward Alcohol Reinforcement: Role of Ethanol Metabolites

This review analyzes literature that describes the behavioral effects of 2 metabolites of ethanol (EtOH): acetaldehyde and salsolinol (a condensation product of acetaldehyde and dopamine) generated in the brain. These metabolites are self‐administered into specific brain areas by animals, showing strong reinforcing effects. A wealth of evidence shows that EtOH, a drug consumed to attain millimolar concentrations, generates brain metabolites that are reinforcing at micromolar and nanomolar concentrations. Salsolinol administration leads to marked increases in voluntary EtOH intake, an effect inhibited by mu‐opioid receptor blockers. In animals that have ingested EtOH chronically, the maintenance of alcohol intake is no longer influenced by EtOH metabolites, as intake is taken over by other brain systems. However, after EtOH withdrawal brain acetaldehyde has a major role in promoting binge‐like drinking in the condition known as the “alcohol deprivation effect”; a condition seen in animals that have ingested alcohol chronically, are deprived of EtOH for extended periods, and are allowed EtOH re‐access. The review also analyzes the behavioral effects of acetate, a metabolite that enters the brain and is responsible for motor incoordination at low doses of EtOH. Also discussed are the paradoxical effects of systemic acetaldehyde. Overall, evidence strongly suggests that brain‐generated EtOH metabolites play a major role in the early (“first‐hit”) development of alcohol reinforcement and in the generation of relapse‐like drinking.     

Differential Central NOS‐NO Signaling Underlies Clonidine Exacerbation of Ethanol‐Evoked Behavioral Impairment

Background: The molecular mechanisms that underlie clonidine exacerbation of behavioral impairment caused by ethanol are not fully known. We tested the hypothesis that nitric oxide synthase (NOS)‐derived nitric oxide (NO) signaling in the locus coeruleus (LC) is implicated in this phenomenon. Methods: Male Sprague–Dawley rats with intracisternal (i.c.) and jugular vein cannulae implanted 6 days earlier were tested for drug‐induced behavioral impairment. The latter was assessed as the duration of loss of righting reflex (LORR) and rotorod performance every 15 minutes until the rat recovered to the baseline walk criterion (180 seconds). In a separate cohort, we measured p‐neuronal NOS (nNOS), p‐endothelial NOS (eNOS), and p‐ERK1/2 in the LC following drug treatment, vehicle, or NOS inhibitor. Results: Rats that received clonidine [60 Ig/kg, i.v. (intravenous)] followed by ethanol (1 or 1.5 g/kg, i.v.) exhibited synergistic impairment of rotorod performance. Intracisternal pretreatment with nonselective NOS inhibitor N^ω‐nitro‐l ‐arginine methyl ester (l ‐NAME, 0.5 mg) or selective nNOS inhibitor N‐propyl‐l ‐arginine (1 μg) exacerbated the impairment of rotorod performance caused by clonidine–ethanol combination. Exacerbation of behavioral impairment was caused by l ‐NAME enhancement of the effect of ethanol, not clonidine. l ‐NAME did not influence blood ethanol levels; thus, the interaction was pharmacodynamic. LORR caused by clonidine (60 μg/kg, i.v.)–ethanol (1 g/kg, i.v.) combination was abolished by selective inhibition of central eNOS (l ‐NIO, 10 μg i.c.) but not by nNOS inhibition under the same conditions. Western blot analyses complemented the pharmacological evidence by demonstrating that clonidine–ethanol combination inhibits phosphorylation (activation) of nNOS (p‐nNOS) and increases the level of phosphorylated eNOS (p‐eNOS) in the LC; the change in p‐nNOS was paralleled by similar change in LC p‐ERK1/2. NOS inhibitors alone did not affect the level of nitrate/nitrite, p‐nNOS, p‐eNOS, or p‐ERK1/2 in the LC. Conclusions: Alterations in NOS‐derived NO in the LC underlie clonidine–ethanol induced behavioral impairment. A decrease in nNOS activity, due at least partly to a reduction in nNOS phosphorylation, mediates rotorod impairment, while enhanced eNOS activity contributes to LORR, elicited by clonidine–ethanol combination.     

The Role of Antisocial, Affective, and Childhood Behavioral Characteristics in Alcoholics' Neuropsychological Performance

Chronic alcoholics demonstrate cognitive deficits when compared with nonalcoholics. These deficits are typically attributed to the direct effects of ethanol and its metabolites on the central nervous system (CNS). There are other factors, however, that differentiate alcoholics from controls, such as personality or behavioral characteristics. These factors may affect neuropsychological performance and thus alter the interpretation of alcoholic cognitive deficits as resulting solely from alcohol's toxic effects. To investigate this question, male and female alcoholics and peer nonalcoholic controls were compared on personality, behavioral, and cognitive measures. Alcoholics had greater numbers of antisocial behaviors, childhood behavioral disorder symptoms (CBD), and affective symptomatology, and had poorer neuropsychological performance than controls. The three personality and behavioral factors were positively intercorrelated with each other, and were negatively related to cognitive performance. The CBD factor proved to be the most consistent predictor of neuropsychological performance for both alcoholics and controls, and males and females. While the behavioral factors differentiated alcoholics from controls and predicted performance, significant differences between the groups in cognitive performance still remained when these factors were taken into account.     

An Expanded Self‐Medication Hypothesis Based on Cognitive‐Behavioral Determinants for Heroin Abusers in Taiwan: A Cross‐Sectional Study

Background: This study proposed and examined an expanded self‐medication hypothesis (eSMH) model based on cognitive behavioral determinants, including the direct effects of negative emotional states, positive outcome expectancies and refusal self‐efficacy on heroin use, and the mediating roles of positive outcome expectancies and refusal self‐efficacy between negative emotional states and heroin use. Methods: A total of 360 male heroin abusers were recruited from a drug abuse treatment center in Taiwan. Participants were asked to complete a set of questionnaires on frequency of heroin use, anxious/depressive mood, positive outcome expectancies, and refusal self‐efficacy. Structural equation modeling was used to examine the eSMH model. Results: Results showed that the eSMH model displayed proper goodness‐of‐fit. Positive outcome expectancies and negative emotional status were significant predictors of heroin use, whereas refusal self‐efficacy was not a significant predictor. Additionally, positive self‐efficacy was a mediator between negative emotional status and heroin use. Conclusion: Results support a reduced eSMH model and suggest a significant role of positive self‐efficacy in the relationship between negative affective states and heroin use. This relationship should be examined in the longitudinal study, and should be given clinical consideration in treatment of individuals struggling with heroin abuse and negative affective states. (Am J Addict 2012;21:S43–S48)     

Transient Cocaine‐Associated Behavioral Symptoms Rated with a New Instrument,the Scale for Assessment of Positive Symptoms for Cocaine‐Induced Psychosis (SAPS‐CIP)

Chronic use of cocaine is associated with a variety of behavioral symptoms. The current report describes the assessment of cocaine‐related behavioral symptoms (CRB) using the Scale for Assessment of Positive Symptoms of Cocaine‐Induced Psychosis (SAPS‐CIP). The CRB section, one of the three domains in the SAPS‐CIP, consists of sub‐domains, including Aggressive/Agitated Behavior, Repetitive/Stereotyped Behavior, and Unusual Social or Sexual Behavior. Severity scores are assigned according to operational criteria, and range from 0 (not present) to 5 (severe). We interviewed 261 unrelated cocaine‐abusing adults using the SAPS‐CIP, and 243 of them met criteria for inclusion in the study. The proportion of subjects endorsing different classes of CRBs varied across categories, with 109 of 243 (44.9%) subjects reporting aggressive and agitated behaviors, 180 subjects (74.1%) repetitive/stereotyped behaviors, and 192 (79.0%) unusual social/sexual behaviors. A substantial minority of the subjects (10.3–25.1%) reported that they experienced marked‐to‐severe behavioral symptoms associated with cocaine use. The proportions of subjects endorsing CRB did not differ by ethnic/racial group or by sex. Correlations among the different domains of CRB were strong, but behaviors rated in the CRB section were less well correlated with psychotic symptoms, which were rated in the hallucination and delusion sections of the instrument. A variety of CRBs are common in cocaine‐dependent subjects, and many of these are highly intercorrelated. CRBs also correlate with hallucinations and delusions induced by cocaine, but to a lesser degree. Our findings suggest that there may be some common vulnerability factors that contribute to both cocaine‐induced psychosis and CRBs.     

Cognitive Performance in Treatment‐Naïve Active Alcoholics

Background: Most studies reporting cognitive deficits in chronic alcoholics have relied on treatment samples (predominantly men) from inpatient or outpatient treatment facilities. However, the majority of chronic alcoholics have never been in treatment and there is increasing evidence that treated and non‐treatment‐seeking alcoholic samples come from different populations with regard to alcohol use and other factors related to the severity of disease. Accordingly, in the present study, we assessed a broad range of cognitive functions in 55 treatment‐naïve alcohol‐dependent (TNAD) individuals and 55 nonalcoholic controls (NAC) matched for age and education. In addition, a goal of the present study was to assess potential differential effects of alcohol dependence on cognitive performance in TNAD men and women. Methods: Comprehensive neuropsychological assessment was conducted on TNAD and NAC. The following 9 performance domains, each consisting of multiple measures, were examined: attention, auditory working memory, verbal processing, abstraction/cognitive flexibility, psychomotor function, immediate memory, delayed memory, reaction time, and spatial processing. Results: Analysis revealed no cognitive deficits in TNAD, relative to NAC, in any of the 9 cognitive domains. TNAD performed better than NAC in the attention domain. In addition, while men performed better than women in the spatial domain, there were no TNAD versus NAC group by gender interactions for any domain. Conclusions: Our results extend findings that TNAD show minimal behavioral effects of chronic heavy alcohol use and are consistent with the contention that TNAD are relatively cognitively intact. Differences between our findings and those often reported for alcoholics recruited from treatment settings may be understood in terms of differences in alcohol use, along with genetic, psychiatric, and nutritional factors. In addition, the lack of differential effects of alcohol dependence on male and female cognitive performance in our study suggests that TNAD men and women do not differ in the severity of cerebral consequences of alcohol dependence.     

“My Older Clients Fall Through Every Crack in the System”: Geriatrics Knowledge of Legal Professionals

With the number of older adult arrestees and prisoners increasing rapidly, legal professionals increasingly provide front‐line identification and response to age‐related health conditions (including cognitive and physical impairments) that may affect legal outcomes, such as the ability to participate in one's defense or stay safe in jail. The goals of this study were to assess the ability of legal professionals to recognize and respond to age‐related conditions that could affect legal outcomes and to identify recommendations to address important knowledge gaps. This was a mixed quantitative–qualitative study. Legal professionals (N = 72) in the criminal justice system were surveyed to describe their demographic characteristics, expertise, and prior aging‐related training and to inform the qualitative interview guide. Those surveyed included attorneys (district attorneys (25%), public defenders and legal advocates (58%)), judges (6%), and court‐affiliated social workers (11%). In‐depth qualitative interviews were then conducted with a subset of 10 legal professionals who worked with older adults at least weekly. Results from the surveys and interviews revealed knowledge deficits in four important areas: age‐related health, identification of cognitive impairment, assessment of safety risk, and optimization of services upon release from jail. Four recommendations to close these gaps emerged: educate legal professionals about age‐related health, train professionals to identify cognitive and sensory impairment, develop checklists to identify those at risk of poor health or safety, and improve knowledge of and access to transitional services for older adults. These findings suggest that geriatrics knowledge gaps of legal professionals exist that may contribute to adverse medical or legal outcomes for older adults involved in the criminal justice system and that partnerships between healthcare and legal professionals are needed to address these challenges.     

Anti–N‐methyl‐D‐aspartate receptor encephalitis: A newly recognized inflammatory brain disease in children

Objective

Anti–N‐methyl‐D ‐aspartate receptor (anti‐NMDAR) encephalitis is a newly recognized antineuronal antibody–mediated inflammatory brain disease that causes severe psychiatric and neurologic deficits in previously healthy children. The present study was undertaken to describe characteristic clinical features and outcomes in children diagnosed as having anti‐NMDAR encephalitis.

Methods

Consecutive children presenting over a 12‐month period with newly acquired psychiatric and/or neurologic deficits consistent with anti‐NMDAR encephalitis and evidence of central nervous system (CNS) inflammation were screened. Children were included in the study if they had confirmatory evidence of anti‐NMDAR antibodies in the serum and/or cerebrospinal fluid. Features at clinical presentation and results of investigations were recorded. Type and duration of treatment and outcomes at last followup were documented.

Results

Seven children were screened, and 3 children with anti‐NMDAR encephalitis were identified. All patients presented with neurologic and/or psychiatric abnormalities, seizures, speech disorder, sleep disturbance, and fluctuating level of consciousness. The 2 older patients had more prominent psychiatric features, while the younger child had significant autonomic instability and prominent involuntary movement disorder. None had an underlying tumor. Immunosuppressive therapy resulted in near or complete recovery; however, 2 of the patients had early relapse necessitating re‐treatment.

Conclusion

Anti‐NMDAR encephalitis is an important cause of neuropsychiatric deficits in children, which must be included in the differential diagnosis of CNS vasculitis and other inflammatory brain diseases. Early diagnosis and treatment are essential for neurologic recovery.

     

Cluster‐Randomized Trial of a Behavioral Intervention to Incorporate a Treat‐to‐Target Approach to Care of US Patients With Rheumatoid Arthritis

Objective

To assess the feasibility and efficacy of implementing a treat‐to‐target approach versus usual care in a US‐based cohort of rheumatoid arthritis patients.

Methods

In this behavioral intervention trial, rheumatology practices were cluster‐randomized to provide treat‐to‐target care or usual care. Eligible patients with moderate/high disease activity (Clinical Disease Activity Index [CDAI] score >10) were followed for 12 months. Both treat‐to‐target and usual care patients were seen every 3 months. Treat‐to‐target providers were to have monthly visits with treatment acceleration at a minimum of every 3 months in patients with CDAI score >10; additional visits and treatment acceleration were at the discretion of usual care providers and patients. Coprimary end points were feasibility, assessed by rate of treatment acceleration conditional on CDAI score >10, and achievement of low disease activity (LDA; CDAI score ≤10) by an intent‐to‐treat analysis.

Results

A total of 14 practice sites per study arm were included (246 patients receiving treat‐to‐target and 286 receiving usual care). The groups had similar baseline demographic and clinical characteristics. Rates of treatment acceleration (treat‐to‐target 47% versus usual care 50%; odds ratio [OR] 0.92 [95% confidence interval (95% CI) 0.64, 1.34]) and achievement of LDA (treat‐to‐target 57% versus usual care 55%; OR 1.05 [95% CI 0.60, 1.84]) were similar between groups. Treat‐to‐target providers reported patient reluctance and medication lag time as common barriers to treatment acceleration.

Conclusion

This study is the first to examine the feasibility and efficacy of a treat‐to‐target approach in typical US rheumatology practice. Treat‐to‐target care was not associated with increased likelihood of treatment acceleration or achievement of LDA, and barriers to treatment acceleration were identified.     

Post‐dilatation trepidation: Post‐dil is “no big dil”

• Selective stent post‐dilatation (PD) in a cohort of STEMI patients did not affect major adverse cardiac events but it did decrease device‐oriented composite events, a secondary composite end point of less clear significance.
• This study suggests that selective stent PD in STEMI does not increase the incidence of acute no‐reflow or long‐term adverse clinical events.
• In primary PCI for STEMI, if the stent appears under‐expanded, then PD, perhaps guided by intravascular imaging (which was not reported in this study), is reasonable.

     

Cross‐cultural comparison of predictors for self‐care behaviors in patients with type 2 diabetes

The aim of the present study was to evaluate how culture moderates the behavioral and psychosocial predictors of diabetes self‐care activities. Patients with type 2 diabetes were recruited in the outpatient department at two sites: Kyoto University hospital in Japan and the Christiana Care Health System in the USA. The data were collected by survey using questionnaires including questions on the frequency of self‐care activities, behavioral and psychosocial predictors, and other background information from 149 Japanese patients and 48 American patients. The cultural impact was observed by multiple regression analyses with interaction terms on the association between emotional support and self‐care activities in diet in female patients. The findings of the present study serve as an example of how cultural context can affect patients with diabetes, and lead to a better understanding of culturally sensitive behavioral intervention.     

Behavioral and Psychosocial Profiles of Alcohol-Exposed Children

BACKGROUND: It is widely known that prenatal alcohol exposure is related to cognitive and behavioral deficits throughout childhood and adolescence. Much research has focused on understanding and quantifying the cognitive profile of children with fetal alcohol syndrome (FAS) with relatively less empirical research on behavioral or psychosocial adjustment. The primary purpose of this study was to examine the behavioral and psychosocial profile of children exposed to heavy amounts of alcohol prenatally. METHOD: Two groups of subjects were evaluated: an alcohol-exposed group (ALC) and a nonexposed control group (NC) each made up of 32 subjects matched for age, gender, and ethnicity. The alcohol-exposed group consisted of children heavily exposed to alcohol in utero, including 19 children diagnosed with FAS. The Personality Inventory for Children (PIC) was completed by the caretaker of each child. Four validity/screening scales and 12 clinical scales were scored for all subjects. RESULTS: Analyses revealed significant group differences on four validity/screening scales and 12 substantive scales. Within the ALC group, the profile of children without FAS was similar to that of children with FAS, with the exception that their profiles were consistent with less cognitive impairment. CONCLUSIONS: These findings indicate that in addition to previously reported cognitive impairments, heavy prenatal alcohol exposure is related to significant impairments in psychosocial functioning. Even children without alcohol-related physical anomalies suffer from impaired psychosocial functioning. Because impairments of this nature can interfere with functioning across multiple domains, effective early intervention programs should be considered for families of alcohol-exposed children. Furthermore, given the similarities of alcohol-exposed children with and without FAS, it is imperative to obtain prenatal alcohol exposure histories on all children experiencing cognitive or psychosocial deficits.     

Central nervous system involvement by Waldenström macroglobulinaemia (Bing‐Neel syndrome): a multi‐institutional retrospective study

Bing‐Neel syndrome (BNS) is a rare complication seen in patients with Waldenström macroglobulinaemia (WM), in which lymphoplasmacytic lymphoma cells colonize the central nervous system. In this retrospective multi‐centre study, we present the clinicopathological features, imaging findings, therapy, response and outcomes of 34 patients with BNS. The median time from WM diagnosis to BNS diagnosis was 3 years, 15% of patients were diagnosed with BNS at the time of WM diagnosis, and 22% of patients developed BNS when responding to active treatment for WM. Patients with BNS presented with variable clinical features including limb motor deficits, change in mental status and cranial nerve palsies. The diagnosis was made using a combination of cerebrospinal fluid cytology, flow cytometry and detection of the MYD88 L265 mutation, and magnetic resonance imaging. The estimated 3‐year overall survival rate was 59%. Of the survivors, 40% have evidence of pathological and/or radiological persistence of disease. Age older than 65 years, platelet count lower than 100 × 10⁹/l, and treatment for WM prior to BNS diagnosis were associated with worse outcome. Exposure to rituximab for treatment of BNS was associated with a better outcome. Multi‐institutional collaboration is warranted to improve treatment and outcomes in patients with BNS.     

Ethanol Acutely Modulates mGluR1‐Dependent Long‐Term Depression in Cerebellum

Background: Acute and chronic ethanol exposure produces profound impairments in motor functioning. Individuals with lower sensitivity to the acute motor impairing effects of ethanol have an increased risk of developing alcohol dependence and abuse, and infants with subtle delays in motor coordination development may have an increased risk for subsequently developing alcoholism. Thus, understanding the mechanism by which ethanol disrupts motor functioning is very important. Methods: Parasagittal slices of the cerebellar vermis (250 μM thick) were prepared from P17 to 20 Sprague–Dawley rats. Whole‐cell recordings of Purkinje cells were obtained with an Axopatch 200B amplifier. Parallel fiber‐Purkinje cell synaptic currents were sampled at 1 kHz and digitized at 10 kHz, and synaptic long‐term depression (LTD) was observed in either external or internal application of ethanol for comparison. Results: We determined whether ethanol acutely affects parallel fiber LTD using whole‐cell patch‐clamp recordings from Purkinje cells. Application of ethanol both externally (50 mM) and internally (17 and 10 mM) significantly suppressed mGluR‐mediate slow currents. Short‐term external ethanol exposure (50 but not 17 mM) during tetanus blocked mGluR‐dependent parallel fiber LTD. Furthermore, internal 17 and 10 mM ethanol completely inhibited this LTD. Conclusions: The results of the current study demonstrate that ethanol acutely suppresses parallel fiber LTD and may influence the mGluR‐mediated slow current intracellularly. This study, plus previous evidence by Carta and colleagues (2006) and Belmeguenai and colleagues (2008), suggests significant actions of ethanol on mGluR‐mediated currents and its dependent plasticity in brain.