Clinical outcomes following ST-elevation myocardial infarction secondary to stent thrombosis treated by percutaneous coronary intervention.

OBJECTIVES: To assess the clinical outcomes of patients presenting with ST-elevation myocardial infarction (STEMI) secondary to stent thrombosis (ST) compared to those presenting with STEMI secondary to a de novo culprit lesion and treated by percutaneous coronary intervention (PCI). BACKGROUND: ST is an infrequent but serious complication of PCI with substantial associated morbidity and mortality, however with limited data. METHODS: We studied consecutive patients who underwent PCI for STEMI from 2005 to 2013 enrolled prospectively in the Melbourne Interventional Group registry. Patients were divided into two groups: the ST group comprised patients where the STEMI was due to ST and the de novo group formed the remainder of the STEMI cohort and all patients were treated by PCI. The primary endpoint was 30-day all-cause mortality. RESULTS: Compared to the de novo group (n = 3,835), the ST group (n = 128; 3.2% of STEMI) had higher rates of diabetes, hypertension and dyslipidemia, established cardiovascular diseases, myocardial infarction, and peripheral vascular disease, all p < .01. Within the ST group, very-late ST was the most common form of ST, followed by late and early ST (64, 19, and 17%, respectively). There was no significant difference in the primary outcome between the ST group and the de novo group (4.7 vs. 7.1%, p = .29). On multivariate analysis, ST was not an independent predictor of 30-day mortality (odds ratio: 0.62, 95% confidence interval: 0.07-1.09, p = .068). CONCLUSION: The short-term prognosis of patients with STEMI secondary to ST who were treated by PCI was comparable to that of patients with STEMI due to de novo lesions.

Trends of Use and Outcomes Associated With Glycoprotein-IIb/IIIa Inhibitors in Patients With Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention.

Background: Glycoprotein IIb/IIIa inhibitors (GPIs) are a treatment option in the management of acute coronary syndromes (ACSs). Evidence supporting the use of GPIs predates trials establishing the benefits of P2Y12 inhibitors, routine early invasive therapy, and thrombectomy devices in patients with ACS. Objective: The aim of this study was to determine trends in GPI use and their associated outcomes in contemporary practice. Methods: We assessed GPI use in patients with ACS undergoing percutaneous coronary intervention (PCI) from the Melbourne Interventional Group registry (2005-2013). The primary endpoint was the 30-day incidence of major adverse cardiovascular events (MACE). The safety endpoint was in-hospital major bleeding. Results: GPIs were used in 40.5% of 12 357 patients with ACS undergoing PCI. GPI use decreased over the study period (P for trend <0.0001). Patients were more likely to receive GPIs if they were younger, presented with a ST-elevation myocardial infarction (STEMI), had more complex (B2/C-type) lesions, and when thrombectomy devices were used (all P < 0.0001). MACE were higher in patients receiving GPI (4.9% vs 4.1%, P = 0.03). Propensity score matching revealed no difference in 30-day mortality and 30-day MACE (odds ratio [OR] = 1.00; 95% CI = 0.99-1.004 and OR = 1.01; 95% CI = 0.99-1.02, respectively). GPI use was associated with more bleeding complications (3.6% vs 1.8%, P < 0.0001). Conclusion and Relevance: GPI use in ACS patients undergoing PCI has declined, and use appears to be dictated by ACS type and lesion complexity, as opposed to high-risk comorbidities. GPI use was associated with a doubling in bleeding complications.

Exploring Practices of Bedside Shift Report and Hourly Rounding. Is There an Impact on Patient Falls?

OBJECTIVE: To describe the relationship of inpatient falls to bedside shift report (BSR) and hourly rounding (HR). BACKGROUND: Falls are a major healthcare concern. Although measures such as BSR and HR are reported to reduce falls, studies are often based on self-reported data related to nurse compliance with protocols for HR and bedside report. METHODS: Observational data were collected on nursing tasks, including BSR and HR. RESULTS: Nine thousand six hundred ninety-three observations were recorded on 11 units at 4 hospitals over 281 shifts. Falls were associated with shift and day of the week but not BSR, HR, or the frequency of encounters with the patient. The regression model included frequency with patient, shift, day of week, and HR. CONCLUSIONS: Increased nurse frequency with patient may signal increased fall risks. Bedside shift report and HR may require robust and sustained interventions to provide lasting effects.

Trends and predictors of recurrent acute coronary syndrome hospitalizations and unplanned revascularization after index acute myocardial infarction treated with percutaneous coronary intervention.

BACKGROUND: Repeat hospitalizations for recurrent acute coronary syndrome (ACS) or unplanned revascularization after acute myocardial infarction (MI) are common, costly and potentially preventable. We aim to describe 10-year trends and identify independent risk factors of these repeat hospitalizations. METHODS: We analyzed data from 9615 patients from the Melbourne Interventional Group registry (2005-2014) who underwent percutaneous coronary intervention (PCI) for their index MI and survived to discharge. Patients with ≥1 hospitalization for recurrent ACS events and/or unplanned revascularization in the year after discharge were included in the recurrent coronary hospitalization group. We assessed yearly trends of recurrent coronary events and identified independent predictors using multivariate analysis. RESULTS: Recurrent coronary hospitalization occurred in 1175 (12.2%) patients. There was a significant decrease in the rate of recurrent ACS hospitalization (15.3%-7.6%, P for trend <.001) and unplanned revascularization (4.2%-2.1%, P for trend = .01), but not in all-cause re-hospitalizations (P for trend = .28). On multivariate analysis, female gender, diabetes mellitus, previous coronary bypass surgery, previous PCI, reduced ejection fraction, heart failure, multi-vessel coronary disease and obstructive sleep apnea were independent predictors of recurrent coronary hospitalizations (all P < .05). CONCLUSIONS: Recurrent hospitalization for ACS or unplanned revascularization has decreased significantly over the past decade. Risk factors for such events are numerous and largely non-modifiable, however they identify a cohort of patients in whom non-culprit vessel PCI in multi-vessel disease, optimization of left ventricular dysfunction and diabetes management may improve outcomes.

Functionalization of Deutero- and Protoporphyrin IX Dimethyl Esters via Palladium-Catalyzed Coupling Reactions.

Herein, we report the functionalization of the ß-positions of deutero- and protoporphyrin IX dimethyl esters. Initial halogenations were carried out on both deutero- and protoporphyrin IX dimethyl esters. Although previously reported, vastly optimized yields with respect to deuteroporphyrin halogenation were obtained. Methods were developed for the bromination of the vinyl groups of protoporphyin IX dimethyl ester. Subsequent palladium-catalyzed coupling reactions were utilized to modify the periphery of these naturally occurring porphyrin derivatives with a variety of functionalities. The described Suzuki, Sonogashira, and "Click" reactions demonstrate the ease at which these porphyrins may be manipulated and even interchangeable, as will be discussed for one example. X-ray crystallographic analysis successfully determined the structure of two derivatives synthesized. Results identified a unique head-to-tail stacking pattern for 3,8-diphenyldeuteroporphyrin IX dimethyl ester, most likely due to the presence of additional aromatic moieties on the periphery of the porphyrin.

Trends and targets in antiviral phototherapy.

Photodynamic therapy (PDT) is a well-established treatment option in the treatment of certain cancerous and pre-cancerous lesions. Though best-known for its application in tumor therapy, historically the photodynamic effect was first demonstrated against bacteria at the beginning of the 20th century. Today, in light of spreading antibiotic resistance and the rise of new infections, this photodynamic inactivation (PDI) of microbes, such as bacteria, fungi, and viruses, is gaining considerable attention. This review focuses on the PDI of viruses as an alternative treatment in antiviral therapy, but also as a means of viral decontamination, covering mainly the literature of the last decade. The PDI of viruses shares the general action mechanism of photodynamic applications: the irradiation of a dye with light and the subsequent generation of reactive oxygen species (ROS) which are the effective phototoxic agents damaging virus targets by reacting with viral nucleic acids, lipids and proteins. Interestingly, a light-independent antiviral activity has also been found for some of these dyes. This review covers the compound classes employed in the PDI of viruses and their various areas of use. In the medical area, currently two fields stand out in which the PDI of viruses has found broader application: the purification of blood products and the treatment of human papilloma virus manifestations. However, the PDI of viruses has also found interest in such diverse areas as water and surface decontamination, and biosafety.

Synthesis and Characterization of Temperature-Sensitive and Chemically Cross-Linked Poly( N-isopropylacrylamide)/Photosensitizer Hydrogels for Applications in Photodynamic Therapy.

A novel poly( N-isopropylacrylamide) (PNIPAM) hydrogel containing different photosensitizers (protoporphyrin IX (PpIX), pheophorbide a (Pba), and protoporphyrin IX dimethyl ester (PpIX-DME)) has been synthesized with a significant improvement in water solubility and potential for PDT applications compared to the individual photosensitizers (PSs). Conjugation of PpIX, Pba, and PpIX-DME to the poly( N-isopropylacrylamide) chain was achieved using the dispersion polymerization method. This study describes how the use of nanohydrogel structures to deliver a photosensitizer with low water solubility and high aggregation tendencies in polar solvents overcomes these limitations. FT-IR spectroscopy, UV-vis spectroscopy, 1H NMR, fluorescence spectroscopy, SEM, and DLS analysis were used to characterize the PNIPAM-photosensitizer nanohydrogels. Spectroscopic studies indicate that the PpIX, Pba, and PpIX-DME photosensitizers are covalently conjugated to the polymer chains, which prevents aggregation and thus allows significant singlet oxygen production upon illumination. Likewise, the lower critical solution temperature was raised to ∼44 °C in the new PNIPAM-PS hydrogels. The PNIPAM hydrogels are biocompatible with >90% cell viability even at high concentrations of the photosensitizer in vitro. Furthermore, a very sharp onset of light-dependent toxicity for the PpIX-based nanohydrogel in the nanomolar range and a more modest, but significant, photocytotoxic response for Pba-PNIPAM and PpIX-DME-PNIPAM nanohydrogels suggest that the new hydrogels have potential for applications in photodynamic therapy.

Stereoselective Synthesis of Bicyclo[6.1.0]nonene Precursors of the Bioorthogonal Reagents s-TCO and BCN.

The cyclooctyne BCN and the trans-cyclooctene s-TCO are widely used in bioorthogonal chemistry. A bottleneck for their synthesis had been a poorly selective cyclopropanation with ethyl diazoacetate. Here, we describe that low catalyst loadings (0.27 mol %) of Rh2( S-BHTL)4 provide the BCN precursor with 79:21 syn/ anti selectivity. The synthesis of the s-TCO precursor was best achieved through a sequence of Rh2(OAc)4 (0.33 mol %)-catalyzed cyclopropanation, followed by ester hydrolysis under epimerizing conditions. Both sequences could be carried out on multigram scale.

Thirty-day outcomes in Indigenous Australians following coronary artery bypass grafting.

BACKGROUND: Indigenous Australians have higher rates of cardiovascular disease and comorbidities compared to their non-indigenous counterparts. AIMS: We sought to evaluate whether indigenous status per se portends a worse prognosis following isolated coronary artery bypass grafting (CABG). METHODS: The outcomes of 778 Indigenous Australians (55 ± 10 years; 32% female) enrolled in the Australian and New Zealand Society of Cardiac and Thoracic Surgeons registry were compared to 36 124 non-Indigenous Australians (66 ± 10 years; 21% female) following isolated CABG. In a secondary analysis, patients were propensity-matched by age, sex, renal function, diabetes and ejection fraction (778 individuals in each group). RESULTS: Indigenous Australians were younger and more likely to be female and current smokers and to have diabetes, hypertension, renal impairment, heart failure and previous CABG (all P < 0.04). Indigenous patients had fewer bypasses with arterial conduits (including less internal mammary artery use) and a higher number of distal vein anastomoses (P < 0.001). Postoperative bleeding rates were higher in indigenous patients (P = 0.001). However, in-hospital and 30-day all-cause mortality and rates of 30-day readmission were similar between both groups, although cardiac mortality was higher in the indigenous cohort (1.5% vs 0.8%, P = 0.02). With propensity-matching, rates of postoperative complications were similar among the two groups, with the exception of bleeding, which remained higher in Indigenous Australians (P = 0.03). CONCLUSIONS: Despite procedural differences and higher rates of baseline comorbidities, Indigenous Australians do not have worse short-term outcomes following isolated CABG. Given the higher rates of baseline comorbidities and lower rates of arterial conduit use, it will be essential to determine long-term outcomes.

Volumetric Differences in Cerebellar Lobes in Individuals from Multiplex Alcohol Dependence Families and Controls: Their Relationship to Externalizing and Internalizing Disorders and Working Memory.

Offspring from families with multiple cases of alcohol dependence have a greater likelihood of developing alcohol dependence and related substance use disorders. Greater susceptibility for these disorders may be related to cerebellar morphology. Because posterior regions of the cerebellum are associated with cognitive abilities, we investigated whether high-risk offspring would display regionally specific differences in cerebellar morphology and whether these would be related to working memory performance. The relationship to externalizing and internalizing psychopathology was of interest because cerebellar morphology has previously been associated with a cognitive affective syndrome. A total of 131 participants underwent magnetic resonance imaging (MRI) with volumes of the cerebellar lobes obtained with manual tracing. These individuals were from high-risk (HR) for alcohol dependence families (N = 72) or from low-risk (LR) control families (N = 59). All were enrolled in a longitudinal follow-up that included repeated clinical assessments during childhood and young-adulthood prior to the scan that provided information on Axis I psychopathology. The Working Memory Index of the Wechsler Memory Scale was given at the time of the scan. Larger volumes of the corpus medullare and inferior posterior lobes and poorer working memory performance were found for the HR offspring relative to LR controls. Across all subjects, a significant positive association between working memory and total volume of corpus of the cerebellum was seen, controlling for familial risk. Presence of an internalizing or externalizing disorder interacting with familial risk was also associated with volume of the corpus medullare.

Cognition overrides orientation dependence in tactile viewpoint selection.

Humans are capable of extracting spatial information through their sense of touch: when someone strokes their hand, they can easily determine stroke direction without visual information. However, when it comes to the coordinate system used to assign the spatial relations to the stimulation, it remains poorly understood how the brain selects the appropriate system for passive touch. In the study reported here, we investigated whether hand orientation can determine coordinate assignment to ambiguous tactile patterns, whether observers can cognitively override any orientation-driven perspectives on touch, and whether the adaptation transfers across body surfaces. Our results demonstrated that the orientation of the hand in the vertical plane determines the perspective taken: an external perspective is adopted when the hand faces the observer and a gaze-centred perspective is selected when the hand faces away. Participants were then adapted to a mirror-reversed perspective through training, and the results revealed that this adapted perspective holds for the adapted surface and generalises to non-adapted surfaces, including across the body midline. These results reveal plasticity in perspective taking which relies on low-level postural cues (hand orientation) but also on higher-order somatosensory processing that can override the low-level cues.

Correlates of female sexual functioning: adult attachment and differentiation of self.

INTRODUCTION: Female sexual functioning is affected by a range of factors including motivation, psychological well-being, and relationship issues. In understanding female sexual dysfunction (FSD), there has been a tendency to privilege diagnostic and medical over relationship issues. AIM: To investigate the association between women's experience of intimacy in close relationships-operationalized in terms of attachment and degree of differentiation of self-and FSD. METHODS: Two hundred thirty sexually active Australian women responded to an invitation to complete a set of validated scales to assess potential correlates of sexual functioning. MAIN OUTCOME MEASURES: The Female Sexuality Function Index, the Experiences in Close Relationships Scale, the Differentiation of Self Inventory, as well as a set of study-specific questions were subject to hierarchical multiple regression analyses. RESULTS: Relational variables of attachment avoidance and to a lesser degree, attachment anxiety were associated with FSD. Participants with lower levels of differentiation of self were more likely to report sexual difficulties. The inability to maintain a sense of self in the presence of intimate others was the strongest predictors of sexual problems. A history of sexual abuse in adulthood and higher levels of psychological distress were also associated with sexual difficulties. CONCLUSIONS: The findings provide support for a relational understanding of female sexual functioning. Attachment avoidance, attachment anxiety, and degree of differentiation of self are shown to be associated with sexual difficulties. The findings support the need to focus on relational and psychological factors in women's experience of sex.

Effects of prenatal alcohol and cigarette exposure on offspring substance use in multiplex, alcohol-dependent families.

BACKGROUND: Prenatal exposures to alcohol, cigarettes, and other drugs of abuse are associated with numerous adverse consequences for affected offspring, including increased risk for substance use and abuse. However, maternal substance use during pregnancy appears to occur more often in those with a family history of alcohol dependence. Utilizing a sample that is enriched for familial alcohol dependence and includes controls selected for virtual absence of familial alcohol dependence could provide important information on the relative contribution of familial risk and prenatal exposures to offspring substance use. METHODS: A sample of multigenerational families specifically ascertained to be at either high or low risk for developing alcohol dependence (AD) provided biological offspring for a longitudinal prospective study. High-risk families were selected based on the presence of 2 alcohol-dependent sisters. Low-risk families were selected on the basis of minimal first and second-degree relatives with AD. High-risk (HR = 99) and Low-risk offspring (LR = 110) were assessed annually during childhood and biennially in young adulthood regarding their alcohol, drug, and cigarette use. At the first childhood visit, mothers were interviewed concerning their prenatal use of substances. RESULTS: High-risk mothers were more likely to use alcohol, cigarettes, and other drugs during pregnancy than low-risk control mothers, and to consume these substances in greater quantities. Across the sample, prenatal exposure to alcohol was associated with increased risk for both offspring cigarette use and substance use disorders (SUD), and prenatal cigarette exposure was associated with increased risk for offspring cigarette use. Controlling for risk status by examining patterns within the HR sample, prenatal cigarette exposure remained a specific predictor of offspring cigarette use, and prenatal alcohol exposure was specifically associated with increased risk for offspring SUD. CONCLUSIONS: Women with a family history of SUD are at increased risk for substance use during pregnancy. Both familial loading for alcohol dependence and prenatal exposure to alcohol or cigarettes are important risk factors in the development of offspring substance use. An inadequate assessment of family history may obscure important interactions between familial risk and prenatal exposures on offspring outcomes.

Experience of Being Fall-Prone and Participating in Research: Fallers' Perspectives.

The importance of giving a voice to groups considered hard-to-reach for research purposes is becoming increasingly apparent, with insights into their experience having the potential to improve research participation. Fall-prone older adults are a cohort underrepresented in research, often excluded in large-scale research and considered difficult to recruit. This study aims to explore older fallers' experiences of being fall-prone and participating in research. Seven older fallers (4 males, aged 69-88) participated in semi-structured telephone interviews following participation in an experimental research project. Interviews explored participants' personal experience of being fall-prone and participating in research. The resulting data was analyzed using thematic analysis. Three primary themes emerged: "Research through the eyes of older fallers", "Living with falls", and "It's all in the mind is it?". Our study gives voice to older fallers who have recently participated in experimental research to learn of their personal views on research participation.

Comparison of Pressure vs Volume Overload Ventricular Wall Stress in Patients With Valvular Heart Disease.

BACKGROUND: Aortic stenosis (AS) and mitral regurgitation (MR) result in different patterns of left ventricular remodeling and hypertrophy. OBJECTIVES: We characterized left ventricular wall stress (LVWS) profiles in pressure and volume-overloaded systems, examined the relationship between baseline LVWS and cardiac remodeling, and assessed the acute effects of valve intervention on LVWS using invasive pressures combined with cardiac magnetic resonance (CMR) imaging measures of left ventricular volumes/mass. METHODS: A total of 47 patients with severe AS undergoing transcatheter aortic valve replacement (TAVR) and 15 patients with severe MR undergoing MitraClip (MC) underwent a 6-minute walk test (6MWT), transthoracic echocardiogram, and CMR before their procedures. Catheters in the left ventricle were used to record hemodynamic changes before and after valve/clip deployment. This was integrated with CMR data to calculate LVWS before and after intervention. RESULTS: The TAVR group demonstrated significant reductions in systolic LVWS post procedure (median 24.7 Pa [IQR: 14 Pa] pre vs median 17.3 Pa [IQR: 12 Pa] post; P < 0.001). The MC group demonstrated significant reductions in diastolic LVWS (median 6.4 Pa [IQR: 5 Pa] pre vs median 4.3 Pa [IQR: 4.1 Pa] post; P = 0.021) with no significant change in systolic LVWS (30.6 ±1.61 pre vs 33 ±2.47 Pa post; P = 0.16). There was an inverse correlation between baseline systolic LVWS and 6MWT in the TAVR group (r = -0.31; P = 0.04). CONCLUSIONS: TAVR results in significant reductions in systolic LVWS acutely. MC results in significant reductions in diastolic LVWS. Higher baseline systolic LVWS in TAVR is associated with shorter 6MWT suggesting that in AS, LVWS may be a useful marker of early decompensation.

Mechanistic differences between linear vs. spirocyclic dialkyldiazirine probes for photoaffinity labeling.

Dialkyldiazirines have emerged as a photo-reactive group of choice for interactome mapping in live cell experiments. Upon irradiation, 'linear' dialkyldiazirines produce dialkylcarbenes which are susceptible to both intramolecular reactions and unimolecular elimination processes, as well as diazoalkanes, which also participate in intermolecular labeling. Cyclobutylidene has a nonclassical bonding structure and is stable enough to be captured in bimolecular reactions. Cyclobutanediazirines have more recently been studied as photoaffinity probes based on cyclobutylidene, but the mechanism, especially with respect to the role of putative diazo intermediates, was not fully understood. Here, we show that photolysis (365 nm) of cyclobutanediazirines can produce cyclobutylidene intermediates as evidenced by formation of their expected bimolecular and unimolecular products, including methylenecyclopropane derivatives. Unlike linear diazirines, cyclobutanediazirine photolysis in the presence of tetramethylethylene produces a [2 + 1] cycloaddition adduct. By contrast, linear diazirines produce diazo compounds upon low temperature photolysis in THF, whereas diazo compounds are not detected in similar photolyses of cyclobutanediazirines. Diazocyclobutane, prepared by independent synthesis, is labile, reactive toward water and capable of protein alkylation. The rate of diazocyclobutane decomposition is not affected by 365 nm light, suggesting that the photochemical conversion of diazocyclobutane to cyclobutylidene is not an important pathway. Finally, chemical proteomic studies revealed that a likely consequence of this primary conversion to a highly reactive carbene is a marked decrease in labeling by cyclobutanediazirine-based probes relative to linear diazirine counterparts both at the individual protein and proteome-wide levels. Collectively, these observations are consistent with a mechanistic picture for cyclobutanediazirine photolysis that involves carbene chemistry with minimal formation of diazo intermediates, and contrasts with the photolyses of linear diazirines where alkylation by diazo intermediates plays a more significant role.

A functional magnetic resonance imaging study of spatial working memory in children with prenatal alcohol exposure: contribution of familial history of alcohol use disorders.

BACKGROUND: Heavy prenatal alcohol exposure leads to widespread cognitive deficits, including problems with spatial working memory (SWM). Neuroimaging studies report structural and functional abnormalities in fetal alcohol spectrum disorders (FASD), but interpretations may be complicated by the co-occurrence of a family history of alcoholism. Since this history is also linked to cognitive deficits and brain abnormalities, it is difficult to determine the extent to which deficits are unique to prenatal alcohol exposure. METHODS: Age-matched subjects selected from 2 neuroimaging studies underwent functional imaging while engaging in a task assessing memory for spatial locations relative to a vigilance condition assessing attention. Pairwise comparisons were made for the following 3 groups: children with histories of heavy prenatal alcohol exposure (ALC, n = 18); those with no prenatal alcohol exposure, but a confirmed family history of alcoholism (FHP, n = 18); and nonexposed, family history negative controls (CON, n = 17). RESULTS: Relative to CON and FHP, the ALC group showed increased blood oxygen level dependent (BOLD) response in the left middle and superior frontal gyri for the SWM condition relative to the vigilance condition (SWM contrast). Additionally, the ALC group showed unique BOLD response increases in the left lingual gyrus and right middle frontal gyrus relative to CON, and left cuneus and precuneus relative to FHP. Both ALC and FHP showed greater activation compared to CON in the lentiform nucleus and insular region. CONCLUSIONS: These results confirm previous studies suggesting SWM deficits in FASD. Differences between the ALC group and the CON and FHP groups suggest the left middle and superior frontal region may be specifically affected in alcohol-exposed children. Conversely, differences from the CON group in the lentiform nucleus and insular region for the ALC and FHP groups may indicate this region is associated with family history of alcoholism rather than specifically with prenatal alcohol exposure.

Effect of predictive cuing on response inhibition in children with heavy prenatal alcohol exposure.

BACKGROUND: Heavy prenatal exposure to alcohol leads to widespread cognitive deficits, including problems with attention and response inhibition. This study examined blood oxygen level-dependent response in children with and without histories of heavy prenatal alcohol exposure during a task of response inhibition consisting of cued and noncued trials. METHODS: Children and adolescents (ages 8 to 18 years) with (alcohol-exposed [AE] = 20) and without (control [CON] = 15) histories of heavy prenatal exposure to alcohol underwent functional magnetic resonance imaging while performing a go/no-go task. Unbeknownst to subjects, a predictive cue preceded the no-go stimulus in 87% of trials. RESULTS: Groups were matched on demographic variables and did not differ on most measures of task performance. However, following cued stimuli, the AE group demonstrated a lower hit rate to go stimuli and more conservative response bias than the CON group. AE participants demonstrated more activation during no-go trials (inhibition) relative to go trials in the left precuneus, cingulate gyrus, anterior cingulate, and right medial frontal gyrus. During cue-dependent response inhibition, the AE group demonstrated less activation in the left precentral and postcentral gyrus compared to the CON group. CONCLUSIONS: Consistent with previous studies of response inhibition, the AE group demonstrated greater frontal and parietal activation when attempting to inhibit prepotent responses than the CON group, despite similar rates of commission errors. This study further demonstrated that the AE group had impaired behavioral performance on cued trials and demonstrated less activation in precentral and postcentral gyri relative to the CON group on these trials. This investigation provides evidence of impaired behavioral and neural processing of sequential information in fetal alcohol spectrum disorders, which can help improve inhibition in typical populations.

The effects of prenatal alcohol exposure and attention-deficit/hyperactivity disorder on psychopathology and behavior.

BACKGROUND: This study examined prevalence of psychiatric disorders and behavioral problems in children with and without prenatal alcohol exposure (AE) and attention-deficit/hyperactivity disorder (ADHD). METHODS: Primary caregivers of 344 children (8 to 16 years, M = 12.28) completed the Computerized Diagnostic Interview Schedule for Children-IV (C-DISC-4.0) and the Child Behavior Checklist (CBCL). Subjects comprised 4 groups: AE with ADHD (AE+, n = 85) and without ADHD (AE-, n = 52), and nonexposed with ADHD (ADHD, n = 74) and without ADHD (CON, n = 133). The frequency of specific psychiatric disorders, number of psychiatric disorders (comorbidity), and CBCL behavioral scores were examined using chi-square and analysis of covariance techniques. RESULTS: Clinical groups had greater frequency of all psychiatric disorders, except for anxiety, where the AE- and CON groups did not differ. There was a combined effect of AE and ADHD on conduct disorder. For comorbidity, children with ADHD had increased psychiatric disorders regardless of AE, which did not have an independent effect on comorbidity. For CBCL scores, there were significant main effects of AE and ADHD on all scores and significant AE × ADHD interactions for Withdrawn/Depressed, Somatic Complaints, Attention, and all Summary scores. There was a combined effect of AE and ADHD on Externalizing, Total Problems, and Attention Problems. CONCLUSIONS: Findings indicate that ADHD diagnosis elevates children's risk of psychiatric diagnoses, regardless of AE, but suggest an exacerbated relation between AE and ADHD on conduct disorder and externalizing behavioral problems in children. Findings affirm a poorer behavioral prognosis for alcohol-exposed children with ADHD and suggest that more than 1 neurobehavioral profile may exist for individuals with AE.

Can We Train Multisensory Integration in Adults? A Systematic Review.

The ability to efficiently combine information from different senses is an important perceptual process that underpins much of our daily activities. This process, known as multisensory integration, varies from individual to individual, and is affected by the ageing process, with impaired processing associated with age-related conditions, including balance difficulties, mild cognitive impairment and cognitive decline. Impaired multisensory perception has also been associated with a range of neurodevelopmental conditions, where novel intervention approaches are actively sought, for example dyslexia and autism. However, it remains unclear to what extent and how multisensory perception can be modified by training. This systematic review aims to evaluate the evidence that we can train multisensory perception in neurotypical adults. In all, 1521 studies were identified following a systematic search of the databases PubMed, Scopus, PsychInfo and Web of Science. Following screening for inclusion and exclusion criteria, 27 studies were chosen for inclusion. Study quality was assessed using the Methodological Index for Non-Randomised Studies (MINORS) tool and the Cochrane Risk of Bias tool 2.0 for Randomised Control Trials. We found considerable evidence that in-task feedback training using psychophysics protocols led to improved task performance. The generalisability of this training to other tasks of multisensory integration was inconclusive, with few studies and mixed findings reported. Promising findings from exercise-based training indicate physical activity protocols warrant further investigation as potential training avenues for improving multisensory integration. Future research directions should include trialling training protocols with clinical populations and other groups who would benefit from targeted training to improve inefficient multisensory integration.