Variability in Azithromycin Susceptibility Results for Neisseria gonorrhoeae Obtained Using Gradient MIC Strip and Agar Dilution Techniques.

Azithromycin is a component of empirical treatment regimens for Neisseria gonorrhoeae infections, but antimicrobial susceptibility testing for this agent is technically challenging. We compared the intertest variability, MIC values, and CLSI/EUCAST categorization of clinical and reference isolates of N. gonorrhoeae treated with azithromycin by testing 107 clinical isolates and nine reference isolates by agar dilution and in duplicates using MIC test strips (Liofilchem, Italy) and Etests (bioMérieux, France). Replicate isolate agreement within 1 log2 between duplicate tests was 87% for MIC test strips and 100% for Etests (P < 0.001). Essential agreement with the agar dilution method was higher for Etests (91%) than for MIC test strips (44%, P < 0.001). The geometric mean MIC was highest for MIC test strips (0.8 mg/liter) and significantly higher than both Etest (0.47 mg/liter, P < 0.001) and agar dilution (0.26 mg/liter, P < 0.001) methods. Etest MICs were higher than those obtained with agar dilution (P < 0.001). Agar dilution, MIC test strip, and Etest methods categorized 96%, 85%, and 95% (P = 0.003) of clinical isolates, respectively, as susceptible/wild type according to CLSI/EUCAST criteria. Our results illustrate the difficulties underlying azithromycin susceptibility testing for N. gonorrhoeae and demonstrate that results can vary using different methods. This variability could influence antimicrobial resistance reporting between laboratories involved in N. gonorrhoeae surveillance programs.

Neurocognitive Recovery After Hospital-Treated Deliberate Self-Poisoning With Central Nervous System Depressant Drugs: A Longitudinal Cohort Study.

Hospital-treated deliberate self-poisoning (DSP) by central nervous system depressant drugs (CNS-D) has been associated with impairments in cognitive and psychomotor functions at the time of discharge. We aimed to replicate this finding and to compare recovery in the first month after discharge for CNS-D and CNS nondepressant drug ingestions. We also examined a series of multivariate explanatory models of recovery of neurocognitive outcomes over time. The CNS-D group was impaired at discharge compared with the CNS-nondepressant group in cognitive flexibility, cognitive efficiency, and working memory. There were no significant differences at discharge in visual attention, processing speed, visuomotor speed, or inhibition speed. Both groups improved in the latter measures over 1 month of follow-up. However, the CNS-D group's recovery was significantly slower for key neurocognitive domains underlying driving in complex traffic situations, namely, cognitive flexibility, cognitive efficiency, and working memory. Patients discharged after DSP with CNS-D drugs have impairments of some critical cognitive functions that may require up to 1 month to recover. Although more pre- than post-DSP variables were retained as explanatory models of neurocognitive performance overall, recovery over time could not be explained by any one of the measured covariates. Tests of cognitive flexibility could be used in clinical settings as a proxy measure for recovery of driving ability. Regulatory authorities should also consider the implications of these results for the period of nondriving advised after ingestion of CNS-D in overdose. Future research, with adequate sample size, should examine contributions of other variables to the pattern of recovery over time.

When I look into my baby's eyes . . . infant emotion recognition by mothers with borderline personality disorder.

Mothers with borderline personality disorder (BPD) have disturbed relationships with their infants, possibly associated with poor nonverbal cue perception. Individuals with BPD are poor at recognizing emotion in adults and tend to misattribute neutral (i.e., no emotion) as sad. This study extends previous research by examining how mothers with BPD perceive known (own) and unknown (control) infant stimuli depicting happy, sad, and neutral emotions. The sample consisted of 13 women diagnosed with BPD and 13 healthy control mothers. All participants completed clinical and parenting questionnaires and an infant emotion recognition task. Compared to control mothers, mothers with BPD were significantly poorer at infant emotion recognition overall, but especially neutral expressions which were misattributed most often as sad. Performance was not related to disturbed parenting but rather mothers' age and illness duration. Neither the BPD nor control mothers showed enhanced accuracy for emotional displays of their own verses unknown infant-face images. Although the sample size was small, this study provides evidence that mothers with BPD negatively misinterpret neutral images, which may impact sensitive responding to infant emotional cues. These findings have implications for clinical practice and the development of remediation programs targeting emotion-perception disturbances in mothers with BPD.

Not so primitive: context-sensitive meta-learning about unattended sound sequences.

Mismatch negativity (MMN), an evoked response potential elicited when a "deviant" sound violates a regularity in the auditory environment, is integral to auditory scene processing and has been used to demonstrate "primitive intelligence" in auditory short-term memory. Using a new multiple-context and -timescale protocol we show that MMN magnitude displays a context-sensitive modulation depending on changes in the probability of a deviant at multiple temporal scales. We demonstrate a primacy bias causing asymmetric evidence-based modulation of predictions about the environment, and we demonstrate that learning how to learn about deviant probability (meta-learning) induces context-sensitive variation in the accessibility of predictive long-term memory representations that underpin the MMN. The existence of the bias and meta-learning are consistent with automatic attributions of behavioral salience governing relevance-filtering processes operating outside of awareness.

Demographic and behavioural factors associated with antimicrobial susceptibility to azithromycin and ceftriaxone in Neisseria gonorrhoeae.

Antimicrobial resistance of Neisseria gonorrhoeae (NG) is of global public health concern. The aim of this study was to explore demographic and behavioural factors associated with antimicrobial susceptibility of NG to ceftriaxone and azithromycin. Gonococcal isolates (n = 391) from clients attending the Auckland Sexual Health Service, New Zealand, from July 2014 - June 2015 (n = 206), and July 2017 - June 2018 (n = 185), were tested for susceptibility to ceftriaxone and azithromycin. Laboratory data were linked with behavioural and demographic data. Geometric mean azithromycin MICs increased across the two time periods (0.239 mg/L in 2014/15 to 0.347 mg/L in 2017/18, p < 0.001), and ceftriaxone MICs decreased (0.007 mg/L in 2014/15 to 0.005 mg/L in 2017/18, p < 0.001). Demographic and behavioural factors were not associated with differences in ceftriaxone MICs; however azithromycin MICs were higher in men who have sex with men (0.356 mg/L) compared with the heterosexual study population (0.192 mg/L, p < 0.001) and were lower in Pacific peoples (0.201 mg/L, p < 0.001) and Maori (0.244 mg/L, p = 0.05) compared with those of European ethnicity (0.321 mg/L). Our findings show that azithromycin MICs increased in our region between 2014 and 2018; associations were seen with sexual orientation and ethnicity.

A Modified Reach-to-Grasp Task in a Supine Position Shows Coordination Between Elbow and Hand Movements After Stroke.

Objective: A modified reach-to-grasp task has been developed for the purpose of investigating arm-hand coordination in a supine position in the functional magnetic resonance imaging environment. The objective of this study was to investigate the kinematics of the reach-to-grasp task, in stroke and healthy participants. Design: Observational cohort study. Setting: Movement laboratory. Participants: Ten stroke participants and 10 age-matched healthy participants performed 10 repetitions of the modified reach-to-grasp task in two conditions-a natural condition and a standardized condition in a splint. Intervention: Not applicable. Main Outcome Measures: Kinematic variables of start time of transport, start time of aperture, movement duration, time of peak velocity (PV), percentage time of PV, peak deceleration (PD), percentage time of PD, peak aperture (PA), time of PA, and percentage time of PA were recorded. The correlation between key events in the grasp and transport trajectories were investigated. Performance between conditions and groups were compared. Results: Both groups demonstrated a significant correlation between the start time of aperture and the start time of transport and between the time of PA and PV in both conditions. A significant correlation was found between the time of PA and the PD in both conditions for the healthy group, but in neither condition for the stroke group. Movements by participants with stroke had a significantly longer movement duration, a smaller PV, and an earlier absolute time of PV and PD, and an earlier percentage time of PV and PD. They also had a smaller aperture than healthy participants. Wearing the splint resulted in a significantly higher PV, later absolute and percentage time of PV, PD, and PA, and a smaller PA compared to moving without the splint. The timing of transport variables time to peak velocity and time to peak deceleration, were strongest determinants of movement duration. Conclusion: The modified reach-to-grasp movement performed without the constraint of the splint, demonstrates similar motor control and coordination between the grasp and transport components of reach-to-grasp as in seated reach-to-grasp. This provides a new task that may be used to explore reach-to-grasp in the fMRI environment.

Auditory lateralization in schizophrenia--mismatch negativity and behavioral evidence of a selective impairment in encoding interaural time cues.

OBJECTIVE: Behavioural evidence suggests that individuals with schizophrenia may exhibit impairment in the encoding of cues to sound location. There are three primary cues used by the auditory system to locate the position of a sound in space: interaural differences in the arrival-time (ITD), phase (IPD), and the loudness (ILD) of the sound at the two ears. The goal in this study was to obtain an electrophysiological index of preattentive detection of change in sound lateralization created by these cues. METHODS: The amplitude of mismatch negativity (MMN) was measured in 18 individuals with schizophrenia and 19 healthy comparison subjects to changes in sound lateralization produced by interaural temporal cues (ITD and IPD) and interaural loudness cues (ILD). Performance was also investigated on a target detection task, where targets were defined by ITD, IPD, or ILD cues. RESULTS: Individuals with schizophrenia had reduced MMN amplitudes and decreased hit rates when deviants were created by interaural temporal cues, but not when loudness cues were used. CONCLUSIONS: Results from both the MMN and behavioural task revealed a selective impairment in the use of temporal cues to sound lateralization in individuals with schizophrenia. SIGNIFICANCE: This finding supports previous research that suggests impairment in the encoding of the temporal information in schizophrenia.

Electrophysiological, cognitive and clinical profiles of at-risk mental state: The longitudinal Minds in Transition (MinT) study.

The onset of schizophrenia is typically preceded by a prodromal period lasting several years during which sub-threshold symptoms may be identified retrospectively. Clinical interviews are currently used to identify individuals who have an ultra-high risk (UHR) of developing a psychotic illness with a view to provision of interventions that prevent, delay or reduce severity of future mental health issues. The utility of bio-markers as an adjunct in the identification of UHR individuals is not yet established. Several event-related potential measures, especially mismatch-negativity (MMN), have been identified as potential biomarkers for schizophrenia. In this 12-month longitudinal study, demographic, clinical and neuropsychological data were acquired from 102 anti-psychotic naive UHR and 61 healthy controls, of whom 80 UHR and 58 controls provided valid EEG data during a passive auditory task at baseline. Despite widespread differences between UHR and controls on demographic, clinical and neuropsychological measures, MMN and P3a did not differ between these groups. Of 67 UHR at the 12-month follow-up, 7 (10%) had transitioned to a psychotic illness. The statistical power to detect differences between those who did or did not transition was limited by the lower than expected transition rate. ERPs did not predict transition, with trends in the opposite direction to that predicted. In exploratory analysis, the strongest predictors of transition were measures of verbal memory and subjective emotional disturbance.

Visual perception and processing in children with 22q11.2 deletion syndrome: associations with social cognition measures of face identity and emotion recognition.

BACKGROUND: People with 22q11.2 deletion syndrome (22q11DS) have difficulty processing social information including facial identity and emotion processing. However, difficulties with visual and attentional processes may play a role in difficulties observed with these social cognitive skills. METHODS: A cross-sectional study investigated visual perception and processing as well as facial processing abilities in a group of 49 children and adolescents with 22q11DS and 30 age and socio-economic status-matched healthy sibling controls using the Birmingham Object Recognition Battery and face processing sub-tests from the MRC face processing skills battery. RESULTS: The 22q11DS group demonstrated poorer performance on all measures of visual perception and processing, with greatest impairment on perceptual processes relating to form perception as well as object recognition and memory. In addition, form perception was found to make a significant and unique contribution to higher order social-perceptual processing (face identity) in the 22q11DS group. CONCLUSIONS: The findings indicate evidence for impaired visual perception and processing capabilities in 22q11DS. In turn, these were found to influence cognitive skills needed for social processes such as facial identity recognition in the children with 22q11DS.

Pre-pulse inhibition and antisaccade performance indicate impaired attention modulation of cognitive inhibition in 22q11.2 deletion syndrome (22q11DS).

BACKGROUND: 22q11.2 deletion syndrome (22q11DS) is associated with a number of physical anomalies and neuropsychological deficits including impairments in executive and sensorimotor function. It is estimated that 25% of children with 22q11DS will develop schizophrenia and other psychotic disorders later in life. Evidence of genetic transmission of information processing deficits in schizophrenia suggests performance in 22q11DS individuals will enhance understanding of the neurobiological and genetic substrates associated with information processing. In this report, we examine information processing in 22q11DS using measures of startle eyeblink modification and antisaccade inhibition to explore similarities with schizophrenia and associations with neurocognitive performance. METHODS: Startle modification (passive and active tasks; 120- and 480-ms pre-pulse intervals) and antisaccade inhibition were measured in 25 individuals with genetically confirmed 22q11DS and 30 healthy control subjects. RESULTS: Individuals with 22q11DS exhibited increased antisaccade error as well as some evidence (trend-level effect) of impaired sensorimotor gating during the active condition, suggesting a dysfunction in controlled attentional processing, rather than a pre-attentive dysfunction using this paradigm. CONCLUSIONS: The findings from the present study show similarities with previous studies in clinical populations associated with 22q11DS such as schizophrenia that may indicate shared dysfunction of inhibition pathways in these groups.

Divergent patterns of social cognition performance in autism and 22q11.2 deletion syndrome (22q11DS).

Individuals with developmental disorders frequently report a range of social cognition deficits including difficulties identifying facial displays of emotion. This study examined the specificity of face emotion processing deficits in adolescents with either autism or 22q11DS compared to typically developing (TD) controls. Two tasks (face emotion recognition and weather scene recognition) were used to explore group differences in visual scanpath strategy and concurrent recognition accuracy. For faces, the autism and 22q11DS groups demonstrated lower emotion recognition accuracy and fewer fixations compared to the TD group. Individuals with autism demonstrated fewer fixations to some weather scene stimuli compared to 22q11DS and TD groups, yet achieved a level of recognition accuracy comparable to the TD group. These findings provide evidence for a divergent pattern of social cognition dysfunction in autism and 22q11DS.

Lasting first impressions: a conservative bias in automatic filters of the acoustic environment.

Even in the unattended auditory environment, what we learn first appears resistant to re-evaluation based on experience. Mismatch negativity (MMN) is an auditory event-related potential elicited to rare deviation from automatically generated predictions about the sound environment. MMN amplitude is thought to reflect the potential importance of a sound for further processing. This study was designed to explore the degree to which past experience with a sound can alter automatic attributions about that sound's importance. MMN was elicited to rare (p=.125) physical "deviants" amongst a sequence of highly probable (p=.875) "standard" sounds. Sound identity alternated across blocks within the sequence (i.e., the former deviant became the new standard and the former standard the new deviant). The time period over which a standard remained the more probable tone was varied over Fast (0.8 min), Medium (1.6 min) and Slow (2.4 min) change conditions. Given that local within-block probabilities remained constant across conditions, any change in MMN size was considered a reflection of more rostral brain regions enabling a longer time scale (across-block) representation of event-probability extraction. Larger MMNs were expected to deviations in blocks with longer standard-stability. Although a significant increase in MMN amplitude was observed with increased rule stability, MMN amplitude was heavily dependent on the initial sequence structure. A "primacy bias" was observed such that prolonged stability produced large increases in the MMN to deviations from the first established standard but substantially smaller MMN to this first standard as a later deviant. The primacy effect in these data implies that the automatic filtering of sound relevance is biased toward a confirmation of initial expectations. Initial experience therefore altered the perceived salience of subsequent events.

Autonomic hyper-vigilance in post-infective fatigue syndrome.

This study examined whether post-infective fatigue syndrome (PIFS) is associated with a disturbance in bidirectional autonomic signalling resulting in heightened perception of symptoms and sensations from the body in conjunction with autonomic hyper-reactivity to perceived challenges. We studied 23 patients with PIFS and 25 healthy matched control subjects. A heartbeat discrimination task and a pressure pain threshold test were used to assess interoceptive sensitivity. Cardiac response was assessed over a 4-min Stroop task. PIFS was associated with higher accuracy in heartbeat discrimination and a lower pressure pain threshold. Increased interoceptive sensitivity correlated strongly with current symptoms and potentiated differences in the cardiac response to the Stroop task, which in PIFS was characterized by insensitivity to task difficulty and lack of habituation. Our results provide the first evidence of heightened interoceptive sensitivity in PIFS. Together with the distinct pattern in cardiac responsivity these findings present a picture of physiological hyper-vigilance and response inflexibility.

Primary and secondary neural networks of auditory prepulse inhibition: a functional magnetic resonance imaging study of sensorimotor gating of the human acoustic startle response.

Feedforward inhibition deficits have been consistently demonstrated in a range of neuropsychiatric conditions using prepulse inhibition (PPI) of the acoustic startle eye-blink reflex when assessing sensorimotor gating. While PPI can be recorded in acutely decerebrated rats, behavioural, pharmacological and psychophysiological studies suggest the involvement of a complex neural network extending from brainstem nuclei to higher order cortical areas. The current functional magnetic resonance imaging study investigated the neural network underlying PPI and its association with electromyographically (EMG) recorded PPI of the acoustic startle eye-blink reflex in 16 healthy volunteers. A sparse imaging design was employed to model signal changes in blood oxygenation level-dependent (BOLD) responses to acoustic startle probes that were preceded by a prepulse at 120 ms or 480 ms stimulus onset asynchrony or without prepulse. Sensorimotor gating was EMG confirmed for the 120-ms prepulse condition, while startle responses in the 480-ms prepulse condition did not differ from startle alone. Multiple regression analysis of BOLD contrasts identified activation in pons, thalamus, caudate nuclei, left angular gyrus and bilaterally in anterior cingulate, associated with EMG-recorded sensorimotor gating. Planned contrasts confirmed increased pons activation for startle alone vs 120-ms prepulse condition, while increased anterior superior frontal gyrus activation was confirmed for the reverse contrast. Our findings are consistent with a primary pontine circuitry of sensorimotor gating that interconnects with inferior parietal, superior temporal, frontal and prefrontal cortices via thalamus and striatum. PPI processes in the prefrontal, frontal and superior temporal cortex were functionally distinct from sensorimotor gating.