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Longitudinal studies of first episode of psychosis (FEP) patients are critical to understanding the dynamic clinical factors influencing functional outcomes; negative symptoms and verbal memory (VM) deficits are two such factors that remain a therapeutic challenge. This study uses white-gray matter contrast at the inner edge of the cortex, in addition to cortical thickness, to probe changes in microstructure and their relation with negative symptoms and possible intersections with verbal memory.
T1-weighted images and clinical data were collected longitudinally for patients (N = 88) over a two-year period. Cognitive data were also collected at baseline. Relationships between baseline VM (immediate/delayed recall) and rate of change in two negative symptom dimensions, amotivation and expressivity, were assessed at the behavioral level, as well as at the level of brain structure.
VM, particularly immediate recall, was significantly and positively associated with a steeper rate of expressivity symptom decline (r = 0.32, q = 0.012). Significant interaction effects between baseline delayed recall and change in expressivity were uncovered in somatomotor regions bilaterally for both white-gray matter contrast and cortical thickness. Furthermore, interaction effects between immediate recall and change in expressivity on cortical thickness rates were uncovered across higher-order regions of the language processing network.
This study shows common neural correlates of language-related brain areas underlying expressivity and VM in FEP, suggesting deficits in these domains may be more linked to speech production rather than general cognitive capacity. Together, white-gray matter contrast and cortical thickness may optimally inform clinical investigations aiming to capture peri-cortical microstructural changes.
Chagas disease is caused by infection with the insect-transmitted protozoan Trypanosoma cruzi, and is the most important parasitic infection in Latin America. The current drugs, benznidazole and nifurtimox, are characterized by limited efficacy and toxic side-effects, and treatment failures are frequently observed. The urgent need for new therapeutic approaches is being met by a combined effort from the academic and commercial sectors, together with major input from not-for-profit drug development consortia. With the disappointing outcomes of recent clinical trials against chronic Chagas disease, it has become clear that an incomplete understanding of parasite biology and disease pathogenesis is impacting negatively on the development of more effective drugs. In addition, technical issues, including difficulties in establishing parasitological cure in both human patients and animal models, have greatly complicated the assessment of drug efficacy. Here, we outline the major questions that need to be addressed and discuss technical innovations that can be exploited to accelerate the drug development pipeline.
There are multiple recent reports of an association between anxious/depressed (A/D) symptomatology and the rate of cerebral cortical thickness maturation in typically developing youths. We investigated the degree to which anxious/depressed symptoms are tied to age-related microstructural changes in cerebral fiber pathways. The participants were part of the NIH MRI Study of Normal Brain Development. Child Behavior Checklist A/D scores and diffusion imaging were available for 175 youths (84 males, 91 females; 241 magnetic resonance imagings) at up to three visits. The participants ranged from 5.7 to 18.4 years of age at the time of the scan. Alignment of fractional anisotropy data was implemented using FSL/Tract-Based Spatial Statistics, and linear mixed model regression was carried out using SPSS. Child Behavior Checklist A/D was associated with the rate of microstructural development in several white matter pathways, including the bilateral anterior thalamic radiation, bilateral inferior longitudinal fasciculus, left superior longitudinal fasciculus, and right cingulum. Across these pathways, greater age-related fractional anisotropy increases were observed at lower levels of A/D. The results suggest that subclinical A/D symptoms are associated with the rate of microstructural development within several white matter pathways that have been implicated in affect regulation, as well as mood and anxiety psychopathology.
We describe the efficacy of enhanced infection control measures, including those recommended in the Centers for Disease Control and Prevention’s 2012 carbapenem-resistant Enterobacteriaceae (CRE) toolkit, to control concurrent outbreaks of carbapenemase-producing Enterobacteriaceae (CPE) and extensively drug-resistant Acinetobacter baumannii (XDR-AB).
Before-after intervention study.
Fifteen-bed surgical trauma intensive care unit (ICU).
We investigated the impact of enhanced infection control measures in response to clusters of CPE and XDR-AB infections in an ICU from April 2009 to March 2010. Polymerase chain reaction was used to detect the presence of blaKPC and resistance plasmids in CRE. Pulsed-field gel electrophoresis was performed to assess XDR-AB clonality. Enhanced infection-control measures were implemented in response to ongoing transmission of CPE and a new outbreak of XDR-AB. Efficacy was evaluated by comparing the incidence rate (IR) of CPE and XDR-AB before and after the implementation of these measures.
The IR of CPE for the 12 months before the implementation of enhanced measures was 7.77 cases per 1,000 patient-days, whereas the IR of XDR-AB for the 3 months before implementation was 6.79 cases per 1,000 patient-days. All examined CPE shared endemic blaKPC resistance plasmids, and 6 of the 7 XDR-AB isolates were clonal. Following institution of enhanced infection control measures, the CPE IR decreased to 1.22 cases per 1,000 patient-days (P = .001), and no more cases of XDR-AB were identified.
Use of infection control measures described in the Centers for Disease Control and Prevention’s 2012 CRE toolkit was associated with a reduction in the IR of CPE and an interruption in XDR-AB transmission.
To identify risk factors associated with methicillin-resistant Staphylococcus aureus (MRSA) acquisition in long-term care facility (LTCF) residents.
Multicenter, prospective cohort followed over 6 months.
Three Veterans Affairs (VA) LTCFs.
All current and new residents except those with short stay (<2 weeks).
MRSA carriage was assessed by serial nares cultures and classified into 3 groups: persistent (all cultures positive), intermittent (at least 1 but not all cultures positive), and noncarrier (no cultures positive). MRSA acquisition was defined by an initial negative culture followed by more than 2 positive cultures with no subsequent negative cultures. Epidemiologic data were collected to identify risk factors, and MRSA isolates were typed by pulsed-field gel electrophoresis (PFGE).
Among 412 residents at 3 LTCFs, overall MRSA prevalence was 58%, with similar distributions of carriage at all 3 facilities: 20% persistent, 39% intermittent, 41% noncarriers. Of 254 residents with an initial negative swab, 25 (10%) acquired MRSA over the 6 months; rates were similar at all 3 LTCFs, with no clusters evident. Multivariable analysis demonstrated that receipt of systemic antimicrobials during the study was the only significant risk factor for MRSA acquisition (odds ratio, 7.8 [95% confidence interval, 2.1–28.6]; P = .002). MRSA strains from acquisitions were related by PFGE to those from a roommate in 9/25 (36%) cases; 6 of these 9 roommate sources were persistent carriers.
MRSA colonization prevalence was high at 3 separate VA LTCFs. MRSA acquisition was strongly associated with antimicrobial exposure. Roommate sources were often persistent carriers, but transmission from roommates accounted for only approximately one-third of MRSA acquisitions.
The Endangered Madagascar giant jumping rat, Hypogeomys antimena, has suffered a major decline in distribution and is now restricted to two seemingly unconnected sub-populations in the largest remaining fragment of deciduous, seasonally dry forest in Menabe, western Madagascar. In a previous study a rapid decrease in numbers of H. antimena was observed in relatively intact forest, suggesting a factor of population decline additional to habitat loss, and provoking fears of a negative trend occurring across its remaining range. In the current study we conducted extensive line transect surveys to estimate active H. antimena burrow density in 2004 and 2005 as an index of population size, and trapping to estimate mean group size, as a multiplier for population size estimation. Within the surveyed areas we estimated the combined size of the two H. antimena sub-populations in 2005 to be c. 36,000, considerably larger than previously assumed. There was no evidence that active burrow density across the species’ known range changed between 2000 and 2005. H. antimena was not uniformly distributed, with higher densities of active burrows found in forest with the highest canopy in areas furthest from forest edges. These core forest areas are vital for the species’ conservation and the recent declaration that the Menabe forest will receive statutory protection provides hope that H. antimena may be safeguarded. However, given its restricted range and low reproductive output, among other factors, H. antimena remains threatened and requires close future monitoring.
To evaluate the prevalence and transmission of methicillin-resistant Staphylococcus aureus (MRSA) nasal colonization, as well as risk factors associated with MRSA carriage, among residents of a long-term care facility (LTCF).
Prospective, longitudinal cohort study.
A 100-bed Veterans Administration LTCF
All current and newly admitted residents of the LTCF during an 8-week study period.
Nasal swab samples were obtained weekly and cultured on MRSA-selective media, and the cultures were graded for growth on a semiquantitative scale from 0 (no growth) to 6 (heavy growth). Epidemiologic data for the periods before and during the study were collected to assess risk factors for MRSA carriage.
Of 83 LTCF residents, 49 (59%) had 1 or more nasal swab cultures that were positive for MRSA; 34 (41%) were consistently culture-negative (designated “noncarriers”). Of the 49 culture-positive residents, 30 (36% of the total of 83 residents) had all cultures positive for MRSA (designated “persistent carriers”), and 19 (23% of the 83 residents) had at least 1 culture, but not all cultures, positive for MRSA (designated “intermittent carriers”). Multivariate analysis showed that participants with at least 1 nasal swab culture positive for MRSA were likely to have had previous hospitalization (odds ratio, 3.9) or wounds (odds ratio, 8.2). Persistent carriers and intermittent carriers did not differ in epidemiologic characteristics but did differ in mean MRSA growth score (3.7 vs 0.7; P < .001).
Epidemiologic characteristics differed between noncarriers and subjects with at least 1 nasal swab culture positive for MRSA. However, in this LTCF population, only the degree of bacterial colonization (as reflected by mean MRSA growth score) distinguished persistent carriers from intermittent carriers. Understanding the burden of colonization may be important when determining future surveillance and control strategies.