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Oxidative stress is implicated in the aetiology of schizophrenia, and the antioxidant defence system (AODS) may be protective in this illness. We examined the major antioxidant glutathione (GSH) in prefrontal brain and its correlates with clinical and demographic variables in schizophrenia.
GSH levels were measured in the dorsolateral prefrontal region of 28 patients with chronic schizophrenia using a magnetic resonance spectroscopy sequence specifically adapted for GSH. We examined correlations of GSH levels with age, age at onset of illness, duration of illness, and clinical symptoms.
We found a negative correlation between GSH levels and age at onset (r = −0.46, p = 0.015), and a trend-level positive relationship between GSH and duration of illness (r = 0.34, p = 0.076).
Our findings are consistent with a possible compensatory upregulation of the AODS with longer duration of illness and suggest that the AODS may play a role in schizophrenia.
Mismatch negativity (MMN) is an event-related potential (ERP) component reflecting auditory predictive coding. Repeated standard tones evoke increasing positivity (‘repetition positivity’; RP), reflecting strengthening of the standard's memory trace and the prediction it will recur. Likewise, deviant tones preceded by more standard repetitions evoke greater negativity (‘deviant negativity’; DN), reflecting stronger prediction error signaling. These memory trace effects are also evident in MMN difference wave. Here, we assess group differences and test-retest reliability of these indices in schizophrenia patients (SZ) and healthy controls (HC).
Electroencephalography was recorded twice, 2 weeks apart, from 43 SZ and 30 HC, during a roving standard paradigm. We examined ERPs to the third, eighth, and 33rd standards (RP), immediately subsequent deviants (DN), and the corresponding MMN. Memory trace effects were assessed by comparing amplitudes associated with the three standard repetition trains.
Compared with controls, SZ showed reduced MMNs and DNs, but normal RPs. Both groups showed memory trace effects for RP, MMN, and DN, with a trend for attenuated DNs in SZ. Intraclass correlations obtained via this paradigm indicated good-to-moderate reliabilities for overall MMN, DN and RP, but moderate to poor reliabilities for components associated with short, intermediate, and long standard trains, and poor reliability of their memory trace effects.
MMN deficits in SZ reflected attenuated prediction error signaling (DN), with relatively intact predictive code formation (RP) and memory trace effects. This roving standard MMN paradigm requires additional development/validation to obtain suitable levels of reliability for use in clinical trials.
We present a concise summary of embryonic development in hagfish and lampreys. With the rise of evolutionary developmental approaches, the rapidly advancing frontier of research on these jawless vertebrates has revealed a number of developmental traits common among cyclostomes (e.g., distribution of trigeminal neural crest cells) and even vertebrates (e.g., brain regionalization), as well as an array of lineage-specific features (e.g., sclerotome differentiations, shift of branchial pouches). In addition to the wealth of data on gene expression patterns, techniques such as reporter expression assay, cell labeling, and functional analysis using morpholino and CRISPR are beginning to identify patterns and mechanisms of tissue inductions and interactions underlying the cyclostome body plan. However, it remains challenging to trace developmental traits to a common ancestry because each of the three living vertebrate lineages (hagfish, lampreys, gnathostomes) and their invertebrate outgroups sits atop a long branch. Fossils and embryos can complement each other to reinforce inferences about stem conditions and, with recent advances, such a reciprocal approach may be within our reach.
Collaborative programs have helped reduce catheter-associated urinary tract infection (CAUTI) rates in community-based nursing homes. We assessed whether collaborative participation produced similar benefits among Veterans Health Administration (VHA) nursing homes, which are part of an integrated system.
This study included 63 VHA nursing homes enrolled in the “AHRQ Safety Program for Long-Term Care,” which focused on practices to reduce CAUTI.
Changes in CAUTI rates, catheter utilization, and urine culture orders were assessed from June 2015 through May 2016. Multilevel mixed-effects negative binomial regression was used to derive incidence rate ratios (IRRs) representing changes over the 12-month program period.
There was no significant change in CAUTI among VHA sites, with a CAUTI rate of 2.26 per 1,000 catheter days at month 1 and a rate of 3.19 at month 12 (incidence rate ratio [IRR], 0.99; 95% confidence interval [CI], 0.67–1.44). Results were similar for catheter utilization rates, which were 11.02% at month 1 and 11.30% at month 12 (IRR, 1.02; 95% CI, 0.95–1.09). The numbers of urine cultures per 1,000 residents were 5.27 in month 1 and 5.31 in month 12 (IRR, 0.93; 95% CI, 0.82–1.05).
No changes in CAUTI rates, catheter use, or urine culture orders were found during the program period. One potential reason was the relatively low baseline CAUTI rate, as compared with a cohort of community-based nursing homes. This low baseline rate is likely related to the VHA’s prior CAUTI prevention efforts. While broad-scale collaborative approaches may be effective in some settings, targeting higher-prevalence safety issues may be warranted at sites already engaged in extensive infection prevention efforts.
Healthy adults (n 30) participated in a placebo-controlled, randomised, double-blinded, cross-over study consisting of two 28 d treatments (β2-1 fructan or maltodextrin; 3×5 g/d) separated by a 14-d washout. Subjects provided 1 d faecal collections at days 0 and 28 of each treatment. The ability of faecal bacteria to metabolise β2-1 fructan was common; eighty-seven species (thirty genera, and four phyla) were isolated using anaerobic medium containing β2-1 fructan as the sole carbohydrate source. β2-1 fructan altered the faecal community as determined through analysis of terminal restriction fragment length polymorphisms and 16S rRNA genes. Supplementation with β2-1 fructan reduced faecal community richness, and two patterns of community change were observed. In most subjects, β2-1 fructan reduced the content of phylotypes aligning within the Bacteroides, whereas increasing those aligning within bifidobacteria, Faecalibacterium and the family Lachnospiraceae. In the remaining subjects, supplementation increased the abundance of Bacteroidetes and to a lesser extent bifidobacteria, accompanied by decreases within the Faecalibacterium and family Lachnospiraceae. β2-1 Fructan had no impact on the metagenome or glycoside hydrolase profiles in faeces from four subjects. Few relationships were found between the faecal bacterial community and various host parameters; Bacteroidetes content correlated with faecal propionate, subjects whose faecal community contained higher Bacteroidetes produced more caproic acid independent of treatment, and subjects having lower faecal Bacteroidetes exhibited increased concentrations of serum lipopolysaccharide and lipopolysaccharide binding protein independent of treatment. We found no evidence to support a defined health benefit for the use of β2-1 fructans in healthy subjects.
β2-1 Fructans are purported to improve health by stimulating growth of colonic bifidobacteria, increasing host resistance to pathogens and stimulating the immune system. However, in healthy adults, the benefits of supplementation remain undefined. Adults (thirteen men, seventeen women) participated in a double-blinded, placebo-controlled, randomised, cross-over study consisting of two 28-d treatments separated by a 14-d washout period. Subjects’ regular diets were supplemented with β2-1 fructan or placebo (maltodextrin) at 3×5 g/d. Fasting blood and 1-d faecal collections were obtained at the beginning and at the end of each phase. Blood was analysed for clinical, biochemical and immunological variables. Determinations of well-being and general health, gastrointestinal (GI) symptoms, regularity, faecal SCFA content, residual faecal β2-1 fructans and faecal bifidobacteria content were undertaken. β2-1 Fructan supplementation had no effect on blood lipid or cholesterol concentrations or on circulating lymphocyte and macrophage numbers, but significantly increased serum lipopolysaccharide, faecal SCFA, faecal bifidobacteria and indigestion. With respect to immune function, β2-1 fructan supplementation increased serum IL-4, circulating percentages of CD282+/TLR2+ myeloid dendritic cells and ex vivo responsiveness to a toll-like receptor 2 agonist. β2-1 Fructans also decreased serum IL-10, but did not affect C-reactive protein or serum/faecal Ig concentrations. No differences in host well-being were associated with either treatment, although the self-reported incidence of GI symptoms and headaches increased during the β2-1 fructan phase. Although β2-1 fructan supplementation increased faecal bifidobacteria, this change was not directly related to any of the determined host parameters.
Disorganized attachment is an important early risk factor for socioemotional problems throughout childhood and into adulthood. Prevailing models of the etiology of disorganized attachment emphasize the role of highly dysfunctional parenting, to the exclusion of complex models examining the interplay of child and parental factors. Decades of research have established that extreme child birth weight may have long-term effects on developmental processes. These effects are typically negative, but this is not always the case. Recent studies have also identified the dopamine D4 receptor (DRD4) as a moderator of childrearing effects on the development of disorganized attachment. However, there are inconsistent findings concerning which variant of the polymorphism (seven-repeat long-form allele or non–seven-repeat short-form allele) is most likely to interact with caregiving in predicting disorganized versus organized attachment. In this study, we examined possible two- and three-way interactions and child DRD4 polymorphisms and birth weight and maternal caregiving at age 6 months in longitudinally predicting attachment disorganization at 36 months. Our sample is from the Maternal Adversity, Vulnerability and Neurodevelopment project, a sample of 650 mother–child dyads. Birth weight was cross-referenced with normative data to calculate birth weight percentile. Infant DRD4 was obtained with buccal swabs and categorized according to the presence of the putative allele seven repeat. Macroanalytic and microanalytic measures of maternal behavior were extracted from a videotaped session of 20 min of nonfeeding interaction followed by a 10-min divided attention maternal task at 6 months. Attachment was assessed at 36 months using the Strange Situation procedure, and categorized into disorganized attachment and others. The results indicated that a main effect for DRD4 and a two-way interaction of birth weight and 6-month maternal attention (frequency of maternal looking away behavior) and sensitivity predicted disorganized attachment in robust logistic regression models adjusted for social demographic covariates. Specifically, children in the midrange of birth weight were more likely to develop a disorganized attachment when exposed to less attentive maternal care. However, the association reversed with extreme birth weight (low and high). The DRD4 seven-repeat allele was associated with less disorganized attachment (protective), while non–seven-repeat children were more likely to be classified as disorganized attachment. The implications for understanding inconsistencies in the literature about which DRD4 genotype is the risk direction are also considered. Suggestions for intervention with families with infants at different levels of biological risk and caregiving risk are also discussed.
Changes to host behaviour induced by some trematode species, as a means of increased trophic transmission, represents one of the seminal examples of host manipulation by a parasite. The amphipod Echinogammarus marinus (Leach, 1815) is infected with a previously undescribed parasite, with infected individuals displaying positive phototaxic and negative geotaxic behaviour. This study reveals that the unknown parasite encysts in the brain, nerve cord and the body cavity of E. marinus, and belongs to the Microphallidae family. An 18 month population study revealed that host abundance significantly and negatively correlated with parasite prevalence. Investigation of the trematode's influence at the transcriptomic level revealed genes with putative neurological functions, such as serotonin receptor 1A, an inebriated-like neurotransmitter, tryptophan hydroxylase and amino acid decarboxylase, present consistent altered expression in infected animals. Therefore, this study provides one of the first transcriptomic insights into the neuronal gene pathways altered in amphipods infected with a trematode parasite associated with changes to its host's behaviour and population structure.
The Executive Committee Working Group on “Cosmic Light” was created in 2014 (at its EC94 Meeting, Apr.30-May 2, Canberra, Australia), in preparation of the contribution of the IAU to the UNESCO “2015 International Year of Light and Light Technologies” (IYL2015), which had been approved by the UN in December 2013 (see http://www.light2015.org/Home.html).
Excavation by Charles McBurney and John Clegg during the early 1960s revealed a sequence with a Mousterian occupation, of which the principal finds were two bout coupé handaxes, stratified close to the base of a Middle Devensian hyaena-den accumulation. The human occupation should belong within the period 64–38 ka with comparative and stratigraphic evidence favouring a date within the earlier part of this range before 50 ka. The hyaena-den occupation probably extends from at least 40 ka (if not 60 ka) until c. 24 ka.
The death of a patient by suicide can severely affect mental health professionals, particularly if it occurs despite major efforts to intervene. Notwithstanding the difficulties faced by clinicians, suicide prevention remains of paramount importance in order to help save lives. This article seeks to promote a pragmatic and compassionate biopsychosocial response using evidence-based interventions to reduce suicide. It introduces practical strategies that psychiatrists can use in everyday clinical practice, in particular the paradigm shift of suicide mitigation to help prevent suicide. We believe that every encounter with a suicidal person is an opportunity to intervene to reduce their distress and, potentially, to save a life. We believe that it is no longer acceptable for clinicians to state that if patients wish to kill themselves they can do so, in the absence of any attempt at a compassionate intervention.