Synaptic terminal density early in the course of schizophrenia: an in vivo UCB-J positron emission tomographic imaging study of synaptic vesicle glycoprotein 2A (SV2a).

BACKGROUND: The synaptic hypothesis is an influential theory of the pathoaetiology of schizophrenia. Supporting this, there is lower uptake of the synaptic terminal density marker UCB-J in patients with chronic schizophrenia compared to controls. However, it is unclear whether these differences are present early in the illness. To address this, we investigated [11C]UCB-J volume of distribution (VT) in antipsychotic-naïve/free patients with schizophrenia (SCZ) recruited from first-episode services compared to healthy volunteers (HV). METHODS: Forty-two volunteers (SCZ n = 21, HV n = 21) underwent [11C]UCB-J positron emission tomography to index [11C]UCB-J VT and distribution volume ratio (DVR) in the anterior cingulate, frontal, and dorsolateral prefrontal cortices, temporal, parietal and occipital lobes, hippocampus, thalamus and amygdala. Symptom severity was assessed in the SCZ group using the Positive and Negative Syndrome Scale (PANSS). RESULTS: We found no significant effects of group on [11C]UCB-J VT or DVR in most regions of interest (effect sizes from d=0.0 to 0.7, p>0.05), other than lower DVR in the temporal lobe (d=0.7, uncorrected p<0.05) and lower VT/fp in the anterior cingulate cortex in patients (d=0.7, uncorrected p<0.05). PANSS total score was negatively associated with [11C]UCB-J VT in the hippocampus in the SCZ group (r =-0.48, p=0.03). CONCLUSIONS: These findings indicate that large differences in synaptic terminal density are not present early in schizophrenia, although there may be more subtle effects. When taken with prior evidence of lower [11C]UCB-J VT in patients with chronic illness, this may indicate synaptic density changes during the course of schizophrenia

An alternative pathway for alphavirus entry

The study of alphavirus entry has been complicated by an inability to clearly identify a receptor and by experiments which only tangentially and indirectly examine the process, producing results that are difficult to interpret. The mechanism of entry has been widely accepted to be by endocytosis followed by acidification of the endosome resulting in virus membrane-endosome membrane fusion. This mechanism has come under scrutiny as better purification protocols and improved methods of analysis have been brought to the study. Results have been obtained that suggest alphaviruses infect cells directly at the plasma membrane without the involvement of endocytosis, exposure to acid pH, or membrane fusion. In this review we compare the data which support the two models and make the case for an alternative pathway of entry by alphaviruses

Glucocorticoids promote structural and functional maturation of foetal cardiomyocytes: a role for PGC-1α

Glucocorticoid levels rise dramatically in late gestation to mature foetal organs in readiness for postnatal life. Immature heart function may compromise survival. Cardiomyocyte glucocorticoid receptor (GR) is required for the structural and functional maturation of the foetal heart in vivo, yet the molecular mechanisms are largely unknown. Here we asked if GR activation in foetal cardiomyocytes in vitro elicits similar maturational changes. We show that physiologically relevant glucocorticoid levels improve contractility of primary-mouse-foetal cardiomyocytes, promote Z-disc assembly and the appearance of mature myofibrils, and increase mitochondrial activity. Genes induced in vitro mimic those induced in vivo and include PGC-1α, a critical regulator of cardiac mitochondrial capacity. SiRNA-mediated abrogation of the glucocorticoid induction of PGC-1α in vitro abolished the effect of glucocorticoid on myofibril structure and mitochondrial oxygen consumption. Using RNA sequencing we identified a number of transcriptional regulators, including PGC-1α, induced as primary targets of GR in foetal cardiomyocytes. These data demonstrate that PGC-1α is a key mediator of glucocorticoid-induced maturation of foetal cardiomyocyte structure and identify other candidate transcriptional regulators that may play critical roles in the transition of the foetal to neonatal heart

Noise Cancellation: Viral Fine Tuning of the Cellular Environment for Its Own Genome Replication

Productive replication of DNA viruses elicits host cell DNA damage responses, which cause both beneficial and detrimental effects on viral replication. In response to the viral productive replication, host cells attempt to attenuate the S-phase cyclin-dependent kinase (CDK) activities to inhibit viral replication. However, accumulating evidence regarding interactions between viral factors and cellular signaling molecules indicate that viruses utilize them and selectively block the downstream signaling pathways that lead to attenuation of the high S-phase CDK activities required for viral replication. In this review, we describe the sophisticated strategy of Epstein-Barr virus to cancel such “noisy” host defense signals in order to hijack the cellular environment

A Program for At-Risk High School Students Informed by Evolutionary Science

Improving the academic performance of at-risk high school students has proven difficult, often calling for an extended day, extended school year, and other expensive measures. Here we report the results of a program for at-risk 9th and 10th graders in Binghamton, New York, called the Regents Academy that takes place during the normal school day and year. The design of the program is informed by the evolutionary dynamics of cooperation and learning, in general and for our species as a unique product of biocultural evolution. Not only did the Regents Academy students outperform their comparison group in a randomized control design, but they performed on a par with the average high school student in Binghamton on state-mandated exams. All students can benefit from the social environment provided for at-risk students at the Regents Academy, which is within the reach of most public school districts

Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe

Using photo-elicitation to understand reasons for repeated self-harm: a qualitative study

Background: Reasons for self-harm are not well understood. One of the reasons for this is that first-hand accounts are usually elicited using traditional interview and questionnaire methods. This study aims to explore the acceptability of using an approach (photo-elicitation) that does not rely on solely verbal or written techniques, and to make a preliminary assessment of whether people can usefully employ images to support a discussion about the reasons why they self-harm. Method: Interviews with eight participants using photo elicitation, a method in which photographs produced by the participant are used as a stimulus and guide within the interview. Results: Participants responded positively to using images to support a discussion about their self-harm and readily incorporated images in the interview. Four main themes were identified representing negative and positive or adaptive purposes of self-harm: self-harm as a response to distress, self-harm to achieve mastery, self-harm as protective and self-harm as a language or form of communication. Conclusions: Employing this novel approach was useful in broadening our understanding of self-harm

Global variation in anastomosis and end colostomy formation following left-sided colorectal resection

Background End colostomy rates following colorectal resection vary across institutions in high-income settings, being influenced by patient, disease, surgeon and system factors. This study aimed to assess global variation in end colostomy rates after left-sided colorectal resection. Methods This study comprised an analysis of GlobalSurg-1 and -2 international, prospective, observational cohort studies (2014, 2016), including consecutive adult patients undergoing elective or emergency left-sided colorectal resection within discrete 2-week windows. Countries were grouped into high-, middle- and low-income tertiles according to the United Nations Human Development Index (HDI). Factors associated with colostomy formation versus primary anastomosis were explored using a multilevel, multivariable logistic regression model. Results In total, 1635 patients from 242 hospitals in 57 countries undergoing left-sided colorectal resection were included: 113 (6·9 per cent) from low-HDI, 254 (15·5 per cent) from middle-HDI and 1268 (77·6 per cent) from high-HDI countries. There was a higher proportion of patients with perforated disease (57·5, 40·9 and 35·4 per cent; P < 0·001) and subsequent use of end colostomy (52·2, 24·8 and 18·9 per cent; P < 0·001) in low- compared with middle- and high-HDI settings. The association with colostomy use in low-HDI settings persisted (odds ratio (OR) 3·20, 95 per cent c.i. 1·35 to 7·57; P = 0·008) after risk adjustment for malignant disease (OR 2·34, 1·65 to 3·32; P < 0·001), emergency surgery (OR 4·08, 2·73 to 6·10; P < 0·001), time to operation at least 48 h (OR 1·99, 1·28 to 3·09; P = 0·002) and disease perforation (OR 4·00, 2·81 to 5·69; P < 0·001). Conclusion Global differences existed in the proportion of patients receiving end stomas after left-sided colorectal resection based on income, which went beyond case mix alone

Physical and mechanical properties of concrete containing hematite as aggregates

Radiation limits above permission limit have harmful effects on living bodies (i.e., carcinogenic, etc.). Heavyweight concrete is used in facilities such as nuclear power plant and radiotherapy room where radioactive impermeability is required. Aggregate and cement play an essential role in both the shielding performance and the structural behavior of concrete. Concretes with 0\% (control), 15\%, 30\%, 45\% and 60\% of conventional aggregate replaced by hematite aggregate for each control concrete, were fabricated with 300, 350, 400 and 450 kg/m(3) cement contents. Water-cement ratio was kept constant at 0.40. In addition to investigation of the mineralogical structure of hematite, physical and mechanical experiments were carried out on the concrete produced. The results show that slump and compressive strength, like other mechanical properties, increase as the hematite aggregate replacement volume increase

Prevention of root caries in institutionalized elders: two-year results

It is well recognized that damage resulting from freeze-thaw cycles is a serious problem causing deterioration and degradation of concrete[1–2]. In general, freeze-thaw cycles change the microstructure of the concrete ultimately leading to internal stresses and cracking. Freeze-thaw damage progress at earlier stage is initiated on surface and near surface of concrete mainly due to the onset of ice forming in capillary pores which expands n volume of concrete[3]. Therefore utilizing stress waves propagating along near surface of concrete is expected to be effective to monitor the damage progress caused by repeated cycles of freeze-thaw in concrete