Increased levels of a pro-inflammatory IgG receptor in the midbrain of people with schizophrenia.

BACKGROUND: There is growing evidence that neuroinflammation may contribute to schizophrenia neuropathology. Elevated pro-inflammatory cytokines are evident in the midbrain from schizophrenia subjects, findings that are driven by a subgroup of patients, characterised as a "high inflammation" biotype. Cytokines trigger the release of antibodies, of which immunoglobulin G (IgG) is the most common. The level and function of IgG is regulated by its transporter (FcGRT) and by pro-inflammatory IgG receptors (including FcGR3A) in balance with the anti-inflammatory IgG receptor FcGR2B. Testing whether abnormalities in IgG activity contribute to the neuroinflammatory abnormalities schizophrenia patients, particularly those with elevated cytokines, may help identify novel treatment targets. METHODS: Post-mortem midbrain tissue from healthy controls and schizophrenia cases (n = 58 total) was used to determine the localisation and abundance of IgG and IgG transporters and receptors in the midbrain of healthy controls and schizophrenia patients. Protein levels of IgG and FcGRT were quantified using western blot, and gene transcript levels of FcGRT, FcGR3A and FcGR2B were assessed using qPCR. The distribution of IgG in the midbrain was assessed using immunohistochemistry and immunofluorescence. Results were compared between diagnostic (schizophrenia vs control) and inflammatory (high vs low inflammation) groups. RESULTS: We found that IgG and FcGRT protein abundance (relative to ß-actin) was unchanged in people with schizophrenia compared with controls irrespective of inflammatory subtype. In contrast, FcGRT and FcGR3A mRNA levels were elevated in the midbrain from "high inflammation" schizophrenia cases (FcGRT; p = 0.02, FcGR3A; p < 0.0001) in comparison to low-inflammation patients and healthy controls, while FcGR2B mRNA levels were unchanged. IgG immunoreactivity was evident in the midbrain, and approximately 24% of all individuals (control subjects and schizophrenia cases) showed diffusion of IgG from blood vessels into the brain. However, the intensity and distribution of IgG was comparable across schizophrenia cases and control subjects. CONCLUSION: These findings suggest that an increase in the pro-inflammatory Fcγ receptor FcGR3A, rather than an overall increase in IgG levels, contribute to midbrain neuroinflammation in schizophrenia patients. However, more precise information about IgG-Fcγ receptor interactions is needed to determine their potential role in schizophrenia neuropathology.

Root morphology and seed and leaf ionomic traits in a Brassica napus L. diversity panel show wide phenotypic variation and are characteristic of crop habit.

BACKGROUND: Mineral nutrient uptake and utilisation by plants are controlled by many traits relating to root morphology, ion transport, sequestration and translocation. The aims of this study were to determine the phenotypic diversity in root morphology and leaf and seed mineral composition of a polyploid crop species, Brassica napus L., and how these traits relate to crop habit. Traits were quantified in a diversity panel of up to 387 genotypes: 163 winter, 127 spring, and seven semiwinter oilseed rape (OSR) habits, 35 swede, 15 winter fodder, and 40 exotic/unspecified habits. Root traits of 14 d old seedlings were measured in a 'pouch and wick' system (n = ~24 replicates per genotype). The mineral composition of 3-6 rosette-stage leaves, and mature seeds, was determined on compost-grown plants from a designed experiment (n = 5) by inductively coupled plasma-mass spectrometry (ICP-MS). RESULTS: Seed size explained a large proportion of the variation in root length. Winter OSR and fodder habits had longer primary and lateral roots than spring OSR habits, with generally lower mineral concentrations. A comparison of the ratios of elements in leaf and seed parts revealed differences in translocation processes between crop habits, including those likely to be associated with crop-selection for OSR seeds with lower sulphur-containing glucosinolates. Combining root, leaf and seed traits in a discriminant analysis provided the most accurate characterisation of crop habit, illustrating the interdependence of plant tissues. CONCLUSIONS: High-throughput morphological and composition phenotyping reveals complex interrelationships between mineral acquisition and accumulation linked to genetic control within and between crop types (habits) in B. napus. Despite its recent genetic ancestry (<10 ky), root morphology, and leaf and seed composition traits could potentially be used in crop improvement, if suitable markers can be identified and if these correspond with suitable agronomy and quality traits.

Preconception stress increases the risk of infertility: results from a couple-based prospective cohort study--the LIFE study.

STUDY QUESTION: Are women's stress levels prospectively associated with fecundity and infertility? SUMMARY ANSWER: Higher levels of stress as measured by salivary alpha-amylase are associated with a longer time-to-pregnancy (TTP) and an increased risk of infertility. WHAT IS KNOWN ALREADY: Data suggest that stress and reproduction are interrelated; however, the directionality of that association is unclear. STUDY DESIGN, SIZE, DURATION: In 2005-2009, we enrolled 501 couples in a prospective cohort study with preconception enrollment at two research sites (Michigan and Texas, USA). Couples were followed for up to 12 months as they tried to conceive and through pregnancy if it occurred. A total of 401 (80%) couples completed the study protocol and 373 (93%) had complete data available for this analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: Enrolled women collected saliva the morning following enrollment and then the morning following their first observed study menses for the measurement of cortisol and alpha-amylase, which are biomarkers of stress. TTP was measured in cycles. Covariate data were captured on both a baseline questionnaire and daily journals. MAIN RESULTS AND THE ROLE OF CHANCE: Among the 401 (80%) women who completed the protocol, 347 (87%) became pregnant and 54 (13%) did not. After adjustment for female age, race, income, and use of alcohol, caffeine and cigarettes while trying to conceive, women in the highest tertile of alpha-amylase exhibited a 29% reduction in fecundity (longer TTP) compared with women in the lowest tertile [fecundability odds ratios (FORs) = 0.71; 95% confidence interval (CI) = (0.51, 1.00); P < 0.05]. This reduction in fecundity translated into a >2-fold increased risk of infertility among these women [relative risk (RR) = 2.07; 95% CI = (1.04, 4.11)]. In contrast, we found no association between salivary cortisol and fecundability. LIMITATIONS, REASONS FOR CAUTION: Due to fiscal and logistical concerns, we were unable to collect repeated saliva samples and perceived stress questionnaire data throughout the duration of follow-up. Therefore, we were unable to examine whether stress levels increased as women continued to fail to get pregnant. Our ability to control for potential confounders using time-varying data from the daily journals, however, minimizes residual confounding. WIDER IMPLICATIONS OF THE FINDINGS: This is the first US study to demonstrate a prospective association between salivary stress biomarkers and TTP, and the first in the world to observe an association with infertility. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (contracts #N01-HD-3-3355, N01-HD-3-3356, N01-HD-3358). There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: Not applicable.

Structures of the dehydrogenation products of methane activation by 5d transition metal cations.

The activation of methane by gas-phase transition metal cations (M(+)) has been studied extensively, both experimentally and using density functional theory (DFT). Methane is exothermically dehydrogenated by several 5d metal ions to form [M,C,2H](+) and H2. However, the structure of the dehydrogenation product has not been established unambiguously. Two types of structures have been considered: a carbene structure where an intact CH2 fragment is bound to the metal (M(+)-CH2) and a carbyne (hydrido-methylidyne) structure with both a CH and a hydrogen bound to the metal separately (H-M(+)-CH). For metal ions with empty d-orbitals, an agostic interaction can occur that could influence the competition between carbene and carbyne structures. In this work, the gas phase [M,C,2H](+) (M = Ta, W, Ir, Pt) products are investigated by infrared multiple-photon dissociation (IR-MPD) spectroscopy using the Free-Electron Laser for IntraCavity Experiments (FELICE). Metal cations are formed in a laser ablation source and react with methane pulsed into a reaction channel downstream. IR-MPD spectra of the [M,C,2H](+) species are measured in the 300-3500 cm(-1) spectral range by monitoring the loss of H (2H in the case of [Ir,C,2H](+)). For each system, the experimental spectrum closely resembles the calculated spectrum of the lowest energy structure calculated using DFT: for Pt, a classic C(2v) carbene structure; for Ta and W, carbene structures that are distorted by agostic interactions; and a carbyne structure for the Ir complex. The Ir carbyne structure was not considered previously. To obtain this agreement, the calculated harmonic frequencies are scaled with a scaling factor of 0.939, which is fairly low and can be attributed to the strong redshift induced by the IR multiple-photon excitation process of these small molecules. These four-atomic species are among the smallest systems studied by IR-FEL based IR-MPD spectroscopy, and their spectra demonstrate the power of IR spectroscopy in resolving long-standing chemical questions.

Baldness, acne and testicular germ cell tumours.

Androgen levels during critical periods of testicular development may be involved in the aetiology of testicular germ cell tumours (TGCT). We evaluated the roles of adolescent and early adult life correlates of androgen exposure and TGCT in a hospital-based case-control study. TGCT cases (n=187) and controls (n=148), matched on age, race and state of residence, participated in the study. Unconditional logistic regression was used to estimate associations between TGCT and male pattern baldness, severe acne, markers of puberty onset and body size. Cases were significantly less likely to report hair loss than controls [odds ratio (OR): 0.6; 95% confidence interval (CI): 0.4, 1.0]. Amount of hair loss, increasing age at onset and increasing rate of loss were all inversely associated with TGCT (rate of hair loss: p-trend=0.03; age at onset: p-trend=0.03; amount of hair loss: p-trend=0.01). History of severe acne was inversely associated with TGCT (OR: 0.5; 95% CI: 0.3, 0.9) and height was positively associated with TGCT (p-trend=0.02). Increased endogenous androgen levels during puberty and early adulthood may be associated with a decreased risk of TGCT. Additional studies of endogenous hormone levels during puberty and early adult life are warranted, especially studies evaluating the role of androgen synthesis, metabolism and uptake.

Developing a user-generated measure of continuity of care: brief report.

OBJECTIVE: This paper describes a measure of continuity of care, establishes its reliability and tests it in a field trial sample for evidence of its validity. In contrast to others, this measure has been generated from the perspectives of service users. As continuity of care is a concern particularly for those with severe mental illness, we have confined our work to this population group. METHOD: Service users in focus groups and expert panels generated the measure. The researchers were themselves service users. Test-retest reliability was assessed with an independent sample. The measure was administered to a final independent field trial sample to determine their experiences of continuity of care and for further psychometric testing. RESULTS: The measure generated by service users has satisfactory psychometric properties. Service users in the field trial sample were more satisfied when continuity, as assessed by this measure, was in place. CONCLUSION: It is possible and valid to construct outcome measures in mental health entirely from the user perspective. This has not been done before.

Out of the silence: towards grassroots and trauma-informed support for people who have experienced sexual violence and abuse.

To experience sexual violence and abuse is to experience silence. This commentary explores some of the ways in which psychiatry reinforces the silencing of sexual violence survivors. We argue that current psychiatric responses to sexual violence typically constitute iatrogenic harm including through: a failure to provide services that meet survivors' needs, a failure to believe or validate disclosures; experiences of medicalisation and diagnoses which can delegitimise people's own knowledge and meaning; 'power over' relational approaches which can prevent compassionate responses and result in staff having to develop their own coping strategies; and poorly addressed and reported experiences of sexual violence within psychiatric settings. We argue that these multiple forms of silencing have arisen in part because of biomedical dominance, a lack of support and training in sexual violence for staff, inconsistent access to structured, reflective supervision, and the difficulties of facing the horror of sexual violence and abuse. We then describe community-based and grassroots responses, and consider the potential of trauma-informed approaches. Whilst this paper has a UK focus, some aspects will resonate globally, particularly given that Western psychiatry is increasingly being exported around the globe.

Literature review and case series of haemorrhagic cholecystitis.

A diagnosis of haemorrhagic cholecystitis is difficult to make as it is rare and mimics other common disorders. We present three patients who presented with haemorrhagic cholecystitis, two of whom were on anti-coagulation at presentation. All 3 patients were treated conservatively, 2 with percutaneous cholecystostomy drainage and 1 patient with intravenous antibiotics. There are few guidelines on the management of such a condition.

Evaluation of Bistar 80SC (bifenthrin) as a tent treatment for protection against mosquitoes in Northern Territory, Australia.

A field trial to assess the efficacy of Bistar 80 SC as a barrier treatment of Australian military tents was conducted over 10 d at Mount Bundey Military Training Area, Northern Territory, Australia, in March 2003. Four pairs of standard eight-person tents were erected, with a single tent in each pair treated with 0.1% Bistar 80 SC as a course spray, and the remainder left as untreated control tents. Carbon dioxide-baited traps were operated in each tent nightly, and biting collections conducted over 8 nights. There was a mean increase in protection of 81% for mosquitoes entering treated tents and 90.4% increase in protection against biting of predominantly Culex annulirostris Skuse. In addition, bifenthrin applied to the military tents enhances the protection of occupants against bites from this important arbovirus vector.

Eye patches: Protein assembly of index-gradient squid lenses.

A parabolic relationship between lens radius and refractive index allows spherical lenses to avoid spherical aberration. We show that in squid, patchy colloidal physics resulted from an evolutionary radiation of globular S-crystallin proteins. Small-angle x-ray scattering experiments on lens tissue show colloidal gels of S-crystallins at all radial positions. Sparse lens materials form via low-valence linkages between disordered loops protruding from the protein surface. The loops are polydisperse and bind via a set of hydrogen bonds between disordered side chains. Peripheral lens regions with low particle valence form stable, volume-spanning gels at low density, whereas central regions with higher average valence gel at higher densities. The proteins demonstrate an evolved set of linkers for self-assembly of nanoparticles into volumetric materials.

Environmental factors associated with distribution and range limits of malaria vector Anopheles farauti in Australia.

Ecological factors associated with the narrow coastal distribution of Anopheles farauti Laveran s.s. were investigated using decision tree software and a recently developed software tool that permits analysis of environmental gradients across distributional boundaries. Significant variables identified by these procedures were then used to develop ecological niche models that permitted detailed--and improved--predictions of the species' overall distribution. These methods identified seven climatic factors (four of temperature factors and three atmospheric moisture factors) from among 40 environmental variables related to the range of this species. In addition, the gradient-analysis tool identified elevation as being particularly important. The distributional hypothesis predicted using ecological niche modeling of these factors included all of the record sites from which An. farauti s.s. was collected in northern Australia and successfully reconstructed its narrow limitation to coastal areas. Omission of elevation from analyses resulted in unrealistic predictions of potential distributional areas > 100 km inland, where the species has not been found.

Problems highlighted when using anticoagulated samples in the standard tube low ionic strength antiglobulin test.

Within the UK blood transfusion services, there is currently no recommendation for the use of either clotted or anticoagulated samples for antibody identification testing. This report describes three cases in which the detection of IgM antibodies was impeded by the use of anticoagulated samples. Two patient samples, referred for compatibility testing, were both identified as having IgM complement-activating anti-S and the remaining case involved an antenatal patient with IgM complement-activating anti-Vel. In all three cases, the coincidental referral and investigation of both clotted and anticoagulated samples led to the discrepancy in serum and plasma test results becoming apparent. Potential errors in selection of suitable blood for transfusion and appropriate antenatal management were avoided by correct identification of the antibodies present using the clotted samples.

The anopheline fauna of Papua New Guinea.

Surveys for anopheline mosquitoes were conducted throughout the mainland of Papua New Guinea from 1992 to 1998 with the aim of mapping the distribution of the anopheline fauna. Larval collections, adult trap, and human landing collections indicated the presence of seven species (other than those belonging to the Anopheles punctulatus group); these were An. bancroftii, An. annulipes, An, karwari, An. longirostris, An. meraukensis, An. novaguinensis, and An. subpictus. The distribution and ecology of these species is discussed.

A comparison of two-dimensional echocardiography vs carotid duplex scanning in older patients with cerebral ischemia.

BACKGROUND: To determine the relative value of two-dimensional (2D) echocardiography vs carotid duplex scanning and to devise an optimal, cost-effective diagnostic approach for older patients with cerebral ischemia, 68 consecutive patients in sinus rhythm who suffered focal cerebral ischemia were studied. All patients underwent 2D echocardiography and carotid duplex scanning in addition to routine clinical evaluation. METHODS: Twenty-five of 68 patients had Q-wave myocardial infarction by electrocardiography; nine (36%) of these 25 had left ventricular mural thrombi demonstrated by 2D echocardiography. In contrast, none of 43 patients without Q-wave myocardial infarction had clinically unsuspected findings diagnosed by 2D echocardiography. Duplex scanning, however, identified significant, abnormal findings in the carotid artery ipsilateral to the involved cerebral hemisphere in 23 patients (34%). CONCLUSIONS: Thus, in older patients in sinus rhythm who suffer a cerebral ischemic event, carotid duplex scanning has a higher diagnostic yield than 2D echocardiography and appears to be a more cost-effective initial test. Our data suggest that in patients with carotid distribution cerebral ischemic events and no obvious cardiac source for emboli by history and physical examination, 2D echocardiography should be limited to those with evidence of Q-wave myocardial infarction by electrocardiography; such management should optimize diagnostic yield and cost effectiveness.

Bupropion SR as an aid to smoking cessation in smokers treated previously with bupropion: a randomized placebo-controlled study.

BACKGROUND: Many persons who attempt to quit smoking have made previous unsuccessful attempts to quit with pharmacologic aids. An understanding of the impact of these previous attempts to quit is vital for selecting medications that may be more successful in a future attempt to quit. In particular, the effect of repeated use of bupropion SR (Zyban; INN, amfebutamone) on abstinence rates has not been studied previously. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled study in 450 smokers who had previously used bupropion in a smoking cessation attempt. The study consisted of a screening phase, a 12-week treatment phase, and a follow-up at month 6. Participants made regular clinic visits throughout the treatment phase during which they received brief counseling sessions to encourage abstinence from smoking. The primary end point was continuous abstinence from smoking from weeks 4 through 7. Secondary efficacy end points were examined throughout the treatment phase and at follow-up after 6 months. RESULTS: In participants receiving bupropion SR, 27% (61 of 226) remained abstinent throughout the period from weeks 4 through 7 compared with 5% (11 of 224) of participants receiving placebo (P <.001). Significantly (P <.001) more participants who received bupropion SR during the treatment phase remained continuously abstinent from the start of week 4 through month 6 (27 of 226; 12%) compared with participants who received placebo (5 of 224; 2%). Eleven participants receiving placebo (5%) and 19 participants receiving bupropion SR (8%) stopped taking the study medication because of an adverse event. CONCLUSIONS: Bupropion SR is an effective medication for retreatment of smokers who have used bupropion SR previously.

An analysis of 110 serious enterococcal infections. Epidemiology, antibiotic susceptibility, and outcome.

A prospective, observational study of 110 patients with serious infections due to Enterococcus spp. in 6 university and community teaching hospitals in Connecticut was conducted to define the epidemiology of community and nosocomial serious enterococcal infections and to determine risk factors, including antibiotic resistances, that contribute to outcome. Serious community and nosocomial enterococcal infections involved a variety of sites, and antibiotic resistance was common. Types of infection by major organ system were cardiovascular, 54% (catheter-related bacteremia 28%, primary bacteremia 18%, endocarditis 6%, septic thrombophlebitis 1%); intra-abdominal, 13% (including cholangitis, 6%); renal, 13%; skin and soft tissue, 5%; bone and joint, 4%; pleuropulmonary, 4%; central nervous system, 3%; deep surgical wound, 3%; and endometritis, 2%. Sixty-one percent of infections were nosocomial; 48% of these occurred in the intensive care unit. Enterococcus faecium was responsible for 20% of all infections. Antibiotic resistances among the infections included high-level gentamicin resistance (26%), ampicillin resistance (10%), and vancomycin resistance (8%). Clinical cure was achieved in 64% of patients; 6.8% of patients relapsed, 6.8% had recurrence of the infection with a different pathogen, and overall mortality was 23%. Ampicillin resistance and a high acute physiology and chronic health evaluation (APACHE) II score were highly predictive of lack of cure.

Reduced left ventricular systolic pump performance and depressed myocardial contractile function in patients > 65 years of age with normal ejection fraction and a high relative wall thickness.

We studied the relation between relative wall thickness, left ventricular systolic pump performance, and myocardial contractile function in 77 older patients with normal ejection fraction who were free of valvular and myocardial ischemic disease. Group 1 comprised 49 patients with relative wall thickness > or = 0.45; group 2 (n = 28) had normal relative wall thickness. Pump performance was characterized by stroke volume index, cardiac index, and stroke work; myocardial function was characterized by midwall shortening and circumferential stress versus shortening relations. Group 1 patients had lower end-diastolic volume (83 +/- 3 vs 124 +/- 5 ml, p < 0.05), cardiac index (2.6 +/- 0.2 vs 3.5 +/- 0.1 L/min/m2, p < 0.05), and stroke work/100 g left ventricular mass (43 +/- 2 vs 53 +/- 3 g-m/100 g, p < 0.005). Although there was no significant difference with regard to ejection fraction or fractional shortening at the endocardium, fractional shortening at the midwall was significantly lower in group 1 than in group 2 (16 +/- 1% vs 19 +/- 1%, p < 0.005). This lower value for midwall shortening was observed despite lower values for endsystolic stress, implying decreased myocardial contractile function. Lower stroke volume index in group 1 patients, likely due to small chamber size, was not offset by increased heart rate, resulting in a low-normal cardiac index; in 33% of group 1 patients, cardiac index was < 2.2 L/min/m2, indicating reduced pump performance. Our data indicate an abnormality in pump performance and myocardial function in patients who have high relative wall thickness and normal ejection fraction.

Evaluation of extent of shortening versus velocity of shortening at the endocardium and midwall in hypertensive heart disease.

To assess the incremental value of velocity of shortening velocity parameters compared with simpler, more widely used, extent of shortening parameters in compensated left ventricular hypertrophy, we studied 52 patients with left ventricular hypertrophy and 63 age-matched controls. Velocity parameters did not provide incremental information beyond that obtained by extent of shortening parameters.

The possibility of an "X" factor. The first documented drug resistance of human malaria.

Malaria was the major cause of casualties among allied forces in the South West Pacific campaigns during 1942 and 1943, despite the suppressive use of quinine and later atebrin. Clinical experiments undertaken at the Land Headquarters Medical Research Unit of the Australian Army in Cairns, under the direction of Neil Hamilton Fairley, demonstrated that atebrin was able to provide complete protection against vivax and falciparum malaria. Fairley presented the experimental results to army commanders in a specially convened conference at Atherton, Queensland, in June 1944 and persuaded the army that the solution to the malaria problem was for men to take 1 tablet (100 mg) of atebrin each day with unvarying regularity while in a malarious area and for 4 weeks afterwards. Subsequently, rigid atebrin discipline was adopted and the incidence of the disease amongst Australian soldiers in New Guinea during 1945 fell to the lowest levels ever recorded to that time by non-immune troops operating for extended periods in highly endemic malarious areas. The one exception to this unprecedented achievement was during the Aitape-Wewak campaign when an epidemic of falciparum malaria developed despite the use of suppressive atebrin. An investigation of this epidemic, involving chemotherapeutic experiments of malaria derived from specially selected patients evacuated to Cairns, showed that some of the parasites were resistant to atebrin. This paper provides an account of how the epidemic was dealt with by commanders in the field; how suspected atebrin-resistant cases came to light; and how these cases were dealt with experimentally. The emergence and spread of drug-resistant falciparum malaria has since become a key factor limiting man's endeavour to combat the disease. The investigation of the Aitape-Wewak epidemic involved the first systematic field and laboratory studies on the resistance of human malaria to any drug. From the scientific point-of-view, it broke new ground and covered uncharted territory which had not been explored previously by other workers. These observations formed the solid foundations on which later advances in this field subsequently have developed.

Advances in early fetal loss research: importance for risk assessment.

The assessment of early fetal losses (EFLs) in relationship to environmental agents offers unique advantages compared to other end points for hazard assessment. There is a high incidence (greater than 20% of all pregnancies end in an EFL), and the interval between exposure and end point is the short duration between conception and event, i.e., approximately 12 weeks. In contrast, cancer, which is the primary end point evaluated in risk assessment models, occurs with much lower frequency, and the latency period is measured in years or decades. EFLs have not been used effectively for risk assessment because most of the events are not detected. Prospective studies provide the only approach whereby it is possible to link exposure to EFLs. Recent methodologic advancements have demonstrated that it is now possible to conduct population-based studies of EFLs. It is likely that EFLs could serve as sentinels to monitor adverse health effects of many potential environmental hazards. The methodology will be demonstrated using lead exposure in utero as an example.