Reward System Dysfunction as a Neural Substrate of Symptom Expression Across the General Population and Patients With Schizophrenia

Dysfunctional patterns of activation in brain reward networks have been suggested as a core element in the pathophysiology of schizophrenia. However, it remains unclear whether this dysfunction is specific to schizophrenia or can be continuously observed across persons with different levels of nonclinical and clinical symptom expression. Therefore, we sought to investigate whether the pattern of reward system dysfunction is consistent with a dimensional or categorical model of psychosis-like symptom expression. 23 patients with schizophrenia and 37 healthy control participants with varying levels of psychosis-like symptoms, separated into 3 groups of low, medium, and high symptom expression underwent event-related functional magnetic resonance imaging while performing a Cued Reinforcement Reaction Time task. We observed lower activation in the ventral striatum during the expectation of high vs no reward to be associated with higher symptom expression across all participants. No significant difference between patients with schizophrenia and healthy participants with high symptom expression was found. However, connectivity between the ventral striatum and the medial orbitofrontal cortex was specifically reduced in patients with schizophrenia. Dysfunctional local activation of the ventral striatum depends less on diagnostic category than on the degree of symptom expression, therefore showing a pattern consistent with a psychosis continuum. In contrast, aberrant connectivity in the reward system is specific to patients with schizophrenia, thereby supporting a categorical view. Thus, the results of the present study provide evidence for both continuous and discontinuous neural substrates of symptom expression across patients with schizophrenia and the general populatio

safety, feasibility, and metabolic response

Background Intensive care unit (ICU)-acquired weakness in critically ill patients is a common and significant complication affecting the course of critical illness. Whole-body vibration is known to be effective muscle training and may be an option in diminishing weakness and muscle wasting. Especially, patients who are immobilized and not available for active physiotherapy may benefit. Until now whole-body vibration was not investigated in mechanically ventilated ICU patients. We investigated the safety, feasibility, and metabolic response of whole-body vibration in critically ill patients. Methods We investigated 19 mechanically ventilated, immobilized ICU patients. Passive range of motion was performed prior to whole-body vibration therapy held in the supine position for 15 minutes. Continuous monitoring of vital signs, hemodynamics, and energy metabolism, as well as intermittent blood sampling, took place from the start of baseline measurements up to 1 hour post intervention. We performed comparative longitudinal analysis of the phases before, during, and after intervention. Results Vital signs and hemodynamic parameters remained stable with only minor changes resulting from the intervention. No application had to be interrupted. We did not observe any adverse event. Whole-body vibration did not significantly and/or clinically change vital signs and hemodynamics. A significant increase in energy expenditure during whole-body vibration could be observed. Conclusions In our study the application of whole-body vibration was safe and feasible. The technique leads to increased energy expenditure. This may offer the chance to treat patients in the ICU with whole-body vibration. Further investigations should focus on the efficacy of whole-body vibration in the prevention of ICU- acquired weakness. Trial registration Applicability and Safety of Vibration Therapy in Intensive Care Unit (ICU) Patients. ClinicalTrials.gov NCT01286610. Registered 28 January 2011

Crystal growth of copper-rich ytterbium compounds: The predicted giant unit cell structures YbCu4.4 and YbCu4.25

Two new phases YbCu4.4 and YbCu4.25 are found as a result of careful phase diagram investigations. Between the congruent and peritectic formation of YbCu4.5 and YbCu3.5, respectively, the phases YbCu4.4 and YbCu4.25 are formed peritectically at 934(2)degC and 931(3)degC. Crystal growth was realised using a Bridgman technique and single crystalline grains of about 50-100 10^{-6}m were analyzed by electron diffraction and single crystal X-ray diffraction. Due to the only slight differences in both compositions and formation temperatures the growth of larger single crystals of a defined superstructure is challenging. The compounds YbCu4.4 and YbCu4.25 fit in Cerny`s (J. Solid State Chem. 174 (2003) 125) building principle {(RECu5)n(RECu2)} where RE = Yb with n = 4 and 3. YbCu4.4 and YbCu4.25 base on AuBe5/MgCu2-type substructures and contain approximately 4570 and 2780 atoms per unit cell. The new phases close the gap in the series of known copper-rich rare earth compounds for n = 1, 2 (DyCu3.5, DyCu4.0) and n = 5 (YbCu4.5, DyCu4.5)

Streptozotocin-induced beta-cell damage, high fat diet, and metformin administration regulate Hes3 expression in the adult mouse brain

Diabetes mellitus is a group of disorders characterized by prolonged high levels of circulating blood glucose. Type 1 diabetes is caused by decreased insulin production in the pancreas whereas type 2 diabetes may develop due to obesity and lack of exercise;it begins with insulin resistance whereby cells fail to respond properly to insulin and it may also progress to decreased insulin levels. The brain is an important target for insulin, and there is great interest in understanding how diabetes affects the brain. In addition to the direct effects of insulin on the brain, diabetes may also impact the brain through modulation of the inflammatory system. Here we investigate how perturbation of circulating insulin levels affects the expression of Hes3, a transcription factor expressed in neural stem and progenitor cells that is involved in tissue regeneration. Our data show that streptozotocin-induced beta-cell damage, high fat diet, as well as metformin, a common type 2 diabetes medication, regulate Hes3 levels in the brain. This work suggests that Hes3 is a valuable biomarker helping to monitor the state of endogenous neural stem and progenitor cells in the context of diabetes mellitus

Granulocyte-colony stimulating factor improves outcome in a mouse model of amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease that results in progressive loss of motoneurons, motor weakness and death within 1–5 years after disease onset. Therapeutic options remain limited despite a substantial number of approaches that have been tested clinically. In particular, various neurotrophic factors have been investigated. Failure in these trials has been largely ascribed to problems of insufficient dosing or inability to cross the blood–brain barrier (BBB). We have recently uncovered the neurotrophic properties of the haematopoietic protein granulocyte-colony stimulating factor (G-CSF). The protein is clinically well tolerated and crosses the intact BBB. This study examined the potential role of G-CSF in motoneuron diseases. We investigated the expression of the G-CSF receptor in motoneurons and studied effects of G-CSF in a motoneuron cell line and in the SOD1(G93A) transgenic mouse model. The neurotrophic growth factor was applied both by continuous subcutaneous delivery and CNS-targeted transgenic overexpression. This study shows that given at the stage of the disease where muscle denervation is already evident, G-CSF leads to significant improvement in motor performance, delays the onset of severe motor impairment and prolongs overall survival of SOD1(G93A)tg mice. The G-CSF receptor is expressed by motoneurons and G-CSF protects cultured motoneuronal cells from apoptosis. In ALS mice, G-CSF increased survival of motoneurons and decreased muscular denervation atrophy. We conclude that G-CSF is a novel neurotrophic factor for motoneurons that is an attractive and feasible drug candidate for the treatment of ALS

Wireless THz link with optoelectronic transmitter and receiver

Photonics might play a key role in future wireless communication systems that operate at terahertz (THz) carrier frequencies. A prime example is the generation of THz data streams by mixing optical signals in high-speed photodetectors. Over previous years, this concept has enabled a series of wireless transmission experiments at record-high data rates. Reception of THz signals in these experiments, however, still relied on electronic circuits. In this paper, we show that wireless THz receivers can also greatly benefit from optoelectronic signal processing techniques, in particular when carrier frequencies beyond 0.1 THz and wideband tunability over more than an octave is required. Our approach relies on a high-speed photoconductor and a photonic local oscillator for optoelectronic downconversion of THz data signals to an intermediate frequency band that is easily accessible by conventional microelectronics. By tuning the frequency of the photonic local oscillator, we can cover a wide range of carrier frequencies between 0.03 and 0.34 THz. We demonstrate line rates of up to 10 Gbit/s on a single channel and up to 30 Gbit/s on multiple channels transmitted over a distance of 58 m. To the best of our knowledge, our experiments represent the first demonstration of a THz communication link that exploits optoelectronic signal processing techniques both at the transmitter and the receiver

Wireless THz link with optoelectronic transmitter and receiver

Photonics might play a key role in future wireless communication systems that operate at terahertz (THz) carrier frequencies. A prime example is the generation of THz data streams by mixing optical signals in high-speed photodetectors. Over previous years, this concept has enabled a series of wireless transmission experiments at record-high data rates. Reception of THz signals in these experiments, however, still relied on electronic circuits. In this paper, we show that wireless THz receivers can also greatly benefit from optoelectronic signal processing techniques, in particular when carrier frequencies beyond 0.1 THz and wideband tunability over more than an octave is required. Our approach relies on a high-speed photoconductor and a photonic local oscillator for optoelectronic downconversion of THz data signals to an intermediate frequency band that is easily accessible by conventional microelectronics. By tuning the frequency of the photonic local oscillator, we can cover a wide range of carrier frequencies between 0.03 and 0.34 THz. We demonstrate line rates of up to 10 Gbit/s on a single channel and up to 30 Gbit/s on multiple channels transmitted over a distance of 58 m. To the best of our knowledge, our experiments represent the first demonstration of a THz communication link that exploits optoelectronic signal processing techniques both at the transmitter and the receiver

Incidence of Influenza in Healthy Adults and Healthcare Workers: A Systematic Review and Meta-Analysis

BACKGROUND: Working in healthcare is often considered a risk factor for influenza; however, this risk has not been quantified. We aimed to systematically review evidence describing the annual incidence of influenza among healthy adults and healthcare workers (HCWs). METHODS AND FINDINGS: We searched OVID MEDLINE (1950 to 2010), EMBASE (1947 to 2010) and reference lists of identified articles. Observational studies or randomized trials reporting full season or annual influenza infection rates for healthy, working age adult subjects and HCWs were included. Influenza infection was defined as a four-fold rise in antibody titer, or positive viral culture or polymerase chain reaction. From 24,707 citations, 29 studies covering 97 influenza seasons with 58,245 study participants were included. Pooled influenza incidence rates (IR) (95% confidence intervals (CI)) per 100 HCWs per season and corresponding incidence rate ratios (IRR) (95% CI) as compared to healthy adults were as follows. All infections: IR 18.7 (95% CI, 15.8 to 22.1), IRR 3.4 (95% CI, 1.2 to 5.7) in unvaccinated HCWs; IR 6.5 (95% CI, 4.6 to 9.1), IRR 5.4 (95% CI, 2.8 to 8.0) in vaccinated HCWs. Symptomatic infections: IR 7.5 (95% CI, 4.9 to 11.7), IRR 1.5 (95% CI, 0.4 to 2.5) in unvaccinated HCWs, IR 4.8 (95% CI, 3.2 to 7.2), IRR 1.6 (95% CI, 0.5 to 2.7) in vaccinated HCWs. CONCLUSIONS: Compared to adults working in non-healthcare settings, HCWs are at significantly higher risk of influenza

The association between frailty and MRI features of cerebral small vessel disease

Abstract: Frailty is a common syndrome in older individuals that is associated with poor cognitive outcome. The underlying brain correlates of frailty are unclear. The aim of this study was to investigate the association between frailty and MRI features of cerebral small vessel disease in a group of non-demented older individuals. We included 170 participants who were classified as frail (n = 30), pre-frail (n = 85) or non-frail (n = 55). The association of frailty and white matter hyperintensity volume and shape features, lacunar infarcts and cerebral perfusion was investigated by regression analyses adjusted for age and sex. Frail and pre-frail participants were older, more often female and showed higher white matter hyperintensity volume (0.69 [95%-CI 0.08 to 1.31], p = 0.03 respectively 0.43 [95%-CI: 0.04 to 0.82], p = 0.03) compared to non-frail participants. Frail participants showed a non-significant trend, and pre-frail participants showed a more complex shape of white matter hyperintensities (concavity index: 0.04 [95%-CI: 0.03 to 0.08], p = 0.03; fractal dimensions: 0.07 [95%-CI: 0.00 to 0.15], p = 0.05) compared to non-frail participants. No between group differences were found in gray matter perfusion or in the presence of lacunar infarcts. In conclusion, increased white matter hyperintensity volume and a more complex white matter hyperintensity shape may be structural brain correlates of the frailty phenotype

Cannabinoid Receptor 2 Signaling Does Not Modulate Atherogenesis in Mice

BACKGROUND:Strong evidence supports a protective role of the cannabinoid receptor 2 (CB(2)) in inflammation and atherosclerosis. However, direct proof of its involvement in lesion formation is lacking. Therefore, the present study aimed to characterize the role of the CB(2) receptor in Murine atherogenesis. METHODS AND FINDINGS:Low density lipoprotein receptor-deficient (LDLR(-/-)) mice subjected to intraperitoneal injections of the selective CB(2) receptor agonist JWH-133 or vehicle three times per week consumed high cholesterol diet (HCD) for 16 weeks. Surprisingly, intimal lesion size did not differ between both groups in sections of the aortic roots and arches, suggesting that CB(2) activation does not modulate atherogenesis in vivo. Plaque content of lipids, macrophages, smooth muscle cells, T cells, and collagen were also similar between both groups. Moreover, CB(2) (-/-)/LDLR(-/-) mice developed lesions of similar size containing more macrophages and lipids but similar amounts of smooth muscle cells and collagen fibers compared with CB(2) (+/+)/LDLR(-/-) controls. While JWH-133 treatment reduced intraperitoneal macrophage accumulation in thioglycollate-elicited peritonitis, neither genetic deficiency nor pharmacologic activation of the CB(2) receptor altered inflammatory cytokine expression in vivo or inflammatory cell adhesion in the flow chamber in vitro. CONCLUSION:Our study demonstrates that both activation and deletion of the CB(2) receptor do not relevantly modulate atherogenesis in mice. Our data do not challenge the multiple reports involving CB(2) in other inflammatory processes. However, in the context of atherosclerosis, CB(2) does not appear to be a suitable therapeutic target for reduction of the atherosclerotic plaque