Non-invasive anodal transcranial direct current stimulation has b

Non-invasive anodal transcranial direct current stimulation has been shown to reduce the activity of inhibitory cortical interneurons when applied to the primary motor or visual cortex. In this double-blind, sham-controlled cross-over study we tested the hypothesis that anodal transcranial direct see more current stimulation of the visual cortex would enhance the therapeutic effects of dichoptic videogame-based treatment. A homogeneous group of 16 young adults (mean age 22.1 +/- 1.1 years) with amblyopia were studied to compare

the effect of dichoptic treatment alone and dichoptic treatment combined with visual cortex direct current stimulation on measures of binocular (stereopsis) and monocular (visual acuity) visual function. The combined treatment led to greater improvements in stereoacuity than dichoptic treatment alone, indicating that direct current stimulation of the visual cortex boosts the

efficacy of dichoptic videogame-based treatment. This intervention warrants further evaluation as a novel therapeutic approach for adults with amblyopia.”
“Hypertension is common in people aged 65 and older. African Americans and women have a higher prevalence of hypertension than white individuals, and in those aged 70 and older, the hypertension was more poorly controlled than in those aged 60-69. The number of trials available in the elderly population compared with KU-60019 the general population are limited; hence, the database for strong recommendations as to goal blood pressure (BP) are limited. The American College of Cardiology with the American Heart Association has recently published a consensus report of management of hypertension in the elderly population. This review presents an overview of this consensus report and reviews specific studies that provide some novel findings regarding goal learn more BP and progression of nephropathy.

In general, the evidence strongly supports a BP goal of less than 150/80 mmHg. The evidence review for the consensus report supports a goal of < 150/80 mmHg for the elderly with scant data in those over age 80. However, it was decided to set the goal to less than 140/90 mmHg unless the patient cannot tolerate it and then try for 140-145 mmHg. The data are scant at best for those over age 80 mmHg but some evidence exists for < 150/80 mmHg. Diuretics and calcium antagonists are the most efficacious single agents for treatment; however, most patients will require two or more drugs to achieve such goals.”
“The objective of this study, the effect of aripiprazole on clinical symptoms and cognitive function in patients with chronic schizophrenia was compared to that of perospirone and olanzapine. The subjects were 31 patients, they were diagnosed with schizophrenia on the basis of the criteria of the DSM-IV. Clinical symptoms were assessed using Brief Psychiatric Rating Scale (BPRS), and cognitive function was assessed using the Wisconsin Card Sorting Test (Keio Version: KWCST) and the St.

Specific inclusion criteria were used to determine whether the on

Specific inclusion criteria were used to determine whether the onset of symptoms could be reliably attributed to the minor trauma.

RESULTS: Of the 85 patients with symptomatic Chiari I malformation seen by the senior author during this time, 11 (12.9%) had a history

of minor head or neck trauma preceding the onset of symptoms. Of these, there were 3 patients (3.5%) in whom the onset of symptoms could be attributed to the trauma based on strict inclusion criteria.

CONCLUSION: Minor head or neck trauma can precipitate the onset of symptoms in a small number of previously asymptomatic patients with Chiari I malformation. Health care professionals must be aware that neurological symptoms that persist or worsen after minor head or selleck products neck trauma could indicate an underlying Chiari I malformation.”
“OBJECTIVE: To examine a case series of reoperations for deep brain stimulation (DBS) leads in which clinical scenarios revealed AZD4547 molecular weight suboptimal outcome from a previous operation. Suboptimally placed DBS leads are one potential reason for unsatisfactory results after surgery for Parkinson’s disease (PD), essential tremor (ET), or dystonia. In a previous study of patients who experienced suboptimal results, 19 of 41 patients

had misplaced leads. Similarly, another report commented that lead placement beyond a 2- to 3-mm window resulted in inadequate clinical benefit, and, in I patient, revision improved outcome. The goal of the current study was to perform an unblinded retrospective chart review of DBS patients with unsatisfactory outcomes who presented for reoperation.

METHODS: Patients who had DBS lead replacements after reoperation were assessed with the use of a retrospective review of an institutional

review board-approved movement disorders database. Cases of reoperation for suboptimal clinical benefit were included, and cases of replacement of DBS leads caused by infection or hardware malfunction were excluded. buy SHP099 Data points studied included age, disease duration, diagnosis, motor outcomes (the Unified Parkinson Disease Rating Scale III in PD, the Tremor Rating Scale in ET, and the Unified Dystonia Rating Scale in dystonia), quality of life (Parkinson’s Disease Questionnaire-3 9 in PD), and the Clinician Global Impression scale. The data from before and after reoperation were examined to determine the estimated impact of repeat surgery.

RESULTS:There were 11 patients with PD, 7 with ET, and 4 with dystonia. The average age of the PD group was 52 years, the disease duration was 10 years, and the average vector distance of the location of the active DBS contact was adjusted 5.5 mm. Six patients (54%) with PD had preoperative off medication on DBS Unified Parkinson Disease Rating Scale scores that could be compared with postoperative off medication on DBS scores.

Among the risk factors for DVT, only the previous DVT was signifi

Among the risk factors for DVT, only the previous DVT was significantly predominant in patients who developed DVT (P = .001). The diameter of the popliteal vein was significantly smaller in patients who developed postoperative DVT than in those who did not (P

= .001). Similarly, the diameter of the gastrocnemius vein was significantly larger in patients with postoperative DVT than in those without (P = .010). TAV and TAF were significantly increased in the popliteal vein in patients who developed postoperative DVT (P = .043, 0.046, respectively). Both groups showed a similar prevalence of reflux in the POPV (P = .841). The preoperative Sonidegib manufacturer NIRS-derived RI was significantly increased in patients who developed DVT relative to those who did not (P = .004). The RI increased as the Caprini score progressed; however, there were no statistically significant differences between the three categories. Using ultrasound- and NIRS-derived parameters of significance as a unit of analysis, an optimal RI cut-off point of >2.3 showed the strongest ability to predict postoperative DVT, followed by a cut-off point >0.25 cm for the diameter of the gastrocnemius vein (GV).

Conclusions: NIRS-derived RI >2.3 may be a promising parameter for identifying patients at risk of developing postoperative DVT despite pharmacologic DVT prophylaxis. A CV diameter of >0.25 cm also seems to contribute to the

development of postoperative DVT. These results might be helpful MDV3100 ic50 to physicians for deciding which patients require more intensive thromboprophylaxis.

(J Vase Surg 2011;54:39S-47S.)”
“Viral myocarditis is an important cause of heart failure for which no specific treatments are available. Direct viral injury to cardiac cells provokes an inflammatory response that significantly contributes to cardiac damage and ensuing morbidity. Despite the central pathogenic role of autoimmune injury, buy SB431542 broad inhibition of the inflammatory response does not result in patient benefit. Many preclinical studies collectively emphasize that modulating distinct inflammatory signaling pathways may yield effective viral clearance while preserving cardiac structure. This review aims to provide an overview of the sometimes contrasting observations from experimental viral myocarditis models and to translate the lessons learned into opportunities for future investigations and therapies.”
“Lectin microarray is a new technology that utilizes a panel of lectins immobilized on well-defined substrate for high-throughout analysis of glycans and glycoproteins. In this article, we have reviewed the fabrication and detection schemes in lectin microarray and discussed its novel applications in glycomics. We have also demonstrated a lectin array on PDMS with MALDI-TOF-MS for glycoprotein analysis. This method has been demonstrated for differential analysis of serum glycoproteins in oral cancer and healthy control subjects.

In some species, juveniles provide supplementary parental

In some species, juveniles provide supplementary parental

care for younger siblings, a behavior known as alloparenting. Although the fitness consequences of alloparenting behavior have been a focus of evolutionary research, less is Forskolin research buy known about how alloparenting behavior impacts affective states. In the socially monogamous prairie vole (Microtus ochrogaster), most juveniles exhibit alloparenting behavior, making the species an ideal model for examining the effects of alloparenting on future behavioral outcomes. We randomly assigned juvenile voles to alloparenting (AL) or no alloparenting (NoAL) groups and behaviorally phenotyped them for anxiety-like and social behaviors using the elevated plus maze (EPM), open field test (OFT), startle box, social interaction test, juvenile affiliation test, and partner preference test. AL voles displayed more anxiety-like

and less exploratory behaviors than NoAL voles, spending significantly less time in the open arms of the EPM and center of an open field. We dissected the CA1 region of the hippocampus and the bed nucleus of the stria terminalis (BNST) from brains of behaviorally phenotyped voles and nontested siblings as well. Decreased brain-derived neurotrophic factor (BDNF) expression in CA1 has generally been associated with increased anxiety-like behavior in other rodents, while an anxiogenic role for BDNF in BNST is less established. Western blot analyses showed that alloparenting experience increased expression of BDNF in the BNST but decreased BDNF expression in the CA1 region Selumetinib cost of hippocampus (CA1) of nontested voles. There were similar differences in BNST BDNF of behaviorally phenotyped voles, and BDNF levels within this region ERK inhibitor were negatively correlated with exploratory behavior (i.e. time in center of OFT). Our results suggest that BDNF signaling in BNST and CA1 fluctuate with alloparenting experience, and they contribute to an increasingly complex “”BDNF hypothesis”"

in which behavioral effects of this molecule are region-specific. (C) 2012 IBRO Published by Elsevier Ltd. All rights reserved.”
“The mammalian target of rapamycin (mTOR) serine/threonine kinase is the catalytic subunit of two multi-protein complexes, referred to as mTORC1 and mTORC2. Signaling downstream of mTORC1 has a critical role in leukemic cell biology by controlling mRNA translation of genes involved in both cell survival and proliferation. mTORC1 activity can be down-modulated by upregulating the liver kinase B1/AMP-activated protein kinase (LKB1/AMPK) pathway. Here, we have explored the therapeutic potential of the anti-diabetic drug, metformin (an LKB1/AMPK activator), against both T-cell acute lymphoblastic leukemia (T-ALL) cell lines and primary samples from T-ALL patients displaying mTORC1 activation. Metformin affected T-ALL cell viability by inducing autophagy and apoptosis.


“Two international scientific societies dedicated


“Two international scientific societies dedicated

to research in neurotoxicology and neurobehavioral toxicology are the International Neurotoxicology Association (INA) and the International Congress on Occupational Health International Scientific Committee on Neurotoxicology and Psychophysiology (ICOH SCNP). From June 5-10, 2011 these two societies held a joint conference in Xi’an China entitled the Xi’an JPH203 clinical trial International Neurotoxicology Conference, Neurotoxicity and Neurodegeneration: Local Effect and Global Impact. At the conference two featured talks presented a brief history of the two societies. This article is a synthesis and expansion of those two presentations. The history of INA and ICOH SCNP is described in relation to the antecedent events leading to the formation of the two societies, their parallel developments, the nature of the societies and their scientific conferences, and a brief description of some of their accomplishments. Together, the historical development of these two societies is an important component of the development of the scientific discipline of neurotoxicology. (C) 2012 Elsevier Inc. All rights reserved.”
“It is well established

that the Nef proteins of human and simian immunodeficiency viruses (HIV and SIV) modulate major histocompatibility complex class I (MHC-I) cell surface expression to protect infected cells against lysis by cytotoxic HKI-272 datasheet T lymphocytes (CTLs). Recent data supported the observation that Nef also manipulates CTLs directly JSH-23 by down-modulating CD8 alpha beta (J. A. Leonard, T. Filzen, C. C. Carter, M. Schaefer, and K. L. Collins, J. Virol. 85: 6867-6881, 2011), but it remained unknown whether this Nef activity is conserved between different lineages of HIV and SIV. In this study, we examined

a total of 42 nef alleles from 16 different primate lentiviruses representing most major lineages of primate lentiviruses, as well as nonpandemic HIV-1 strains and the direct precursors of HIV-1 (SIVcpz and SIVgor). We found that the vast majority of these nef alleles strongly down-modulate CD8 beta in human T cells. Primate lentiviral Nefs generally interacted specifically with the cytoplasmic tail of CD8 beta, and down-modulation of this receptor was dependent on the conserved dileucine-based motif and two adjacent acidic residues (DD/E) in the C-terminal flexible loop of SIV Nef proteins. Both of these motifs are known to be important for the interaction of HIV-1 Nef with AP-2, and they were also shown to be critical for down-modulation of CD4 and CD28, but not MHC-I, by SIV Nefs. Our results show that down-modulation of CD4, CD8 beta, and CD28 involves largely overlapping (but not identical) domains and is most likely dependent on conserved interactions of primate lentiviral Nefs with cellular adaptor proteins.

Similarly, CD4 T cell-secreted interleukin-21, a critical

Similarly, CD4 T cell-secreted interleukin-21, a critical Veliparib datasheet regulator of both peripheral activated B cells and CD8 T cells, was sustained during viral persistence. The ASC survival factors B cell-activating factor of the tumor necrosis factor (TNF) family (BAFF) and a proliferating-inducing ligand (APRIL) were also significantly elevated in the infected CNS, albeit delayed relative to the chemokines. Unlike IFN-gamma-dependent BAFF upregulation, APRIL induction was IFN-gamma independent. Moreover, both APRIL and BAFF were predominantly

localized to astrocytes. Last, the expression kinetics of the APRIL and BAFF receptors coincided with CNS accumulation of ASC. Therefore, the factors associated with ASC migration, differentiation, and survival are all induced during acute viral encephalomyelitis, E7080 research buy prior to ASC accumulation in the CNS. Importantly, the CNS expression kinetics implicate rapid establishment, and subsequent maintenance, of an environment capable of supporting differentiation

and survival of protective antiviral ASC, recruited as plasmablasts from lymphoid organs.”
“BST-2/CD317/tetherin is a host factor that inhibits the release of HIV-1 and other unrelated viruses. A current model proposes that BST-2 physically tethers virions to the surface of virus-producing cells. The HIV-1-encoded Vpu protein effectively antagonizes the activity of BST-2. How Vpu accomplishes this task remains unclear; however, it is known that Vpu has the ability to down-modulate BST-2 from the cell surface. Here this website we analyzed the effects of Vpu on BST-2 by performing a series of kinetic studies with HeLa, 293T, and CEMx174 cells. Our results indicate that the surface downregulation of BST-2 is not due to an accelerated internalization or reduced recycling of internalized

BST-2 but instead is caused by interference with the resupply of newly synthesized BST-2 from within the cell. While our data confirm previous reports that the high-level expression of Vpu can cause the endoplasmic reticulum (ER)-associated degradation of BST-2, we found no evidence that Vpu targets endogenous BST-2 in the ER in the course of a viral infection. Instead, we found that Vpu acts in a post-ER compartment and increases the turnover of newly synthesized mature BST-2. Our observation that Vpu does not affect the recycling of BST-2 suggests that Vpu does not act directly at the cell surface but may interfere with the trafficking of newly synthesized BST-2 to the cell surface, resulting in the accelerated targeting of BST-2 to the lysosomal compartment for degradation.”
“Influenza virus kinetics (VK) is used as a surrogate of infectiousness, while the natural history of influenza is described by symptom dynamics (SD).

tPA also participates in various forms of chronic

neurode

tPA also participates in various forms of chronic

neurodegeneration. Accordingly, we assessed tPA activity levels in mouse models of Alzheimer’s disease (AD) and spinocerebellar ataxia type-1 (SCA1). Decreased tPA activity was detected in the cortex and subcortex of AD mice, whereas increased tPA activity was found in the cerebellum of SCA1 mice. These findings extend the existing hypotheses that low tPA activity promotes AD, whereas increased tPA activity contributes to cerebellar degeneration. Collectively, selleck inhibitor our results exemplify the utility of the amidolytic assay and emphasise tPA as a complex mediator of brain function and dysfunction. On the basis of this evidence, we propose that alterations in tPA activity levels could be used as a biomarker for perturbations in brain homeostasis. Laboratory Investigation Selleck MRT67307 (2011) 91, 1079-1091; doi:10.1038/labinvest.2011.67;

published online 25 April 2011″
“Bacterial cell shape is, in part, mediated by the peptidoglycan (murein) sacculus. Penicillin-binding proteins (PBPs) catalyze the final stages of murein biogenesis and are the targets of p-lactam antibiotics. Several low molecular mass PBPs including PBP4, PBP5, PBP6 and DacD seem to possess DD-carboxypeptidase (DD-CPase) activity, but these proteins are dispensable for survival in laboratory culture. The physiological functions of DD-CPases in vivo are unresolved and it is unclear why bacteria retain these seemingly non-essential and enzymatically redundant enzymes. However, PBP5 clearly contributes to maintenance of cell shape in some PBP mutant backgrounds. In this review, we focus on recent findings concerning the physiological SB525334 functions of the DD-CPases in vivo, identify gaps in the current knowledge of these proteins and suggest some possible courses for future study that might help reconcile current models of bacterial cell morphology.”
“The purpose of the present Study is to investigate the relationships among subjective and objective quality of life (QOL), and

levels of life skills, and their clinical determinants in outpatients with schizophrenia by using schizophrenia disease-specific QOL measures.. Data collected from 64 Outpatients were analyzed. Subjective QOL was measured with the Schizophrenia Quality of Life Scale (SQLS) and objective QOL with the Quality of Lire Scale (QLS). Patients’ family members completed the Life Skills Profile (LSP). Clinical symptoms were also assessed with several scales including the Brief Psychiatric Rating Scale (BPRS) and the Calgary Depression Scale for Schizophrenia (CDSS). Only the motivation/energy scale, but lot the Other scales of the SQLS, correlated with the QLS. The LSP rated by the family showed significant correlations with both the SQLS and the QLS. The CDSS score predicted each scale of the SQLS, and the BPRS negative symptoms score predicted the QLS. The LSP was predicted by the BPRS negative symptoms score and the CDSS score independently.

Here we summarize recent studies elucidating the transcriptional

Here we summarize recent studies elucidating the transcriptional and post-transcriptional regulation of SREBP-1c through nutrition and the action of hormones, particularly insulin, and the resulting implications for dyslipidemia of obesity, metabolic syndrome and type 2 diabetes.”
“Rationale N-Methyl-D-aspartate (NMDA) receptors have an CUDC-907 important role in different forms of behavioral and neural plasticity. Evidence suggests that these receptors may also

be involved in plasticity arising from long-term treatment with different drugs of abuse, including tolerance, sensitization, and physical dependence. There is abundant evidence demonstrating that NMDA receptors are involved in tolerance to opiate-induced antinociception; however, the role of these receptors in sensitization to the locomotor effects of opiates is more controversial.

Objective The ability of NMDA receptor antagonists to modify the development of sensitization to the locomotor stimulant effect of three different opiates was examined.

In selected studies, the ability of the antagonists to modify tolerance to the antinociceptive effects of the opiates was also examined.

Materials and methods Adult male Sprague-Dawley rats were used to assess the effects of NMDA receptor antagonists (MK-801, memantine or LY235959) on tolerance and sensitization to three opiates: morphine, methadone, or buprenorphine. It was predicted that low, selective doses of the antagonists ARN-509 chemical structure would inhibit the

development of opiate tolerance to and sensitization.

Results Consistent with our predictions, the noncompetitive NMDA receptor antagonists MK-801 and memantine and the competitive NMDA receptor antagonist LY235959 inhibited the development of sensitization to the locomotor stimulant effect of morphine. Additionally, MK-801 inhibited the development of tolerance and sensitization to methadone and buprenorphine in a similar manner.

Conclusions The results, together with previous research, suggest that NMDA receptors are broadly involved in opiate-induced plasticity, including the development of opiate tolerance and sensitization.”
“Nitric oxide (NO) is a free radical gas that has been shown to be produced by nitric oxide synthase (NOS) in different cell types and recognized to act as a neurotransmitter or neuromodulator in the nervous system. NOS isoforms are expressed and/or can be induced in the related structures of trigeminal nerve system, in which the regulation of NOS biosynthesis at different levels of gene expression may allow for a fine control of NO production. Several lines of evidence suggest that NO may play a role through multiple mechanisms in orofacial pain processing. This report will review the latest evidence for the role of NO involved in orofacial pain and the potential cellular mechanisms are also discussed. (C) 2011 Elsevier Inc. All rights reserved.

At her 6-month follow-up, she was independent and had improved to

At her 6-month follow-up, she was independent and had improved to ASIA E. Computed tomography confirmed fusion.

CONCLUSION: Spinal instrumentation eventually fails from pseudarthrosis and can cause neurological injury. In patients with atlantoaxial instability, direct C1-C2 screw fixation with posterior interspinous wiring using autograft offers the best chance for fusion. Cervical spine pathology can cause intracranial hemorrhage, and unconventional causes of injury must be considered

when routine workup is negative.”
“Urban air particulate matter (PM) has previously been associated with a variety of adverse health effects. It is now believed that the smallest particles, ultrafine or nanoparticles, are linked to the greatest health effects. The physicochemistry of these particles is likely to provide information regarding their toxicity. PS-341 mw Therefore, the aim of this study was to further the understanding of the heterogeneous and changing particle concentrations in urban air, in conjunction with gaining an understanding of the physicochemistry of the particles. A Dekati electrical low-pressure impactor was used to collect the particles and real-time data in a busy traffic corridor

in Swansea, Wales, over a period of 10 nonconsecutive weeks. Particle Epacadostat molecular weight concentrations in the street canyon were analyzed and particle physicochemistries investigated using a variety of techniques. Particle number concentrations were found to vary both diurnally and from day to day in the traffic corridor. Of all particles, the nano to fine size fraction was consistently identified in the highest concentrations (maximum: 140,000 particles cm-3). Particle physicochemistry was found to vary as a function of size, with larger particles exhibiting a greater variety of morphologies (and consequently particle types) and associated metals.”
“Airborne LGX818 asbestos fibers are associated with many serious detrimental effects on human health,

while the hazard posed by waterborne fibers remains an object of debate. In adopting a precautionary principle, asbestos content in water needs to be kept as low as possible and polluting waters with asbestos should be avoided. Turci et al. (2008) recently reported a method for the decontamination of asbestos-polluted waters or landfill leachates from chrysotile that combines power ultrasound (US) with oxalic acid (Ox), an acidic chelating molecule. In the previous study, the occurrence of antigorite, a polymorph of serpentine, the mineral group encompassing chrysotile asbestos, acted as a confounding factor for complete removal of chrysotile from water. The effects of US + Ox on pure chrysotile asbestos from Val Malenco, Italian Central Alps, were examined in this investigation.

They are believed to be associated with members of the transmembr

They are believed to be associated with members of the transmembrane AMPA receptor regulatory protein (TARP) family. TARPs mediate the delivery of AMPA receptors to the plasma membrane and mediate their synaptic trafficking. Moreover, TARPs modulate essential electrophysiological properties of AMPA receptors. Here, we compare the influence of rat TARPs (gamma 2, gamma 3, gamma 4, and gamma 8) on pharmacological properties of rat GluR1(Q)flip. We show that agonist potencies are increased by all TARPs, but to individually different extents. On the other hand, all

TARPs increase agonist potencies at the virtually non-desensitizing mutant GluRI-L479Y almost identically. Comparison AZD9291 of the influence of individual TARPs on relative agonist efficacies confirmed that the TARPs can be functionally subdivided into two subgroups, Ruboxistaurin concentration one consisting of gamma 2 and gamma 3 and one consisting of gamma 4 and gamma 8. Surprisingly, we found that TARPs convert certain AMPA receptor antagonists to agonists. The potency of one of these converted antagonists is dependent on the particular TARP. Moreover, TARPs (except gamma 4) reduce the ion channel block by the synthetic Joro spider toxin analog 1-naphthylacetyl spermine (NASP). In addition, TARPs increase the permeability of the receptor to calcium, indicating that TARPs directly modulate important ion pore properties. In summary, the data presented

herein will Selleckchem PD0332991 illustrate and help to understand the previously unexpected complexities of modulation of AMPA receptor pharmacological properties by TARPs.

(C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Background One course of antenatal corticosteroids reduces the risk of respiratory distress syndrome and neonatal death. Weekly doses given to women who remain undelivered after a single course may have benefits (less respiratory morbidity) or cause harm (reduced growth in utero). We aimed to find out whether multiple courses of antenatal corticosteroids would reduce neonatal morbidity and mortality without adversely affecting fetal growth.

Methods 1.858 women at 25-32 weeks’ gestation who remained undelivered 14-21 days after an initial course of antenatal corticosteroids and continued to be at high risk of preterm birth were randomly assigned to multiple courses of antenatal corticosteroids (n=937) or placebo (n=921), every 14 days until week 33 or delivery, whichever came first. The primary outcome was a composite of perinatal or neonatal mortality, severe respiratory distress syndrome, intraventricular haemorrhage (grade III or IV), periventricular leucomalacia, bronchopulmonary dysplasia, or necrotising enterocolitis. Analysis was by intention to treat. All patients and caregivers were unaware of the treatment given. This trial is registered as number ISRCTN2654148.