Nicotine induces glutamate release from thalamocortical terminals in prefrontal cortex.

It has been proposed that activation of nicotinic acetylcholine receptors (nAChRs) can activate the prefrontal cortex, enhancing attention and cognition. Nicotine can stimulate the release of several different neurotransmitters in many brain regions. In the present study, we found that stimulation of nAChRs by nicotine or the endogenous agonist, acetylcholine (ACh), induces a large spontaneous increase in glutamate release onto layer V pyramidal neurons of the prefrontal cortex. This release of glutamate, measured by spontaneous excitatory postsynaptic currents (sEPSCs) in the prefrontal cortical slice, depends on intact thalamocortical terminals. It can be suppressed by mu-opioids or eliminated by blocking action potentials. The increase in sEPSCs is sensitive to low concentrations of nicotine, suggesting the involvement of high-affinity (eg alpha(4)beta(2)) nAChRs. Recent work has shown alterations in prefrontal alpha(4)beta(2) nAChRs in autism and schizophrenia, two conditions that are distinguished by abnormal prefrontal cortical activation as well as difficulty in certain aspects of cognition and integrating social and emotional cues. We show that mice lacking the beta(2) nAChR subunit do not show increased sEPSCs with either nicotine or ACh, again implicating high-affinity nicotinic receptors. These findings give new insight into the mechanism by which nicotine affects excitatory neurotransmission to the output neurons of the cerebral cortex in a pathway that is critical for cognitive function and reward expectation.     

Treatment intensity significantly influencing fibrosis in bone marrow independently of the cytogenetic response: meta-analysis of the long-term results from two prospective controlled trials on chronic myeloid leukemia.

Bone marrow fibrosis (MF) has been shown to indicate therapy failure in Ph(+) chronic myeloid leukemia (CML). However, the results on the development of MF during interferon-alpha therapy of CML are controversial. The significance of the interferon dose has not been considered as yet. In total, 627 bone marrow biopsies taken prospectively from 200 patients with CML recruited in two studies using different doses of interferon-alpha +/- low-dose cytosine arabinoside were examined for MF before and during therapy. The results showed that the risk of MF depended significantly on the interferon-alpha dose applied (P<0.000005). MF progressed during low-dose therapy (3 x 5 x 10(6) IU/week), but was prevented from progression when applying high dose (5 x 10(6) IU/m(2)/per day). MF disappeared when high-dose interferon-alpha was combined with low-dose cytosine arabinoside (P<0.000005). The risk of death markedly increased when MF occurred or progressed (P<0.0009), independent of all other prognostic factors evaluated including the cytogenetic response. In conclusion, the effectiveness of interferon-alpha on MF depends on the treatment intensity. MF reverses when combining high-dose interferon-alpha with low-dose cytosine arabinoside, but progresses when applying low-dose interferon-alpha. MF appears to be a significant early indicator of ineffective therapy in CML.     

Imaging of the symptomatic type II accessory navicular bone

Accessory ossicles of the foot are commonly mistaken for fractures. The accessory navicular is one of the most common accessory ossicles of the foot. There is a higher incidence in women and the finding might be bilateral in 50?90%. This entity is usually asymptomatic, although populations with medial foot pain have a higher prevalence. Three types of accessory navicular bone have been described. The type II accessory navicular is the most commonly symptomatic variant with localized chronic or acute on chronic medial foot pain and tenderness with associated inflammation of overlying soft tissues. Plain radiographic identification of the accessory navicular is insufficient to attribute symptomatology. Ultrasound allows for comparison with the asymptomatic side and localization of pain. Bone scintigraphy has a high sensitivity but positive findings lack specificity. Magnetic resonance imaging is of high diagnostic value for demonstrating both bone marrow and soft tissue oedema.     

Implementing the National Local Public Health System Performance Assessment: evaluation of a readiness process in Kentucky.

The objectives of the study described in this article were to test training and resource materials for preparing Kentucky public health agency staff to lead the National Local Public Health System Performance Assessment and to identify barriers encountered in implementation. Readiness supports provided to five Kentucky district and county health departments that led the system assessment process in 12 counties were evaluated using training pre- and posttests, performance assessment posttests, observations, and interviews. The training and materials provided in this study appeared to be the minimum needed for these Kentucky health departments. Training sequences need to allow time for independent study of assessment processes, and training in using and interpreting the assessment instrument should be included. Partner orientation materials targeted for nonpublic health partners would be useful. In Kentucky, barriers to completing the assessment included questions about its purpose and benefits and the lack of a self-identified local public health system. Formal training of health department staff, committed leadership, and adequate personnel resources can help overcome these barriers. The health departments that brought together system partners for the performance assessment considered it a valuable community-building educational event.     

Amantadine influences cognitive processing in patients with multiple sclerosis

We investigated the effect of amantadine on cognitive processing in patients with multiple sclerosis (MS) and fatigue with objective electrophysiological measures. Behavioral methods (Reaction Time, RT) and two different Event Related Potential (ERP) components measuring i) stimulus selection (Selection Negativity, SN) and ii) response selection (Lateralized Readiness Potential, LRP) were employed. Twenty-four patients with clinical definite MS (10 relapsing remitting and 14 secondary progressive) and confirmed fatigue in the past three months (Fatigue Severity Scale (FSS) > 4) were included. Patients were randomized in a double-blind, placebo-controlled cross-over design. We found a difference between the two treatments for ERP measures to stimuli with relevant colour starting at about 200 ms. This negativity had a higher amplitude during amantadine treatment regardless of treatment order. The RT did not differ significantly between the treated and untreated groups. Additional analysis indicated that patients with a disease duration of less than 7 years had a significant test position (practice effect), but no treatment effect, while patients with a longer MS duration showed no practice effect, but rather an improved reaction speed and increased ERP amplitude effects when treated with amantadine. The present findings suggest that amantadine exerts beneficial effects on early cognitive processes in patients with MS, but appears to be limited to subjects with a longer duration of the disease.     

Interleukin-1 and interleukin-6 gene polymorphisms and the risk of breast cancer in caucasian women.

PURPOSE: Genetic polymorphisms of cytokine-encoding genes are known to predispose to malignant disease. Interleukin (IL)-1 and IL-6 are crucially involved in breast carcinogenesis. Whether polymorphisms of the genes encoding IL-1 (IL1) and IL-6 (IL6) also influence breast cancer risk is unknown. EXPERIMENTAL DESIGN: In the present case-control study, we ascertained three polymorphisms of the IL1 gene cluster [-889 C/T polymorphism of the IL1alpha gene (IL1A), -511 C/T polymorphism of the IL1beta promoter (IL1B promoter), a polymorphism of IL1beta exon 5 (IL1B exon 5)], an 86-bp repeat in intron 2 of the IL1 receptor antagonist gene (IL1RN), and the -174 G/C polymorphism of the IL6 gene (IL6) in 269 patients with breast cancer and 227 healthy controls using PCR and pyrosequencing. RESULTS: Polymorphisms within the IL1 gene cluster and the respective haplotypes were not associated with the presence and the phenotype of breast cancer. The IL6 polymorphism was significantly associated with breast cancer. Odds ratios for women with one or two high-risk alleles versus women homozygous for the low-risk allele were 1.5 (95% confidence interval, 1.04-2.3; P = 0.04) and 2.0 (95% confidence interval, 1.1-3.6; P = 0.02), respectively. No association was ascertained between presence of the IL6 polymorphism and various clinicopathologic variables. CONCLUSIONS: Although polymorphisms within the IL1 gene cluster do not seem to influence breast cancer risk or phenotype, presence of the -174C IL6 allele increases the risk of breast cancer in Caucasian women in a dose-dependent fashion.     

Single-site port robotic-assisted hysterectomy: an update

Single-incision approach in robotic gynecology is a relatively new concept. The role of single-port systems in robotic hysterectomy, their advantages and disadvantages, as well as the technical challenges, are still under investigation. A systematic review was performed by searching in PubMed and Scopus databases. In 810 out of 1225 patients, hysterectomy was performed for non-neoplastic disease. Single-Site^® was the most common port system. Duration of the procedure and relative blood loss ranged from 60 to 311 min and 7 to 750 ml, respectively. The weight of the removed uteri ranged from 39 to 520 g. 4.9% of the included patients presented complications, among which bleeding, vaginal haematoma, laceration and dehiscence, umbilical hernia, and visceral injuries. Conversion rate to laparotomy reached 2.8%. Although some technical difficulties are still described in the literature, the single-port approach is becoming more standardized nowadays and performed by more surgeons. The initial phase of the learning curve can be achieved after five cases, while a proficiency in intracorporeal cuff suturing after 14 cases. Uterus weight and previous abdominal surgical history can still be limitations of the technique. Compared to our previous study, we can see that the technique has been used in more elderly or obese patients. The complication rate can reach 4.9% while the conversion rate can reach 2.8%. However, we consider that complication and conversion rates as well as surgical time could be improved with experience. Regarding post-operative pain and cosmetic outcomes, the lack of information do not allow us to draw any safe conclusions.     

Considerations on the EU definition of a nanomaterial: Science to support policy making

In recent years, an increasing number of applications and products containing or using nanomaterials have become available. This has raised concerns that some of these materials may introduce new risks for humans or the environment. A clear definition to discriminate nanomaterials from other materials is prerequisite to include provisions for nanomaterials in legislation. In October 2011 the European Commission published the ‘Recommendation on the definition of a nanomaterial’, primarily intended to provide unambiguous criteria to identify materials for which special regulatory provisions might apply, but also to promote consistency on the interpretation of the term ‘nanomaterial’. In this paper, the current status of various regulatory frameworks of the European Union with regard to nanomaterials is described, and major issues relevant for regulation of nanomaterials are discussed. This will contribute to better understanding the implications of the choices policy makers have to make in further regulation of nanomaterials. Potential issues that need to be addressed and areas of research in which science can contribute are indicated. These issues include awareness on situations in which nano-related risks may occur for materials that fall outside the definition, guidance and further development of measurement techniques, and dealing with changes during the life cycle.