AFQ056, a new mGluR5 antagonist for treatment of fragile X syndrome

Fragile X syndrome, the most common form of inherited intellectual disability, is caused by a lack of FMRP, which is the product of the Fmr1 gene. FMRP is an RNA-binding protein and a component of RNA-granules found in the dendrites of neurons. At the synapse, FMRP is involved in regulation of translation of specific target mRNAs upon stimulation of mGluR5 receptors. In this study, we test the effects of a new mGluR5 antagonist (AFQ056) on the prepulse inhibition of startle response in mice. We show that Fmr1 KO mice have a deficit in inhibition of the startle response after a prepulse and that AFQ056 can rescue this phenotype. We also studied the effect of AFQ056 on cultured Fmr1 KO hippocampal neurons; untreated neurons showed elongated spines and treatment resulted in shortened spines. These results suggest that AFQ056 might be a potent mGluR5 antagonist to rescue various aspects of the fragile X phenotype.     

Seasonality in contaminant accumulation in Arctic marine pelagic food webs using trophic magnification factor as a measure of bioaccumulation

Seasonality in biomagnification of persistent organic pollutants (POPs; polychlorinated biphenyls, chlorinated pesticides, and brominated flame retardants) in Arctic marine pelagic food webs was investigated in Kongsfjorden, Svalbard, Norway. Trophic magnification factors (TMFs; average factor change in concentration between two trophic levels) were used to measure food web biomagnification in biota in May, July, and October 2007. Pelagic zooplankton (seven species), fish (five species), and seabirds (two species) were included in the study. For most POP compounds, highest TMFs were found in July and lowest were in May. Seasonally changing TMFs were a result of seasonally changing POP concentrations and the δ1?N-derived trophic positions of the species included in the food web. These seasonal differences in TMFs were independent of inclusion/exclusion of organisms based on physiology (i.e., warm- versus cold-blooded organisms) in the food web. The higher TMFs in July, when the food web consisted of a higher degree of boreal species, suggest that future warming of the Arctic and increased invasion by boreal species can result in increased food web magnification. Knowledge of the seasonal variation in POP biomagnification is a prerequisite for understanding changes in POP biomagnification caused by climate change.     

Higher optic nerve sheath diameters are associated with lower ocular blood flow velocities in glaucoma patients

Purpose

To investigate the relationship between optic nerve sheath diameter (ONSD) and retrobulbar blood flow velocities, as measured by color Doppler imaging (CDI) in glaucoma patients.

Methods

We performed a prospective, randomized, observer-masked study involving a total of 197 subjects. Once enrolled, they were divided by three groups: healthy controls (n?=?51), normal-tension glaucoma patients (NTG, n?=?58), and primary, open-angle glaucoma patients (POAG, n?=?88). All subjects underwent a general ophthalmological examination, an ultrasound-based assessment of the ONSD, and a hemodynamic study of the retrobulbar vascularization using CDI. Non-parametric tests, chi-square contingency tables, and the Deming correlations were used to explore differences and correlations between variables in the diagnostic groups.

Results

ONSD was not different between experimental groups (p?=?0.28). ONSD correlated positively with the pulsatility index of the ophthalmic artery in healthy individuals (p?=?0.007), but not in glaucoma patients (NTG: p?=?0.41; POAG: p?=?0.22). In NTG patients, higher ONSD values were associated with lower end-diastolic and mean flow velocities in the short ciliary arteries (p?=?0.005 in both correlations). No such correlation was found in healthy nor POAG groups (p range between 0.15 to 0.96). ONSD was not associated with any CDI-related variable of the central retinal artery in any cohort. Venous outflow velocities were not associated with ONSD in any of the three groups.

Conclusions

ONSD is negatively correlated with retrobulbar blood flow velocities in glaucoma patients, but not in healthy controls.     

The Effects of Smokeless Tobacco on Heart Rate and Neuromuscular Reactivity in Athletes and Nonathletes

It may be tempting for prepubescent athletes to imitate their elders who lift weights for strength and to improve performance. Physicians and coaches disagree on the long-term effects.     

Tinnitus, anxiety and automatic processing of affective information: an explorative study

Anxiety is found to play an important role in the severity complaint of tinnitus patients. However, when investigating anxiety in tinnitus patients, most studies make use of verbal reports of affect (e.g., self-report questionnaires and/or interviews). These methods reflect conscious appraisals of anxiety, but do not map underlying processing mechanisms. Nonetheless, such mechanisms, like the automatic processing of affective information, are important as they modulate emotional experience and emotion-related behaviour. Research showed that highly anxious people process threatening information (e.g., fearful and angry faces) faster than non-anxious people. Therefore, this study investigates whether tinnitus patients process affective stimuli (happy, sad, fearful, and angry faces) in the same way as highly anxious people do. Our sample consisted out of 67 consecutive tinnitus patients. Relationships between tinnitus severity, pitch, loudness, hearing loss, and the automatic processing of affective information were explored. Results indicate that especially in severely distressed tinnitus patients, the severity complaint is highly related to the automatic processing of fearful (r = 0.37, p < 0.05), angry (r = 0.44, p < 0.00) and happy (r = ?0.44, p < 0.00) faces, and these relationships became even stronger after controlling for hearing loss. Furthermore, in contrast with findings on the relation between audiological characteristics (pitch and loudness) and conscious report of anxiety, we did find that the audiological characteristic, loudness, tends to be in some degree related to the automatic processing of fearful faces (r = 0.25, p = 0.08). We conclude that tinnitus is an anxiety-related problem on an automatic processing level.     

Distortion product otoacoustic emissions: An objective technique for the screening of hearing loss in children treated with platin derivatives

In order to develop a sensitive audiometric protocol for identifying ototoxicity in children, a retrospective study of 16 children treated with cisplatin and/or carboplatin was performed. Audiometric testing was done by means of pure-tone threshold audiometry (PTA), high-frequency audiometry (HFA), and distortion product otoacoustic emissions (DPOAEs).

Cisplatin caused a sensorineural high-frequency hearing loss in the study group compared to the controls (p?<?0.01). Sixty-six percent of the cisplatin patients had a grade 2 or 3 ototoxicity. However, ototoxicity was not found in the patients treated with carboplatin. An excellent correlation was found between DPOAE levels and results obtained by audiometry (r?=?0.82).

Patients exposed to cisplatin are at significant risk for the development of drug-induced sensorineural hearing loss. Because of the several advantages of DPOAEs (noninvasive, objective, rapid, easy to use, sensitive) this method should be added in the audiological follow-up in infants and toddlers.     

Foreign body reactions in lymph nodes of oncology patients with joint prostheses--light-, electron microscopic and immunohistological investigations

Foreign body reactions in lymph nodes caused by wear particles from joint prostheses can mimic different lymphadenopathies, including metastatic cancer. The knowledge of these alterations is particularly important for pathologists performing frozen section diagnosis for oncology patients. As recent investigations of pseudocapsules have revealed that most of the wear particles are submicron-sized, transmission electron microscopic investigations were additionally performed. The histological investigation of the pelvic lymph nodes of 22 oncology patients with joint prostheses showed that the bone cement wear prevailed. At least small amounts of polyethylene wear particles were also found in all cases. Metallic wear particles were detected in 90% of the cases. The wear particles induce a macrophage-rich foreign body reaction that can cause an architectural effacement of the lymph nodes. The electron microscopic investigations showed that submicron-sized wear particles prevail. Some of them form conglomerates in size ranges detectable by light microscopy. The immunohistochemical studies showed that the foreign body reactions comprised mature CD163- and PGM1-positive macrophages and few lymphocytes, predominantly T-lymphocytes. The knowledge of the characteristic alterations of regional lymph nodes seems important in order to avoid misinterpretations. Therefore, in particular the detection of intracytoplasmatic wear particles is helpful in this respect.     

Alpha-Linolenic Acid: Is It Essential to Cardiovascular Health?

There is a large body of scientific evidence that has been confirmed in randomized controlled trials indicating a cardioprotective effect for omega-3 fatty acids from fish. For alpha-linolenic acid (ALA), which is the omega-3 fatty acid from plants, the relation to cardiovascular health is less clear. We reviewed the recent literature on dietary ALA intake, ALA tissue concentrations, and cardiovascular health in humans. Short-term trials (6–12 weeks) in generally healthy participants mostly showed no or inconsistent effects of ALA intake (1.2–3.6 g/d) on blood lipids, low-density lipoprotein oxidation, lipoprotein(a), and apolipoproteins A-I and B. Studies of ALA in relation to inflammatory markers and glucose metabolism yielded conflicting results. With regard to clinical cardiovascular outcomes, there is observational evidence for a protective effect against nonfatal myocardial infarction. However, no protective associations were observed between ALA status and risk of heart failure, atrial fibrillation, and sudden death. Findings from long-term trials of ALA supplementation are awaited to answer the question whether food-based or higher doses of ALA could be important for cardiovascular health in cardiac patients and the general population.     

Comparison of the overall intelligibility,articulation, resonance,and voice characteristics between children using cochlear implants and those using bilateral hearing aids: A pilot study

The purpose of this study was to determine and to compare the overall intelligibility, articulation, resonance, and voice characteristics in children using cochlear implants (CI) and children using conventional hearing aids (HA). Nine prelingually deaf children using CI and six children with a prelingual severe hearing loss using HA, were selected to participate. Objective (DSI, nasalance scores) as well as subjective assessment techniques (perceptual evaluations) were used. Both the CI and HA children demonstrated normal vocal quality and resonance but showed the presence of articulation disorders. In the CI children, intelligibility was significantly better compared to the HA children. Significantly more phonetic and phonological disorders were present in the HA children. The results of this study show a poorer intelligibility of the HA children in comparison with the CI children which is probably due to the occurrence of significantly more phonetic and phonological disorders. Future detailed analysis in a larger sample of CI and HA children may help further clarify the issue of speech and voice characteristics and may demonstrate an important prognostic value.