Nucleic acid sensing Toll-like receptors in autoimmunity

Trafficking and activation of the nucleic acid sensing TLRs is subject to unique regulatory requirements imposed by the risk of self-recognition. Like all TLRs these receptors traffick through the Golgi, however, access to the secretory pathway is controlled by a binding partner present in the ER. Receptor activation in the endolysosome is regulated through a proteolytic mechanism that requires activity of compartment-resident proteases, thereby preventing activation in other regions of the cell. Advances in our understanding of the cell biology of these receptors have been paralleled by efforts to understand their precise roles in autoimmunity. Mouse models have revealed that TLR7 and TLR9 make unique contributions to the types of self-molecules recognized in disease and possibly disease severity. Currently, methods of inhibiting TLR7 and TLR9 are being tested in clinical trials for systemic lupus erythamatosus.     

Candidate pheromone receptors provide the basis for the response of distinct antennal neurons to pheromonal compounds

Males of the moth species Heliothis virescens are able to detect the female-released pheromone with remarkable sensitivity and specificity, distinguishing between highly related pheromonal compounds. In the past, electrophysiological studies succeeded in assigning sensory hairs to identified compounds revealing three functional types of long sensilla trichodea housing neurons specifically responding to distinct semiochemicals. The specific responsiveness implies that the sensory neurons express different receptor types tuned to pheromone components. In this study we demonstrate that heterologously expressed candidate pheromone receptors from Heliothis responded to several pheromonal compounds, including the major sex-pheromone component Z-11-hexadecenal indicating a limited specificity of each receptor type. Nonetheless, based on functional analysis and in situ hybridization studies the analysed receptor types could tentatively be assigned to types of long sensilla trichodea, containing the pheromone-binding proteins (PBPs) HvirPBP1 and HvirPBP2 in the sensillum lymph. Substituting organic solvent with PBPs to solubilize the hydrophobic pheromone compounds in functional assays revealed an increase in sensitivity and especially specificity. It was found that in the presence of HvirPBP2, cells expressing the receptor type HR13 specifically responded to the main component of the sex pheromone blend only. The data provide further evidence that a combination of a distinct receptor type and binding protein underlie the specific response observed in the detection of a pheromone component in vivo.     

Influence of racket properties on injuries and performance in tennis

Racket properties may affect tennis elbow development. Shock and vibration to the arm is influenced by the location of ball impacts on the racket head, racket stiffness, and grip force. Beginners experience increased arm loads, and they hit the ball lower on the racket head. Tennis rackets behave differently during actual play compared with the performance predicted by physics.     

Combined PET/CT in the follow-up of differentiated thyroid carcinoma: what is the impact of each modality?

Purpose ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is a well-established method in the follow-up of patients with differentiated thyroid carcinoma (DTC), elevated thyroglobulin (Tg) and negative ¹³¹I scans. This retrospective clinical study was designed to evaluate the impact of computed tomography (CT) and that of FDG-PET in combined FDG-PET/CT examinations on the restaging of DTC patients. Methods Forty-seven FDG-PET/CT scans of 33 patients with a history of DTC, elevated Tg levels and negative ¹³¹I uptake or additionally suspected ¹³¹I-negative lesions were studied. PET and CT images were analysed independently by an experienced nuclear medicine specialist and a radiologist. Afterwards a final consensus interpretation, the gold standard in our department, was provided for the fused PET/CT images and, if available, for supplementary investigations. Results Thirty-five investigations (74%) revealed pathological FDG-PET/CT findings. In summary, 25 local recurrences, 62 lymph node metastases and 122 organ metastases (41 lung, 60 bone, 21 other organs) were diagnosed. In 36 out of 47 examinations (77%), the original PET diagnoses were modified in the final consensus interpretation owing to the CT assessments. In 8 of the 35 pathological FDG-PET/CT examinations (23%), the final consensus interpretation of the PET/CT images led to an alteration in the treatment plan. Conclusion PET/CT is a powerful fusion of two pre-existing imaging modalities, which not only improves the diagnostic value in restaging DTC patients with elevated Tg and negative ¹³¹I scan, but also provides accurate information regarding subsequent treatment options and may lead to a change in treatment management.     

Aberrant development of neuromuscular junctions in glycosylation-defective Largemyd mice

Mice deficient in the glycosyltransferase Large are characterized by severe muscle and central nervous system abnormalities. In this study, we show that the formation and maintenance of neuromuscular junctions in Large^myd mice are greatly compromised. Neuromuscular junctions are not confined to the muscle endplate zone but are widely spread and are frequently accompanied by exuberant nerve sprouting. Nerve terminals are highly fragmented and binding of α-bungarotoxin to postsynaptic acetylcholine receptors (AChRs) is greatly reduced. In vitro, Large^myd myotubes are responsive to agrin but produce aberrant AChR clusters, which are larger in area and less densely packed with AChRs. In addition, AChR expression on the cell surface is diminished suggesting that AChR assembly or transport is defective. These results together with the finding that O-linked glycosylation at neuromuscular junctions of Large^myd mice is compromised indicate that the action of Large is necessary for proper neuromuscular junction development.     

Oral health status of adults in Southern Vietnam - a cross-sectional epidemiological study

Background

Dental caries is one of the primary causes of tooth loss among adults. It is estimated to affect a majority of Americans aged 55 and older, with a disproportionately higher burden in disadvantaged populations. Although a number of treatments are currently in use for caries prevention in adults, evidence for their efficacy and effectiveness is limited.

Methods/Design

The Prevention of Adult Caries Study (PACS) is a multicenter, placebo-controlled, double-blind, randomized clinical trial of the efficacy of a chlorhexidine (10% w/v) dental coating in preventing adult caries. Participants (n = 983) were recruited from four different dental delivery systems serving four diverse communities, including one American Indian population, and were randomized to receive either chlorhexidine or a placebo treatment. The primary outcome is the net caries increment (including non-cavitated lesions) from baseline to 13 months of follow-up. A cost-effectiveness analysis also will be considered.

Discussion

This new dental treatment, if efficacious and approved for use by the Food and Drug Administration (FDA), would become a new in-office, anti-microbial agent for the prevention of adult caries in the United States.

Trial Registration Number

NCT00357877     

Time-resolved analysis of fMRI signal changes using Brain Activation Movies

Conventional fMRI analyses assess the summary of temporal information in terms of the coefficients of temporal basis functions. Based on established finite impulse response (FIR) analysis methodology we show how spatiotemporal statistical parametric maps may be concatenated to form Brain Activation Movies (BAMs), dynamic activation maps representing the temporal evolution of brain activation throughout task performance. These BAMs enable comprehensive assessment of the dynamics in functional topology without restriction to predefined regions and without detailed information on the stimulus paradigm. We apply BAM visualization to two fMRI studies demonstrating the additional spatiotemporal information available compared to standard fMRI result presentation. Here we show that BAMs allow for unbiased data visualization providing dynamic activation maps without assumptions on the neural activity except reproducibility across trials. It may thus be useful in proceeding from static to dynamic brain mapping, widening the range of fMRI in neuroscience. In addition, BAMs might be helpful tools in visualizing the temporal evolution of activation in "real-time" for better and intuitive understanding of temporal processes in the human brain.     

Carpal tunnel syndrome and keyboard use at work: a population-based study

OBJECTIVE: To investigate the relationship between carpal tunnel syndrome (CTS) and keyboard use at work in a general population. METHODS: A health status questionnaire was mailed to 2,465 persons of working age (25-65 years) who were randomly selected from the general population of a representative region of Sweden. The questionnaire required the subjects to provide information about the presence and severity of pain, numbness and tingling in each body region, employment history, and work activities, including average time spent using a keyboard during a usual working day. Those reporting recurrent hand numbness or tingling in the median nerve distribution were asked to undergo a physical examination and nerve conduction testing. The prevalence of CTS, defined as symptoms plus abnormal results on nerve conduction tests, was compared between groups of subjects that differed in their intensity of keyboard use, adjusting for age, sex, body mass index, and smoking status. RESULTS: Eighty-two percent responded to the questionnaire, and 80% of all symptomatic persons attended the examinations. Persons who had reported intensive keyboard use on the questionnaire were significantly less likely to be diagnosed as having CTS than were those who had reported little keyboard use, with a prevalence that increased from 2.6% in the highest keyboard use group (> or = 4 hours/day), to 2.9% in the moderate use group (1 to <4 hours/day), 4.9% in the low use group (<1 hour/day), and 5.2% in the no keyboard use at work group (P for trend = 0.032). Using > or = 1 hour/day to designate high keyboard use and <1 hour/day to designate low keyboard use, the prevalence ratio of CTS in the groups with high to low keyboard use was 0.55 (95% confidence interval 0.32, 0.96). CONCLUSION: Intensive keyboard use appears to be associated with a lower risk of CTS.