Evidence for superior encoding of detailed visual memories in deaf signers.

Recent evidence shows that deaf signers outperform hearing non-signers in some tests of visual attention and discrimination. Furthermore, they can retain visual information better over short periods, i.e., seconds. However, it is unknown if deaf signers' retention of detailed visual information is superior following more extended periods. We report a study investigating this possibility. Our data revealed that deaf individuals outperformed hearing people in a visual long-term memory test that probed the fine detail of new memories. Deaf individuals also performed better in a scene-discrimination test, which correlated positively with performance on the long-term memory test. Our findings provide evidence that deaf signers can demonstrate superior visual long-term memory, possibly because of enhanced visual attention during encoding. The relative contributions of factors including sign language fluency, protracted practice, and neural plasticity are still to be established. Our findings add to evidence showing that deaf signers are at an advantage in some respects, including the retention of detailed visual memories over the longer term.

Prolonged tedizolid use in cutaneous non-tuberculous mycobacterial infection.

Cutaneous non-tuberculous mycobacterial (NTM) infections are an emerging infectious disease and require a protracted course of combination antibiotics. Antimicrobial choice is limited by resistance and toxicity. Tedizolid is a new oxazolidinone antibiotic with in vitro activity against some NTM, but its use in the management of extrapulmonary NTM has not been described. We report on the utility of prolonged tedizolid use (8 months), after linezolid intolerance, in combination therapy in a case of difficult Mycobacterium chelonae cutaneous infection. Although tedizolid contributed to clinical remission, it may have also contributed to a multifocal peripheral neuropathy. Its efficacy may also have been limited by continued immunosuppression, with evidence to suggest disease relapse or treatment failure after completion of combination therapy. Tedizolid can be considered, with caution, in combination therapy for difficult cases of cutaneous NTM infection.

Talking with hands: body representation in British Sign Language users.

Body representation (BR) refers to the mental representation of motor, sensory, emotional and semantic information about the physical body. This cognitive representation is used in our everyday life, continuously, even though most of the time we do not appreciate it consciously. In some cases, BR is vital to be able to communicate. A crucial feature of signed languages (SLs), for instance, is that body parts such as hands are used to communicate. Nevertheless, little is known about BR in SL: is the communicative function of the body overwriting the physical constraints? Here, we explored this question by comparing twelve British Sign Language (BSL) learners to seventeen tango dancers (body expertise but not for communication) and fourteen control subjects (no special body expertise). We administered the Body Esteem Scale (BES), the Hand Laterality Task (HLT) and the Mental Motor Chronometry (MMC). To control for visual imagery, we administered ad hoc control tasks. We did not identify parameters able to differentiate between SL users and the other groups, whereas the more implicit parameters distinguished clearly tango dancers from controls. Importantly, neither tasks on visual imagery nor the BES revealed differences. Our findings offer initial evidence that linguistic use of the body not necessarily influences the cognitive components we explored of body representation.

The hepatobiliary complications of malnutrition and nutritional support in adults.

Hepatobiliary complications of hypoalimentation and parenteral nutrition (PN) are widely recognised. Hypoalimentation includes conditions such as anorexia nervosa (AN), obesity malnutrition and liver disease following bariatric surgery. Treatment of the underlying condition causing hypoalimentation can result in an improvement in liver dysfunction. Liver function test abnormalities are also commonly found in patients on PN, with the three main complications being steatosis, cholestasis and biliary system sludge/stones. Patients with intestinal failure receiving PN often have multiple possible aetiologies for liver dysfunction (rather than solely caused by the PN); hence, it is now more commonly referred to as intestinal failure-associated liver disease (IFALD). Liver enzyme abnormalities are very common with long-term PN use and do not always help with monitoring progression of IFALD. A systematic approach is required for investigating liver function abnormalities related to PN. The key management in IFALD is through prevention of sepsis, promoting intestinal health and restoring intestinal continuity where possible. A variety of imaging modalities can be used to investigate, and monitor, the liver disease. Most importantly, patients on PN for more than 28 days should be managed in a large centre with experience in managing intestinal failure to minimise the risk of such complications. Early identification of liver dysfunction is essential and, should it progress despite the above measures, early discussion with an intestinal transplant centre should be encouraged.

Human axillary skin condition is improved following incorporation of glycerol into the stratum corneum from an antiperspirant formulation.

The study objectives were to demonstrate that glycerol, when topically applied from a roll-on antiperspirant formulation, can be delivered directly to human skin ex vivo and the axillary stratum corneum (SC) in vivo, and to assess whether it improves the quality of the axillary skin barrier. Ex vivo human skin absorption of glycerol was measured following application of a roll-on antiperspirant formulation containing 4% 13C3-glycerol. Skin distribution of 13C3-glycerol over 24 h was assessed using gas chromatography-mass spectrometry. In vivo axillary SC penetration was measured by confocal Raman spectroscopy and multivariate curve-resolution software 1 h after topical application of a roll-on antiperspirant formulation containing 8% deuterated glycerol (d5-glycerol). A clinical study was conducted to determine the efficacy of a roll-on antiperspirant formulation containing 4% glycerol in reducing shaving-induced visual irritation and in increasing axillary-skin hydration. Ex vivo skin absorption studies indicated that the formulation delivered 13C3-glycerol into the SC at all timepoints over the 24-h period. In vivo Raman measurements (1 h after application) demonstrated that d5-glycerol was detectable to a depth of at least 10 µm in the axillary SC. Application of 4% glycerol from a roll-on antiperspirant formulation to the axilla was associated with significantly less visible irritation and greater skin hydration than observed with the control (glycerol-free) product. These studies demonstrate that glycerol, incorporated in a roll-on antiperspirant formulation, is delivered directly and rapidly to all depths of the axillary SC, and results in improvements in visible irritation and hydration in the axilla.

Hair and Aging.

Hair is the ultimate personal beauty tool of self-expression. It is more malleable than skin and it is more personal than clothing; however, hair does not remain constant with age. Hair is arguably in peak condition at about 30 years of age. With time, there is a gradual change in many aspects of hair: hair diameter is reduced, hair density is decreased, androgenic alopecia may develop, and pigmentation may be diminished, producing a significant psychological impact. These age-related changes can be exacerbated by blast drying, heat straightening, perming, and coloring. In this review, the changes in hair fiber and array (collection of fiber) properties that occur during aging and the impact on styling and potential interventions that consumers undergo to circumvent these issues are discussed.

Clinical studies in dermatology require a post-treatment observation phase to define the impact of the intervention on the natural history of the complaint.

The use of a post-treatment period of observation or "regression phase" is common in pharmaceutical and cosmetic clinical dermatology studies. Regression phases can be incorporated into a variety of study designs, ranging from simple post-treatment observation for a defined period, as has been used for moisturizers, antidandruff formulations, and treatments for acne, to more complex randomized intermittent-treatment designs, as used in studies of psoriasis pharmacotherapies. Extensive information can be derived from a regression phase. Notably, it can provide useful data on the persistence of effect and time to relapse after treatment cessation, which are particularly relevant to skin conditions in which consumer or patient adherence to treatment is suboptimal. By incorporating a regression phase, a clinical study can more closely reflect "real-world" behavior, e.g., the switching by consumers from antidandruff to beauty shampoos. The regression phase can also help to differentiate between products that show similar effectiveness during the treatment phase, and monitoring post-treatment physiological end points can provide valuable evidence on the safety and mechanism of action of the therapy.

Celiac Disease: Background and Historical Context.

Medical descriptions of celiac disease date to the first century BC, and the first modern description was published in 1888. Further insights were gained throughout the 1900s, culminating in the identification of the dietary component, the major genetic determinant, and the autoantigen by the turn of the century. Understanding of the age of onset, population prevalence, and the extent of subclinical celiac disease developed in tandem. Thanks to advances in genomics, currently established loci account for over 50 % of the genetic risk. Nonetheless, much remains to be discovered. Advances in high-throughput genomic, biochemical, and cell analyses, as well as the bioinformatics needed to process the data, promise to deepen our understanding further. Here we present a primer of celiac disease, viewing the condition in turn from the historical, epidemiological, immunological, molecular, and genetic points of view. Research into any ailment has specific requirements: study subjects must be identified and relevant tissue samples collected and stored with the appropriate timing and conditions. These requirements are summarized. To conclude, a short discussion of future prospects is presented.

Influences of gender and socioeconomic status on the motor proficiency of children in the UK.

As the development of movement skills are so crucial to a child's involvement in lifelong physical activity and sport, the purpose of this study was to assess the motor proficiency of children aged 4-7 years (range=4.3-7.2 years), whilst considering gender and socioeconomic status. 369 children (176 females, 193 males, aged=5.96 ± 0.57 years) were assessed for fine motor precision, fine motor integration, manual dexterity, bilateral co-ordination, balance, speed and agility, upper-limb co-ordination and strength. The average standard score for all participants was 44.4 ± 8.9, classifying the participants towards the lower end of the average score. Multivariate analysis of covariance identified significant effects for gender (p<0.001) and socioeconomic status (p<0.001). Females outperformed males for fine motor skills and boys outperformed girls for catch and dribble gross motor skills. High socioeconomic status significantly outperformed middle and/or low socioeconomic status for total, fine and gross motor proficiency. Current motor proficiency of primary children aged 4-7 years in the UK is just below average with differences evident between gender and socioeconomic status. Teachers and sport coaches working with primary aged children should concentrate on the development of movement skills, whilst considering differences between genders and socioeconomic status.

Genes of the interleukin-18 pathway are associated with susceptibility to Barrett's esophagus and esophageal adenocarcinoma.

OBJECTIVES: To investigate the association of genetic polymorphisms of the interleukin-18 (IL-18) pathway to Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). Most cases of EAC arise in a background of reflux-induced BE. Genetic influences in this pathway are poorly understood. IL-18 is a multifunctional cytokine implicated in anti-tumor immunity. A number of polymorphisms of the IL-18 and IL-18 receptor-accessory protein (IL-18RAP) genes have been reported to alter gene expression and have recently been linked to inflammatory processes and various tumors, but have not heretofore been studied in BE and EAC. METHODS: Two IL-18 promoter polymorphisms -137 G/C and -607 C/A, (rs187238 and rs1946518) and one IL-18RAP polymorphism (rs917997, C/T) were analyzed. Each single-nucleotide polymorphism (SNP) was genotyped in the following groups: EAC, BE, reflux esophagitis (RE), and controls and analyzed for association with disease status. RESULTS: The IL-18RAP rs917997C allele is strongly associated with a protective effect in BE (P = 0.0002) and EAC (P = 6 × 10(-7)), which approaches genome-wide levels of significance for allele association without incurring significant multiple testing. The CC genotype at IL-18RAP locus rs917997 was associated with a protective effect against esophageal disease (P = 6 × 10(-4), odds ratio (OR) = 0.59, and 95% confidence interval (CI) 0.43-0.80 for BE; and P = 2 × 10(-6), OR = 0.46, and 95% CI 0.34-0.64 for EAC). The genotype frequencies of IL-18-607 C/A were weakly associated with BE (P = 0.02), and this trend was also seen between controls and EAC (P = 0.07). The CC genotype was associated with an increased risk of BE (OR = 1.45, 95% CI 1.07-1.98) and approached significance for EAC (OR = 1.34, 95% CI 0.98-1.82). Allele and genotype frequencies at these loci were not significantly different between the RE group and controls. Although no significant association was observed between the disease groups at the -137 G/C locus, the -137G/-607C haplotype was associated with increased risk of BE (P = 0.006) with haplotype frequencies of 55% in controls and 65% in BE. CONCLUSIONS: These data show a strong association of the IL-18RAP SNP rs917997 locus with BE and EAC and suggestive association of the Barrett's population with the IL-18-607 C/A promoter polymorphism. As both of these SNPs have been demonstrated as expression quantitative trait loci affecting expression of the respective genes, this strongly implicates IL-18 signaling in susceptibility to BE and EAC.

Meta-analysis of genome-wide association studies in celiac disease and rheumatoid arthritis identifies fourteen non-HLA shared loci.

Epidemiology and candidate gene studies indicate a shared genetic basis for celiac disease (CD) and rheumatoid arthritis (RA), but the extent of this sharing has not been systematically explored. Previous studies demonstrate that 6 of the established non-HLA CD and RA risk loci (out of 26 loci for each disease) are shared between both diseases. We hypothesized that there are additional shared risk alleles and that combining genome-wide association study (GWAS) data from each disease would increase power to identify these shared risk alleles. We performed a meta-analysis of two published GWAS on CD (4,533 cases and 10,750 controls) and RA (5,539 cases and 17,231 controls). After genotyping the top associated SNPs in 2,169 CD cases and 2,255 controls, and 2,845 RA cases and 4,944 controls, 8 additional SNPs demonstrated P<5 × 10(-8) in a combined analysis of all 50,266 samples, including four SNPs that have not been previously confirmed in either disease: rs10892279 near the DDX6 gene (P(combined) =  1.2 × 10(-12)), rs864537 near CD247 (P(combined) =  2.2 × 10(-11)), rs2298428 near UBE2L3 (P(combined) =  2.5 × 10(-10)), and rs11203203 near UBASH3A (P(combined) =  1.1 × 10(-8)). We also confirmed that 4 gene loci previously established in either CD or RA are associated with the other autoimmune disease at combined P<5 × 10(-8) (SH2B3, 8q24, STAT4, and TRAF1-C5). From the 14 shared gene loci, 7 SNPs showed a genome-wide significant effect on expression of one or more transcripts in the linkage disequilibrium (LD) block around the SNP. These associations implicate antigen presentation and T-cell activation as a shared mechanism of disease pathogenesis and underscore the utility of cross-disease meta-analysis for identification of genetic risk factors with pleiotropic effects between two clinically distinct diseases.

Preferences for communication in clinic from deaf people: a cross-sectional study.

AIMS AND OBJECTIVES: To explore the preferences of deaf people for communication in a hospital consultation. METHODS: Design--cross-sectional survey, using a structured, postal questionnaire. Setting--survey of readers of two journals for deaf and hard of hearing people. Participants--999 self-selected individuals with hearing loss in the UK, including those who use sign language and those who use speech. Main outcome measures--preferred mode of communication. RESULTS: A total of 11% of participants preferred to use sign language within everyday life, 70% used speech and 17% used a mixture of sign and speech. Within a clinic setting, 50% of the sign language users preferred to have a consultation via a sign language interpreter and 43% indicated they would prefer to only have a consultation directly with a signing health professional; 7% would accept a consultation in speech as long as there was good deaf awareness from the health professional, indicated by a knowledge of lip-reading/speech-reading. Of the deaf speech users, 98% preferred to have a consultation in speech and of this group 71% indicated that they would only accept this if the health professional had good deaf awareness. Among the participants who used a mixture of sign language and speech, only 5% said they could cope with a consultation in speech with no deaf awareness whereas 46% were accepting of a spoken consultation as long as it was provided with good deaf awareness; 30% preferred to use an interpreter and 14% preferred to have a consultation directly with a signing health professional. CONCLUSIONS: The hospital communication preferences for most people with deafness could be met by increasing deaf awareness training for health professionals, a greater provision of specialized sign language interpreters and of health professionals who can use fluent sign language directly with clients in areas where contact with deaf people is frequent.

Evaluation of 6 candidate genes on chromosome 11q23 for coeliac disease susceptibility: a case control study.

BACKGROUND: Recent whole genome analysis and follow-up studies have identified many new risk variants for coeliac disease (CD, gluten intolerance). The majority of newly associated regions encode candidate genes with a clear functional role in T-cell regulation. Furthermore, the newly discovered risk loci, together with the well established HLA locus, account for less than 50% of the heritability of CD, suggesting that numerous additional loci remain undiscovered. Linkage studies have identified some well-replicated risk regions, most notably chromosome 5q31 and 11q23. METHODS: We have evaluated six candidate genes in one of these regions (11q23), namely CD3E, CD3D, CD3G, IL10RA, THY1 and IL18, as risk factors for CD using a 2-phase candidate gene approach directed at chromosome 11q. 377 CD cases and 349 ethnically matched controls were used in the initial screening, followed by an extended sample of 171 additional coeliac cases and 536 additional controls. RESULTS: Promotor SNPs (-607, -137) in the IL18 gene, which has shown association with several autoimmune diseases, initially suggested association with CD (P < 0.05). Follow-up analyses of an extended sample supported the same, moderate effect (P < 0.05) for one of these. Haplotype analysis of IL18-137/-607 also supported this effect, primarily due to one relatively rare haplotype IL18-607C/-137C (P < 0.0001), which was independently associated in two case-control comparisons. This same haplotype has been noted in rheumatoid arthritis. CONCLUSION: Haplotypes of the IL18 promotor region may contribute to CD risk, consistent with this cytokine's role in maintaining inflammation in active CD.

Mycobacterium cosmeticum as an unusual cause of ascites.

Despite an increase in the prevalence of non-tuberculous mycobacterium (NTM), the diagnosis remains difficult and its treatment controversial. Prolonged duration of treatment is frequently needed and eradication is often unlikely.

Facilitated neurotrophin release in sensitized human skin.

The neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) play a pivotal role in the generation and maintenance of hyperalgesia. In the present study we analyzed NGF and BDNF levels in human skin of the upper arm and axilla skin sites by dermal microdialysis and multiplexed assay. Skin sensitization and inflammatory responses were evoked experimentally by repetitive shaving of one axilla provoking local erythema and reduced heat pain thresholds. Acute excitation of skin nociceptors was performed by perfusion of the microdialysis catheters with citric acid pH 3. At baseline, neurotrophin concentrations did not differ significantly between the investigated skin sites. On average, NGF concentration was 5.8 fg/microug protein/ml sample volume and BDNF concentration was 87.5 fg/microg/ml. Citric acid perfusion marginally increased NGF levels to 7.3 fg/microg/ml on average in the upper arm and control axilla. Similarly, BDNF values increased at these control skin sites to about 122 fg/microg/ml following proton stimulation. In contrast, perfusion of the inflamed axilla with citric acid significantly enhanced the release of both NGF and BDNF. On average, NGF levels were analyzed at 14.6 fg/microg/ml and BDNF values at 202 fg/microg/ml. These data demonstrate enhanced level of neurotrophin release in inflamed human skin in vivo which might well contribute to peripheral sensitization. Analyses of neurotrophic factors by dermal microdialysis are useful endogenous markers to further explore their role in neuronal sensitization processes in human.

Newly identified genetic risk variants for celiac disease related to the immune response.

Our genome-wide association study of celiac disease previously identified risk variants in the IL2-IL21 region. To identify additional risk variants, we genotyped 1,020 of the most strongly associated non-HLA markers in an additional 1,643 cases and 3,406 controls. Through joint analysis including the genome-wide association study data (767 cases, 1,422 controls), we identified seven previously unknown risk regions (P < 5 x 10(-7)). Six regions harbor genes controlling immune responses, including CCR3, IL12A, IL18RAP, RGS1, SH2B3 (nsSNP rs3184504) and TAGAP. Whole-blood IL18RAP mRNA expression correlated with IL18RAP genotype. Type 1 diabetes and celiac disease share HLA-DQ, IL2-IL21, CCR3 and SH2B3 risk regions. Thus, this extensive genome-wide association follow-up study has identified additional celiac disease risk variants in relevant biological pathways.

An evaluation of cyclooxygenase-2 as a prognostic biomarker in mid-gut carcinoid tumours.

BACKGROUND/AIMS: Mid-gut carcinoids (MGC) are the most common of the gastrointestinal carcinoid tumours. There is a lack of reliable prognostic indicators for MGC. Cox-2 and Bcl-2 were evaluated as prognostic biomarkers in a cohort of well-characterised non-appendiceal MGC. METHODS: Tissue from the primary MGC tumours of 37 patients was subjected to immunohistochemical detection of Cox-2 and Bcl-2. In 9 cases, tissue from secondary lesions was also examined. The study assessed whether tumour-associated Cox-2 and Bcl-2 expression were related to patient survival. RESULTS: Cox-2 expression was demonstrated in 30/36 primary tumours. When all tumours were analysed, Cox regression analysis indicated a trend towards worsening survival with increasing Cox-2 histoscore (intensity x proportion; hazard ratio 1.53, 95% CI 0.93, 2.52; p = 0.09). Analysis of Cox-2-positive tumours revealed a highly significant association between increasing histoscore and decreased survival (hazard ratio 3.03, 95% CI 1.33, 6.91; p = 0.008). Tumour-associated Bcl-2 expression had no effect on patient survival (hazard ratio 1.12, 95% CI 0.42, 2.99; p = 0.82). There was no significant association between Cox-2 and Bcl-2 expression (chi(2) p = 0.16), or Cox-2 histoscore and Bcl-2 expression (MWU p = 0.59). Analysis of the Cox-2 histoscores of primary tumours and their corresponding secondary lesions revealed a statistically significant trend towards increasing histoscore in the latter (Wilcoxon p = 0.04). CONCLUSIONS: This study has provided evidence that Cox-2 expression in primary MGC may be associated with a more negative prognostic outlook.