Investigating the relationship between mild traumatic brain injury and Alzheimer's disease and related dementias: a systematic review.

The objective of this systematic review is to synthesize the relevant literature published after 2016 to ascertain the current landscape of science that relates mild traumatic brain injury (mTBI) to the onset of Alzheimer's disease and related dementias (ADRD) and identify areas of need for future research. We conducted database searches and retrieved articles that were published after 2016 that utilized cognitive assessments to understand the relationship between mTBI and ADRD. We identified eight relevant articles in the review process, four of which presented a significant relationship between mTBI and disease or cognitive impairment outcomes. The studies included in this systematic review underscore the need for future research investigating a possible causal relationship between mTBI and ADRDs given the high prevalence of mTBI among brain injury patients and the lack of literature specifically addressing this issue. Future research should standardize the definitions of mTBI, AD, and ADRDs to create reliable and reproducible results that more comprehensively capture the nuances of this relationship.

Multidrug-Resistant Bacteria Isolated From Surgical Site of Dogs, Surgeon's Hands and Operating Room in a Veterinary Teaching Hospital in Brazil.

Surgical environment can play as a source of multidrug-resistance organism, what can pose as a big threat to the patients and health care professionals. This study aimed to evaluate the prevalence and antimicrobial resistance profile of Gram-positive cocci (GPC) and Gram-negative bacilli (GNB) isolated from the surgical environment. All samples were collected during the intraoperative period of clean/clean-contaminated (G1) and contaminated (G2) surgery. A total of 150 samples were collected from the superficial surgical site in the beginning (n = 30) and the end (n = 30) of the procedure, surgeon's hands before (n = 30) and after (n = 30) antisepsis, and the surgical environment (n = 30). MALDI-TOF MS and antimicrobial susceptibility testing by disk diffusion method were performed for species identification, and determination of the resistance profile. Sixty-eight isolates of GPC and 15 of GNB were obtained. Staphylococcus spp. were the most frequent species isolated from surgical site (55.26% [21/38]), surgeon's hands (46.15% [6/13]), and environment (56.67% [17/30]). GPC were mostly resistance to penicillin (85.71% [54/63]), and erythromycin (77.78% [49/63]), and GNB were mostly resistance to cefazolin (58.33% [7/12]), and azithromycin (58.33% [7/12]). High incidence of multidrug resistance was observed in coagulase-negative staphylococci (86.21% [25/29]), coagulase-positive staphylococci (86.67% [13/15]), Enterococcus spp. (68.42% [13/19]) and Gram-negative bacilli (60% [9/15]). The high rate of resistance of commensal bacteria found in our study is worrying. Coagulase-negative staphylococci are community pathogens related to nosocomial infections in human and veterinary hospitals, their presence in healthy patients and in veterinary professionals represent an important source of infection in the One Health context. Continuous surveillance and application of antimicrobial stewardship programs are essential in the fight against this threat.

Polarisation-sensitive optical coherence tomography measurement of retardance in fibrosis, a non-invasive biomarker in patients with systemic sclerosis.

Polarisation-sensitive optical coherence tomography (PS-OCT) offers a novel, non-invasive method of assessing skin fibrosis in the multisystem disease systemic sclerosis (SSc) by measuring collagen retardance. This study aimed to assess retardance as a biomarker in SSc. Thirty-one patients with SSc and 27 healthy controls (HC) underwent PS-OCT imaging. 'Skin score' was assessed by clinical palpation (0-3 scale). A subset of ten patients and ten age/sex-matched HC had a biopsy and longitudinal imaging. Histological assessment included quantification of epidermal thickness, collagen content (to assess fibrosis) and matrix metalloproteinase (MMP) activity (in situ zymography). PS-OCT images were assessed for epidermal thickness (structure) and fibrosis (retardance). Positive correlation was observed between epidermal thickness as measured by histology and structural PS-OCT (r = 0.79; p < 0.001). Retardance was: HC mean 0.21 (SD 0.21) radian/pixel; SSc skin score 0, 0.30 (0.19); skin score 1, 0.11 (0.16); skin score 2, 0.06 (0.12); skin score 3, 0.36 (0.35). Longitudinal retardance decreased at one-week across groups, increasing at one-month for HC/skin score 0-1; HC biopsy site retardance suggests scarring is akin to fibrosis. Relationships identified between retardance with both biopsy and skin score data indicate that retardance warrants further investigation as a suitable biomarker for SSc-related fibrosis.

A validated photonumeric scale for infraorbital dark circles and its application in evaluating the efficacy of a cosmetic treatment product in a split-face randomized clinical trial.

OBJECTIVE: As a result of their complex aetiology and periodicity, dark circles are difficult to characterize and measure, with current assessment techniques relying on specialist equipment, image analysis or proprietary grading scales. There is therefore a need to develop and validate a photonumeric scale for assessing infraorbital dark circles, which can provide an objective and consumer relevant tool for evaluating this condition and the efficacy of treatment products and procedures. METHODS: A panel of expert clinical evaluators reviewed approximately three thousand facial photographs collected over a 5-year period and selected images representing a dynamic range of dark circles. A 10-point photonumeric scale was created, with corresponding descriptors and images for each grade of the scale. To rigorously validate the scale, linearity, sensitivity and precision were assessed by colorimetry and in-clinic evaluation. Reproducibility was assessed photographically with both experienced and inexperienced clinical evaluators, whereas intragrader repeatability was assessed live in-clinic. The scale was then employed in a split-face randomized clinical trial on 58 subjects to evaluate the efficacy of a cosmetic treatment product over 8 weeks. RESULTS: Colour analysis of the images showed the scale was linear, with statistically significant correlations observed when colour data (CIElab; Individual Typology Angle) were plotted against the corresponding grades (r > 0.9, P < 0.001). Colour difference (Delta E) was calculated between the infraorbital zone and the surrounding skin, and when data were plotted against the grades, a statistically significant correlation was observed (r = 0.99, P < 0.01). The magnitude of the Delta E suggested that changes in grade are visibly perceptible to the human eye, and therefore, the scale is sensitive and clinically relevant. Intergrader reproducibility showed strong correlation (0.96) and >90% agreement between experienced evaluators, whereas intragrader repeatability assessment showed >90% perfect agreement between grades. Use of this scale in a clinical trial demonstrated the efficacy of a cosmetic product, with a mean statistically significant (P < 0.001) decrease in grade of 0.74 compared to baseline, and 0.59 versus the untreated control, after 8 weeks of treatment. CONCLUSION: Our photonumeric scale for infraorbital dark circles is sensitive and robust and provides an objective and easy-to-use tool to evaluate dark circles and their treatment.

OBJECTIF: En raison de leur étiologie et de leur périodicité complexes, les cernes sont difficiles à caractériser et à mesurer, les techniques d'évaluation actuelles reposant sur des équipements spécialisés, l'analyse d'images ou des échelles de notation exclusives. Il est donc nécessaire de développer et de valider une échelle photonumérique pour évaluer les cernes infraorbitaires, laquelle peut fournir un outil objectif et pertinent pour le consommateur et tester l'efficacité des produits et des procédures de traitement. MÉTHODES: Un panel d'évaluateurs cliniques experts a examiné environ trois mille photographies du visage recueillies sur une période de 5 ans, ainsi que des images sélectionnées représentant une plage dynamique de cernes. Une échelle photonumérique à 10 points a été créée, avec des descripteurs et des images correspondants à chaque grade de l'échelle. Afin de valider rigoureusement l'échelle, la linéarité, la sensibilité et la précision ont été évaluées par colorimétrie et en clinique. La reproductibilité a été évaluée sur le plan photographique par des évaluateurs cliniques expérimentés et inexpérimentés, tandis que la répétabilité intragrade a été évaluée en direct en clinique. L'échelle a ensuite été utilisée dans un essai clinique randomisé à deux parties sur 58 sujets, afin d'évaluer l'efficacité d'un produit de traitement cosmétique sur 8 semaines. RÉSULTATS: L'analyse des couleurs des images a montré que l'échelle était linéaire, avec des corrélations statistiquement significatives observées lorsque les données de couleurs (CIElab ; angle de typologie individuel) ont été tracées par rapport aux grades correspondants (r > 0,9, P < 0,001). La différence de couleur (Delta E) a été calculée entre la zone infraorbitaire et la peau environnante, et lorsque les données ont été tracées par rapport aux grades, une corrélation statistiquement significative a été observée (r = 0,99, P < 0,01). L'ampleur du delta E a suggéré que les changements de grade sont visiblement perceptibles à l'œil humain, l'échelle étant par conséquent sensible et cliniquement pertinente. La reproductibilité intergrade a montré une forte corrélation (0,96) et une concordance > 90 % entre les évaluateurs expérimentés, tandis que l'évaluation de la répétabilité intragrade a montré une concordance parfaite > 90 % entre les grades. L'utilisation de cette échelle lors d'un essai clinique a démontré l'efficacité d'un produit cosmétique, avec une diminution moyenne statistiquement significative (P < 0,001) du grade de 0,74 par rapport à la référence, et de 0,59 par rapport au témoin non traité, après 8 semaines de traitement. CONCLUSION: Notre échelle photonumérique pour les cernes infraorbitaires est sensible et robuste, fournissant un outil objectif et facile à utiliser afin d'évaluer les cernes et leur traitement.

Fluorescence Quenching of Carbonyl-Twisted 5-Acyl-1-dimethylaminonaphthalenes by Alcohols.

Derivatives of 1-dimethylamino-5-propionylnaphthalene that constrain the carbonyl group into a five-, six-, and seven-membered ring were prepared, and their fluorescence quenching in protic solvents was studied. Evidence for enhanced quenching due to carbonyl twisting out of the molecular plane is presented, but this effect is heavily masked by the strong quenching by all of the derivatives and by the ring size-dependent deactivation seen in polar, aprotic solvents. Calculations show strong, ring size-dependent vibrational coupling between the carbonyl group and the naphthalene ring in the first excited state.

Matrix Assisted Laser Desorption Ionization-Time-of-Flight mass spectrometry identification of Mycobacterium bovis in Bovinae.

In this study, Matrix Assisted Laser Desorption Ionization-Time-of-Flight (MALDI-TOF) mass spectrometry was used to identify Mycobacterium bovis from cattle and buffalo tissue isolates from the North and South regions of Brazil, grown in solid medium and previously identified by Polymerase Chain Reaction (PCR) based on Region of Difference 4 (RD4), sequencing and spoligotyping. For this purpose, the protein extraction protocol and the mass spectra reference database were optimized for the identification of 80 clinical isolates of mycobacteria. As a result of this optimization, it was possible to identify and differentiate M. bovis from other members of the Mycobacterium tuberculosis complex with 100% specificity, 90.91% sensitivity and 91.25% reliability. MALDI-TOF MS methodology described herein provides successful identification of M. bovis within bovine/bubaline clinical samples, demonstrating its usefulness for bovine tuberculosis diagnosis in the future.

Mass spectrometry-based proteomics reveals the distinct nature of the skin proteomes of photoaged compared to intrinsically aged skin.

OBJECTIVE: With increasing age, skin is subject to alterations in its organization, which impact on its function as well as having clinical consequences. Proteomics is a useful tool for non-targeted, semi-quantitative simultaneous investigation of high numbers of proteins. In the current study, we utilize proteomics to characterize and contrast age-associated differences in photoexposed and photoprotected skin, with a focus on the epidermis, dermal-epidermal junction and papillary dermis. METHODS: Skin biopsies from buttock (photoprotected) and forearm (photoexposed) of healthy volunteers (aged 18-30 or ≥65 years) were transversely sectioned from the stratum corneum to a depth of 250 µm. Following SDS-PAGE, each sample lane was segmented prior to analysis by liquid chromatography-mass spectrometry/mass spectrometry. Pathway analysis was carried out using Ingenuity IPA. RESULTS: Comparison of skin proteomes at buttock and forearm sites revealed differences in relative protein abundance. Ageing in skin on the photoexposed forearm resulted in 80% of the altered proteins being increased with age, in contrast to the photoprotected buttock where 74% of altered proteins with age were reduced. Functionally, age-altered proteins in the photoexposed forearm were associated with conferring structure, energy and metabolism. In the photoprotected buttock, proteins associated with gene expression, free-radical scavenging, protein synthesis and protein degradation were most frequently altered. CONCLUSION: This study highlights the necessity of not considering photoageing as an accelerated intrinsic ageing, but as a distinct physiological process.

OBJECTIF: Avec l'âge, la peau est sujette à des altérations dans son organisation, et outre le fait d'avoir des conséquences cliniques cela a un impact sur sa fonction. La protéomique est un outil utile pour l'évaluation non ciblée, semi-quantitative, simultanée d'un nombre élevé de protéines. Dans cette étude, nous utilisons la protéomique pour caractériser et comparer les différences associées à l'âge entre une peau photoexposée et une peau photoprotégée, avec une attention particulière sur l'épiderme, la jonction dermo-épidermique et le derme papillaire. MÉTHODES: Des biopsies de peau de la fesse (photoprotégée) et de l'avant-bras (photoexposée) de volontaires sains (âgés de 18 à 30 ans ou de ≥ 65 ans) ont été sectionnées transversalement depuis la couche cornée jusqu'à une profondeur de 250 µm. Suite à une électrophorèse SDS-PAGE, chaque échantillon a été segmenté avant l'analyse par chromatographie en phase liquide couplée à la spectrométrie de masse/spectrométrie de masse. Une analyse des voies de signalisation a été réalisée à l'aide d'Ingenuity IPA. RÉSULTATS: La comparaison des protéomes de la peau des sites des fesses et de l'avant-bras a révélé des différences dans l'abondance relative de protéines. Le vieillissement de la peau de l'avant-bras photoexposée montre une augmentation de 80% des protéines altérées avec l'âge, contrairement à la peau des fesses photoprotégée où une réduction de 74 % des protéines altérées avec l'âge a été mesurée. Sur le plan de la fonction, les protéines altérées par l'âge dans la peau de l'avant-bras photoexposée étaient associées à une structure, une énergie et un métabolisme. Dans la peau des fesses photoprotégée, les protéines associées à l'expression génique, la neutralisation des radicaux-libres, la synthèse des protéines et la dégradation des protéines étaient le plus fréquemment altérés. CONCLUSION: Cette étude souligne la nécessité de ne pas considérer le photovieillissement comme un vieillissement accéléré intrinsèque, mais comme un processus physiologique distinct.

National profile of foot orthotic provision in the United Kingdom, part 2: podiatrist, orthotist and physiotherapy practices.

BACKGROUND: A national survey recently provided the first description of foot orthotic provision in the United Kingdom. This article aims to profile and compare the foot orthoses practice of podiatrists, orthotists and physiotherapists within the current provision. METHOD: Quantitative data were collected from podiatrists, orthotists and physiotherapists via an online questionnaire. The topics, questions and answers were developed through a series of pilot phases. The professions were targeted through electronic and printed materials advertising the survey. Data were captured over a 10 month period in 2016. Differences between professions were investigated using Chi squared and Fischer's exact tests, and regression analysis was used to predict the likelihood of each aspect of practice in each of the three professions. RESULTS: Responses from 357 podiatrists, 93 orthotists and 49 physiotherapists were included in the analysis. The results reveal statistically significant differences in employment and clinical arrangements, the clinical populations treated, and the nature and volume of foot orthoses caseload. CONCLUSION: Podiatrists, orthotists and physiotherapists provide foot orthoses to important clinical populations in both a prevention and treatment capacity. Their working context, scope of practice and mix of clinical caseload differs significantly, although there are areas of overlap. Addressing variations in practice could align this collective workforce to national allied health policy.

Identificação por espectrometria de massa MALDI-TOF de Salmonella spp. e Escherichia coli isolados de carcaças bovinas / MALDI-TOF mass spectrometry identification of Salmonella spp. and Escherichia coli isolated from bovine carcasses

O objetivo deste trabalho foi introduzir a técnica de espectrometria de massa com fonte de ionização e dessorção a laser assistida por matriz e analisador de tempo-de-voo (MALDI-TOF) para incrementar o método tradicional microbiológico na detecção de Salmonella spp. e Escherichia coli em carcaças bovinas. Foram avaliadas 270 amostras de 90 carcaças de bovinos. Para isolamento de Salmonella spp. e E. coli, foram utilizadas, respectivamente, as metodologias descritas na ISO 6579:2002 e no Compendium of Methods for the Microbiological Examination of Foods. As análises por MALDI-TOF foram realizadas a partir de isolados cultivados em ágar nutriente ou em caldo triptona de soja, provenientes das amostras com características bioquímicas positivas (n=7), inconclusivas (n=4) e negativas (n=85) para Salmonella spp. e bioquímicas positivas (n=37) e negativas (n=85) para E. coli. Os perfis de massas foram adquiridos com o espectrômetro de massas MALDI-TOF Autoflex III SmartBeam e os espectros brutos foram processados usando o programa MALDI Biotyper (Bruker Daltonics). De acordo com a identificação preliminar, com base na morfologia das colônias e nas reações bioquímicas, sete isolados foram considerados positivos para Salmonella spp. Através do MALDI Biotyper, esses sete isolados foram classificados como pertencentes ao gênero Salmonella e, além disso, identificados como S. enterica. Quatro isolados que apresentaram características fenotípicas não usuais e resultados inconclusivos nos testes bioquímicos para Salmonella foram identificados como pertencentes aos gêneros Citrobacter e Proteus após análise por MALDI. Para E. coli, 37 amostras foram positivas pelos testes bioquímicos da espécie, o que foi confirmado por MALDI Biotyper. A metodologia MALDI-TOF permitiu a rápida confirmação da identidade de Salmonella spp. e E. coli, podendo ser utilizada para detecção desses microrganismos em isolados bacterianos de carcaças bovinas.(AU)

The aim of this study was to introduce matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) mass spectrometry to improve the traditional microbiological method for the detection of Salmonella spp. and Escherichia coli in beef carcasses. Two hundred seventy samples from 90 beef carcasses were evaluated. The methodologies described in ISO 6579:2002 and in the Compendium of Methods for the Microbiological Examination of Foods were used for Salmonella spp. and E. coli isolation, respectively. MALDI-TOF analysis were performed on tryptone soya broth suspension isolates or directly from nutrient agar colonies, from the positive, inconclusive or negative biochemically tested samples for Salmonella and E. coli. Mass profiles were acquired on an Autoflex III SmartBeam MALDI-TOF mass spectrometer and the raw spectra were processed using the MALDI Biotyper software (Bruker Daltonics). According to the preliminary identification based on colony morphology and the biochemical reactions, seven isolates were positive for Salmonella spp. Through MALDI Biotyper these seven isolates were also classified as belonging to the genus Salmonella and further identified as S. enterica. Four isolates showing unusual phenotypic characteristics and inconclusive results in biochemical tests for Salmonella were identified as belonging to Citrobacter and Proteus genera after MALDI analysis. Regarding Escherichia coli, 37 were positive for species biochemical testing which MALDI Biotyper confirmed. MALDI-TOF methodology allowed rapid Salmonella spp. and E. coli identity confirmation and may be used to detect these microrganisms within bacterial isolates from beef carcasses.(AU)

National profile of foot orthotic provision in the United Kingdom, part 1: practitioners and scope of practice.

BACKGROUND: Foot orthoses have been advocated in the management of a wide range of clinical foot and lower limb problems and are within the scope of podiatry, orthotic and physiotherapy practice. Previous reports into the provision of orthoses have consistently identified significant issues with services and devices, but data were never specific to foot orthoses. The aim of this first of a series of papers was to report the first ever national multi professional profile of foot orthosis provision in the United Kingdom. METHODS: Quantitative and qualitative data were collected from podiatrists, orthotists and physiotherapists via an online questionnaire. The topics, questions and answers were developed through a series of pilot phases. The professions were targeted through electronic and printed materials. Data were captured over a 10 month period in 2016. RESULTS: A total of 499 responses were included in analysis, including 357 podiatrists, 93 orthotists and 49 physiotherapists. The results reveal wide ranging practices across podiatrists, orthotists and physiotherapists, provision of orthoses through different health care departments (uni and multidisciplinary), for different health conditions (acute and chronic), and involving different types of orthoses (prefabricated and customised). CONCLUSION: Foot orthoses in the United Kingdom are provided in areas of well recognised health and rehabilitation priorities. A wide range of orthotic devices and practices are employed and different professions provide foot orthoses in different ways.

Novel approaches to characterize age-related remodelling of the dermal-epidermal junction in 2D, 3D and in vivo.

BACKGROUND/PURPOSE: The dermal-epidermal junction (DEJ) forms epidermal protrusions down into the dermis (rete ridges) and dermal projections up into the epidermis (dermal papillae). Usually visualized in two-dimensions (2D), our knowledge of how the DEJ changes with ageing is limited. We aimed to characterize how this structure exists in 3D and changes with age. METHODS: Photoprotected and photoexposed skin were imaged using reflectance confocal microscopy (RCM) in young and aged individuals. Biopsies of the imaged areas were processed for histological sectioning and for imaging using micro-computed X-ray tomography (microCT). RESULTS: Images obtained from RCM and microCT were used to 3D reconstruct the DEJ. DEJ heights obtained from microCT images showed strong correlation with histology-measured heights. We proposed a novel definition of rete ridges (RRm ) and dermal papillae (DPm ), which allowed easier automated measurement of reduced DPm and RRm volumes in aged skin from microCT reconstructions. An algorithm to map DPm connectivity showed reduced lengths of DPm branches with age. CONCLUSION: Three-dimensional images illustrated the complex topography of the DEJ and highlighted the distinct morphology of dermal papillae compared with rete ridges, which is not evident when evaluating 2D sections. Ex vivo imaging was more successful in differentiating DEJ architecture with respect to age.

Skin aging: molecular pathology, dermal remodelling and the imaging revolution.

Skin is a multifunctional organ but, alongside every other organ system, is subject to both intrinsic (chronological) and extrinsic (environmental) aging, resulting in a loss of functional capacity. Cutaneous aging manifests as an observable change in the external appearance of the skin, the major accelerator of the aging process being our interactions with our environment, such as chronic exposure to solar irradiation (UV, IR or visible wavelengths of light). The aim of this contribution, therefore, was to provide a review of the pathological mechanisms which may play roles in the development of extrinsic, mainly photo-, aging and to review how these molecular changes impact on the structure of the organ as a whole, resulting in loss of function. Finally, we will describe the advances which are occurring in imaging techniques which may allow further characterisation of aged skin.

ADAM23 negatively modulates alpha(v)beta(3) integrin activation during metastasis.

The ADAM23 gene is frequently silenced in different types of tumors, and, in breast tumors, silencing is correlated with tumor progression, suggesting that it might be associated with the acquisition of a metastatic phenotype. ADAM23 exerts its function mainly through the disintegrin domain, because its metalloprotease domain is inactive. Analysis of ADAM23 binding to integrins has revealed a specific interaction with alpha(v)beta(3) integrin mediated by the disintegrin domain. Altered expression of alpha(v)beta(3) integrin has been observed in different types of tumors, and expression of this integrin in the activated form has been shown to promote metastasis formation. Here, we investigated the possibility that interaction between ADAM23 and alpha(v)beta(3) integrin might negatively modulate alpha(v)beta(3) activation during metastatic progression. ADAM23 expression was knocked down using short hairpin RNA in the MDA-MB-435 cell line, which has been extensively used as a model for alpha(v)beta(3) integrin activation. Ablation of ADAM23 enhanced alpha(v)beta(3) integrin activation by at least 2- to 4-fold and ADAM23 knockdown cells showed enhanced migration and adhesion to classic alpha(v)beta(3) integrin ligands. Ablation of ADAM23 expression also enhanced pulmonary tumor cell arrest in immunodeficient mice. To complement our findings with clinical evidence, we showed that silencing of ADAM23 gene by DNA promoter hypermethylation in a collection of 94 primary breast tumors was significantly associated with lower distant metastases-free and disease-specific survivals and was an independent prognostic factor for poor disease outcome. Our results strongly support a functional role of ADAM23 during metastatic progression by negatively modulating alpha(v)beta(3) integrin activation.

Epigenetic silencing of the adhesion molecule ADAM23 is highly frequent in breast tumors.

Altered cell adhesion is causally involved in tumor progression, and the identification of novel adhesion molecules altered in tumors is crucial for our understanding of tumor biology and for the development of new prognostic and therapeutic strategies. Here, we provide evidence for the epigenetic downregulation in breast tumors of the A Desintegrin And Metalloprotease domain 23 gene (ADAM 23), a member of a new family of surface molecules with roles in cell-cell adhesion and/or cell-matrix interactions. We examined the mRNA expression and methylation status of the 5' upstream region of the ADAM23 gene in different breast tumor cell lines as well as in primary breast tumors. We found ADAM23 5' hypermethylation in eight out of 12 (66.7%) tumor cell lines and in nine out of 13 (69.2%) primary tumors. Promoter hypermethylation was strongly associated with reductions in both mRNA and protein expression, with a threshold of 40-60% of modified CpG dinucleotides being required for the complete silencing of ADAM23 mRNA expression. Treatment of MCF-7 and SKBR-3 cell lines with 5'-Aza-2'-deoxycytidine led to a reactivation of ADAM23 mRNA expression and a marked decrease in the methylation level. It is worth noting that primary breast tumors with a more advanced grade showed a higher degree of methylation, suggesting that the adhesion molecule ADAM23 may be downregulated during the progression of breast cancer. Oncogene (2004) 23, 1481-1488. doi:10.1038/sj.onc.1207263 Published online 8 December 2003

Noise levels within the ear and post-nasal space in neonates in intensive care.

BACKGROUND: Noise exposure in neonatal units has long been suspected of being a cause of hearing loss associated with such units. The noise intensity to which the neonate is exposed varies with the type of ventilatory support used. Also, the post-nasal space is an enclosed cavity that is close to the inner ear and an area of turbulent and hence potentially noisy airflow. AIM: To determine noise intensities within the ear and post-nasal space in neonates on different modes of ventilatory support using probe microphones, measures previously not undertaken. METHODS: A portable instrument with a probe microphone was used for the measurements. Three groups of infants were included: (a) those receiving no respiratory support (NS); (b) those receiving conventional ventilation (CV); (c) those receiving continuous positive airways pressure (CPAP) support. RESULTS: The mean in-the-ear noise intensities (at 1 kHz) were 41.7 dB SPL (NS), 39.5 dB SPL (CV), and 55.1 dB SPL (CPAP). The noise intensities in the post-nasal space in those receiving CPAP support were higher than in the other groups, reached mean levels of up to 102 dB SPL at some frequencies, and increased with increasing flow rates. CONCLUSIONS: The most important finding is the high noise intensities in the post-nasal space of those receiving CPAP support. Given the proximity of the post-nasal space to the inner ear, enough noise could be transmitted, especially in infants receiving the higher flow rates, to cause cochlear damage and hence hearing loss. It would therefore be wise, wherever possible, to avoid using the higher flow rates.

A refined molecular karyotype for the reference strain of the Trypanosoma cruzi genome project (clone CL Brener) by assignment of chromosome markers.

We present a useful refinement of the molecular karyotype of clone CL Brener, the reference clone of the Trypanosoma cruzi Genome Project. The assignment of 210 genetic markers (142 expressed sequence tags (ESTs), seven cDNAs, 32 protein-coding genes, eight sequence tagged sites (STSs), 21 repetitive sequences) to the chromosomal bands separated by pulsed field gel electrophoresis (PFGE) identified 61 chromosome-specific markers, two size-polymorphic chromosomes and seven linkage groups. Fourteen new repetitive elements were isolated in this work and mapped to the chromosomal bands. We found that at least ten repetitive elements can be mapped to each chromosomal band, which may render the whole genome sequence assembly a difficult task. To construct the integrated map of chromosomal band XX, we used yeast artificial chromosome (YAC) overlapping clones and a variety of probes (i.e. known gene sequences, ESTs, STSs generated from the YAC ends). The total length covered by the YAC contig was approximately 1.3 Mb, covering 37% of the entire chromosome. We found some degree of polymorphism among YACs derived from band XX. These results are in agreement with data from phylogenetic analysis of T. cruzi which suggest that clone CL Brener is a hybrid genotype [Mol. Biochem. Parasitol. 92 (1998) 253; Proc. Natl. Acad. Sci. USA 98 (2001) 7396]. The physical map of the chromosomal bands, together with the isolation of specific chromosomal markers, will contribute in the global effort to sequence the nuclear genome of this parasite.

USH1C: a rare cause of USH1 in a non-Acadian population and a founder effect of the Acadian allele.

Usher syndrome (USH) is characterized by the associated findings of hearing loss and retinitis pigmentosa (RP), leading to progressive loss of vision. Three forms of USH can be distinguished clinically. In the most severe form, USH1, profound congenital deafness is associated with vestibular dysfunction and RP. To determine the frequency of USH1C mutations as a cause for USH1, 128 probands with Usher syndrome type 1 including seven from Acadian and 121 from non-Acadian populations were systematically screened for mutations in USH1C using a combined single-strand conformational polymorphisms (SSCP)/heteroduplex and sequencing method. All seven Acadian USH1 patients were found to be homozygous for both the 216G>A mutation and the 9-repeat VNTR which characterizes the Acadian allele, confirming previous evidence for a founder effect by haplotype analysis. However, USH1C mutations were identified in only two non-Acadian USH1 probands (1.65%) including one from Pakistan who was homozygous for a 238-239insC mutation and one from Canada was also homozygous for the Acadian allele. The low prevalence of USH1C mutations in the present study suggests that the high prevalence of the 238-239insC in Germany may reflect a founder effect. Comparison of the affected haplotypes in the Canadian patient with the Acadian USH1 patients yielded evidence for a founder effect. Our data suggest that USH1C is a relatively rare form of USH1 in non-Acadian populations and that in addition to the 216G>A Acadian mutation, the 238-239insC mutation appears to be common in some populations.