Search

Acute lung injury (ALI) is a complex syndrome involving the interplay of both environmental (such as the addition of mechanical ventilation) and genetic factors. Clinical models have identified risk factors for development and poor outcome but these strategies remain imprecise. To better understand the mechanisms of pathogenesis associated with mechanisms of ALI, candidate genes identified by global expression profiling or related literature searches are being explored for relevant polymorphisms (single base pair substitutions) that can affect both ALI susceptibility and outcome. This article summarizes several specific genetic association studies that have been conducted in ALI and reviews supporting data from in vitro and in vivo models of the disease and clinical observations. Although valuable information has been reported to date, intense analyses are needed in this developing discipline to assure significant clinical utility. The detailing of specific associated polymorphisms will continue to provide new insights in the understanding of disease pathogenesis, and promise to reveal novel molecular targets and personalized treatments to prevent the disease.

Introduction: More systematic reviews related to orthodontic topics are published each year, although little has been done to evaluate their search and selection methodologies., Methods: Systematic reviews related to orthodontics published between January 1, 2000, and December 31, 2004, were searched for their use of multiple electronic databases and secondary searches. The search and selection methods of identified systematic reviews were evaluated against the Cochrane Handbook's guidelines., Results: Sixteen orthodontic systematic reviews were identified in this period. The percentage of reviews documenting and using each criterion of article searching has changed over the last 5 years, with no recognizable directional trend. On average, most systematic reviews documented their electronic search terms (88%) and inclusion-exclusion criteria (100%), and used secondary searching (75%). Many still failed to search more than MEDLINE (56%), failed to document the database names and search dates (37%), failed to document the search strategy (62%), did not use several reviewers for selecting studies (75%), and did not include all languages (81%)., Conclusions: The methodology of systematic reviews in orthodontics is still limited, with key methodological components frequently absent or not appropriately described.

Objective: To evaluate facial soft tissue changes after the use of fixed functional appliances in Class II division 1 malocclusion cases using a systematic review of the literature., Materials and Methods: Several electronic databases (PubMed, Medline, Medline In-Process & Other Non-Indexed Citations, Cochrane Database, Embase, Web of Sciences, and Lilacs) were searched with the help of a senior Health Sciences librarian. Abstracts that appeared to fulfill the initial selection criteria were selected by consensus. The original articles were then retrieved. Their references were also hand-searched for possible missing articles. Clinical trials assessing facial soft tissue changes with the use of fixed functional appliances without any surgical intervention or syndromic characteristics were considered. A comparable untreated control group was required to factor out normal growth changes. Four articles using Herbst and one using Jasper Jumper fulfilled the selection criteria. An individual analysis of these articles was made and some methodological flaws were identified., Results: Although fixed functional appliances produce some significant statistical changes in the soft tissue profile, the magnitude of the changes may not be perceived as clinically significant., Conclusions: The conclusions from this systematic review should be considered with caution because only a secondary level of evidence was found. Long-term double-blinded prospective randomized clinical trials are needed. Three-dimensional quantification of the soft tissue changes is required to overcome current limitations in our understanding of the soft tissue changes obtained with the use of fixed functional appliances.

The objective of this study was to evaluate the diagnostic capability of Little's Irregularity Index (LII) in order to estimate the arch length discrepancy (ALD) in a dental arch. Dental casts with a full permanent dentition, excluding third molars, from 200 12- to-16-year-old schoolchildren from a representative high school located in Lima, Peru, were used. Incisal irregularity was measured using the LII, whereas ALD was calculated as the difference between available and required space in each dental arch anterior to the first permanent molars. The receiver-operator characteristic (ROC) curve was used to contrast the LII with three different dichotomized ALDs and locate optimized cut-off points. Correlation between ALD and LII was -0.68 (P < 0.001). According to ROC curves, LIIs of 2.45, 4.00, and 4.55 mm were the optimized cut-off points to estimate negative ALDs higher than 0, 3, and 6 mm, respectively. LII's highest diagnostic capability was found for estimating negative ALD greater than 3 mm with a sensibility of 0.78 and a specificity of 0.76. Based on the present findings, LII could potentially be used in epidemiological surveys as a valid and less time-consuming measurement of crowding compared with ALD; however, further studies are needed to test the reliability of this approach in field settings.

Introduction: The objective of this validation study was to compare standard plaster models (the current gold standard for cast measurements) with their digital counterparts made with emodel software (version 6.0, GeoDigm, Chanhassen, Minn) for the analysis of tooth sizes and occlusal relationships--specifically the Bolton analysis and the peer assessment rating (PAR) index and their components., Methods: Dental casts were poured from 24 subjects with 8 malocclusion types grouped according to American Board of Orthodontics categories. Measurements were made with a digital caliper to the nearest 0.01 mm from plaster models and with the software from the digital models. A paired samples t test was used to compare reliability and validity of measurements between plaster and digital methods., Results: Reproducibility of digital models via the concordance correlation coefficient was excellent in most cases and good in some. Although statistically significant differences in some measurements were found for the reliability and validity of the digital models via the average mean of the absolute differences of repeated measurements, none was clinically significant. Grouping of the measurements according to the 8 American Board of Orthodontics categories produced no significant difference (Kruskal-Wallis test). No measurement associated with Bolton analysis or PAR index made on plaster vs digital models showed a clinically significant difference. The PAR analysis and its constituent measurements were not significantly different clinically between plaster and emodel media., Conclusions: Preliminary results did not indicate that digital models would cause an orthodontist to make a different diagnosis of malocclusion compared with plaster models; digital models are not a compromised choice for treatment planning or diagnosis.

The aim of this study was to determine which dental esthetic self-perception evaluation tool discriminated better between orthodontically treated or untreated Peruvian young adults. A total of 630 students were randomly chosen from the 2000 admitted in 2002 to a private university in Peru. Students undergoing active orthodontic treatment at the time of examination were excluded. Self-perceived dental esthetic appearance was evaluated through Standardized Continuum of Aesthetic Need, Oral Aesthetic Subjective Index Scale, and Visual Analogue Scale (VAS). A stepwise multivariate discriminant analysis was developed to classify orthodontic treatment according to the three evaluation tools. A total of 199 students (31.6%) reported a history of orthodontic treatment. Differences between orthodontically treated and untreated groups were found only for the mean VAS score (P < .001). Although three different approaches were used to evaluate dental esthetic self-perception, only VAS allowed the discrimination of the self-perceived dental appearance between orthodontically treated and untreated Peruvian university young adults. Similarities in the self-perceived dental appearance of treated and untreated groups reported in previous epidemiological studies could be explained because different evaluation instruments were used. Further studies are required to support current findings.

Bartter syndrome (BS) is a heterogeneous group of autosomal recessive hypokalaemic salt-losing tubulopathies. Five types of BS caused by different genetic defects have been identified, and one of them is associated with sensorineural deafness (BSND). Mutations in the recently described BSND gene, mapped in chromosome 1p31, have been reported to be associated with BSND. This gene encodes barttin, an essential beta-subunit subunit for ClC-Ka and ClC-Kb channels. Both subunits are co-expressed in basolateral membranes of renal tubules, in the ascending limb of the loop of Henle, and in the stria vascularis of the inner ear. We studied two apparently unrelated Spanish families from the Canary Islands, with five members showing this pathology. Sequence analysis of the BSND gene showed that the affected members were homozygous for a C-to-T transition in exon 1, while their parents were heterozygous. This alteration results in a missense mutation, G47R, which has been previously shown to abolish the stimulatory effect on the subunit barttin of the ClC-Kb channel. Our results indicate that families with the G47R mutation indeed present polyhydramnios, premature birth and salt loss. Nevertheless, glomerular filtration rate was normal in all patients. Clinical manifestations are moderate in patients with the G47R mutation compared to other published data form patients with BSND. This constitutes the first report of BSND cases in Spain.

The objectives of this study were to evaluate the frequency and severity of the malocclusion and treatment needs in Peruvian young adults. The second aim was to compare the orthodontic treatment needs according to sex and socio-economic status (SES). This cross-sectional study was conducted at the University Dental Clinic of a private university in Lima, Peru. A total of 267 freshmen (from 16 to 25 years old) were randomly selected from a pool of 780 students. Students wearing an orthodontic appliance or reporting a history of orthodontic treatment were excluded from the study. Clinical examinations were conducted using the Dental Aesthetic Index (DAI). Mann-Whitney and Kruskal-Wallis tests were used to compare the DAI scores according to sex and SES, respectively. The mean DAI score was 28.87 points (IC(95%) 27.77; 29.97, where IC indicates interval of confidence). Around one-third of the sample presented severe or very severe malocclusion, which implies a highly desirable or mandatory orthodontic treatment need. No statistically significant difference was found between the DAI scores according to sex (P = .592) and SES (P = .397). Approximately one-third of the evaluated Peruvian young adults would need orthodontic treatment according to the DAI. In this population, malocclusion was characterized by a relatively high frequency of missing teeth, appreciable dental crowding, and inadequate anteroposterior relationships.

Objectives: To determine dentists" perceptions of the usefulness of digital technologies in improving dental practice and resolving practice issues; to determine dentists" willingness to use digital and electronic technologies; to determine perceived obstacles to the use of digital and electronic technologies in dental offices; and to determine dentists" attitudes toward Internet privacy issues., Methods: An anonymous, self-administered survey of Canadian dentists was conducted by mail. A potential mailing list of 14,052 active Canadian dentists was compiled from the 2003 records of provincial regulatory bodies. For each province, 7.8% of the dentists were randomly selected with the help of computer software. The surveys were mailed to this stratified random sample of 1,096 dentists., Results: The response rate was 28% (312/1,096). Of the 312 respondents, 4 (1%) were in full-time academic positions, 16 (5%) were not practising, and 9 (3%) provided incomplete data. Therefore, 283 survey responses were available for analysis. More than 60% of the dentists indicated that computer technology was quite capable or very capable of improving their current practice by increasing patient satisfaction, decreasing office expenses, increasing practice efficiency, increasing practice production, improving record quality and improving case diagnosis and treatment planning. More than 50% of respondents reported that digital photography and digital radiography were quite useful or very useful. About 70% of the dentists agreed or strongly agreed with using digital and electronic technologies to consult with dental specialists. Cost of equipment and lack of comfort with technology were regarded as significant or insurmountable obstacles by substantial proportions of respondents., Conclusions: Respondents generally viewed digital and electronic technologies as useful to the profession. Increased office efficiency and production were perceived as positive effects of digital and electronic technologies. These technologies are more often used for consulting with colleagues rather than for consulting with patients. The major obstacles to the general use of these technologies were related to cost, lack of comfort with technology and differences in legislation between provinces and countries. Privacy issues were not perceived as a significant barrier.

Introduction: Elastomeric chains are used extensively in orthodontic treatment, and their clinical behavior should be evaluated in vivo. The aim of this randomized clinical trial was to determine whether elastomeric chains made by different fabrication procedures have different force-decay levels., Methods: Twenty-four consecutive orthodontic patients at a university orthodontic clinic who fulfilled the selection criteria were grouped to evaluate force decay at 1 hour, 24 hours, 48 hours, 7 days, 14 days, and 21 days. Oral hygiene and diet pH (between 5.8 and 7) were controlled. For each patient, 2 types of elastomeric chains (injection molded and die-cut stamped) made by the same company were randomly assigned to a different arch and arch side (split-mouth design). Each traction unit (3-piece elastomeric chain with ligature wire) was adjusted to deliver an initial calibrated force of 200 g during canine retraction. This force level was reactivated for each study period with a new calibrated traction unit. Mean and standard deviations for the force decay in grams and percentages were calculated. Student t tests for independent and paired samples were used., Results: No statistically significant difference was found in the force decay between elastomeric chain types during the 3-week study period. The mean remaining force (about 150 g) after 3 weeks was considered clinically adequate for canine retraction. The behavior of the elastomeric chains in both arches was statistically and clinically similar., Conclusions: Both types of elastomeric chain produced the same clinical effects.

Objectives: To determine the frequency of computers in Canadian dental offices and to assess their use; to evaluate Internet access and use in Canadian dental offices; and to compare use of computers and the Internet by Canadian dentists, by the general public and by other dental groups., Methods: An anonymous, self-administered survey of Canadian dentists was conducted by mail. A potential mailing list of 14,052 active Canadian dentists was compiled from the 2003 records of provincial regulatory bodies. For each province, 7.8% of the general dentists were randomly selected with the help of computer software. The surveys were mailed to this stratified random sample of 1,096 dentists., Results: The response rate was 28%. Of the 312 respondents, 4 (1%) were in full-time academic positions, 15 (5%) were not practising, and 9 (3%) provided incomplete data. Therefore, 284 survey responses were available for descriptive analysis. Two hundred and fifty-seven (90%) of the respondents had a computer in their primary practice. Computers were used mainly for administrative tasks (accounting, bookkeeping and scheduling) rather than clinical tasks. Internet access was common (185/250 or 74%), and high-speed Internet access (93/250 or 37%) was increasingly common, judging from the results of previous studies on computer use. The main reasons given for not having in-office Internet access were security or privacy concerns and no reported need for or interest in the service., Conclusions: Computer use was high in this sample of Canadian dentists, but a small proportion of dental offices remained without computers. Canadian dentists" use of the Internet was greater than that of American dentists, private enterprise and the North American public in general.

An anonymous, self-administered, mail-out survey of Canadian Orthodontists was conducted to evaluate the characteristics of orthodontic Internet use. The response rate was 45.6% (304 of 667). A total of 76.6% of orthodontists reported having Internet access at work, and an additional 12.4% reported having Internet access from a different location. Statistically significant associations between Internet usage and office staff size (P < .001) and years of practice (P = .046) were observed. Offices with larger staffs had greater Internet access. Number of staffs and number of case starts were positively correlated (P < .001, r = 0.498). The odds ratio for having Internet access on the basis of increased case starts from the less than 100 to 300-399 categories was 5.67. Although not statistically significant, there was a trend for greater Internet access by younger practitioners.

The objective of this study was to compare, combined and individually, the mesiodistal (MD) and buccolingual (BL) tooth sizes as well as their respective crown proportions in the permanent dentition in dental arches with moderate, mild, and no crowding. Dental casts from two-hundred 12 to 16-year-old school children from a typical high school from Lima, Peru, were used. The MD and BL tooth sizes of all permanent teeth except second and third molars were measured, and their crown proportion (MD/BL ratio) was estimated. Each dental arch was classified as presenting moderate (-5.1 mm or more of discrepancy), mild (-0.1 and -5 mm of discrepancy), and no crowding (zero or a positive discrepancy). Combined and tooth-specific comparisons among the crowding groups for the tooth sizes as well as crown proportions were performed with a multivariate analysis of variance (MANOVA, using Wilks lambda). Combined MD tooth sizes and crown proportions differed among crowding groups. Subsequent individual comparisons indicated differences for MD tooth size of all upper teeth and for lower premolars and central incisors. Differences were also detected for crown proportions of the upper second premolar, canine, and both incisors; as well as for the lower first premolar, canine, and central incisor. No differences were found for the BL tooth sizes among crowding groups. MD tooth sizes and crown proportions from specific teeth are significantly different between dental arches with moderate, mild, and noncrowded arches. This study helps to understand the odontometric component of the dental crowding multifactorial origin.

Background: The authors conducted a literature review to evaluate immediate transverse, anteroposterior, and vertical dental and skeletal changes produced by rapid maxillary expansion (RME)., Types of Studies Reviewed: The authors reviewed clinical trials that assessed immediate dental and/or skeletal changes after RME using cephalometric analysis, model casts or both. No surgical or other simultaneous treatment was accepted during the evaluation period., Results: The authors searched electronic databases and found 31 articles that met the initial inclusion criteria. The authors later rejected 12 of these articles because they did not report immediate changes, three because they lacked detailed descriptions of their results and two because of their nonconventional appliance designs. Fourteen articles satisfied th final inclusion criteria; however, they had methodological deficiencies., Clinical Implications: The greatest changes resulting from RME in the studies analyzed were dental and skeletal transverse changes. Few vertical and anteroposterior immediate changes were statistically significant, though they probably are not clinically important.

The aim of this study was to assess the correlation between the Fishman maturation prediction method (FMP) and the cervical vertebral maturation (CVM) method for skeletal maturation stage determination. Hand-wrist and lateral cephalograms from 79 subjects (52 females and 27 males) were used. Hand-wrist radiographs were analyzed using the FMP to determine skeletal maturation level (advanced, average, or delayed) and stage (relative position of the individual in the pubertal growth curve). Cervical vertebrae (C2, C3, and C4) outlines obtained from lateral cephalograms were analyzed using the CVM to determine skeletal maturation stage. Intraexaminer reliability (Intraclass correlation coefficient [ICC]) for both methods was calculated from 10 triplicate hand-wrist and lateral cephalograms from the same patients. An ICC coefficient of 0.985 for FMP and an ICC of 0.889 for CVM were obtained. A Spearman correlation value of 0.72 (P < .001) was found between the skeletal maturation stages of both methods. When the sample was subgrouped according to skeletal maturation level, the following correlation values were found: for early mature adolescents 0.73, for average mature adolescents 0.70, and for late mature adolescents 0.87. All these correlation values were statistically different from zero (P < .024). Correlation values between both skeletal maturation methods were moderately high. This may be high enough to use either of the methods indistinctively for research purposes but not for the assessment of individual patients. Skeletal level influences the correlation values and, therefore, it should be considered whenever possible.

Background: The authors conducted a systematic review of the literature to determine the treatment effects of the Invisalign orthodontic system (Align Technology), Santa Clara, Calif.)., Types of Studies Reviewed: The authors reviewed clinical trials that assessed Invisalign's treatment effects in nongrowing patients. They did not consider trials involving surgical or other simultaneous fixed or removable orthodontic treatment interventions., Results: The authors searched electronic databases (PubMed, MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, Evidence Based Medicine Reviews, EMBASE Excerpta Medica, Thomsen's ISI Web of Science and LILACS) with the help of a senior health sciences librarian. They used "Invisalign" as the sole search term, and 22 documents appeared in the combined search. Thereafter, they used "clinical trials," "humans" and "Invisalign treatment effects" as abstract selection criteria. Only two published articles met these inclusion criteria, though after reading the actual articles, the authors determined that they did not adequately evaluate Invisalign treatment effects. Both articles identified methodological issues., Clinical Implications: The inadequately designed studies the authors found represented only a lower level of evidence (level II). Therefore, the authors found that no strong conclusions could be made regarding the treatment effects of Invisalign appliances. Future prospective randomized clinical trials are required to support, with sound scientific evidence, the claims about Invisalign's treatment effects. Clinicians will have to rely on their Invisalign clinical experience, the opinions of experts and the limited published evidence when using Invisalign appliances.

Background: The pathogenic mechanisms and molecular events involved in the development and progression of diabetic nephropathy (DN) are not completely known. Recent data indicate that diabetes includes an inflammatory component that is related to diabetic complications. Tumor necrosis factor (TNF)-alpha, a cytokine with mainly proinflammatory activity, may be synthesized by renal cells. Our objective was to analyze intrarenal TNF-alpha gene expression and its relationship with urinary albumin excretion (UAE). We also investigated the effect of inhibition of angiotensin-converting enzyme on TNF-alpha expression and UAE., Methods: Streptozotocin-induced diabetic rats received either no treatment or an angiotensin-converting enzyme inhibitor (enalapril). After eight weeks, renal expression of TNF-alpha was evaluated by real-time polymerase chain reaction., Results: Renal cortical messenger RNA levels of TNF-alpha increased significantly and were twice as high in diabetic rats than in nondiabetic control rats. Enalapril administration nearly completely abolished the increase in TNF-alpha messenger RNA expression to the level observed in control rats. UAE was significantly correlated with urinary levels of TNF-alpha (r=0.68, P<0.05) and with renal TNF-alpha expression (r=0.51, P<0.05)., Conclusion: DN was associated with increased renal expression of TNF-alpha and UAE. Enalapril administration prevented this enhanced expression of TNF-alpha and decreased urinary cytokine excretion and albuminuria. These data provide a novel insight into the pathogenic mechanisms of DN, and support the hypothesis that inflammatory mechanisms may play a significant role in the development and progression of renal injury secondary to diabetes mellitus.

Many oil industry related sites have become contaminated due to the activities characteristic of this industry, such as oil exploration and production, refining, and petro-chemistry. In Mexico, reported hydrocarbon spills for the year 2000 amounted to 185203, equivalent to 6252 tons (PEMEX, 2000). The first step for the remediation of these polluted sites is to assess the size and intensity of the oil contamination affecting the subsoil and groundwater, followed by a health risk assessment to establish clean up levels. The aim of this work was to characterize the soil and water in a north-central Mexico Oil Storage and Distribution Station (ODSS), in terms of TPHs, gasoline and diesel fractions, BTEX, PAHs, MTBE, and some metals. Besides, measurements of the explosivity index along the ODSS were made and we describe and discuss the risk health assessment analysis performed at the ODSS, as well as the recommendations arising from it. Considering soils with TPH concentrations higher than 2000 mg kg(-1), the contaminated areas corresponding to the railway zone is about 12776.5 m2, to the south of the storage tanks is about 6558 m2, and to the south of the filling tanks is about 783 m2. Total area to be treated is about 20107 m2 (volume of 20107 m3), considering 1m depth.

Objective: To analyze 6 different types of visible anterior occlusion, exclusive of extraoral facial features, in terms of their esthetic appeal, as perceived by 91 randomly selected adult laypersons with different levels of education in Lima, Peru., Methods: Photographic images of 3 examples of each occlusion type (open bite [OB], deep bite [DB], crossbite [CB], end-to-end bite [EE], crowded bite [CwB] and ideal bite [IB]) were prepared. Evaluators used a visual analogue scale (VAS) to rate their perceptions of the esthetic appeal of each view. Analysis of variance (ANOVA) was used to test differences in mean scores among occlusion types and to test the effect of evaluator characteristics on perceived attractiveness., Results: The mean score was highest for IB, followed by EE, DB, CB, CwB and OB. Oneway ANOVA with Bonferroni post hoc test showed no difference between the highestscoring occlusion types (IB and EE, p > 0.99); each of the remaining groups was significantly different from both IB and EE (p < 0.001). The scores for DB, CB, CwB and OB were progressively lower, although not significantly different from one another (p > 0.05). Univariate ANOVA to determine the effects of evaluator characteristics (age, level of education, gender and interaction between level of education and gender) showed that gender was a significant factor (p < 0.034) for all bite groups except OB. Level of education was significant only for OB (p = 0.020) and age only for EE (p = 0.011). The interaction between level of education and gender was significant for all bite types (p < 0.046)., Conclusions: Lay evaluators identified ideal and EE bite occlusal relationships as esthetically most pleasing. They judged DB, CB, CwB and OB bite relationships as less esthetically pleasing but did not differentiate between these types of malocclusions.

There is a trend to consider the gene pool of the Basques as a 'living fossil' of the earliest modern humans that colonized Europe. To investigate this assumption, we have typed 45 binary markers and five short tandem repeat loci of the Y chromosome in a set of 168 male Basques. Results on these combined haplotypes were analyzed in the context of matching data belonging to approximately 3000 individuals from over 20 European, Near East and North African populations, which were compiled from the literature. Our results place the low Y-chromosome diversity of Basques within the European diversity landscape. This low diversity seems to be the result of a lower effective population size maintained through generations. At least some lineages of Y chromosome in modern Basques originated and have been evolving since pre-Neolithic times. However, the strong genetic drift experienced by the Basques does not allow us to consider Basques either the only or the best representatives of the ancestral European gene pool. Contrary to previous suggestions, we do not observe any particular link between Basques and Celtic populations beyond that provided by the Paleolithic ancestry common to European populations, nor we find evidence supporting Basques as the focus of major population expansions.

The aim of this study was to determine the influence of growth stunting on the maturation stage of the medium phalanx of the third finger (MP3) and the dental development of the left mandibular canine in 280 high school children (140 stunted and 140 normal controls; equally distributed by sex) between 9.5 and 16.5 years of age, from a representative Peruvian school. Periapical radiographs of the MP3 from the left hand were used to determine the skeletal maturity stage, according to an adaptation of the Hägg and Taranger method. Panoramic radiographs were used to determine the dental maturity stage of the lower left canine, according to Demirjian method. Stunting was determined by relating height and age, according to the World Health Organization recommendations. There was no statistically significant difference in the skeletal maturation stage (P = .134) and the dental development stage (P = .497) according to nutritional status, even when considering different age groups (P > .183). A high correlation (r = 0.85) was found between both maturity indicators regardless of the nutritional status (growth stunted, r = 0.855 and normal controls, r = 0.863) or sex (boys, r = 0.809 and girls, r = 0.892). When skeletal level was considered, correlations values were similar between advanced (r = 0.903) and average (r = 0.895) maturers but lower (r = 0.751) for delayed maturers. Growth stunting was not associated with dental development and skeletal maturity stages in Peruvian school children.

The objective was to evaluate long-term transverse, anteroposterior and vertical skeletal changes after rapid maxillary expansion (RME). The data were clinical trials that assessed skeletal changes through cephalometric analysis. No surgical or other simultaneous treatment during the evaluation period was accepted. Electronic databases (PubMed, Medline, Medline In-Process & Other Non-Indexed Citations, Cochrane Database of Systematic Reviews, ASP Journal Club, DARE, CCTR, Embase, Web of Sciences and Lilacs) were searched with the help of a senior Health Sciences librarian. Abstracts that appeared to fulfill the initial selection criteria were selected by consensus. The original articles were then retrieved. A methodological checklist was used to evaluate the quality of the selected articles. Their references were also hand-searched for possible missing articles. Articles without an adequate control group to factor out growth changes were excluded. Only three articles (one measuring transverse and two anteroposterior and vertical changes) measured RME stability after active expansion, all of them had some methodological flaws, which limit the attainable conclusions. An individual analysis of these articles was made. Long-term transverse skeletal maxillary increase is approximately 25% of the total dental expansion for prepubertal adolescents. Better long-term outcomes are expected in transverse changes because of RME in less skeletally mature patients. RME appears not to produce clinically significant anteroposterior or vertical changes in the position of the maxilla and mandible. The conclusions from this systematic review should be considered with caution because only a secondary level of evidence was found. Long-term randomized clinical trials are needed.

Introduction: The objective of this study was to identify the intra-arch occlusal characteristics that best discriminated 3 groups with different grades of dental arch discrepancies. This cross-sectional analysis was conducted in Lima, Peru, in 2003., Methods: Intra-arch measurements were made on 150 sets of dental casts of high school students (aged 12-16; 75 boys, 75 girls). Stepwise multiple discriminant analysis (SMDA) was used to obtain a better understanding of the morphological relationships between tooth and dental-arch variables and their relationship with crowding., Results: Mesiodistal tooth sizes and crown proportions of some teeth differed among significantly crowded, mild-to-moderately crowded, and spaced dental arches. Buccolingual tooth sizes were similar in the 3 groups. Of the arch dimensions evaluated, only intermolar arch width and arch length differed between the groups. An SMDA was developed to classify dental-arch discrepancies in the permanent dentition based on several intra-arch occlusal characteristics. The variable with the highest discriminatory capability between groups was arch length. When arch length was taken out of the SMDA, the explanatory capability from the variability on the dental arch discrepancies diminished from 51% to 14%. When the remaining arch dimension variable (intermolar width) was taken out, the explanatory capability diminished more (from 14% to 8%)., Conclusions: Although other tooth-size and arch dimensions are indicators of crowding, arch length is the most important factor.

Introduction: The purpose of this meta-analysis was to quantify the amount of true incisor intrusion attained during orthodontic treatment., Methods: Electronic databases (PubMed, Medline, Medline In-Process & Other Non-Indexed Citations, all EBM reviews [Cochrane Database of Systematic Reviews, ASP Journal Club, DARE, and CCTR], Embase, Web of Science, and Lilacs) were searched with the help of a senior health sciences librarian. The goal was to identify clinical trials that assessed true incisor intrusion through cephalometric analysis and factored out craniofacial growth when required. From the selected abstracts, original articles were retrieved, and their references were hand searched for missing articles., Results: Twenty-eight articles met the initial inclusion criteria, but 24 were rejected because they did not quantify true incisor intrusion or factor out normal growth impact when required. The remaining 4 articles showed that true incisor intrusion is attainable (0.26 to 1.88 mm for the maxillary incisors and -0.19 to 2.84 mm for the mandibular incisors) but with large variability depending on the appliance used. A meta-analysis with results from the 2 articles that used the segmental technique was completed. The combined mean estimates of intrusion and 95% CI were 1.46 mm (1.05-1.86 mm) for the maxillary incisors and 1.90 mm (1.22-2.57 mm) for the mandibular incisors., Conclusions: True incisor intrusion is achievable in both arches, but the clinical significance of the magnitude of true intrusion as the sole treatment option is questionable for patients with severe deepbite. In nongrowing patients, the segmented arch technique can produce 1.5 mm of incisor intrusion in the maxillary arch and 1.9 mm in the mandibular arch.

Mitochondrial DNA sequences and restriction fragment length polymorphisms were retrieved (with >80% efficiency) from a 17th-18th century sample of 213 teeth from Tenerife. The genetic composition of this population reveals an important ethnic heterogeneity. Although the majority of detected haplotypes are of European origin, the high frequency of sub-Saharan African haplotypes (15.63%), compared to that of the present-day population (6.6%), confirms the importance of the Canary Islands in the black slave trade of that epoch. The aboriginal substrate, inferred from the U6b1 haplotypes (8.59%), has also decreased due to European input. Finally, the presence of Amerindian lineages (1.5%) reveals that the Canary Islands have also received genetic flow from America., ((c) 2005 Wiley-Liss, Inc.)

This systematic review evaluates long-term dental arch changes after rapid maxillary expansion treatment on orthodontic patients with constricted arches. Clinical trials that assessed dental arch changes through measurements on dental casts or cephalometric radiographs were selected. No patients with surgical or other simultaneous treatment during the active expansion period were accepted. Electronic databases were searched with the help of a senior Health Sciences librarian. Original articles were retrieved from the selected abstracts, and their references were also scanned for possible missing articles. Forty-one articles met the initial inclusion criteria, but 35 were later rejected because they lacked a control group or only evaluated dental changes or used a semirapid technique. Some of them also lacked a reported measurement error. From the remaining articles, two did not report a long-term evaluation. From the final four articles, two measured changes through dental casts and two assessed changes through radiographs (one through lateral cephalometric radiographs and one through posteroanterior radiographs). Similar maxillary molar and cuspid expansion could be found in adolescents and young adults. Significantly less indirect mandibular molar and cuspid expansion was attained in young adults compared with adolescents. A significant overall gain in the maxillary and mandibular arch perimeter was found in adolescents. More transverse dental arch changes were found after puberty as compared with before, but the difference may not be clinically significant. No anteroposterior dental changes were found on lateral cephalometric radiographs.

The lower permanent incisor tooth width sum has been proposed as the best predictor for the tooth width sums of the unerupted canine and premolars (SPCP) for populations from different ethnic origins. Only two previous studies have refuted it. The purpose of the present study was to determine which sum or combination of sums of permanent tooth widths presented the best prediction capability for the SPCP in a Peruvian sample, to calculate a specific linear regression equation for this population, and to evaluate the clinical significance. A total of 150 children with complete permanent dentitions were selected. Fifty more children were used as a validation sample for the application of a multiple linear regression equation (MLRE). They did not present clinically visible dental caries or proximal restorations and no active or previous orthodontic treatment. Their dental casts were measured to 0.1 mm with a sliding caliper with a Vernier scale. Three-way analysis of variance, Pearson Correlation Test, Fisher Z values and a MLRE were used for the statistical analysis. The combination of the sums of permanent upper and lower central incisors and upper first molars was the best predictor for the SPCP in this sample. A MLRE was calculated including sex and arch as additional predictor variables. The MLRE determination coefficient was 60% with a standard error of 0.8 mm. This new MLRE underestimates (less than 1 mm discrepancy) the actual SPCP in only 7% of the cases on the basis of a validation sample.

Background: The authors were not able to identify any systematic reviews or meta-analysis on the dental or skeletal changes associated with slow maxillary expansion (SME). Therefore, they conducted a study to evaluate skeletal and dental changes after fixed SME treatment in orthodontic patients with constricted arches., Methods: The authors included in their evaluation clinical trials that assessed skeletal and dental arch changes through measurements on dental casts or cephalometric radiographs. The authors did not consider trials involving surgical or other simultaneous treatment interventions during the active expansion period., Results: With the help of a health sciences librarian, the authors searched the following electronic databases: PubMed, MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, Evidence Based Medicine Reviews (Cochrane Database of Systematic Reviews, American College of Physicians Journal Club, Database of Abstracts of Reviews of Effects and Cochrane Central Register of Controlled Trials), EMBASE Excerpta Medica, Thomsen's ISI Web of Sciences and LILACS. Eight articles met the initial inclusion criteria. The authors found that a significant deficiency in the studies was the lack of a control group to factor out changes in the dental arch and skeletal structures associated with normal growth., Conclusions and Clinical Implications: The authors found only a lower level of evidence. Therefore, they could make no strong conclusions on dental or skeletal changes that occurred after SME treatment. Clinicians need to rely on their clinical experience, experts' opinions and the presented limited evidence concerning SME treatments.

A high-resolution, Y-chromosome analysis using 46 binary markers has been carried out in two Jordan populations, one from the metropolitan area of Amman and the other from the Dead Sea, an area geographically isolated. Comparisons with neighboring populations showed that whereas the sample from Amman did not significantly differ from their Levantine neighbors, the Dead Sea sample clearly behaved as a genetic outlier in the region. Its high R1*-M173 frequency (40%) has until now only been found in northern Cameroonian samples. This contrasts with the comparatively low presence of J representatives (9%), which is the modal clade in Middle Eastern populations, including Amman. The Dead Sea sample also showed a high presence of E3b3a-M34 lineages (31%), which is only comparable to that found in Ethiopians. Although ancient and recent ties with sub-Saharan and eastern Africans cannot be discarded, it seems that isolation, strong drift, and/or founder effects are responsible for the anomalous Y-chromosome pool of this population. These results demonstrate that, at a fine scale, the smooth, continental clines detected for several Y-chromosome markers are often disrupted by genetically divergent populations.

Data Sources: Medline and Embase were searched, using the following keywords: "hypodontia", "oligodontia", "anodontia", "agenesis", and "prevalence or incidence". Reference lists from retrieved articles were also examined., Study Selection: For inclusion, an article had to satisfy the following criteria: presence of an English abstract; the sample was representative for the underlying general population; the diagnosis of dental agenesis was based on a radiographic examination; the report presented information on the ethnic background; and the report presented prevalence of agenesis except third molars., Data Extraction and Synthesis: Data from Caucasian populations in North America, Australia and Europe were included in a meta-analysis. For the prevalence in African-American, Chinese and Arab groups, only indications could be reported because of a limited number of studies. Multiple-regression analysis was applied to evaluate the influence of chronological age, sample size, continent and year of publication. Statistical significance was established at P<0.05. The prevalence of agenesis per tooth type, affected patients and number of missing teeth per patient was calculated as far as reported in the papers. For the comparison of the prevalence for males and females, the relative risk (RR) was calculated., Results: The search identified 141 articles, of which 31 met the inclusion criteria. Agenesis differs by continent and gender: the prevalence for both sexes was higher in Europe (males 4.6%; females 6.3%) and Australia (males 5.5%; females 7.6%) than for North-American Caucasians (males 3.2%; females 4.6%). In addition, the prevalence of dental agenesis in females was significantly higher than in males for all three continents, with an RR of 1.37 (95% CI, 1.28-1.45). The mandibular second premolar was the most affected tooth, followed by the maxillary lateral incisor and the maxillary second premolar. Unilateral occurrence of dental agenesis is more common than bilateral occurrence. Bilateral agenesis of maxillary lateral incisors is more common, however, than unilateral agenesis. In most patients, dental agenesis involved only one (48%) or two teeth (35%)., Conclusions: The prevalence of dental agenesis in Europe and Australia is higher than in North America. The overall prevalence of agenesis in the maxilla is comparable with that in the mandible, but a marked difference was found between both jaws regarding tooth type. Absence of one or two permanent teeth is found in the majority of the subjects with dental agenesis.

Alu sequences are short, interspersed elements that have generated more than one million copies in the human genome. They propagate by transcription followed by reverse transcription and integration, causing mutations, recombination, and changes in pre-mRNA splicing. We have recently identified a 345-bp long Alu Ya5 element inserted in codon 650 within exon 11 of the chloride channel ClC-5 gene (CLCN5) of a patient with Dent's disease. A microsatellite pedigree analysis indicated that the insertion occurred in the germline of the maternal grandfather. Dent's disease is an X-linked renal tubular disorder characterized by low-molecular-weight proteinuria, hypercalciuria, nephrolithiasis, and nephrocalcinosis. Here, we found, by RT-PCR amplification of RNA extracted from the patient's blood and subsequent DNA sequencing, that the Alu insertion led to an aberrant splicing of the CLCN5 pre-mRNA that skipped exon 11. Using the ESE finder and RESCUE-ESE Web interfaces, we identified two high-score exonic splicing enhancer (ESE) sequences in the site of insertion. The functional significance of these ESE motifs is suggested by our observation that these sequences are highly conserved among mammal CLCN5 genes. Therefore, we suggest that the Alu insertion causes exon skipping by interfering with splicing regulatory elements. The altered splicing would predict a truncated ClC-5 protein that lacks critical domains for sorting and chloride channel function.

Data Sources: PubMed and the Cochrane Controlled Clinical Trials Register were searched. Reference lists from retrieved articles were also searched by hand for additional studies., Study Selection: For inclusion, an article had to satisfy the following criteria: cases in primary and early mixed dentition with unilateral posterior crossbite; be a randomised controlled trials (RCT) or prospective and retrospective studies with concurrent untreated as well as normal controls; clinical trials must have compared at least two treatment strategies without any untreated or normal control group involved; and be written in English, German, French or a Scandinavian language., Data Extraction and Synthesis: Data extraction was carried out independently and in duplicate. Quality of the studies was assessed and categorised as low, medium and high. Interexaminer conflicts were resolved by discussion to reach a consensus., Results: The search identified 1001 articles, of which 12 met the inclusion criteria. Only two RCT of early treatment of crossbite have been performed, and these two studies support grinding as treatment in the primary dentition. As treatment strategies, quad-helix (QH), expansion plates and rapid maxillary expansion (RME) are effective in the early mixed dentition with high success rates. There is, however, no scientific evidence available that shows which of the treatment modalities, that is, grinding, QH, expansion plates or RME, is the most effective., Conclusions: Most of the studies have the serious drawback of lack of power because of small sample size, bias and confounding variables, lack of method error analysis and blinding in measurements, and deficient or lack of statistical methods. Thus, the studies were not of high enough quality level to draw any evidence-based conclusions. Better-controlled RCT with sufficient sample sizes are needed to obtain reliable scientific evidence identifying which treatment is the most effective for early correction of unilateral posterior crossbite. Future studies should also include assessments of long-term stability as well as analysis of costs and side-effects of the interventions.

Discrepancies in tooth width ratios could affect the excellence in the finishing of orthodontic cases. This study compares tooth width ratios in crowded and noncrowded dental arches. Tooth widths were measured from 143 dental casts (40 crowded and 33 spaced in male individuals and 43 crowded and 27 spaced in female individuals). Simultaneous crowded or spaced arches were selected. Tooth width measurements were made with a sliding caliper with a Vernier scale neared 0.1 mm. Inter- (0.990) and intraexaminer (0.993) reliability with mean differences of 0.03 mm (-0.03; 0.07) and 0.01 mm (-0.04; 0.05), respectively, were attained. Bolton analysis was applied to calculate the tooth width ratios (anterior and total). Descriptive statistics, Student's t-test, and analysis of variance were applied. There was no significant difference between the anterior and total tooth width ratios according to sex (P > .05). Both anterior and total ratios were significantly greater in subjects with crowding (P = .003 and P = .026, respectively), but no statistical difference by arch type in anterior and total tooth mass excess was found (P > .05). Differences among subjects with noncrowded and crowded dentitions were of 0.39 and 0.51 mm for the excess of anterior and total upper tooth mass, respectively, with respect to lower mass excess. Although the anterior and overall ratios and the differences between the upper and lower tooth width sums are greater in subjects with crowding, no clinically significant difference is observed (less than one mm).

Haplotype, allele frequencies and population data of 11 Y-chromosome STR loci DYS19, DYS385, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS438 and DYS439 were determined from a sample of 168 unrelated autochthonous male individuals from the Basque Country. The eight surnames and birth places of the grandparents of all analyzed individuals were of Basque origin. A total of 89 haplotypes were identified by the 11 Y-STR loci. The haplotype diversity (97.49%) and discrimination capacity (52.98%) were calculated. Comparisons were made with previously published haplotype data on other Iberian population samples and significant differences were found.

Europe has been influenced by both intra- and intercontinental migrations. Since the Iberian peninsula was a refuge during the Last Glacial Maximum, demographic factors associated with contraction, isolation, subsequent expansion and gene flow episodes have contributed complexity to its population history. In this work, we analysed 26 Y-chromosome biallelic markers in 568 chromosomes from 11 different Iberian population groups and compared them to published data on the Basques and Catalans to gain insight into the paternal gene pool of these populations and find out to what extent major demographic processes account for their genetic structure. Our results reveal a reduced, although geographically correlated, Y-chromosomal interpopulation variance (1.2%), which points to a limited heterogeneity in the region. Coincidentally, spatial analysis of genetic distances points to a focal distribution of Y-chromosome haplogroups in this area. These results indicate that neither old or recent Levantine expansions nor North African contacts have influenced the current Iberian Y-chromosome diversity so that geographical patterns can be identified.

The MRN complex consists of the two evolutionarily conserved components Mre11 and Rad50 and the third less-conserved component Nbs1/Xrs2. This complex mediates telomere maintenance in addition to a variety of functions in response to DNA double-strand breaks, including homologous recombination, nonhomologous end joining (NHEJ), and activation of DNA damage checkpoints. Mutations in the Mre11 gene cause the human ataxia-telangiectasia-like disorder (ATDL). Here, we show that null mutations in the Drosophila mre11 and rad50 genes cause both telomeric fusion and chromosome breakage. Moreover, we demonstrate that these mutations are in the same epistasis group required for telomere capping and mitotic chromosome integrity. Using an antibody against Rad50, we show that this protein is uniformly distributed along mitotic chromosomes, and that Rad50 is unstable in the absence of its binding partner Mre11. To define the roles of rad50 and mre11 in telomere protection, mutant chromosome preparations were immunostained for both HP1 and HOAP, two proteins that protect Drosophila telomeres from fusion. Cytological analysis revealed that mutations in rad50 and mre11 drastically reduce accumulation of HOAP and HP1 at telomeres. This suggests that the MRN complex protects Drosophila telomeres by facilitating recruitment of HOAP and HP1 at chromosome ends.

A sound statistical or clinical reason for proposing several single linear regression equations (SLRE) for predicting unerupted canine and premolar tooth-width sums is needed. The purpose of this study was to develop a methodology to evaluate the number and the clinical significance of SLRE required. A 6-step methodology is presented that permits evaluating the number and the clinical significance of SLRE required for predicting unerupted canine and premolar tooth-width sums. It is important not only to evaluate the statistical need for specific SLRE in different populations, but also to state the clinical significance of their differences against commonly used SLRE.

Insulin induces vasodilatation in human subjects and increases L-arginine transport and NO synthesis in human umbilical vein endothelial cells (HUVEC). Cell signalling events associated with insulin effects on activity and mRNA expression of the human cationic amino acid transporters 1 (hCAT-1) and 2B (hCAT-2B) are unknown. L-arginine transport and eNOS activity were determined in HUVEC exposed to insulin. mRNA levels for hCAT-1, hCAT-2B and eNOS were quantitated by real time RT-PCR and endothelial NO synthase (eNOS) protein was identified by Western blot analysis. Intracellular Ca2+, L-arginine and L-citrulline levels, L-[3H]citrulline formation from L-[(3)H]arginine, cGMP formation, nitrite level, ATP release and membrane potential were determined. Insulin increased L-arginine transport and the mRNA levels for hCAT-1 and hCAT-2B and eNOS expression and activity. Insulin also induced membrane hyperpolarization and increased intracellular Ca2+, L-[3H]citrulline, cGMP and nitrite formation. Insulin-mediated stimulation of the L-arginine/NO pathway is thus associated with increased hCAT-1 and hCAT-2B mRNA, and eNOS expression, via mechanisms involving membrane hyperpolarization, mitogen-activated protein kinases p42 and p44, phosphatidylinositol 3-kinase, NO and protein kinase C. We have characterized a cell signalling pathway by which hyperinsulinaemia could lead to vasodilatation in human subjects, and which could have implications in patients in whom plasma insulin levels are altered, such as in diabetes mellitus.

Sepsis is a complex syndrome that develops when the initial, appropriate host response to an infection becomes amplified, and is then dysregulated. Among other factors, the innate immune system is of central importance to the early containment of infection. Death from infection is strongly heritable in human populations. Hence, genetic variations that disrupt innate immune sensing of infectious organisms could explain the ability of the immune system to respond to infection, the diversity of the clinical presentation of sepsis, the response to current medical treatment, and the genetic predisposition to infection in each individual patient. Such genetic variations may identify patients at high risk for the development of sepsis and organ dysfunction during severe infections. Single base variations, known as single nucleotide polymorphisms (SNPs), are the most commonly used variants. There has been great interest in exploring SNP in those genes involved in the inflammatory cascade resulting from the systemic inflammatory response to micro organisms. The rationale for studying gene SNPs in critical illnesses seeks to identify potential markers of susceptibility, severity, and clinical outcome; seeks to identify potential markers for responders and non-responders in clinical trials, and seeks to identify targets for therapeutic intervention. In this review, we focus on the current state of association studies of those genes governing the powerful bacterial infection-induced inflammation and provide guidelines for future studies describing disease associations with genetic variations based on current recommendations. We envision a time in the near future when genotyping will be include in the standard evaluation of critically ill patients and will help to prioritize a therapeutic option.

Previous studies have demonstrated different tooth-width ratio discrepancies in different populations. The objective of this study was to determine maxillary to mandibular tooth-size ratios in a Peruvian sample; 200 children were selected who had complete permanent dentition, without clinically visible dental caries or proximal restorations, and no previous or active orthodontic treatment. Their dental casts were measured to the nearest 0.1 mm with a sliding caliper and a Vernier scale. The Kolmogorov-Smirnov test, t test, and Pearson correlation test were used. No significant differences were found in anterior (P =.713) and total (P =.174) tooth-size sums according to sex. The anterior tooth-width ratios were 77.78% +/- 2.44% for females and 78.39% +/- 2.81% for males (P =.103). The total ratios were 90.79% +/- 1.71% for females and 91.33% +/- 2.07% for males (P =.048). For this reason, the combined male and female anterior total ratio was calculated (78.09 +/- 2.64%). There were clinically significant tooth-size discrepancies in almost one third of the sample. The 2-standard deviation range from the Bolton standard did not predict clinically significant anterior and total tooth-width ratio discrepancies.

We report the detection and characterization of the first vancomycin-resistant VanB-type Enterococcus faecium to be isolated in a Spanish hospital. Sequence analysis of the vanB gene showed that this isolate belonged to subtype vanB2. Moreover, PCR amplification analysis indicated that the vanB gene cluster was linked to a Tn5382-like transposon.

The purpose of this systematic review was to evaluate the predictive value of hand-wrist radiographic assessment of skeletal maturity in estimating facial growth timing and velocity. A search of PubMed, Medline, Cochrane Database of Systematic Reviews, Embase, Web of Sciences, and Lilacs identified 16 articles that met the following inclusion criteria: use of hand-wrist radiographs for skeletal maturation determination, facial growth evaluated through cephalometric radiographs, and cross-sectional or longitudinal studies. Five articles were rejected because of major methodological issues. Most of the remaining articles had small sample size, and there was no report of randomization or method error. Skeletal maturity determined by hand-wrist radiographic analysis was well related to overall facial growth velocity. Maxillary and mandibular growth velocities were related to skeletal maturity, but their relationship was less robust than that for overall facial growth. The available articles have not adequately defined a relationship between cranial base growth velocity and skeletal maturity. Hand-wrist radiographic assessment of skeletal maturity for use in facial growth prediction should include bone staging as well as ossification events. The role of skeletal maturity assessment in clinical and research applications is discussed and recommendations are provided.

The prehistoric colonisation of the Canary Islands by the Guanches (native Canarians) woke up great expectation about their origin, since the Europeans conquest of the Archipelago. Here, we report mitochondrial DNA analysis (HVRI sequences and RFLPs) of aborigine remains around 1000 years old. The sequences retrieved show that the Guanches possessed U6b1 lineages that are in the present day Canarian population, but not in Africans. In turn, U6b, the phylogenetically closest ancestor found in Africa, is not present in the Canary Islands. Comparisons with other populations relate the Guanches with the actual inhabitants of the Archipelago and with Moroccan Berbers. This shows that, despite the continuous changes suffered by the population (Spanish colonisation, slave trade), aboriginal mtDNA lineages constitute a considerable proportion of the Canarian gene pool. Although the Berbers are the most probable ancestors of the Guanches, it is deduced that important human movements have reshaped Northwest Africa after the migratory wave to the Canary Islands.

Dent's disease is an X-linked renal tubular disorder characterized by low-molecular-weight proteinuria, hypercalciuria, nephrocalcinosis, nephrolithiasis, and eventual renal failure. Various types of mutations in the renal chloride channel gene, CLCN5, have been identified in patients with this disease. We studied a Spanish patient with Dent's disease and found, by polymerase chain reaction amplification of the CLCN5 exons, an abnormally large exon 11. Sequencing analysis revealed that this was attributable to the insertion in codon 650 of an Alu element of the "young" Ya5 subfamily. The Alu element was inserted with the same orientation as the CLCN5 gene and arose de novo on the maternal chromosome. Polymorphism analysis indicated that the insertion occurred in the germline of the maternal grandfather. The presence of a long poly(A) tract and evidence for a 16-bp target-site duplication implied that the Alu element was integrated by retrotransposition. This mutation predicts a truncated ClC-5 protein that lacks part of the carboxy-terminus and is likely to result in loss of function of the chloride channel. Insertions of Alu sequences, which are rarely found in coding regions, have occasionally been reported to cause other genetic diseases. However, this is the first report of a retrotransposon insertion in the CLCN5 gene associated with Dent's disease.

Background: World-wide phylogeographic distribution of human complete mitochondrial DNA sequences suggested a West Asian origin for the autochthonous North African lineage U6. We report here a more detailed analysis of this lineage, unraveling successive expansions that affected not only Africa but neighboring regions such as the Near East, the Iberian Peninsula and the Canary Islands., Results: Divergence times, geographic origin and expansions of the U6 mitochondrial DNA clade, have been deduced from the analysis of 14 complete U6 sequences, and 56 different haplotypes, characterized by hypervariable segment sequences and RFLPs., Conclusions: The most probable origin of the proto-U6 lineage was the Near East. Around 30,000 years ago it spread to North Africa where it represents a signature of regional continuity. Subgroup U6a reflects the first African expansion from the Maghrib returning to the east in Paleolithic times. Derivative clade U6a1 signals a posterior movement from East Africa back to the Maghrib and the Near East. This migration coincides with the probable Afroasiatic linguistic expansion. U6b and U6c clades, restricted to West Africa, had more localized expansions. U6b probably reached the Iberian Peninsula during the Capsian diffusion in North Africa. Two autochthonous derivatives of these clades (U6b1 and U6c1) indicate the arrival of North African settlers to the Canarian Archipelago in prehistoric times, most probably due to the Saharan desiccation. The absence of these Canarian lineages nowadays in Africa suggests important demographic movements in the western area of this Continent.

Objective: Previous animal studies have shown that certain modes of mechanical ventilation (MV) can injure the lungs. Most of those studies were performed with models that differ from clinical causes of respiratory failure. We examined the effects of positive end-expiratory pressure (PEEP) in the setting of a clinically relevant, in vivo animal model of sepsis-induced acute lung injury ventilated with low or injurious tidal volume., Methods: Septic male Sprague-Dawley rats were anesthetized and randomized to spontaneous breathing or four different strategies of MV for 3 h at low (6 ml/kg) or high (20 ml/kg) tidal volume (V(T)) with zero PEEP or PEEP above inflection point in the pressure-volume curve. Sepsis was induced by cecal ligation and perforation. Mortality rates, pathological evaluation, lung tissue cytokine gene expression, and plasma cytokine concentrations were analyzed in all experimental groups., Results: Lung damage, cytokine synthesis and release, and mortality rates were significantly affected by the method of MV in the presence of sepsis. PEEP above the inflection point significantly attenuated lung damage and decreased mortality during 3 h of ventilation with low V(T) (25% vs. 0%) and increased lung damage and mortality in the high V(T) group (19% vs. 50%). PEEP attenuated lung cytokine gene expression and plasma concentrations during mechanical ventilation with low V(T)., Conclusions: The use of a PEEP level above the inflection point in a sepsis-induced acute lung injury animal model modulates the pulmonary and systemic inflammatory responses associated with sepsis and decreases mortality during 3 h of MV.

(1) Studies were undertaken to determine the nature of the receptors mediating contractile effects of tachykinins in the uteri of nonpregnant women, and to analyse the expression of preprotachykinins (PPT), tachykinin receptors and the cell-surface peptidase, neprilysin (NEP), in the myometrium from pregnant and nonpregnant women. (2) The neurokinin B (NKB) precursor PPT-B was expressed in higher levels in the myometrium from nonpregnant than from pregnant women. Faint expression of PPT-A mRNA was detectable in the myometrium from nonpregnant but not pregnant women. PPT-C, the gene encoding the novel tachykinin peptide hemokinin-1 (HK-1), was present in trace amounts in the uteri from both pregnant and nonpregnant women. (3) Tachykinin NK(2) receptors were more strongly expressed in tissues from nonpregnant than from pregnant women. NK(1) receptor mRNA was present in low levels in tissues from both pregnant and nonpregnant women. A low abundance transcript corresponding to the NK(3) receptor was present only in tissues from nonpregnant women. (4) The mRNA expression of the tachykinin-degrading enzyme NEP was lower in tissues from nonpregnant than from pregnant women. (5) Substance P (SP), neurokinin A (NKA) and NKB, in the presence of the peptidase inhibitors thiorphan, captopril and bestatin, produced contractions of myometrium from nonpregnant women. The order of potency was NKA>>SP>/=NKB. The potency of NKA was unchanged in the absence of peptidase inhibitors. (6) The tachykinin NK(2) receptor-selective agonist [Lys(5)MeLeu(9)Nle(10)]NKA(4-l0) was approximately equipotent with NKA, but the tachykinin NK(1) and NK(3) receptor-selective agonists [Sar(9)Met(O(2))(11)]SP and [MePhe(7)]NKB were ineffective in the myometrium from nonpregnant women. (7) The uterotonic effects of [Lys(5)MeLeu(9)Nle(10)]NKA(4-10) were antagonized by the tachykinin NK(2) receptor-selective antagonist SR48968. Neither atropine, nor phentolamine nor tetrodotoxin affected responses to [Lys(5)MeLeu(9)Nle(10)]NKA(4-10). (8) These data are consistent with a role of tachykinins in the regulation of human uterine function, and reinforce the importance of NK(2) receptors in the regulation of myometrial contraction.

Objective: To review the complex interactions of markers of genetic susceptibility for critical illness and acute lung injury. These may affect the responses of critically ill patients to acute lung injury and acute respiratory distress syndrome and may affect outcome., Data Sources and Study Selection: Published research and review articles related to genetic factors associated with susceptibility to critical illnesses and pulmonary disease., Data Extraction and Synthesis: Critical illness in adults often is followed by acute lung injury, a phenomenon of acute diffuse lung inflammation. Physicians have long known that each patient responds differently to drugs and has a different risk for a particular event or outcome. Now, there is some evidence that cellular and humoral immune responses are subject to polymorphic genetic control, which explains the well-known diversity of clinical manifestations and outcomes in critically ill patients with the same disease. By revealing altered expression of relatively few genes involved in the responses to lung injury and repair, some investigators have found that these responses, and susceptibility to acute lung injury, are heritable. In the last 5 yrs, we have discovered that an individual's risks and cellular responses can be related to his or her own unique DNA., Conclusions: The search for an association between functional variants of a gene and clinical phenotype may help to identify key pathophysiological processes of disease. In the future, we will know much about which therapy is best for each individual patient in the intensive care unit.