Rothmund-Thomson syndrome type 1 caused by biallelic ANAPC1 gene mutations.

Background: Rare syndromic skin disorders may represent a diagnostic challenge. Aims: We report a unique case associating cutaneous manifestations and developmental delay. Materials & Methods: The affected 14 months old boy had poikiloderma, facial dysmorphism with deep-set eyes, atrichia, as well as nail dysplasia and non-descended testes. In addition, his psychomotor development was delayed. Exome sequencing and molecular karyotyping via array-CGH (oligo-array, 180k Agilent, design 22060) were performed. Results: Mutations in RECQL4 (found in patients with RTS2) were first excluded. In the ANAPC1 gene, a novel combination of a recurrent intronic mutation (c.2705-198C>T) and a deletion of the second ANAPC1 allele was detected, thus confirming the clinical diagnosis of RTS1. The deletion on chromosome 2q13 comprised further genes and spanned 1,7 megabases. Heterozygous deletions in this region are known as 2q13 microdeletion syndrome and are associated with developmental delay, autism and facial dysmorphism. Discussion: The genetic findings most probably explain both, the RTS1 features and the developmental delay. Genetic diagnosis in RTS is indispensable to confirm the specific subtype and its associated risks: juvenile cataracts are features of RTS1 (ANAPC1 gene), whereas a high risk of osteosarcoma is part of RTS2 (RECQL4 gene). Thus, the patient described here is at high risk for the development of juvenile cataracts and requires regular ophthalmologic examination. Conclusion: This case report underlines the necessity of thorough clinical diagnosis prior to genetic diagnosis of RTS1, since the recurrent intronic ANAPC1 mutation is otherwise missed.

Shear-sensitive nanocapsule drug release for site-specific inhibition of occlusive thrombus formation.

Essentials Vessel stenosis due to large thrombus formation increases local shear 1-2 orders of magnitude. High shear at stenotic sites was exploited to trigger eptifibatide release from nanocapsules. Local delivery of eptifibatide prevented vessel occlusion without increased tail bleeding times. Local nanocapsule delivery of eptifibatide may be safer than systemic antiplatelet therapies. SUMMARY: Background Myocardial infarction and stroke remain the leading causes of mortality and morbidity. The major limitation of current antiplatelet therapy is that the effective concentrations are limited because of bleeding complications. Targeted delivery of antiplatelet drug to sites of thrombosis would overcome these limitations. Objectives Here, we have exploited a key biomechanical feature specific to thrombosis, i.e. significantly increased blood shear stress resulting from a reduction in the lumen of the vessel, to achieve site-directed delivery of the clinically used antiplatelet agent eptifibatide by using shear-sensitive phosphatidylcholine (PC)-based nanocapsules. Methods PC-based nanocapsules (2.8 × 1012 ) with high-dose encapsulated eptifibatide were introduced into microfluidic blood perfusion assays and into in vivo models of thrombosis and tail bleeding. Results Shear-triggered nanocapsule delivery of eptifibatide inhibited in vitro thrombus formation selectively under stenotic and high shear flow conditions above a shear rate of 1000 s-1 while leaving thrombus formation under physiologic shear rates unaffected. Thrombosis was effectively prevented in in vivo models of vessel wall damage. Importantly, mice infused with shear-sensitive antiplatelet nanocapsules did not show prolonged bleeding times. Conclusions Targeted delivery of eptifibatide by shear-sensitive nanocapsules offers site-specific antiplatelet potential, and may form a basis for developing more potent and safer antiplatelet drugs.

Methicillin-resistant Staphylococcus aureus in cattle food chains - prevalence, diversity, and antimicrobial resistance in Germany.

Livestock-associated methicillin-resistant Staphylococcus aureus (MRSA) have been found in various farm animal species throughout the world. It was the objective of this study to estimate the prevalence of MRSA in different cattle food chains (milk, beef, and veal) in Germany, to analyze the MRSA diversity along each food chain and to compare the characteristics of the different subtypes. Samples were collected between 2009 and 2012 from dairy herds (bulk tank milk), veal herds (dust from the stables), veal calves, and beef cattle at slaughter (nasal swabs) and carcasses of veal calves (surface cuts) and beef as well as veal at retail. Sampling was proportionally distributed over the country according to the cattle population (on-farm sampling), slaughterhouse capacity (abattoir samples), and the human population (meat at retail). Methicillin-resistant S. aureus were isolated using harmonized methods from all sample types and populations investigated. The highest proportion of positive samples was found in nasal swabs from veal calves at slaughter in 2012 (144/320; 45.0%) and the lowest rate in bulk tank milk in 2009 (14/388; 4.1%). Most isolates, irrespective of the origin, were from spa types t011 and t034. Both have been assigned to the clonal complex (CC) 398. Few isolates (15/632; 2.4%) were from spa types not associated with the CC398. Spa-type patterns were similar along individual food chains but differed between food chains. Antimicrobial resistance patterns differed between isolates from the different food chains and spa types. Isolates from the veal chain displayed the highest resistance rates. We conclude that there is substantial diversity in the MRSA prevalence across different cattle production sectors.

Emerging antimicrobial resistance in commensal Escherichia coli with public health relevance.

In 2009, 1462 Escherichia coli isolates were collected in a systematic resistance monitoring approach from primary production, slaughterhouses and at retail and evaluated on the basis of epidemiological cut-off values. Besides resistance to antimicrobial classes that have been extensively used for a long time (e.g. sulphonamides and tetracyclines), resistance to (fluoro)quinolones and third-generation cephalosporins was observed. While in the poultry production chain the majority (60%) of isolates from laying hens was susceptible to all antimicrobials tested, most isolates from broilers, chicken meat and turkey meat showed resistance to at least one (85-93%) but frequently even to several antimicrobial classes (73-84%). In the cattle and pig production chain, the share of isolates showing resistance to at least one antimicrobial was lowest (16%) in dairy cows, whereas resistance to at least one antimicrobial ranged between 43% and 73% in veal calves, veal and pork. Resistance rates to ciprofloxacin and nalidixic acid in isolates from broilers were 41.1% and 43.1%, respectively. Likewise, high resistance rates to (fluoro)quinolones were observed in isolates from chicken meat and turkey meat. In contrast, ciprofloxacin resistance was less frequent in E. coli isolates from the cattle and pig production chain with highest rate in veal calves (13.3%). Highest resistance rates to cephalosporins were observed in broilers and chicken meat, with 5.9% and 6.2% of the isolates showing resistance. In dairy cattle and veal, no isolates with cephalosporin resistance were detected, whereas 3.3% of the isolates from veal calves showed resistance to ceftazidime. Resistance to (fluoro)quinolones and cephalosporins in E. coli isolates is of special concern because they are critically important antimicrobials in human antimicrobial therapy. The emergence of this resistance warrants increased monitoring. Together with continuous monitoring of antimicrobial usage, management strategies should be regularly assessed and adapted.

Prevalence, antimicrobial resistance, and molecular characterization of methicillin-resistant Staphylococcus aureus from bulk tank milk of dairy herds.

It was the objective of the study to estimate the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in bulk tank milk from German dairy herds and to characterize isolates from bulk tank milk with respect to their Staph. aureus protein A (spa) and staphylococcal cassette chromosome mec (SCCmec) type, their phenotypic antimicrobial resistance and resistance- resp. virulence-associated genes using broth microdilution and a microarray for Staph. aureus. Bulk tank milk samples (25 mL) were tested for MRSA using a 2-step selective enrichment protocol. Presumptive MRSA were confirmed by PCR. Thirty-six isolates collected from bulk tank milk of dairy herds in 2009 and 2010 were included in the characterization. All isolates displayed spa-types assigned to the clonal complex CC398. Based on the epidemiological cut-off values for the interpretation of minimum inhibitory concentrations isolates were resistant to tetracycline (100%), clindamycin (58%), erythromycin (52%), quinupristin/dalfopristin (36%), and kanamycin (27%). Isolates did not carry genes associated with typical virulence factors for Staph. aureus such as the Panton-Valentine leukocidin. However, they did carry hemolysin genes. Livestock-associated MRSA of CC398 does occur in German dairy herds and the strains have similar properties as described for strains from pigs.

Quo vadis? - Monitoring Campylobacter in Germany.

Campylobacter is a poorly recognized foodborne pathogen, leading the statistics of bacterially caused human diarrhoea in Europe during the last years. In this review, we present qualitative and quantitative German data obtained in the framework of specific monitoring programs and from routine surveillance. These also comprise recent data on antimicrobial resistances of food isolates. Due to the considerable reduction of in vitro growth capabilities of stressed bacteria, there is a clear discrepancy between the detection limit of Campylobacter by cultivation and its infection potential. Moreover, antimicrobial resistances of Campylobacter isolates established during fattening of livestock are alarming, since they constitute an additional threat to human health. The European Food Safety Authority (EFSA) discusses the establishment of a quantitative limit for Campylobacter contamination of broiler carcasses in order to achieve an appropriate level of protection for consumers. Currently, a considerable amount of German broiler carcasses would not comply with this future criterion. We recommend Campylobacter reduction strategies to be focussed on the prevention of fecal contamination during slaughter. Decontamination is only a sparse option, since the reduction efficiency is low and its success depends on the initial contamination concentration.

Early history of European domestic cattle as revealed by ancient DNA.

We present an extensive ancient DNA analysis of mainly Neolithic cattle bones sampled from archaeological sites along the route of Neolithic expansion, from Turkey to North-Central Europe and Britain. We place this first reasonable population sample of Neolithic cattle mitochondrial DNA sequence diversity in context to illustrate the continuity of haplotype variation patterns from the first European domestic cattle to the present. Interestingly, the dominant Central European pattern, a starburst phylogeny around the modal sequence, T3, has a Neolithic origin, and the reduced diversity within this cluster in the ancient samples accords with their shorter history of post-domestic accumulation of mutation.

The Neanderthalian molar from Hunas, Germany.

In this paper, we present a well-preserved isolated human molar found in 1986 in the Hunas cave ruin, south-east Bavaria. The tooth was located at the bottom of layer F2, which belongs to a long stratigraphic sequence comprising faunal remains as well as archaeological levels (Mousterian). A stalagmite from layer P at the base of the stratigraphic sequence was recently dated to 79.373+/-8.237 ka (base) and 76.872+/-9.686 ka (tip) by TIMS-U/Th (Stanford University). We identified the tooth as a right (possibly third) mandibular molar. Characteristic parameters such as crown and root morphology, fissure pattern, enamel thickness, occlusal and interproximal wear, dental dimensions and indices, and radiological features indicate that the Hunas molar represents the tooth of a Neanderthal. This is corroborated by both the palaeontological and archaeological findings (Mousterian) of layer F2.

Syphilis 2001--a palaeopathological reappraisal.

The origin and subsequent spread of the treponematoses, especially that of venereal syphilis, has been the subject of considerable scientific attention. Various theories were put forth and palaeopathological specimens were used for their validation in recent times. One influential contribution was the paper by Baker & Armelagos in 1988. Numerous new findings and results on both sides of the Atlantic call for a new evaluation of the available osseous material. A review of the recent literature leads to the suggestion of a worldwide distribution of non-venereal treponemal disease since the emergence of Homo and to a first epidemic outbreak of venereal syphilis in Europe of the late 15th and the early 16th century, which was a time of change and enormous sexual liberty. Old World specimens with pathological alterations attributed to venereal syphilis and dated to precolumbian times seem to invalidate the Columbian theory and call for a more differentiated analysis of the phenomenon of syphilis than a theory based on a single factor can provide. With the help of molecular methods which now allow a positive identification of Treponema pallidum pallidum, causative agent of venereal syphilis, in palaeopathological material, it seems possible to elucidate the matter of origin and spread of syphilis further and to evaluate previous diagnoses of treponemal disease.

[Cortical thickness of the mandible with special reference to miniplate osteosynthesis. Morphometric analysis of autopsy material]. / Kortikalisdicke am Unterkiefer unter besonderer Berücksichtigung der Miniplattenosteosynthese. Morphometrische Analyse an Sektionsmaterial.

Thirty-two human mandibles were marked with three typical fracture lines: a low condylar fracture, a fracture of the mandibular angle, and one through the mental foramen on each side. The mandibles were sectioned at the fixation sites of the miniplate screws. The thickness of the cortical layer was measured with a scaled magnifying glass at the points of anthropological interest and at the marked screw holes. The inferior cortical layer turned out to be thickest in the anterior area. In contrast, it was very thin at the mandibular angle, which might explain the higher complication rate in treating fractures in this region. The thickness of the lingual cortex increased up to the symphysis, whereas the buccal cortical layer showed a decline in size from the mandibular angle up to the chin. The cortical bone at the alveolar ridge was porous. The cortical supply for miniplate osteosynthesis at the condylus ranged from 1.1 mm up to 1.74 mm, which seems to be limited, but due to the small diameter of the condylus most common screws obtain additional anchorage in the inner cortex. The thickness of the cortical layer at the mandibular angle increased from 1.47 mm at the ramus up to 1.97 mm at the beginning of the corpus, reaching 2.14-2.38 mm for the lower plate at the mental foramen. The results for the upper plate were slightly lower.

Dental print media and their value in forensic odontology.

Teeth are one of the most important factors in the identification of unknown cadavers. One of the most efficient methods the police have of publicizing a case is to publish the victim's dental x-rays of treatment records in the dental print media which dentists will often recognize and thus be able to contribute to the identification. To evaluate the efficiency of this procedure, 177 cases published between 1975 and 1995 were reviewed. The results show that only 3% of the cases were identified from recognition in the dental print media. A survey of 500 dentists was carried out to gauge the efficacy of the presentation of identification cases in their dental print media. According to these results a revised method of presentation needs to be developed to improve the efficiency of this odontoforensic publicity medium. New technologies could also open new avenues for forensic identification such as digital x-raying or online data transfer. The Internet itself could be useful regarding international cooperation of forensic odontologists in the identification of unknown corpses.

[Tooth root length and tooth neck diameter as indicators in sex determination of human teeth]. / Zahnwurzellänge und Zahnhalsdurchmesser als Indikatoren zur Geschlechtsbestimmung an menschlichen Zähnen.

The length of the dental root and the diameter of the tooth neck are odontometric parameters which to date have rarely been used for the differentiation of the sexes. Teeth of 166 individuals from the early medieval burial ground of Eichstetten (south Germany) were available for examination. A correlation analysis was performed to show the possible dimensional interrelation of teeth which, however, applies only to the dental neck parameters. Using only diameters of the tooth neck and length of dental roots, it was possible to perform a new sex determination for 68 of the 166 individuals. It shows a good coincidence with a traditional sex determination. A traditional sex determination, performed in advance, as well as the archeological assignment of typical sex related grave goods were used for verification. For future sex determination based on teeth, examinations are recommended to be restricted to the six-year molar, the first upper premolar and, in particular, the canine. Also the dental neck diameter proved to be more useful than the crown diameter. Dental root lengths can be neglected. By comparing the results with those of a second Alamannic burial ground it could be established that discriminant analyses performed within the same population are highly congruent.

Mandibular condyles and rami are asymmetric structures.

The purpose of this study was to determine the degree of bony asymmetry between the right (R) and left (L) mandibular condyles and rami. On 25 dry skulls, condylar height, breadth and length, as well as ramus height and breadth were assessed. On each skull the average of the three measurements on the right and left sides, respectively, were calculated with the corresponding reference points being redetermined for each measurement. The raw absolute differences magnitude of R - L as well as the relative absolute differences magnitude of R - L/R + L were computed. The relative absolute differences showed that asymmetries were of similar magnitude (between 1.20% and 2.58%) for all variables except for condylar height (11.06%). After taking three additional measurements with reference points chosen only once, the intra-individual measurement error, consisting of reproducibility of the reference points and accuracy in measuring the distance between the chosen points, was assessed with the help of a statistical variance component technique. Estimates of the 95% range of the absolute differences were computed. Between 60% and 88% of the measured differences were outside the predicted 95% range, thus much too large to be explained by random measurement error; hence, they were due to real individual asymmetries. We concluded that asymmetries of mandibular condyles and rami are part of the biologic variation of humans. It still remains unclear, however, when such asymmetries should be considered "unphysiological."

Richard Owen and the comparative anatomy of teeth.

One hundred fifty years ago, Richard Owen published the first detailed monograph on the comparative anatomy of teeth entitled Odontography; or, A Treatise on the Comparative Anatomy of the Teeth; their Physiological Relations, Mode of Development, and Microscopic Structure, in the Vertebrate Animals. The treatise is considered to be the first fundamental work of odontology. The 150th anniversary of its publication is an appropriate time to rediscover the roots and development of this scientific discipline, as well as the life and work of its author.

Twenty-five thousand-year-old triple burial from Dolní Vestonice: an ice-age family?

In 1986 a paleolithic triple burial was discovered near Dolní Vestonice (Czech Republic). The occurrence of anatomic variants in all three skeletons gave rise to speculations that the buried individuals may have been closely related. To test this hypothesis the skeletons were submitted to a systematic kinship analysis based on odontologic and other non-metric traits. Statistical tests showed that the coincident occurrence of several rare traits in the individuals is highly unlikely to occur at random. This and further data included in the analysis therefore suggest that the three individuals buried together were genetically related and actually belonged to one family.

Comparative anatomy of teeth from past to present.

The comparative anatomy of teeth has a long tradition in research, starting more than two thousand years ago in antiquity. In the 19th century, Richard Owen's oeuvre Odontography (1840-45) contributed much to establish odontology as an independent scientific discipline. After a short outline of the historical development of the comparative anatomy of teeth, we describe the contents and importance of Owen's Odontography. Finally, we sketch the contemporary situation of dental morphology, which in the course of the last thirty years has developed into an important and internationally highly recognized multidisciplinary field.

Düsseldorf data on the PCR-based locus HumFES/FPS (human c-fes/fps proto oncogene).

This paper reports PCR-based genotype distribution and allele frequencies of the locus HumFES/FPS (human c-fes/fps proto oncogene). For this study 300 unrelated Caucasoids of German ancestry living in Düsseldorf were analyzed. Seven of the eight alleles previously described and fourteen of the corresponding thirty-six diploid genotypes were detected. The proportions of heterozygotes and homozygotes observed and expected and the parameters of forensic interest, e.g. the mean paternity exclusion chance, were calculated. No deviations from the Hardy-Weinberg equilibrium were observed. A preliminary German data base (3,238 individuals) was created by using the weighted arithmetical mean which included data from Düsseldorf.

Determining mandibular condyle and ramus height with the help of an Orthopantomogram--a valid method?

The asymmetry of condylar and rami heights was determined from orthopantomograms of 25 macerated skulls and compared with the results of the 'true' values obtained by direct measurements of the skulls. The correlation between the two measuring methods was low.