Modellkomplexe zur Sauerstoffaktivierung auf Basis des 1,3,4-Thiadiazols

Das Ziel der vorliegenden Arbeit waren die Synthese und Untersuchung von Modellverbindungen zur Sauerstoffaktivierung auf der Basis neuer Ligandensysteme des 1,3,4-Thiadiazols unter Ausarbeitung einer Synthesestrategie zur Derivatisierung der heteroaromatischen 1,3,4-Thiadiazol-Liganden, deren Koordinationsverhalten in Abhängigkeit ihres 2,5-Substitutionsmusters untersucht wurde, sowie die fortführende Bearbeitung bereits bekannter Ligandensysteme zur Erzeugung von homo- und heterovalenten Übergangsmetallkomplexverbindungen.rnDie unter der Verwendung der modifizierten Liganden TPDE, H1TPDP und H1BPMP resultierenden dinuklearen Komplexverbindungen zeigen unterschiedlich starke antiferromagnetische Wechselwirkungen in Abhängigkeit der vorhandenen Brückenliganden. In der Verbindung [Fe6O2(OH)(L´)2(OOCMe3)9(OEt)2] trat eine Fragmentierung des Liganden H1TPDP auf. Das cisoide Ligandensubstitutionsmuster der entstandenen sechskernigen Verbindung ist verantwortlich für die interessanten magnetischen Eigenschaften des Komplexes. rnNeue Perspektiven zur Erzeugung von Modellverbindungen zur Sauerstoffaktivierung wurden mit dem Mono-Chelatliganden H1ETHP und den Bis-Chelatliganden HL2H, H2L2H und H2BATP aufgezeigt. Die Umsetzung von H1ETHP mit verschiedenen Übergangsmetallsalzen resultierte für die Metalle Cr(III), Fe(III), Co(III) und Ni(II) in mononuklearen Verbindungen des Typs [M(ETHP)2]X (X = ClO4, FeCl4, OMe, Cl, Br) sowie in zwei tetranuklearen Verbindungen mit Mn(II) und Cu(II). [Mn4(ETHP)6] besitzt ein propellerförmiges, planares [Mn4O6]2+-System mit einen Spingrundzustand von S = 5. In allen Verbindungen von H1ETHP konnte eine mono-κN-Koordination des 1,3,4-Thiadiazol-Rückgrates über eines seiner beiden endozyklischen Stickstoffdonoratome beobachtet werden. rnAus Umsetzungen der Bis-Chelatliganden wurden fast ausschließlich polynukleare Übergangsmetallkomplexe erhalten. Insbesondere der Ligand H2L2H zeigt eine ausgeprägte Tendenz zur Ausbildung trinuklearer, linearer Komplexe, welche auf Grund ihrer ungeraden Anzahl von Übergangsmetallionen einen Spingrundzustand S ≠ 0 aufweisen.rn Die mit dem Liganden HL2H erhaltenen Verbindungen unterstreichen die hohe Flexibilität dieser Systeme hinsichtlich der Erzeugung polynuklearer und heterovalenter Komplexverbindungen. So konnten in Abhängigkeit vom verwendeten Übergangsmetallsalz trinukleare, pentanukleare, aber auch hepta- und oktanukleare Verbindungen synthetisiert werden. Insbesondere die Komplexe des Mangans und des Cobalts zeigen ein heterovalentes [MnIIMnIII4]- bzw. [CoII2CoIII3]-Motiv, was sich in Spingrundzuständen von S ≠ 0 äußert. Der diamagnetische, achtkernige Fe8-Cluster besitzt eine pseudo C3-symmetrische Anordnung der Metall-Zentren, während für die heptanukleare Cu7-Kette durch ihre stark unterschiedlichen Kupfer-Koordinationsgeometrien interessante magnetische Austauschwechselwirkungen beobachtet werden konnten. Der dreikernige µ3-oxo-verbrückte Komplex des Liganden H2BATP zeigt als interessante strukturelle Eigenschaft ein ein µ3-Verbrückungsmuster des eingesetzten Sulfat-Anions. rnIn allen Komplexen der Bis-Chelatliganden HL2H, H2L2H und H2BATP konnte ein µ2-κN,κN-Koordiantionsmodus des 1,3,4-Thiadiazols und somit eine Abhängigkeit der Verbrückung vom Ligandensubstitutionsmuster beobachtet werden.rn

Clonal spread of methicillin-resistant Staphylococcus pseudintermedius in Europe and North America: an international multicentre study

OBJECTIVES: The aim of this study was to determine the phenotypic and genotypic resistance profiles of methicillin-resistant Staphylococcus pseudintermedius (MRSP) and to examine the clonal distribution in Europe and North America. METHODS: A total of 103 MRSP isolates from dogs isolated from several countries in Europe, the USA and Canada were characterized. Isolates were identified by PCR-restriction fragment length polymorphism (RFLP), antimicrobial susceptibility was determined by broth dilution or gradient diffusion, and antimicrobial resistance genes were detected using a microarray. Genetic diversity was assessed by multilocus sequence typing (MLST), PFGE and spa typing. Staphylococcal cassette chromosome mec (SCCmec) elements were characterized by multiplex PCR. RESULTS: Thirteen different sequence types (STs), 18 PFGE types and 8 spa types were detected. The hybrid SCCmec element II-III described in a MRSP isolate was present in 75 (72.8%) isolates. The remaining isolates either had SCCmec type III (n=2), IV (n=6), V (n=14) or VII-241 (n=4) or were non-typeable (n=2). The most common genotypes were ST71(MLST)-J(PFGE)-t02(spa)-II-III(SCCmec) (56.3%) and ST68-C-t06-V (12.6%). In addition to mecA-mediated beta-lactam resistance, isolates showed resistance to trimethoprim [dfr(G)] (90.3%), gentamicin/kanamycin [aac(6')-Ie-aph(2')-Ia] (88.3%), kanamycin [aph(3')-III] (90.3%), streptomycin [ant(6')-Ia] (90.3%), streptothricin (sat4) (90.3%), macrolides and/or lincosamides [erm(B), lnu(A)] (89.3%), fluoroquinolones (87.4%), tetracycline [tet(M) and/or tet(K)] (69.9%), chloramphenicol (cat(pC221)) (57.3%) and rifampicin (1.9%). CONCLUSIONS: Two major clonal MRSP lineages have disseminated in Europe (ST71-J-t02-II-III) and North America (ST68-C-t06-V). Regardless of their geographical or clonal origin, the isolates displayed resistance to the major classes of antibiotics used in veterinary medicine and thus infections caused by MRSP isolates represent a serious therapeutic challenge.

Genetic variations in IL28B and allergic disease in children

Environmental changes affecting the relationship between the developing immune system and microbial exposure have been implicated in the epidemic rise of allergic disease in developed countries. While early developmental differences in T cell function are well-recognised, there is now emerging evidence that this is related to developmental differences in innate immune function. In this study we sought to examine if differences associated with innate immunity contribute to the altered immune programming recognised in allergic children. Here, we describe for the first time, the association of carriage of the T allele of the tagging single nucleotide polymorphism rs12979860 3 kb upstream of IL28B, encoding the potent innate immune modulator type III interferon lambda (IFN-λ3), and allergy in children (p = 0.004; OR 4.56). Strikingly, the association between rs12979860 genotype and allergic disease is enhanced in girls. Furthermore, carriage of the T allele at rs12979860 correlates with differences in the pro-inflammatory profile during the first five years of life suggesting this contributes to the key differences in subsequent innate immune development in children who develop allergic disease. In the context of rising rates of disease, these immunologic differences already present at birth imply very early interaction between genetic predisposition and prenatal environmental influences.

Vascular endothelial cell-specific phosphotyrosine phosphatase (VE-PTP) activity is required for blood vessel development

VE-PTP, a receptor-type phosphotyrosine phosphatase, associates with the tyrosine kinase receptor Tie-2 and VE-cadherin and enhances the adhesive function of the latter. Here, VE-PTP was found to be restricted to endothelial cells, with a preference for arterial endothelium. Mutant mice expressing a truncated, secreted form of VE-PTP lacking the cytoplasmic and transmembrane domains and the most membrane-proximal extracellular fibronectin type III repeat, showed severe vascular malformations causing lethality at 10 days of gestation. Although blood vessels were initially formed, the intraembryonic vascular system soon deteriorated. Blood vessels in the yolk sac developed into dramatically enlarged cavities. In explant cultures of mutant allantoides, endothelial cells were found next to vessel structures growing as cell layers. No signs for enhanced endothelial apoptosis or proliferation were observed. Thus, the activity of VE-PTP is not required for the initial formation of blood vessels, yet it is essential for their maintenance and remodeling.

Aeromonas exoenzyme T of Aeromonas salmonicida is a bifunctional protein that targets the host cytoskeleton

Type III protein secretion has been shown recently to be important in the virulence of the fish pathogen Aeromonas salmonicida. The ADP-ribosylating toxin Aeromonas exoenzyme T (AexT) is one effector protein targeted for secretion via this system. In this study, we identified muscular and nonmuscular actin as substrates of the ADP-ribosylating activity of AexT. Furthermore, we show that AexT also functions as a GTPase-activating protein (GAP), displaying GAP activity against monomeric GTPases of the Rho family, specifically Rho, Rac, and Cdc42. Transfection of fish cells with wild type AexT resulted in depolymerization of the actin cytoskeleton and cell rounding. Point mutations within either the GAP or the ADP-ribosylating active sites of AexT (Arg-143 as well as Glu-398 and Glu-401, respectively) abolished enzymatic activity, yet did not prevent actin filament depolymerization. However, inactivation of the two catalytic sites simultaneously did. These results suggest that both the GAP and ADP-ribosylating domains of AexT contribute to its biological activity. This is the first bacterial virulence factor to be described that has a specific actin ADP-ribosylation activity and GAP activity toward Rho, Rac, and Cdc42, both enzymatic activities contributing to actin filament depolymerization.

Modulation of chemokine gene expression by Shiga-toxin producing Escherichia coli belonging to various origins and serotypes

Infection with Shiga-toxin producing Escherichia coli (STEC) may result in the development of the haemolytic-uremic syndrome (HUS), the main cause of acute renal failure in children. While O157:H7 STEC are associated with large outbreaks of HUS, it is difficult to predict whether a non-O157:H7 isolate can be pathogenic for humans. The mucosal innate immune response plays a central role in the pathogenesis of HUS; therefore, we compared the induction of IL-8 and CCL20 in human colon epithelial cells infected with strains belonging to different serotypes, isolated from cattle or from HUS patients. No correlation was observed between strain virulence and chemokine gene expression. Rather, the genetic background of the strains seems to determine the chemokine gene expression profile. Investigating the contribution of different bacterial factors in this process, we show that the type III secretion system of O157:H7 bacteria, but not the intimate adhesion, is required to stimulate the cells. In addition, H7, H10, and H21 flagellins are potent inducers of chemokine gene expression when synthesized in large amount.

Outbreaks of an ulcerative and haemorrhagic disease in Arctic char Salvelinus alpinus caused by Aeromonas salmonicida subsp. smithia

Arctic char Salvelinus alpinus farmed in different places in Austria and free of the viral diseases viral haemorrhagic septcaemia (VHS), infectious haematopoietic necrosis (IHN) and infectious pancreatic necrosis (IPN) experienced disease and mortality. Diseased fish showed skin ulceration and pathological signs of sepsis. Aeromonas sp. was isolated as pure culture from the kidney of freshly euthanized diseased fish. Three independent isolates from outbreaks that occurred on 2 of the affected farms were analyzed phylogenetically by DNA sequence analysis of the rrs and gyrB genes and phenotypically with biochemical reactions. All 3 isolates were identified as Aeromonas salmonicida subsp. smithia. Analysis of virulence genes in these isolates revealed the presence of a Type III secretion system as well as several related virulence effector genes including aexT, encoding the Aeromonas exotoxin AexT, aopP and aopH. These genes are characteristic for virulent strains of typical and atypical subspecies of A. salmonicida.

Serotyping of Toxoplasma gondii in cats (Felis domesticus) reveals predominance of type II infections in Germany.

BACKGROUND Cats are definitive hosts of Toxoplasma gondii and play an essential role in the epidemiology of this parasite. The study aims at clarifying whether cats are able to develop specific antibodies against different clonal types of T. gondii and to determine by serotyping the T. gondii clonal types prevailing in cats as intermediate hosts in Germany. METHODOLOGY To establish a peptide-microarray serotyping test, we identified 24 suitable peptides using serological T. gondii positive (n=21) and negative cat sera (n=52). To determine the clonal type-specific antibody response of cats in Germany, 86 field sera from T. gondii seropositive naturally infected cats were tested. In addition, we analyzed the antibody response in cats experimentally infected with non-canonical T. gondii types (n=7). FINDINGS Positive cat reference sera reacted predominantly with peptides harbouring amino acid sequences specific for the clonal T. gondii type the cats were infected with. When the array was applied to field sera from Germany, 98.8% (85/86) of naturally-infected cats recognized similar peptide patterns as T. gondii type II reference sera and showed the strongest reaction intensities with clonal type II-specific peptides. In addition, naturally infected cats recognized type II-specific peptides significantly more frequently than peptides of other type-specificities. Cats infected with non-canonical types showed the strongest reactivity with peptides presenting amino-acid sequences specific for both, type I and type III. CONCLUSIONS Cats are able to mount a clonal type-specific antibody response against T. gondii. Serotyping revealed for most seropositive field sera patterns resembling those observed after clonal type II-T. gondii infection. This finding is in accord with our previous results on the occurrence of T. gondii clonal types in oocysts shed by cats in Germany.

Radialer externer Fixateur zur geschlossenen Behandlung problematischer suprakondylärer Humerusfrakturen Typ III und IV bei Kindern und Jugendlichen

Operationsziel Geschlossene, anatomische Reposition und sichere Fixation von problematischen suprakondylären Typ-III- und Typ-IV-Humerusfrakturen, die mit den herkömmlichen Operationsmethoden nur schwierig geschlossen zu behandeln sind. Indikationen Gemäß der AO-Kinderklassifikation der suprakondylären Humerusfrakturen vom Typ III und IV: Frakturen, welche nicht geschlossen mittels üblicher Repositionsmethoden reponierbar sind sowie Frakturen, die nicht mittels der üblichen, gekreuzten perkutanen Kirschner-Draht-Technik zu fixieren sind. Bei schweren Schwellungszuständen, offener Fraktur oder initial neurologischen und/oder vaskulären Problemen („pulseless pink hand“) sowie bei mehrfachverletzten Kindern, welche eine optimale Rehabilitation benötigen und die Extremität gipsfrei sein sollte. Bei Kindern mit Komorbiditäten (z. B. Anfälle, Spastizität), die eine bessere Stabilität benötigen. Kontraindikationen Prinzipiell keine Kontraindikationen Operationstechnik Im nichtreponierten Zustand unter Durchleuchtungskontrolle Einbringen einer einzelnen Schanz-Schraube in den lateralen (radialen) Aspekt des distalen Fragments, welches sich in der streng seitlichen Röntgenprojektion als „Sand-Uhr“- bzw. Kreisform des Capitulum humeri darstellt. Je nach Größe dieses distalen Fragments kann die Schanz-Schraube rein epiphysär oder metaphysär liegen. Danach in absolut streng seitlicher Projektion des distalen Humerus im Bereich des meta-diaphysären Übergangs Einbohren einer 2. Schanz-Schraube unabhängig von der Ersten, die möglichst rechtwinklig zur Längsachse des Humerus in der a.-p.-Ebene zu liegen kommen sollte, um spätere Manipulationen mittels „Joy-Stick“-Technik zu erleichtern. Sind die beiden Schanz-Schrauben mehr oder weniger in beiden Ebenen parallel, so ist die Fraktur praktisch anatomisch reponiert. Nach erreichter Reposition Feinjustierung aller Achskomponenten. Sicherung der Flexion/Extension mittels einem von radial, distal eingebrachten sog. Anti-Rotations-Kirschner-Drahts, der die Stabilität signifikant erhöht und eine Drehung des distalen Fragments um die einzelne Schanz-Schraube verhindert. Postoperative Behandlung Keine zusätzliche Gipsruhigstellung notwendig. Es sollte eine funktionelle Nachbehandlung erfolgen. Ergebnisse Gemäß unserer Langzeitstudien bewegen die meisten Kinder bereits zum Zeitpunkt der ambulanten Pin-Entfernung in der Frakturambulanz ihren Ellbogen weitgehend normal. Bei einer Follow-up-Zeit über 40 Monate hatten 30/31 Kindern eine seitengleiche Achse und Beweglichkeit.

Comparison of Salmonella enterica serovar Typhimurium colitis in germfree mice and mice pretreated with streptomycin.

Salmonella enterica subspecies 1 serovar Typhimurium is a common cause of bacterial enterocolitis. Mice are generally protected from Salmonella serovar Typhimurium colonization and enterocolitis by their resident intestinal microflora. This phenomenon is called "colonization resistance" (CR). Two murine Salmonella serovar Typhimurium infection models are based on the neutralization of CR: (i) in specific-pathogen-free mice pretreated with streptomycin (StrSPF mice) antibiotics disrupt the intestinal microflora; and (ii) germfree (GF) mice are raised without any intestinal microflora, but their intestines show distinct physiologic and immunologic characteristics. It has been unclear whether the same pathogenetic mechanisms trigger Salmonella serovar Typhimurium colitis in GF and StrSPF mice. In this study, we compared the two colitis models. In both of the models Salmonella serovar Typhimurium efficiently colonized the large intestine and triggered cecum and colon inflammation starting 8 h postinfection. The type III secretion system encoded in Salmonella pathogenicity island 1 was essential in both disease models. Thus, Salmonella serovar Typhimurium colitis is triggered by similar pathogenetic mechanisms in StrSPF and GF mice. This is remarkable considering the distinct physiological properties of the GF mouse gut. One obvious difference was more pronounced damage and reduced regenerative response of the cecal epithelium in GF mice. Overall, StrSPF mice and GF mice provide similar but not identical models for Salmonella serovar Typhimurium colitis.

Flagella and chemotaxis are required for efficient induction of Salmonella enterica serovar Typhimurium colitis in streptomycin-pretreated mice.

Salmonella enterica subspecies 1 serovar Typhimurium is a common cause of gastrointestinal infections. The host's innate immune system and a complex set of Salmonella virulence factors are thought to contribute to enteric disease. The serovar Typhimurium virulence factors have been studied extensively by using tissue culture assays, and bovine infection models have been used to verify the role of these factors in enterocolitis. Streptomycin-pretreated mice provide an alternative animal model to study enteric salmonellosis. In this model, the Salmonella pathogenicity island 1 type III secretion system has a key virulence function. Nothing is known about the role of other virulence factors. We investigated the role of flagella in murine serovar Typhimurium colitis. A nonflagellated serovar Typhimurium mutant (fliGHI) efficiently colonized the intestine but caused little colitis during the early phase of infection (10 and 24 h postinfection). In competition assays with differentially labeled strains, the fliGHI mutant had a reduced capacity to get near the intestinal epithelium, as determined by fluorescence microscopy. A flagellated but nonchemotactic cheY mutant had the same virulence defects as the fliGHI mutant for causing colitis. In competitive infections, both mutants colonized the intestine of streptomycin-pretreated mice by day 1 postinfection but were outcompeted by the wild-type strain by day 3 postinfection. Together, these data demonstrate that flagella are required for efficient colonization and induction of colitis in streptomycin-pretreated mice. This effect is mostly attributable to chemotaxis. Recognition of flagellar subunits (i.e., flagellin) by innate immune receptors (i.e., Toll-like receptor 5) may be less important.

Role of the Salmonella pathogenicity island 1 effector proteins SipA, SopB, SopE, and SopE2 in Salmonella enterica subspecies 1 serovar Typhimurium colitis in streptomycin-pretreated mice.

Salmonella enterica subspecies 1 serovar Typhimurium (serovar Typhimurium) induces enterocolitis in humans and cattle. The mechanisms of enteric salmonellosis have been studied most extensively in calf infection models. The previous studies established that effector protein translocation into host cells via the Salmonella pathogenicity island 1 (SPI-1) type III secretion system (TTSS) is of central importance in serovar Typhimurium enterocolitis. We recently found that orally streptomycin-pretreated mice provide an alternative model for serovar Typhimurium colitis. In this model the SPI-1 TTSS also plays a key role in the elicitation of intestinal inflammation. However, whether intestinal inflammation in calves and intestinal inflammation in streptomycin-pretreated mice are induced by the same SPI-1 effector proteins is still unclear. Therefore, we analyzed the role of the SPI-1 effector proteins SopB/SigD, SopE, SopE2, and SipA/SspA in elicitation of intestinal inflammation in the murine model. We found that sipA, sopE, and, to a lesser degree, sopE2 contribute to murine colitis, but we could not assign an inflammation phenotype to sopB. These findings are in line with previous studies performed with orally infected calves. Extending these observations, we demonstrated that in addition to SipA, SopE and SopE2 can induce intestinal inflammation independent of each other and in the absence of SopB. In conclusion, our data corroborate the finding that streptomycin-pretreated mice provide a useful model for studying the molecular mechanisms of serovar Typhimurium colitis and are an important starting point for analysis of the molecular events triggered by SopE, SopE2, and SipA in vivo.

Pretreatment of mice with streptomycin provides a Salmonella enterica serovar Typhimurium colitis model that allows analysis of both pathogen and host.

Salmonella enterica subspecies 1 serovar Typhimurium is a principal cause of human enterocolitis. For unknown reasons, in mice serovar Typhimurium does not provoke intestinal inflammation but rather targets the gut-associated lymphatic tissues and causes a systemic typhoid-like infection. The lack of a suitable murine model has limited the analysis of the pathogenetic mechanisms of intestinal salmonellosis. We describe here how streptomycin-pretreated mice provide a mouse model for serovar Typhimurium colitis. Serovar Typhimurium colitis in streptomycin-pretreated mice resembles many aspects of the human infection, including epithelial ulceration, edema, induction of intercellular adhesion molecule 1, and massive infiltration of PMN/CD18(+) cells. This pathology is strongly dependent on protein translocation via the serovar Typhimurium SPI1 type III secretion system. Using a lymphotoxin beta-receptor knockout mouse strain that lacks all lymph nodes and organized gut-associated lymphatic tissues, we demonstrate that Peyer's patches and mesenteric lymph nodes are dispensable for the initiation of murine serovar Typhimurium colitis. Our results demonstrate that streptomycin-pretreated mice offer a unique infection model that allows for the first time to use mutants of both the pathogen and the host to study the molecular mechanisms of enteric salmonellosis.

Oligodeoxynucleotide Duplexes Containing (5′S)-5′-C-Alkyl-Modified 2′-Deoxynucleosides: Can an Alkyl Zipper across the DNA Minor-Groove Enhance Duplex Stability?

10.1002/hlca.200390311.abs A series of oligonucleotides containing (5′S)-5′-C-butyl- and (5′S)-5′-C-isopentyl-substituted 2′-deoxyribonucleosides were designed, prepared, and characterized with the intention to explore alkyl-zipper formation between opposing alkyl chains across the minor groove of oligonucleotide duplexes as a means to modulate DNA-duplex stability. From four possible arrangements of the alkyl groups that differ in the density of packing of the alkyl chains across the minor groove, three (duplex types I–III, Fig. 2) could experimentally be realized and their duplex-forming properties analyzed by UV-melting curves, CD spectroscopy, and isothermal titration calorimetry (ITC), as well as by molecular modeling. The results show that all arrangements of alkyl residues within the minor groove of DNA are thermally destabilizing by 1.5–3°/modification in Tm. We found that, within the proposed duplexes with more loosely packed alkyl groups (type-III duplexes), accommodation of alkyl residues without extended distorsion of the helical parameters of B-DNA is possible but does not lead to higher thermodynamic stability. The more densely packed and more unevenly distributed arrangement (type-II duplexes) seems to suffer from ecliptic positioning of opposite alkyl groups, which might account for a systematic negative contribution to stability due to steric interactions. The decreased stability in the type-III duplexes described here may be due either to missing hydrophobic interactions of the alkyl groups (not bulky enough to make close contacts), or to an overcompensation of favorable alkyl-zipper formation presumably by loss of structured H2O in the minor groove.

Operative Treatment of Acute Fractures of the Tarsal Navicular Body: Midterm Results With a New Classification.

BACKGROUND Treatment of displaced tarsal navicular body fractures usually consists of open reduction and internal fixation. However, there is little literature reporting results of this treatment and correlation to fracture severity. METHODS We report the results of 24 patients treated in our institution over a 12-year period. Primary outcome measurements were Visual-Analogue-Scale Foot and Ankle score (VAS-FA), AOFAS midfoot score, and talonavicular osteoarthritis at final follow-up. According to a new classification system reflecting talonavicular joint damage, 2-part fractures were classified as type I, multifragmentary fractures as type II, and fractures with talonavicular joint dislocation and/or concomitant talar head fractures as type III. Spearman's coefficients tested this classification's correlation with the primary outcome measurements. Mean patient age was 33 (range 16-61) years and mean follow-up duration 73 (range 24-159) months. RESULTS Average VAS-FA score was 74.7 (standard deviation [SD] 16.9), and average AOFAS midfoot score was 83.8 (SD = 12.8). Final radiographs showed no talonavicular arthritis in 5 patients, grade 1 in 7, grade 2 in 3, grade 3 in 6, and grade 4 in 1 patient. Two patients had secondary or spontaneous talonavicular fusion. Spearman coefficients showed strong correlation of the classification system with VAS-FA score (r = -0.663, P < .005) and talonavicular arthritis (r = 0.600, P = .003), and moderate correlation with AOFAS score (r = -.509, P = .011). CONCLUSION At midterm follow-up, open reduction and internal fixation of navicular body fractures led to good clinical outcome but was closely related to fracture severity. A new classification based on the degree of talonavicular joint damage showed close correlation to clinical and radiologic outcome. LEVEL OF EVIDENCE Level IV, retrospective case series.