Human Gb3/CD77 synthase produces P1 glycotope-capped N-glycans, which mediate Shiga toxin 1 but not Shiga toxin 2 cell entry.

The human Gb3/CD77 synthase, encoded by the A4GALT gene, is an unusually promiscuous glycosyltransferase. It synthesizes the Galα1→4Gal linkage on two different glycosphingolipids (GSLs), producing globotriaosylceramide (Gb3, CD77, Pk) and the P1 antigen. Gb3 is the major receptor for Shiga toxins (Stxs) produced by enterohemorrhagic Escherichia coli. A single amino acid substitution (p.Q211E) ramps up the enzyme's promiscuity, rendering it able to attach Gal both to another Gal residue and to GalNAc, giving rise to NOR1 and NOR2 GSLs. Human Gb3/CD77 synthase was long believed to transfer Gal only to GSL acceptors, therefore its GSL products were, by default, considered the only human Stx receptors. Here, using soluble, recombinant human Gb3/CD77 synthase and p.Q211E mutein, we demonstrate that both enzymes can synthesize the P1 glycotope (terminal Galα1→4Galß1→4GlcNAc-R) on a complex type N-glycan and a synthetic N-glycoprotein (saposin D). Moreover, by transfection of CHO-Lec2 cells with vectors encoding human Gb3/CD77 synthase and its p.Q211E mutein, we demonstrate that both enzymes produce P1 glycotopes on N-glycoproteins, with the mutein exhibiting elevated activity. These P1-terminated N-glycoproteins are recognized by Stx1 but not Stx2 B subunits. Finally, cytotoxicity assays show that Stx1 can use P1 N-glycoproteins produced in CHO-Lec2 cells as functional receptors. We conclude that Stx1 can recognize and use P1 N-glycoproteins in addition to its canonical GSL receptors to enter and kill the cells, while Stx2 can use GSLs only. Collectively, these results may have important implications for our understanding of the Shiga toxin pathology.

One of the two N-glycans on the human Gb3/CD77 synthase is essential for its activity and allosterically regulates its function.

N-glycosylation is a posttranslational modification that influences many protein properties, such as bioactivity, folding or solubility. The same principles apply to key enzymes in glycosylation pathways, including glycosyltransferases, that also undergoing N-glycosylation, changes in which may affect their activity. Human Gb3/CD77 synthase (encoded by A4GALT) is a Golgi-resident glycosyltransferase, which catalyzes the synthesis of Galα1→4Gal disaccharide on glycosphingolipid- and glycoprotein-derived acceptors, creating Gb3 or P1 antigens and P1 glycotopes (Galα1→4Galß1→4GlcNAc-R), respectively. The molecules that contain Galα1→4Gal serve as receptors for pathogens and Shiga toxins, which are the major virulence factors of Shiga toxin-producing Escherichia coli (STEC). Human Gb3/CD77 synthase contains two N-glycosylation sites at positions N121 and N203. Using the recombinant soluble glycovariants of human Gb3/CD77 synthase with mutated N-glycosylation sequons expressed in HEK293E cells, we show that the glycovariants devoid of N-glycan at position N203 or simultaneously at N121 and N203 sites reveal no enzymatic activity. In contrast, the N-glycan at position N121 plays a negligible role, whereas the presence of both N-glycans is required for efficient secretion of the enzyme. Moreover, utilizing specific glycosidases, we have found that the fully N-glycosylated enzyme contains one complex and one hybrid/oligomannose N-glycan, while single mutants contain only the complex type. Finally, in silico analysis using the AlphaFold enzyme model showed that N-glycan attached to N203 sequon is located in a protein motif near the active site and may allosterically influence the activity. All these findings highlight the prerequisite role of N-glycosylation in human Gb3/CD77 synthase activity (N203 sequon) and solubility (both N121 and N203), with a particularly prominent role of N-glycan at position N203 in the regulation of enzyme activity.

Ludwik Hirszfeld: A pioneer of transfusion and immunology during the world wars and beyond.

Ludwik Hirszfeld (1884-1954) was a Polish physician, immunologist and microbiologist. Together with Emil von Dungern, he showed that blood groups are heritable traits and established the terminology of the ABO blood group system. He discovered A1 and A2 blood groups, and showed for the first time, in a large-scale population study, that blood group frequency differs between populations. During World War I, he volunteered as an army physician. In the interwar period, he helped to create the National Institute of Hygiene in Warsaw and was instrumental in developing transfusion centres in Poland. During World War II, which he barely survived, he co-organized secret medical courses in the Warsaw Ghetto and played a major role in containing the typhus epidemic that ran rampant there since 1941. After the war, he was the first in Poland to put the theory of serological conflict between mother and foetus into clinical practice, saving the lives of almost 200 children by introducing exchange transfusions.

Missing the sweet spot: one of the two N-glycans on human Gb3/CD77 synthase is expendable.

N-glycosylation is a ubiquitous posttranslational modification that may influence folding, subcellular localization, secretion, solubility and oligomerization of proteins. In this study, we examined the effects of N-glycans on the activity of human Gb3/CD77 synthase, which catalyzes the synthesis of glycosphingolipids with terminal Galα1→4Gal (Gb3 and the P1 antigen) and Galα1→4GalNAc disaccharides (the NOR antigen). The human Gb3/CD77 synthase contains two occupied N-glycosylation sites at positions N121 and N203. Intriguingly, we found that while the N-glycan at N203 is essential for activity and correct subcellular localization, the N-glycan at N121 is dispensable and its absence did not reduce, but, surprisingly, even increased the activity of the enzyme. The fully N-glycosylated human Gb3/CD77 synthase and its glycoform missing the N121 glycan correctly localized in the Golgi, whereas a glycoform without the N203 site partially mislocalized in the endoplasmic reticulum. A double mutein missing both N-glycans was inactive and accumulated in the endoplasmic reticulum. Our results suggest that the decreased specific activity of human Gb3/CD77 synthase glycovariants resulted from their improper subcellular localization and, to a smaller degree, a decrease in enzyme solubility. Taken together, our findings show that the two N-glycans of human Gb3/CD77 synthase have opposing effects on its properties, revealing a dual nature of N-glycosylation and potentially a novel regulatory mechanism controlling the biological activity of proteins.

Two Paralogous Gb3/CD77 Synthases in Birds Show Different Preferences for Their Glycoprotein and Glycosphingolipid Substrates.

Most glycosyltransferases show remarkable gross and fine substrate specificity, which is reflected in the old one enzyme-one linkage paradigm. While human Gb3/CD77 synthase is a glycosyltransferase that synthesizes the Galα1→4Gal moiety mainly on glycosphingolipids, its pigeon homolog prefers glycoproteins as acceptors. In this study, we characterized two Gb3/CD77 synthase paralogs found in pigeons (Columba livia). We evaluated their specificities in transfected human teratocarcinoma 2102Ep cells by flow cytofluorometry, Western blotting, high-performance thin-layer chromatography, mass spectrometry and metabolic labelling with 14C-galactose. We found that the previously described pigeon Gb3/CD77 synthase (called P) can use predominately glycoproteins as acceptors, while its paralog (called M), which we serendipitously discovered while conducting this study, efficiently synthesizes Galα1→4Gal caps on both glycoproteins and glycosphingolipids. These two paralogs may underlie the difference in expression profiles of Galα1→4Gal-terminated glycoconjugates between neoavians and mammals.

How glycosylation affects glycosylation: the role of N-glycans in glycosyltransferase activity.

N-glycosylation is one of the most important posttranslational modifications of proteins. It plays important roles in the biogenesis and functions of proteins by influencing their folding, intracellular localization, stability and solubility. N-glycans are synthesized by glycosyltransferases, a complex group of ubiquitous enzymes that occur in most kingdoms of life. A growing body of evidence shows that N-glycans may influence processing and functions of glycosyltransferases, including their secretion, stability and substrate/acceptor affinity. Changes in these properties may have a profound impact on glycosyltransferase activity. Indeed, some glycosyltransferases have to be glycosylated themselves for full activity. N-glycans and glycosyltransferases play roles in the pathogenesis of many diseases (including cancers), so studies on glycosyltransferases may contribute to the development of new therapy methods and novel glycoengineered enzymes with improved properties. In this review, we focus on the role of N-glycosylation in the activity of glycosyltransferases and attempt to summarize all available data about this phenomenon.

The role of MMP-12 gene polymorphism - 82 A-to-G (rs2276109) in immunopathology of COPD in polish patients: a case control study.

BACKGROUND: Major symptoms of chronic obstructive pulmonary disease (COPD) are chronic bronchitis and emphysema leading from lung tissue destruction, that is an effect of an imbalance between metalloproteinases (MMPs) and their tissue inhibitors activity. As potential factor involved in this COPD pathogenesis, MMP-12 is considered. We investigated the role of genetic polymorphism and protein level of MMP-12 in the COPD development among Poles. METHODS: We analyzed - 82 A > G SNP in the promoter region of MMP-12 gene (rs2276109) among 335 smoked COPD patients and 309 healthy individuals, including 110 smokers. Additionally, 60 COPD patients and 61 controls (23 smokers) were tested for serum levels of MMP-12 using ELISA. All subjects were analyzed for lung function using spirometry (FEV1% and FEV1/FVC parameters). RESULTS: We observed that -82G allele and -82GG homozygous genotype frequencies of the SNP rs2276109 were significantly lower in COPD patients than in controls (12.5% vs 16.9%, respectively; χ2 = 4.742, p = 0.02 for allele and 0.5% vs 3.9%, respectively; χ2 = 9.0331, p = 0.01 for genotype). Moreover, -82G allele was more frequent in controls smokers than in non-smokers (22.3% vs 14.1%, χ2 = 6.7588, p = 0.01). Serum level of MMP-12 was significantly higher in COPD patients than in controls groups (6.8 ng/ml vs 3.3 ng/ml, respectively; F = 7.433, p < 0.0001), although independently of analyzed gene polymorphisms. Additionally, no correlation between parameters of lung function (FEV1% and FEV1/FVC) and protein level was found. CONCLUSIONS: We found that -82G allele of SNP rs2276109 was associated with reduced risk of COPD, and COPD patients released more MMP-12 than healthy individuals, but independently on this SNP.

Duffy blood group system - the frequency of Duffy antigen polymorphisms and novel mutations in the Polish population.

Duffy blood group genes are highly polymorphic with the distribution of alleles varying between different populations and ethnic groups. The aim of this study was to genotype Duffy blood group antigens and to establish FY alleles frequency in the Polish population and screen for novel FY gene mutations. Duffy phenotype and genotype frequencies analysis was based on studies of 596 persons. All these subjects were genotyped by high-resolution melting (HRM) method. It was shown that phenotype Fy(a+b+), defined by genotypes FY*A/FY*B (33%), FY*A/FY*B298A (13%), and FY*A/FY*02W.01 (2.8%) was the most common in Polish population (˜49%), followed by Fy(a-b+), ˜29%, determined by genotypes arising from FY*B allele and all its variants. Fy(a+b-) phenotype occurred with a frequency of 21.3% and was defined by the following genotypes: FY*A/A (21%), and FY*A/02N.01 (0.3%). Among the Polish population the frequencies of FY*A, FY*B, and FY*B298A alleles were 45.7%, 36% and 15.5%, respectively. The alleles FY*B298A and FY*B combined together, represented higher frequency (51%) than FY*A. Alleles FY*02W.01 and FY*02N.01 had frequencies 2.51% and 0.25%, respectively. The distribution of Duffy genotypes in the Polish population was in accordance with Hardy-Weinberg equilibrium (p = 0.9682). Alleles in the genotypes are independent from each other (r = 0.0278, R2 = 0.00077). New mutations identified in the promoter region (c.-79T > C) and the coding region of the FY gene (c.147C > A and c.175 G > A) did not affect the Duffy antigen expression on erythrocyte. Although FY alleles frequency is known in different populations, no data for Polish population is available.

The Incidence of Ocular Injuries in Isolated Orbital Fractures.

BACKGROUND: Prompt identification of significant ocular injuries in patients who sustain an orbital fracture is important to prevent any potential long-term visual sequelae. The true incidence of these injuries has not been determined, however. As a consequence, most surgeons choose to have all patients evaluated by an ophthalmologist. The objective of this study was to conclusively identify the incidence of significant ocular injuries in patients with isolated orbital fractures and to determine their predictors to guide more efficient patient care. METHODS: A prospective cohort study powered to detect a 15% incidence of ocular injuries was designed. All patients presenting to our center with computed tomography findings of an isolated orbital fracture were included and evaluated by plastic surgery and ophthalmology services. Patients were followed up for a minimum of 1 week to identify any delayed injuries. RESULTS: Eighty patients were enrolled from 2012 to 2014. There were 46 men and 34 women with a mean age of 42.8 years. Assault was the most common mechanism of injury. There were 8 ocular injuries (10%): ruptured globe (1), uveal prolapse (1), retrobulbar hemorrhage (2), hyphema (2), hemorrhagic glaucoma with hyphema (1), and scleral tear (1). Predictors for significant ocular injuries were grossly abnormal visual acuity and abnormal pupillary reactivity of the affected eye. CONCLUSIONS: The incidence of significant ocular injuries in isolated orbital fractures is lower than previously reported. Patients presenting with grossly abnormal visual acuity or abnormal pupillary reactivity are at high risk and should receive prompt ophthalmology service evaluation.

Normocephalic Pancraniosynostosis: A Report of a Surgical Technique.

Normocephalic pancraniosynostosis is defined as the premature fusion of 3 or, more major sutures in the absence of another primary etiology, including primary, microcephaly, ventriculoperitoneal shunting, hypothyroidism, rickets, mucopolysaccharidoses, or other lysosomal storage diseases. It is very rare, thus far only 6 patients have been reported in the literature. Patients tend to present much later than those with single sutural, synostoses, and up to half have evidence of elevated intracranial pressure. The authors wish to present another patient, with emphasis on a unique treatment approach.

Human Gb3/CD77 synthase reveals specificity toward two or four different acceptors depending on amino acid at position 211, creating P(k), P1 and NOR blood group antigens.

Human Gb3/CD77 synthase (α1,4-galactosyltransferase, P(k) synthase), encoded by A4GALT gene, is known for synthesis of Gal(α1-4)Gal moiety in globotriaosylceramide (Gb3Cer, CD77, P(k) blood group antigen), a glycosphingolipid of the globo series. Recently, it was shown that c.631C > G mutation in A4GALT, which causes p.Q211E substitution in the open reading frame of the enzyme, broadens the enzyme specificity, making it able also to synthesize Gal(α1-4)GalNAc moiety, which constitutes the defining terminal disaccharide of the NOR antigen (carried by two glycosphingolipids: NOR1 and NOR2). Terminal Gal(α1-4)Gal disaccharide is also present in another glycosphingolipid blood group antigen, called P1, which together with P(k) and NOR comprises the P1PK blood group system. Despite several attempts, it was never clearly shown that P1 antigen is synthesized by Gb3/CD77 synthase, leaving open an alternative hypothesis that there are two homologous α1,4-galactosyltransferases in humans. In this study, using recombinant Gb3/CD77 synthase produced in insect cells, we show that the consensus enzyme synthesizes both the P(k) and P1 antigens, while its p.Q211E variant additionally synthesizes the NOR antigen. This is the first direct biochemical evidence that Gb3/CD77 synthase is able to synthesize two different glycosphingolipid antigens: P(k) and P1, and when p.Q211E substitution is present, the NOR antigen is also synthesized.

Evaluation of an amino acid residue critical for the specificity and activity of human Gb3/CD77 synthase.

Human Gb3/CD77 synthase (α1,4-galactosyltransferase) is the only known glycosyltransferase that changes acceptor specificity because of a point mutation. The enzyme, encoded by A4GALT locus, is responsible for biosynthesis of Gal(α1-4)Gal moiety in Gb3 (CD77, Pk antigen) and P1 glycosphingolipids. We showed before that a single nucleotide substitution c.631C > G in the open reading frame of A4GALT, resulting in replacement of glutamine with glutamic acid at position 211 (substitution p. Q211E), broadens the enzyme acceptor specificity, so it can not only attach galactose to another galactose but also to N-acetylgalactosamine. The latter reaction leads to synthesis of NOR antigens, which are glycosphingolipids with terminal Gal(α1-4)GalNAc sequence, never before described in mammals. Because of the apparent importance of position 211 for enzyme activity, we stably transfected the 2102Ep cells with vectors encoding Gb3/CD77 synthase with glutamine substituted by aspartic acid or asparagine, and evaluated the cells by quantitative flow cytometry, high-performance thin-layer chromatography and real-time PCR. We found that cells transfected with vectors encoding Gb3/CD77 synthase with substitutions p. Q211D or p. Q211N did not express Pk, P1 and NOR antigens, suggesting complete loss of enzymatic activity. Thus, amino acid residue at position 211 of Gb3/CD77 synthase is critical for specificity and activity of the enzyme involved in formation of Pk, P1 and NOR antigens. Altogether, this approach affords a new insight into the mechanism of action of the human Gb3/CD77 synthase.

Safety of Outpatient Isolated Orbital Floor Fracture Repair.

Orbital fractures are common, accounting for nearly 40% of all facial fractures. Open repair is required to restore preinjury orbital volume and relieve any extra-ocular muscle entrapment. Monitoring for postoperative intraorbital hemorrhage, and its consequent potential for visual impairment, has triggered most surgeons to observe their patients in the hospital overnight postoperatively. The real risk of postoperative hemorrhage in this patient group, however, is uncertain and the need to contain healthcare costs clear. The objective of this study was thus to determine the incidence of emergent postoperative complications in patients undergoing orbital fracture repair to determine the feasibility of performing this operation on an outpatient basis. Patients who sustained isolated orbital fractures and underwent open repair at this level-1 trauma center between January 2002 and January 2012 using International Classification of Disease-9 and Current Procedural Terminology 2012 coding were identified. Demographic data and postoperative complications were identified by reviewing the electronic medical record. Furthermore, critical analysis of available published evidence was performed. Ninety-three patients who satisfied the inclusion criteria were selected. There were no patients of an intraorbital hematoma or other immediate postoperative complications that required operative intervention. Average hospital length of stay was 0.85 days. Repair of orbital fractures on an outpatient basis appears to be safe. The theoretical risk of a complicating intraorbital hematoma seems to be between 0 and 3.2%. This can be minimized through: the use of open surgical access site and perforated floor replacement materials, careful early monitoring, education of patients, and admission of those at potentially elevated risk.

Use of a Titanium Microplate to Anchor Subunit Reconstruction at the Nasal-Cheek Junction.

Reconstruction of combined nose, cheek, and/or inferior eyelid defects is facilitated by stable anchorage at the nasal-cheek junction. The previously reported techniques of drill holes and Mitek anchors are not without disadvantages. The authors present a simple means of anchoring soft tissue flaps at the nasal-cheek junction: a titanium miniplate secured with a screw at each end. Our case report describes successful, lasting, and complication-free anchorage of cheek, forehead, and eyelid flaps to a single miniplate placed along the piriform aperture.

Management of Zygomatic Fractures: A National Survey.

INTRODUCTION: Repair of zygomatic fractures can be classified into the early closed reduction or the more recent open reduction and rigid internal fixation (ORIF) methods. Surgical training and literature advocate ORIF, but the actual frequency of the different techniques in clinical practice is unknown. The purpose of this study was to determine the current trends in the management of zygomatic fractures among US surgeons and elucidate their influences. METHODS: A 10-question survey was developed and distributed to over 16,000 practicing US facial trauma surgeons, including plastic surgeons (PS), oral and maxillofacial surgeons (OMFS), and otorhinolaryngologists (ENT). The survey queried training background, zygoma fracture treatment preferences, and rationale. Responses were tabulated and both univariate and bivariate statistical analyses completed. RESULTS: One thousand six hundred eleven (10%) total responses were received. Zygomatic fractures are treated most commonly by OMFS (61%), then PS (20%) and ENT (19%), with 71% of repairs being performed in private practice. Open reduction and rigid internal fixation is the most common treatment modality (81%), with most surgeons using 2 to 3 sites for exposure, reduction, and fixation with titanium miniplates (70%). Thirty-five percent of surgeons perform routine orbital floor exploration. Forty-three percent quoted training and 32% reported accuracy of repair as the primary reason for choosing ORIF. CONCLUSIONS: This is the largest reported survey on the repair of zygoma fractures. The response rate suggests dominance of OMFS in zygoma fracture care, an area pioneered by PS. Evolution of technique is also evident by predominance of ORIF with emphasis of multiple points of exposure, reduction, and fixation with rigid hardware.

Can mutations in the gene encoding transcription factor EKLF (Erythroid Krüppel-Like Factor) protect us against infectious and parasitic diseases?

Transcription factor EKLF (Erythroid Krüppel-Like Factor) belongs to the group of Krüppellike factors, which regulate proliferation, differentiation, development and apoptosis of mammalian cells. EKLF factor is present in erythroid cells, where it participates in regulation of hematopoiesis, expression of genes encoding transmembrane proteins (including blood group antigens), and heme biosynthesis enzymes. It is also a key factor in downregulation of γ-globins and activation of ß-globin gene expression. The EKLF factor consists of two domains: proline-rich transactivation domain and DNA-binding domain containing three zinc finger motifs, which recognize DNA. EKLF can act as a transcription activator (for example in the case of ß-globin gene) or repressor, which depends on the type of posttranslational modification (phosphorylation, SUMOylation, ubiquitination and acetylation). Mutations in the gene encoding EKLF may cause hemoglobinopathies, such as hereditary persistence of fetal hemoglobin and ß-thalassemia intermedia, and congenital dyserythropoietic anemia type IV, which is a hematopoietic disorder. These changes may impede invasion of red blood cells by malaria merozoites and cause faster removal of invaded erythrocytes. In addition, mutations in KLF1 may decrease the number of erythrocyte surface antigens that belong to blood group systems such as MN, P1PK, Lutheran, Duffy, Diego and OK. Such antigens can be receptors for protozoans (such as Plasmodium falciparum or Plasmodium vivax), bacteria (like uropathogenic strains of Escherichia coli, Neisseria meningitidis), and toxins (Shiga toxins), which may cause several dangerous diseases including malaria, pyelonephritis, hemorrhagic colitis, hemolytic uremic syndrome (HUS) and meningitis. Here, we propose a hypothesis on possible liaisons between mutations in the gene encoding EKLF and resistance to pathogens.

C-arm assisted zygoma fracture repair: a critical analysis of the first 20 cases.

PURPOSE: Currently used open reduction and internal fixation techniques of zygoma fracture repair are not optimal. Surgical exposure of those sites needed to allow for accurate reduction and for rigid fixation has a high possibility of negative consequences. The objective of the present study was to present a single-incision, single-fixation site zygoma fracture repair technique using a single zygoma c-arm view to quantitatively determine its accuracy, complication rate, and practical aspects in a clinical series. MATERIALS AND METHODS: In a prospective study, consecutive patients with isolated, unilateral, displaced zygoma fractures not requiring orbital floor exploration treated using a c-arm-assisted repair technique at the author's institution from 2009 to 2011 were included. Objective outcomes assessed included accuracy of zygoma realignment (on postoperative computed tomogram), ocular globe projection symmetry (using a Naugle exophthalmometer), complication rate, and operative duration. Statistical analysis was performed using the Student t test. RESULTS: Twenty patients were included. Differences in zygoma projection, width, and height between the uninjured and repaired sides of the face were clinically noteworthy (>3 mm) in the first patient only. Average differences of these parameters for all 20 patients were clinically and statistically insignificant. Differences in ocular globe projection between the uninjured and repaired sides of the face for each patient were no greater than 2 mm. The average difference in globe projection for all 20 patients was also clinically and statistically insignificant. No major complications occurred, and the average operative duration was 76 minutes. CONCLUSIONS: The present study shows that the c-arm-assisted zygoma fracture repair technique is accurate, has a low complication rate, can be performed quickly, and has a relatively low level of difficulty.

Simple computed tomography-based calculations of orbital floor fracture defect size are not sufficiently accurate for clinical use.

PURPOSE: The precise computed tomography-based calculation of the size of an orbital floor (OF) fracture defect is tedious and time-consuming. The aims of this study were to evaluate the accuracy of simple, rapid methods of calculating OF fracture defect size and to determine their suitability for clinical use. MATERIALS AND METHODS: A retrospective review of the electronic medical records of patients with OF fractures presenting to Baylor Scott and White Hospital between October 2009 and April 2013 was performed. True OF defect sizes (the outcome variable) were calculated using a previously validated formula, on the basis of measurements obtained from coronally reformatted thin (<3-mm) axial computed tomographic images. Estimated OF defect sizes (the predictor variable) were calculated using geometric area formulas, assuming that the defect approximated the shape of an ellipse, circle, square, or rectangle on the basis of measurements obtained from coronal and sagittal computed tomographic images. Accuracy, sensitivity, specificity, and negative and positive predictive values in declaring a defect critical were determined for each method. RESULTS: Ninety-nine patients with OF fractures were identified (69 men, 30 women; mean age = 46.9 years); 55 patients had a true OF defects of critical (≥2 cm(2)) or greater size. Geometric formulas showed ranges of accuracy (0.76 to 0.93), sensitivity (0.62 to 1.0), and specificity (0.63 to 0.91). The accuracy of defect size approximation using the area of an ellipse was highest. CONCLUSIONS: The geometric formulas estimated OF defect area with good but, in the authors' opinion, clinically unacceptable accuracy. Although highly sensitive, the formulas lacked specificity and tended to overestimate true defect sizes in most cases. Using rapid, simple geometric methods to assess the sizes of OF defects may lead to inappropriate surgical decisions. Thus, the most accurate estimation of OF defect size still requires the calculation of average defect length from coronal computed tomographic images, knowledge of slice thickness, and knowledge of the number of slices involved.

Contralateral Dorsally Based Septal Mucoperichondrial Page Flap, for Nasal Lining Reconstruction.

BACKGROUND: Although excellent techniques for reconstruction of nasal cover and support have been described, reconstruction of large nasal lining defects remains a challenge. Currently available methods have several shortcomings including limited size, airway obstruction, need for multiple procedures, and creation of septal fistulae. METHODS: We present 2 cases of nasal lining reconstruction for the lower and mid nasal vaults using a contralateral dorsally based septal mucoperichondrial page flap transposed dorsal to nasal septum and superficial to the ipsilateral upper lateral cartilage. Appropriate, uncomplicated, reconstruction of nasal lining was confirmed in both cases. DISCUSSION: In the lower vault, the flap permits a single-stage reconstruction, without obstruction of the external nasal valve or compromise of caudal septal support. In the mid-vault, the flap allows for reconstruction without creation of a septal fistula or narrowing of the internal nasal valve. In both locations, the size of the flap may be increased by extending it onto nasal floor, and support may be added by combining the flap with septal cartilage. CONCLUSION: The contralateral dorsally based septal mucoperichondrial flap is a useful option for reconstruction of lower and mid nasal vault lining defects.

[Blood groups - minuses and pluses. Do the blood group antigens protect us from infectious diseases?]. / Grupy krwi-minusy i plusy. Czy antygeny grupowe krwi chronia nas przed chorobami zakaznymi?

Human blood can be divided into groups, which is a method of blood classification based on the presence or absence of inherited erythrocyte surface antigens that can elicit immune response. According to the International Society of Blood Transfusion, there are 341 blood group antigens collected in 35 blood group systems. These antigens can be proteins, glycoproteins or glycosphingolipids, and function as transmembrane transporters, ion channels, adhesion molecules or receptors for other proteins. The majority of blood group antigens is present also on another types of cells. Due to their localization on the surface of cells, blood group antigens can act as receptors for various pathogens or their toxins, such as protozoa (malaria parasites), bacteria (Helicobacter pylori, Vibrio cholerae and Shigella dysenteriae) and viruses (Noroviruses, Parvoviruses, HIV). If the presence of group antigen (or its variant which arised due to mutation) is beneficial for the host (e.g. because pathogens are not able to bind to the cells), the blood group may become a selection trait, leading to its dissemination in the population exposed to that pathogen. There are thirteen blood group systems that can be related to pathogen resistance, and it seems that the particular influence was elicit by malaria parasites. It is generally thought that the high incidence of blood groups such as O in the Amazon region, Fy(a-b-) in Africa and Ge(-) in Papua-New Guinea is the result of selective pressure from malaria parasite. This review summarizes the data about relationship between blood groups and resistance to pathogens.