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Antlion larvae are fluid-feeding ambush predators that feed on arthropods trapped in their funnel-shaped pits built in sandy habitats; however, details are lacking about their feeding mechanism. Here, we tested the hypothesis that the antlion, Myrmeleon crudelis, has adaptations that facilitate fluid feeding in sandy habitats. We measured contact angles of water droplets and used the capillary-rise technique to assess mouthpart wettability. A structural organization was discovered that provides a hydrophobic-hydrophilic wetting dichotomy that simultaneously supports self-cleaning and fluid uptake and is enabled by antiparallel movements of the maxillae. The mouthparts also are augmented by their mechanical properties, including maxillae and mandible tips that might be heavily sclerotized, as determined by confocal microscopy, which likely facilitates piercing prey. Our findings provide insight into how antlion larvae have overcome the challenges of fluid feeding in sandy habitats, which probably contributed to their success and widespread distribution., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2022. Published by The Company of Biologists Ltd.)

Introduction: There is evidence that electroacupuncture (EA) acts through the modulation of brain activity, but little is known about its influence on corticospinal excitability of the primary motor cortex (M1)., Objective: To investigate the influence of EA parameters on the excitability of M1 in healthy individuals., Methods: A parallel, double blind, randomized controlled trial in healthy subjects, evaluating the influence of an EA intervention on M1 excitability. Participants had a needle inserted at LI4 in the dominant hand and received electrical stimulation of different frequencies (10 or 100 Hz) and amplitude (sensory or motor threshold) for 20 min. In the control group, only a brief (30 s) electrical stimulation was applied. Single and paired pulse transcranial magnetic stimulation coupled with electromyography was applied before and immediately after the EA intervention. Resting motor threshold, motor evoked potential, short intracortical inhibition and intracortical facilitation were measured., Results: EA increased corticospinal excitability of M1 compared to the control group only when administered with a frequency of 100 Hz at the sensory threshold ( p  < 0.05). There were no significant changes in the other measures., Conclusion: The results suggest that EA with an intensity level at the sensorial threshold and 100 Hz frequency increases the corticospinal excitability of M1. This effect may be associated with a decrease in the activity of inhibitory intracortical mechanisms., Trial Registration Number: U1111-1173-1946 (Registro Brasileiro de Ensaios Clínicos; http://www.ensaiosclinicos.gov.br/).

Background: Bioprosthetic heart valve has limited durability and lower long-term performance especially in rheumatic heart disease (RHD) patients that are often subject to multiple redo operations. Minimally invasive procedures, such as transcatheter valve-in-valve (ViV) implantation, may offer an attractive alternative, although data is lacking. The aim of this study was to evaluate the baseline characteristics and clinical outcomes in rheumatic vs. non-rheumatic patients undergoing ViV procedures for severe bioprosthetic valve dysfunction. Methods: Single center, prospective study, including consecutive patients undergoing transcatheter ViV implantation in aortic, mitral and tricuspid position, from May 2015 to September 2020. RHD was defined according to clinical history, previous echocardiographic and surgical findings. Results: Among 106 patients included, 69 had rheumatic etiology and 37 were non-rheumatic. Rheumatic patients had higher incidence of female sex (73.9 vs. 43.2%, respectively; p = 0.004), atrial fibrillation (82.6 vs. 45.9%, respectively; p < 0.001), and 2 or more prior surgeries (68.1 vs. 32.4%, respectively; p = 0.001). Although, device success was similar between groups (75.4 vs. 89.2% in rheumatic vs. non-rheumatic, respectively; p = 0.148), there was a trend toward higher 30-day mortality rates in the rheumatic patients (21.7 vs. 5.4%, respectively; p = 0.057). Still, at median follow-up of 20.7 [5.1-30.4] months, cumulative mortality was similar between both groups ( p = 0.779). Conclusion: Transcatheter ViV implantation is an acceptable alternative to redo operations in the treatment of patients with RHD and severe bioprosthetic valve dysfunction. Despite similar device success rates, rheumatic patients present higher 30-day mortality rates with good mid-term clinical outcomes. Future studies with a larger number of patients and follow-up are still warranted, to firmly conclude on the role transcatheter ViV procedures in the RHD population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lopes, Rosa, Palma, Vieira, Fernandes, de Santis, Spina, Fonseca, de Sá Marchi, Abizaid, de Brito, Tarasoutchi, Sampaio and Ribeiro.)

Background: Despite treatment with effective antimalarial drugs, the mortality rate is still high in severe cases of the disease, highlighting the need to find adjunct therapies that can inhibit the adhesion of Plasmodium falciparum-infected erythrocytes (Pf-iEs)., Objectives: In this context, we evaluated a new heparan sulfate (HS) from Nodipecten nodosus for antimalarial activity and inhibition of P. falciparum cytoadhesion and rosetting., Methods: Parasite inhibition was measured by SYBR green using a cytometer. HS was assessed in rosetting and cytoadhesion assays under static and flow conditions using Chinese hamster ovary (CHO) and human lymphatic endothelial cell (HLEC) cells expressing intercellular adhesion molecule-1 (ICAM1) and chondroitin sulfate A (CSA), respectively., Findings: This HS inhibited merozoite invasion similar to heparin. Moreover, mollusk HS decreased cytoadherence of P. falciparum to CSA and ICAM-1 on the surface of endothelial cells under static and flow conditions. In addition, this glycan efficiently disrupted rosettes., Conclusions: These findings support a potential use for mollusk HS as adjunct therapy for severe malaria.

The anticoagulant and antithrombotic properties of three structurally correlated sea urchin-derived 3-linked sulfated α-glycans and their low molecular-weight derivatives were screened comparatively through various in vitro and in vivo methods. These methods include activated partial thromboplastin time, the inhibitory activity of antithrombin over thrombin and factor Xa, venous antithrombosis, the inhibition of platelet aggregation, the activation of factor XII, and bleeding. While the 2-sulfated fucan from Strongylocentrotus franciscanus was observed to be poorly active in most assays, the 4-sulfated fucan from Lytechinus variegatus , the 2-sulfated galactan from Echinometra lucunter and their derivatives showed multiple effects. All marine compounds showed no capacity to activate factor XII and similar low bleeding tendencies regardless of the dose concentrations used to achieve the highest antithrombotic effect observed. The 2-sulfated galactan showed the best combination of results. Our work improves the background about the structure-function relationship of the marine sulfated glycans in anticoagulation and antithrombosis. Besides confirming the negative effect of the 2-sulfated fucose and the positive effect of the 2-sulfated galactose on anticoagulation in vitro, our results also demonstrate the importance of this set of structural requirements on antithrombosis in vivo, and further support the involvement of high-molecular weight and 4-sulfated fucose in both activities.

Fucosylated chondroitin sulfate (FucCS) is a potent anticoagulant polysaccharide extracted from sea cucumber. Its anticoagulant activity is attributed to the presence of unique branches of sulfated fucose. Although this glycosaminoglycan exerts an antithrombotic effect following oral administration, high doses are necessary to achieve the maximum effect. The diminished activity of FucCS following oral administration is likely due to its degradation in the gastrointestinal tract and its limited ability to cross the intestinal cell membranes. The latter aspect is particularly difficult to overcome. However, gastro-resistant tablet formulation may help limit the degradation of FucCS in the gastrointestinal tract. In the present work, we found that the oral administration of FucCS as gastro-resistant tablets produces a more potent and prolonged anticoagulant effect compared with its administration as an aqueous solution, with no significant changes in the bleeding tendency or arterial blood pressure. Experiments using animal models of arterial thrombosis initiated by endothelial injury demonstrated that FucCS delivered as gastro-protective tablets produced a potent antithrombotic effect, whereas its aqueous solution was ineffective. However, there was no significant difference between the effects of FucCS delivered as gastro-resistant tablets or as aqueous solution in a venous thrombosis model, likely due to the high dose of thromboplastin used. New oral anticoagulants tested in these experimental models for comparison showed significantly increased bleeding tendencies. Our study provides a framework for developing effective oral anticoagulants based on sulfated polysaccharides from marine organisms. The present results suggest that FucCS is a promising oral anticoagulant.

Snake envenoming is an important public health problem around the world, particularly in tropics. Beyond deaths, morbidity induced by snake venoms, such as myotoxicity, is of pivotal consequence to population. Bothrops jararacussu is the main venomous snake in southeast region of Brazil, and particularly presents strong myotoxic effect. The only available therapy, antibothropic antivenom, poorly affects venom-induced myotoxicity. The aim of this study is to assess the ability of fucosylated chondroitin sulfate (fucCS), a glycosaminoglycan with anticoagulant and antithrombotic properties, and its derivatives to inhibit toxic activities of B. jararacussu crude venom and its isolated toxins, named bothropstoxins (BthTX-I and BthTX-II). The in vitro myotoxic activities induced by crude venom, by BthTX-I alone and by toxins together were abolished by fucCS. Carboxyl reduction (fucCS-CR) kept this ability whereas defucosilation (defucCS) abrogates myoprotection. We observed the same pattern in the response of these polysaccharides in antagonizing the increase in plasma creatine kinase (CK) levels, the reduction of skeletal muscle CK content and the rise of myeloperoxidase (MPO) activity induced by crude venom and isolated toxins. FucCS inhibited edematogenic activity and partially prevented the reduction of total leukocytes in blood when pre-incubated with crude venom. Furthermore, the venom procoagulant effect was completely antagonized by increasing concentrations of fucCS, although this polyanion could stop neither the tail bleeding nor the skin hemorrhage induced by Bothrops jararaca venom. The B. jararacussu phospholipase, hyaluronidase, proteolytic and collagenase activities were inhibited in vitro. The results suggest that fucCS could be able to interact with both toxins, and it is able to inhibit BthTX-II phospholipase activity. Light microscopy of extensor digitorum longus muscle (EDL) muscle showed myoprotection by fucCS, once necrotic areas, edema and inflammatory cells were all decreased as compared to venom injection alone. Altogether, data show that fucCS was able to inhibit myotoxicity and inflammation induced by B. jararacussu venom and its phospholipase toxins, BthTX-I and BthTX-II. Thus, fucosylated chondroitin sulfate is a new polyanion with potential to be used as an adjuvant in the treatment of snakebites in the future., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Heparanase-1 activation, albuminuria, and a decrease in glomerular heparan sulfate (HS) have been described in diabetic nephropathy (DN). Glycosaminoglycan (GAG)-based drugs have been shown to have renoprotective effects in this setting, although recent trials have questioned their clinical effectiveness. Here, we describe the effects of fucosylated chondroitin sulfate (FCS), a novel GAG extracted from a marine echinoderm, in experimentally induced DN compared to a widely used GAG, enoxaparin (ENX)., Methods: Diabetes mellitus (DM) was induced by streptozotocin in male Wistar rats divided into three groups: DM (without treatment), FCS (8 mg/kg), and ENX (4 mg/kg), administered subcutaneously. After 12 weeks, we measured blood glucose, blood pressure, albuminuria, and renal function. The kidneys were evaluated for mesangial expansion and collagen content. Immunohistochemical quantifications of macrophages, TGF-β, nestin and immunofluorescence analysis of heparanase-1 and glomerular basement membrane (GBM) HS content was also performed. Gene expression of proteoglycan core proteins and enzymes involved in GAG assembly/degradation were analyzed by TaqMan real-time PCR., Results: Treatment with GAGs prevented albuminuria and did not affect the glucose level or other functional aspects. The DM group exhibited increased mesangial matrix deposition and tubulointerstitial expansion, and prevention was observed in both GAG groups. TGF-β expression and macrophage infiltration were prevented by the GAG treatments, and podocyte damage was halted. The diabetic milieu resulted in the down-regulation of agrin, perlecan and collagen XVIII mRNAs, along with the expression of enzymes involved in GAG biosynthesis. Treatment with FCS and ENX positively modulated such changes. Heparanase-1 expression was significantly reduced after GAG treatment without affecting the GBM HS content, which was uniformly reduced in all of the diabetic animals., Conclusions: Our results demonstrate that the administration of FCS prevented several pathological features of ND in rats. This finding should stimulate further research on GAG treatment for this complication of diabetes.

Pharmaceutical grade heparins from porcine intestine and bovine lung consist mainly of repeating tri-sulfated units, of the disaccharide →4-α-IdoA2S-1→4-α-GlcNS6S-1→. Heparin preparations from bovine intestine, in contrast, are more heterogeneous. Nuclear magnetic resonance (NMR) and disaccharide analysis after heparinase digestions show that heparin from bovine intestine contains α-glucosamine with significant substitutive variations: 64% are 6-O-sulfated and N -sulfated, as in porcine intestinal heparin while 36% are 6-desulfated. Desulfated α-iduronic acid units are contained in slightly lower proportions in bovine than in porcine heparin. NMR data also indicate N-, 3- and 6-trisulfated α-glucosamine (lower proportions) and α-GlcNS-1→4-α-GlcA and α-IdoA2S-1→4-α-GlcNAc (higher amounts) in bovine than in porcine heparin. Porcine and bovine heparins can be fractionated by anion exchange chromatography into three fractions containing different substitutions on the α-glucosamine units. Each individual fraction shows close disaccharide composition and anticoagulant activity, regardless of their origin (bovine or porcine intestine). However, these two heparins differ markedly in the proportions of the three fractions. Interestingly, fractions with the typical heparin disaccharides of porcine intestine are present in bovine intestinal heparin. These fractions contain high in vitro anticoagulant activity, reduced antithrombotic effect and high bleeding tendency. These observations indicate that the prediction of haemostatic effects of heparin preparations cannot rely exclusively on structural analysis and anticoagulant assays in vitro . Minor structural components may account for variations on in vivo effects. In conclusion, we suggest that pharmaceutical grade bovine intestinal heparin, even after purification procedures, is not an equivalent drug to porcine intestinal heparin.

Increasing reports of bleeding and peri- or post-operative blood dyscrasias in Brazil were possibly associated with the use of heparin from bovine instead of porcine intestine. These two pharmaceutical grade heparins were analysed for potential differences. NMR analyses confirmed that porcine heparin is composed of mainly trisulfated disaccharides -->4-alpha-IdoA2S-1-->4-alpha-GlcNS6S-1-->. Heparin from bovine intestine is also composed of highly 2-sulfated alpha-iduronic acid residues, but the sulfation of the alpha-glucosamine units vary significantly: approximately 50% are 6- and N -disulfated, as in porcine heparin, while approximately 36% are 6-desulfated and approximately 14% N -acetylated. These heparins differ significantly in their effects on coagulation, thrombosis and bleeding. Bovine heparin acts mostly through factor Xa. Compared to porcine heparin on a weight basis, bovine heparin exhibited approximately half of the anticoagulant and antithrombotic effects, but similar effect on bleeding. These two heparins also differ in their protamine neutralisation curves. The doses of heparin from bovine intestine required for effective antithrombotic protection and the production of adverse bleeding effects are closer than those for porcine heparin. This observation may explain the increasing bleeding observed among Brazilian patients. Our results suggest that these two types of heparin are not equivalent drugs.

We report the effects of a chemically oversulfated chondroitin sulfate and a naturally fucosylated chondroitin sulfate on the coagulation system. The former has been recently identified as a contaminant of heparin preparations and the latter has been proposed as an alternative anticoagulant. The mechanism of action of these polymers on coagulation is complex and target different components of the coagulation system. They have serpin-independent anticoagulant activity, which preponderates in plasma. They also have serpin-dependent anticoagulant activity but differ significantly in the target coagulation protease and preferential serpin. Their anticoagulant effects differ even more markedly when tested as inhibitors of coagulation proteases using plasma as a source of serpins. It is possible that the difference is due to the high availability of fucosylated chondroitin sulfate whereas oversulfated chondroitin sulfate has strong unspecific binding to plasma protein and low availability for the binding to serpins. When tested using a venous thrombosis experimental model, oversulfated chondroitin sulfate is less potent as an antithrombotic agent than fucosylated chondroitin sulfate. These highly sulfated chondroitin sulfates activate factor XII in in vitro assays, based on kallikrein release. However, only fucosylated chondroitin sulfate induces hypotension when intravenously injected into rats. In conclusion, the complexity of the regulatory mechanisms involved in the action of highly sulfated polysaccharides in coagulation requires their analysis by a combination of in vitro and in vivo assays. Our results are relevant due to the urgent need for new anticoagulant drugs or alternative sources of heparin.

Sulfated polysaccharides from marine invertebrates have well-defined structures and constitute a reliable class of molecules for structure-activity relationship studies. We tested the effects of two of these polysaccharides, namely a sulfated fucan and a fucosylated chondroitin sulfate, on coagulation, thrombosis and bleeding. The compounds share similar 2,4-disulfated fucose units, which are required for high anticoagulant activity in this class of polymer. These residues occur either as branches in fucosylated chondroitin sulfate or as components of the linear chain in the sulfated fucan. These polysaccharides possess anticoagulant activity but differ significantly in their mechanisms of action. The fucosylated chondroitin sulfate inhibits thrombin by heparin cofactor II, whereas sulfated fucan inhibits thrombin by both antithrombin and heparin cofactor II. In addition, these polysaccharides also have serpin-independent anticoagulant activities. Fucosylated chondroitin sulfate, but not sulfated fucan, activates factor XII. As a result of the complex anticoagulant mechanism, the invertebrate polysaccharides differ in their effects on experimental thrombosis. For instance, the sulfated fucan inhibits venous thrombosis at lower doses than fucosylated chondroitin sulfate. In contrast, fucosylated chondroitin sulfate is significantly more potent than sulfated fucan in arterial thrombosis. Finally, fucosylated chondroitin sulfate increases bleeding, while sulfated fucan has only a discrete effect. In conclusion, the location of 2,4-disulfated fucose units in the polysaccharide chains dictates the effects on coagulation, thrombosis and bleeding.

Evaluated were the anticoagulant and antithrombotic activities, and bleeding effect of two chemically sulfated polysaccharides, obtained from citric pectin, with different average molar masses. Both low-molecular-weight (Pec-LWS, 3,600 g/mol) and high-molecular-weight sulfated pectins (Pec-HWS, 12,000 g/mol) had essentially the same structure, consisting of a (1-->4)-linked alpha-D-GalpA chain with almost all its HO-2 and HO-3 groups substituted by sulfate. Both polysaccharides had anticoagulant activity in vitro, although Pec-HWS was a more potent antithrombotic agent in vivo, giving rise to total inhibition of venous thrombosis at a dose of 3.5 mg/kg body weight. Surprisingly, in contrast with heparin, Pec-HWS and Pec-LWS are able to directly inhibit alpha-thrombin and factor Xa by a mechanism independent of antithrombin (AT) and/or heparin co-factor II (HCII). Moreover, Pec-HWS provided a lower risk of bleeding than heparin at a dose of 100% effectiveness against venous thrombosis, indicating it to be a promising antithrombotic agent.

This paper presents the traditions of assisted childbirth in the Brazilian state of Bahia in the 19th Century and develops the hypothesis that two obstetrical traditions coexisted in the capital, Salvador, namely the doctor-midwives--who used technical resources and knowledge acquired from obstetrics as a medical specialty--and the traditional midwives, whose know-how was purely of an empirical-sensorial nature. Despite all efforts employed by the doctors to win over the confidence of Bahian families, the midwives continued to be predominant in the art of 'delivering' children and treating female illnesses. The analysis focuses on the social and professional segments that were active in assisted birth; the role of the Bahian College of Medicine (Faculdade de Medicina da Bahia) in the training and certification of midwives and the use of newspapers as a way to legitimize the doctor-midwives; it also discusses the scant coverage of the midwives in these media.

We compared sulfated galactans (SGs) from two species of red algae using specific coagulation assays and experimental models of thrombosis. These polysaccharides have an identical saccharide structure and the same size chain, but with slight differences in their sulfation patterns. As a consequence of these differences, the two SGs differ in their anticoagulant and venous antithrombotic activities. SG from G. crinale exhibits procoagulant and prothrombotic effects in low doses (up to 1.0 mg/kg body weight), but in high doses (>1.0 mg/kg) this polysaccharide inhibits both venous and arterial thrombosis in rats and prolongs ex-vivo recalcification time. In contrast, SG from B. occidentalis is a very potent anticoagulant and antithrombotic compound in low doses (up to 0.5 mg/kg body weight), inhibiting venous experimental thrombosis and prolonging ex-vivo recalcification time, but these effects are reverted in high doses. Only at high doses (>1.0 mg/kg) the SG from B. occidentalis inhibits arterial thrombosis. As with heparin, SG from G. crinale does not activate factor XII, while the polysaccharide from B. occidentalis activates factor XII in high concentrations, which could account for its procoagulant effect at high doses on rats. Both SGs do not modify bleeding time in rats. These results indicate that slight differences in the proportions and/or distribution of sulfated residues along the galactan chain may be critical for the interaction between proteases, inhibitors and activators of the coagulation system, resulting in a distinct pattern in anti- and procoagulant activities and in the antithrombotic action.

Fucosylated chondroitin sulfate is a potent anticoagulant polysaccharide extracted from sea cucumber. Its anticoagulant activity is attributed to the presence of sulfated fucose branches. We have shown that intravascular injection of fucosylated chondroitin sulfate inhibits thrombus formation in a venous and an arterial shunt model in rats. Since this compound resists digestion by enzymes that cleave mammalian glycosaminoglycans, we investigated the possibility that fucosylated chondroitin sulfate might be absorbed after oral administration. In fact, after oral administration of fucosylated chondroitin sulfate to rats, we observed a dose-dependent increase in the plasma anticoagulant activity, as assessed by assays for activated partial thromboplastin time (aPTT) and thrombin time (TT) (about 3- and 5-fold, respectively) and by anti-IIa activity. Furthermore, animals receiving daily oral doses of this glycosaminoglycan showed a decrease in thrombus weight on experimental models of venous and arterial shunt thrombosis. This antithrombotic action clearly has a strong relationship with anticoagulant activity. Similar doses of heparin administered orally had no effect on the plasma anticoagulant activity or on the thrombus weight. Finally, we observed that fucosylated chondroitin sulfate given orally to rats did not modify the bleeding time. Overall, our results indicate that fucosylated chondroitin sulfate is absorbed after oral administration and could become a promising oral anticoagulant.

The main objective of this paper is the characterization of the spectroscopic properties of new materials that are prospective laser media. This approach allows for the comparison of the properties of the Cr3+ in different environments. Here, we have studied the photoluminescence and optical absorption of Cs2NaScF6:Cr3+ single crystals. On the basis of near-infrared luminescence measurements at 2, 77, and 300 K the observed lines originated from the Cr3+-centres were associated with the 4T2(4F) --> 4A2(4F) transition and the lifetimes were obtained. In spite of the quenching observed as a function of temperature at least 10% of the 2 K emission intensity for Cs2NaScF6 doped with 1% of Cr3+ remains at room temperature. Besides, the 2 K emission broad band could be well described in terms of normal modes of the octahedral complex [CrF6]3-, and the Racah and crystal-field parameters calculated.

The purpose of this study was to investigate the sagittal and vertical effects on the maxilla induced by surgically assisted rapid palatal expansion. Twenty patients (average age, 25.6 years) who required a surgically assisted rapid palatal expansion procedure were available for this study. Each patient was banded with a Haas-type palatal expander, maxillary surgery was performed, and the expander was activated. Presurgical and postexpansion lateral cephalograms were taken for each patient. The measurements of SNA, Frankfort horizontal-nasion-A point, sella-nasion-palatal plane, A-point-nasion-perpendicular (in millimeters), 1-nasion-A-point, 1-sella-nasion, 1-nasion-perpendicular (in millimeters) were made on each cephalogram, and the presurgical and postexpansion tracings were superimposed on the cranial base to determine the changes in the anterior nasal spine and posterior nasal spine positions. Results showed that from the presurgical cephalogram to the postexpansion cephalogram SNA, Frankfort horizontal-nasion-A point and A-point-nasion-perpendicular had a mean increase of 0.60 degrees (P <.05), 0.65 degrees (P <.05), and 0.55 mm (P <.05), respectively; 1-nasion-A-point decreased 2.18 degrees (P <.05) and 1-sella-nasion decreased 1.53 degrees (P <.05). No significant maxillary vertical displacement was noted from the first cephalogram to the second. In conclusion, surgically assisted RPE did not significantly affect the maxilla vertically; however, it did induce a slight forward movement of the maxilla and a slight retroclination of the maxillary incisors sagittally (P <.05).

Preprosthetic surgery is a rapidly changing area of dentistry. A knowledge of the range, capabilities, and limitations of the commonly used surgical procedures is a must for anyone treating a patient who will receive a complete denture prosthesis. It cannot be overemphasized that the establishment of a clear treatment plan and close coordination of all parties involved in the reconstructive effort are essential to achieve the best overall result.

Treatment of skeletally mature patients is often complicated by inadequately treated or undiagnosed transverse skeletal discrepancy. This report emphasizes diagnosis of transverse maxillo-mandibular discrepancy and describes recommendations for treatment. Proper treatment strategy must consider the type and magnitude of transverse deficiency, patient's growth status, dentofacial esthetics, stability factors, and periodontal tissue health. Indications for surgically assisted maxillary expansion are listed, and the recommended surgical technique to improve frontal dentofacial esthetics, provide better stability, and enhance long-term periodontal health is described. Specific modifications in surgical technique to help prevent postoperative complications are included. New recommendations for sequencing, timing, and correction of transverse deficiency are presented.

A small number of patients with the phenotypic features of Noonan syndrome have also developed giant cell lesions of the jaws similar to those seen in cherubism. This case report describes an individual with the features of the recently described Noonan-like/multiple giant cell lesion syndrome. Previously reported cases and issues relative to diagnosis and management are considered.

Accurate prediction of postsurgical function and esthetics of the nose and upper lip requires an understanding of the relationship between maxillary surgical movement and soft tissue change. Thirty-two patients underwent Le Fort I osteotomies, some with concomitant mandibular procedures. Preoperative, postoperative, and 1-year postsurgical data derived from cephalometric and nasolabial cast analysis were compared to assess skeletodental changes, soft tissue changes, and stability. A multiple stepwise regression (including age, gender, alar cinch suture, V-Y closure, and contouring of the anterior nasal spine as variables) indicated that accurate prediction equations could be formulated, particularly if the patients were grouped by vector-specific maxillary movements. In general, the base of the nose widened in all patients regardless of the vector of surgical maxillary movement. An associated shortening of the nose was found. The nasolabial angle decreased or remained constant in most patients. The upper lip widened and lengthened at the philtral columns. Narrow noses widened more than did broad noses and alar cinch suturing widened the alar base even more. Results indicated that soft tissue changes associated with maxillary surgery may be more affected by the position of the soft tissue incision and methods used in closure than by the surgically induced hard tissue change.

The transmandibular implant is specifically designed for the reconstruction and rehabilitation of the severely atrophic mandible utilizing an extraoral approach. The unique design and surgical protocol of the transmandibular system have proven to be predictable and successful. The indications, implant design and materials, surgical technique, advantages, and disadvantages of the transmandibular system are presented in this article.

The Dentofacial Deformity Program of the University of Michigan was established in 1984 to provide a consulting service for the diagnosis, treatment recommendations, and management of patients with dentofacial deformities. This program was designed as a service commitment for the patient, referring doctors, and the medical and dental communities. Educational and research aspects of the program provide benefits for orthodontic and oral and maxillofacial surgery graduate students, and the dental school faculty. The organization, data analysis, and education, research, and service benefits of this program are discussed.

Le Fort I osteotomies frequently involve impaction of the maxilla into the nasal cavity, potentially affecting nasal form. It has been speculated that a concomitant change in nasal function may occur. The purpose of this study was to determine if there is an association between maxillary position and nasal function and to evaluate the influence of Le Fort I surgery on nasal function. Presurgical and postsurgical nasal resistance and percent nasal respiration were compared in 36 patients. Results indicated a mean change in nasal resistance 1 year after surgery, but mean percent nasal respiration did not change significantly. No prediction could be made for any patient relative to the effect of maxillary surgery on the nasal function parameters. No consistent association could be found between the amount or direction of maxillary surgical movement or the position of the maxilla and nasal respiration.

Fifteen edentulous patients with complaints regarding denture comfort and/or function were treated with the transmandibular implant. All patients were restored with conventional maxillary dentures opposed by implant-supported removable prostheses. Two to 4 years after surgery, these patients were evaluated for vertical and horizontal maxillary bone loss with a radiographic analysis developed by the authors. With this technique, attention was focused on vertical alveolar ridge resorption in the anterior maxilla. Although the sample size was small, the findings from this study indicate that vertical bone loss in the anterior maxilla does occur when a maxillary denture is opposed by an implant-supported overdenture. Comparison of these results with a previous study that evaluated anterior maxillary resorption when a complete maxillary denture opposed natural mandibular anterior teeth and a distal extension removable partial denture demonstrated no statistically significant difference.

The purpose of this retrospective clinical study was to determine the efficacy of allogeneic bone for secondary alveolar cleft osteoplasty. Twenty-four patients with unilateral cleft lip and palate treated with allogeneic bone grafts were examined by a surgeon, orthodontist, and prosthodontist 20 to 47 months after surgery. Radiographic and clinical examination of the periodontal status of the teeth adjacent to the cleft and their antimeres were compared for differences with Student's t test and the Wilcoxon test. Radiographs indicated complete bone bridging in 21 patients. Two of the remaining three patients had a 1-mm radiolucent gap in the cleft site. The third patient had a 6-mm-wide radiolucency and recurrence of an oronasal fistula which was regrafted with autogenous bone. No statistically significant differences between the cleft and noncleft tooth antimeres were found for plaque, gingivitis, bleeding, sulcus depth, or level of attachment. A statistically significant difference in the amount of attached gingiva was found between the cleft and noncleft tooth antimeres. Nine patients with missing lateral incisor teeth avoided prosthetic replacement by orthodontic movement of the canine tooth into the grafted edentulous space. In those cases where the maxillary canine was unerupted at the time of the surgery, eruption into the graft occurred. Stability of the maxillary segments was sufficient to allow prosthodontic restoration with a fixed partial denture in those cases where it was indicated.

A surgical technique for the bone graft repair of alveolar clefts is described, and an evaluation of the conditions of 30 patients who have undergone that procedure is reported. Evaluation was made specifically for the preoperative and postoperative presence of oronasal fistula, postoperative eruption of previously unerupted teeth into the graft, soft and hard tissue periodontal status, and radiographic evidence of bone fill in the previous cleft defect resulting in alveolar segmental stabilization.

A case of multiosseous osteosarcoma in a 15-year-old girl is presented. Neoplastic foci were initially diagnosed in the right ilium and left mandible. The clinical course was complicated by pregnancy and chemotherapeutic side effects. Postmortem examination revealed multiple tumor emboli in the lungs. The literature concerning metastatic and multicentric origins of multiosseous osteosarcomas is reviewed. The case presented probably represents mandibular metastasis from the ilium.

This study examines the short-term stability of bimaxillary surgery following Le Fort I impaction with simultaneous bilateral sagittal split osteotomies and mandibular advancement using two standard techniques of postsurgical fixation. Fifteen adults had skeletal plus dental maxillomandibular fixation, and fifteen adults had rigid internal fixation using bone plates in the maxilla and bicortical bone screws between the proximal and distal segments in the mandible. The group with rigid internal fixation did not undergo maxillomandibular fixation. Radiographic cephalograms were analyzed during the postsurgical period to evaluate skeletal and dental stability. There was no statistical difference in postsurgical stability with rigid internal fixation or skeletal plus dental maxillomandibular fixation other than the vertical position of the maxillary molar; the skeletal plus dental maxillomandibular fixation group had a significant amount of postsurgical intrusion of the maxillary molar when compared with the rigid internal fixation group. Although the other measures showed no statistically significant difference between the experimental groups, the amount of variability in postsurgical stability in the group with skeletal plus dental maxillomandibular fixation was greater than that found in the group with rigid internal fixation.

This study examined the immediate and postsurgical changes in the hard and soft tissues of the chin after advancement genioplasty by means of oblique osteotomy of the mandibular symphysis. Twenty-three patients who had undergone this procedure were evaluated cephalometrically for up to 6 months after surgery. The results indicated that the position of the genial segment is stable after advancement. There was a good correlation between the amount of hard versus soft tissue change with surgery in the horizontal direction but a poor correlation in the vertical plane. There was, however, a great amount of variability from one patient to the next in most of the variables examined. Follow-up results were generally very stable.

The development of interpositional and onlay bone grafting techniques for atrophic mandibles is reviewed. A further modification of the visor osteotomy is presented along with follow-up evaluation of the conditions of 16 patients. Results of radiographic measurements show the procedure to be stable, vertical resorption of the augmented mandible in the body regions being 11.2% over a mean follow-up of 8.8 months. Neurosensory evaluation showed altered sensation and dysesthesia as a significant problem in these patients. The results are presented and discussed.

Twenty-four orthognathic surgery patients were studied to determine the impact of a high-calorie liquid supplement on preventing or minimizing catabolism commonly associated with surgery. The experimental group of 12 subjects, chosen at random, consumed blenderized foods ad libitum and a high-calorie dietary supplement providing a minimum of 50% of energy requirements. The remaining 12 subjects consumed only blenderized foods and served as the control group. The nutritional status of all patients was assessed one day before surgery and on Day 7 of the first, third, and sixth postoperative week. In general, nutrient intake in the experimental group remained similar to that before surgery, whereas intake in the control group decreased significantly, particularly at the one-week postoperative evaluation. It was concluded that the addition of a high-calorie liquid supplement to the dietary regimen of orthognathic surgery patients helped maintain nutrient intake at a level comparable to that before surgery. This resulted in better maintenance of body weight and somatic protein compartments compared with the control group.

For purposes of examining the pulpal reaction to segmental osteotomy, six adult female Macaca fascicularis monkeys received identical anterior maxillary osteotomies involving the incisors only. The mobilized segment was displaced distally a distance of approximately 2 mm, then splinted in place for a week. The healing and revascularization of the bone proceeded well, with no ischemic areas visible on the microangiograms other than in the animal examined immediately after operation. The osteotomy site was bridged with new bone at three months. The majority of the pulps of the mobilized segment and all teeth examined distal to the segment remained vital. No degenerative change other than the temporary disappearance of sensory nerves was observed in the vital pulps of the segments. By the six-month period, the sensory nerve supply to the dental pulp had regenerated completely.

Single arch stabilization of segmental osteotomies is desirable because it eliminates intermaxillary fixation while it, in turn, improves oral hygiene and communication and patient comfort, function, and acceptability. Orthodontic appliances with stabilizing arch wires are the method of choice if available. Arch bars modified for segmental stabilization function very well as an alternative to orthodontic appliances. Cast splints are also useful for these cases, although cost and the need for expert laboratory support limit their acceptability. Certain other devices, such as palatal and lingual plates and interocclusal wafers, provide additional support for several of the above-mentioned stabilization systems.

The authors present a case of thrombosis of the umbilical vein in a foetus in the 27th week of pregnancy, discovered via ultrasound diagnosis. The foetus presented with marked ascites and anasarca. Despite foetal death there were no visceral malformations, and no pathological criteria presented by the mother. The characteristic features and sensitivity of sonographic diagnosis in umbilical vein thromboses are discussed as part of the extensive pathology of the umbilical cord.

The healing and revascularization of onlayed autologous and lyophilized allogeneic rib grafts to the edentulous maxilla in the Macaca fascicularis monkey were studied using clinical, histologic, and microangiographic methods at varying intervals of up to eight months. Results indicated that healing and revascularization were similar but resorption of the allografts occurred approximately three months later than resorption of the autografts. Both grafting systems appeared to have minimal osteogenic potential. Osteoinduction and the final bony augmentation obtained were less than were seen with comparable autologous and allogeneic interpositional grafts.

It has been suggested that repair of skin and mucosal wounds carried out in animals in utero leaves little or no trace of the operative procedure when examined at birth. This study examined the palates of lambs affected surgically in utero postnatally for scarring and transverse palatal growth. Nineteen pregnant sheep were affected at 120 days gestation. Surviving lambs followed for 6 months demonstrated altered palatal morphology.