Pulmonary and thoracic infection by Fusobacterium nucleatum. / Infección pulmonar y torácica por Fusobacterium nucleatum.

INTRODUCTION: Fusobacterium nucleatum is an anaerobic bacillus that is part of the oral microbiota and dental pla que. This can cause local and potentially remote infections, which are exceptional in pediatrics. Ob jective: To present the case of a patient with lung injury with chest wall invasion by Fusobacterium nucleatum. CLINICAL CASE: An 11-year-old female immunocompetent patient who consulted due to a two-week history of cough, night sweats, without fever or weight loss, and increased volume at the left spleen thoracic level. There was no history of chest wall trauma or travel outside the country. Two weeks before the onset of symptoms, she was treated for dental caries. Imaging studies and CT scan showed left spleen pneumonia, which invades the pleura and the chest wall. A minimal thoracotomy was performed, releasing a thick, foul-smelling liquid. The studies for common germs and tubercu losis were negative. Hematology ruled out tumor lesions. The anaerobic study reported the develo pment of Fusobacterium nucleatum. The patient was treated with penicillin followed by amoxicillin presenting good clinical and radiological responses. The dental procedure was suspected as the cause of infection. CONCLUSIONS: Fusobacterium nucleatum can occasionally cause remote or extra-oral in fections in immunocompetent patients, such as pneumonia with chest wall invasion, therefore it is necessary to bear it in mind.

Contribution of human papilloma virus to the incidence of squamous cell carcinoma of the head and neck in a European population with high smoking prevalence.

BACKGROUND: Increases in incidence of oropharyngeal squamous cell carcinoma (OPSCC) in countries with falling tobacco use have been attributed to a growing role of human papilloma virus (HPV) in the carcinogenesis. Trends of HPV prevalence in populations with persistently high portions of smokers are poorly characterised. PATIENTS AND METHODS: Registry data from East Germany were used to determine incidence trends between 1998 and 2011. Data from patients treated at the Charité University Medicine Berlin between 2004 and 2013 (cohort 1, N=436) were used for estimation of trends in HPV prevalence, smoking and survival. HPV prevalence was prospectively confirmed in cohort 2 (N=213) comprising all primary HNSCC cases at the Charité in 2013. RESULTS: Between 1998 and 2011 incidence of both OPSCC and non-OPSCC increased. An increase in HPV prevalence (% of HPV+ cases in 2004-2006 versus 2012-2013: 27% versus 59%, P=0.0004) accompanied by a moderate decrease in the portion of current smokers was observed in OPSCC but not in non-OPSCC. The change in disease epidemiology in OPSCC was associated with significant improvement in overall survival. Increased HPV prevalence in OPSCC (48%) compared to non-OPSCC (11%) was confirmed in cohort 2. CONCLUSIONS: Despite clear differences to the United States in terms of tobacco use, the increase in OPSCC incidence in a European population was also mainly attributed to HPV, and the HPV status significantly affected prognosis. For clinical trial design it is important to consider the large group of smokers within HPV-induced OPSCC.

The revised dengue fever classification in German travelers: clinical manifestations and indicators for severe disease.

BACKGROUND: The number of dengue cases imported to Germany has increased significantly in recent years. Among returning travelers, dengue is now a frequent cause of hospitalization. The aim of this study was to determine the proportion of patients with severe disease hospitalized in a European, non-endemic country applying the revised 2009 WHO classification system and to determine predictors of severe disease. METHODS: A retrospective single-center analysis of clinical data from 56 patients, 31 (55 %) women and 25 (45 %) men, between 14 and 70 years of age treated in a tertiary care hospital between 1996 and 2010 was conducted. RESULTS: Thirty-nine patients (69.6 %) presented with dengue fever without warning signs, 11 (19.6 %) with warning signs and 6 (10.7 %) with signs for severe dengue fever. Two patients (4 %) developed dengue shock syndrome. Non-European descent (p = 0.001), plasma protein level <6.5 mg/dl (p = 0.001), platelets <30/nl (p = 0.017) and activated partial thromboplastin time (aPTT) >44 s (p = 0.003) were associated with severe disease. CONCLUSIONS: A significant proportion of patients hospitalized with symptomatic imported dengue fever in Germany have evidence of severe disease. Simple routine laboratory parameters such as complete blood count, plasma protein level and aPTT are helpful tools for identifying adult patients at risk for severe disease.

Frontofacial advancement by internal distraction devices. A technical modification for the management of craniofacial dysostosis in early childhood.

Normal craniofacial growth is characterized by a different growth pattern of neuro- and viscerocranium. In craniofacial dysostosis (CFD) syndromes there is complex disturbance of this physiological growth pattern. Modern surgical management of CFD is staged with respect to the severity of the deformity, the age and the development of the patient. Early single stage management of anterior cranial vault deformity and midfacial retrusion in children affected by syndromic craniosynostosis is possible when anterior cranial vault remodelling is performed together with gradual Le Fort III midfacial advancement. One pair of internal distraction devices, placed in accordance with the midfacial growth vector after initial cranial vault remodelling, can be sufficient for this purpose. Technical aspects of this modified frontofacial advancement procedure are presented and discussed based on a case report with a postoperative follow up time of 50 months.

Pharmacokinetic profile in late pregnancy and cord blood concentration of tipranavir and enfuvirtide.

The data on the use of tipranavir and enfuvirtide in pregnancy are very limited. We performed a pharmacokinetic profile in a pregnant woman with multidrug-resistant HIV-1 infection at 37 weeks gestation. Tipranavir levels were in the therapeutic range and the cord blood concentration at delivery was relatively high when compared with other protease inhibitors. No enfuvirtide was detected in the fetal compartment. Tipranavir and enfuvirtide were successfully used in pregnancy, but possible toxicities must be kept in mind.

Effect of induced hypotensive anaesthesia vs isovolaemic haemodilution on blood loss and transfusion requirements in orthognathic surgery: a prospective, single-blinded, randomized, controlled clinical study.

Induced hypotensive anaesthesia and isovolaemic haemodilution are well-established blood-sparing techniques in major surgery. This prospective study compared them for blood loss, transfusion requirements, and surgical field quality during standardized orthognathic operations. In a surgeon-blinded trial, 60 healthy patients requiring either Le Fort I osteotomy or bimaxillary surgery were randomly allocated to receive normotensive anaesthesia, induced hypotensive anaesthesia, or induced hypotensive anaesthesia combined with isovolaemic haemodilution. Blood loss and haemoglobin level were measured intraoperatively and calculated on postoperative day 3. The surgeons rated surgical field quality. Mean blood loss was 1021.63, 392.38 (p<0.05) and 1191.65ml in the normotensive, hypotensive and haemodilution groups, respectively. Mean haemoglobin level immediately after surgery was 9.3, 10.3, and 7.4g/dl (p<0.05), respectively. No hypotensive group patients received transfusions; four normotensive group patients required allogenic transfusions; seven haemodilution group patients needed autogenous retransfusions (p<0.05). Surgical field quality was significantly better in the hypotensive than in the normotensive (p<0.05) or haemodilution (p<0.05) groups. In orthognathic surgery, hypotensive anaesthesia significantly reduces blood loss and transfusion requirements and minimizes allogenic transfusions risks. Induced hypotensive anaesthesia combined with isovolaemic haemodilution has no additional blood-sparing effects but impairs surgical field quality.

Ultrasonic characterization of human cancellous bone in vitro using three different apparent backscatter parameters in the frequency range 0.6-15.0 mhz.

Ultrasonic techniques based on measurements of apparent backscatter may provide a useful means for diagnosing bone diseases such as osteoporosis. The term "apparent" means that the backscattered signals are not compensated for the frequency-dependent effects of attenuation and diffraction. We performed in vitro apparent backscatter measurements on 23 specimens of human cancellous bone prepared from the left and right femoral heads of seven donors. A mechanical scanning system was used to obtain backscattered signals from each specimen at several sites. Scans were performed using five different ultrasonic transducers with center frequencies of 1, 2.25, 5, 7.5, and 10 MHz. The -6 dB bandwidths of these transducers covered a frequency range of 0.6-15.0 MHz. The backscattered signals were analyzed to determine three ultrasonic parameters: apparent integrated backscatter (AIB), frequency slope of apparent backscatter (FSAB), and time slope of apparent backscatter (TSAB). Linear regression analysis was used to examine the correlation of these ultrasonic parameters with five measured physical characteristics of the specimens: mass density, X-ray bone mineral density, Young's modulus, yield strength, and ultimate strength. A total of 75 such correlations were examined (3 ultrasonic parameters x 5 specimen characteristics x 5 transducers). Good correlations were observed for AIB using the 5 MHz (r = 0.70 - 0.89) and 7.5 MHz (r = 0.75-0.93) transducers; for FSAB using the 2.25 MHz (r = 0.70 - 0.88), 5 MHz (r = 0.79 - 0.94), and 7.5 MHz (r = 0.80 - 0.92) transducers; and for TSAB using the 5 MHz (r = 0.68 - 0.89), 7.5 MHz (r = 0.75 - 0.89), and 10 MHz (r = 0.75 - 0.92) transducers.

In vitro antibacterial activity of Lucilia sericata maggot secretions.

Maggots of the green blowfly, Lucilia sericata, are used as an alternative to surgical intervention and long-term antiseptic therapy for the treatment of chronic wounds. The secretions of maggots are known to have antibacterial properties. To quantify the bactericidal effect of secretions from larvae of L. sericata, an in vitro test model based on the modified European quantitative suspension test (EN 1040) was developed, in which a co-culture of maggots and bacteria (Micrococcus luteus,Escherichia coli, methicillin-sensitive Staphylo-coccus aureus) in tryptic soy broth was tested. The numbers of bacterial colonies with and without maggot exposure were compared after 24, 48 and 72 h of exposure. The mean log(10) reduction factor (RF) for bacterial elimination per maggot was >4 at all examined times for all tested bacteria. Thus, maggot secretion fulfilled the required definitions of an antiseptic. In addition, the maggots' ability to ingest bacteria was also evaluated. Maggots contained viable bacteria after 48 h of contact with the respective organisms. These maggots also continued excreting bacteria. Therefore, maggots should be disposed of after use as they must be regarded as medical waste.

Ultrasonic characterization of cancellous bone using apparent integrated backscatter.

Apparent integrated backscatter (AIB) is a measure of the frequency-averaged (integrated) backscattered power contained in some portion of a backscattered ultrasonic signal. AIB has been used extensively to study soft tissues, but its usefulness as a tissue characterization technique for cancellous bone has not been demonstrated. To address this, we performed measurements on 17 specimens of cancellous bone over two different frequency ranges using a 1 MHz and 5 MHz broadband ultrasonic transducer. Specimens were obtained from bovine tibiae and prepared in the shape of cubes (15 mm side length) with faces oriented along transverse (anterior, posterior, medial and lateral) and longitudinal (superior and inferior) principal anatomic directions. A mechanical scanning system was used to acquire multiple backscatter signals from each direction for each cube. AIB demonstrated highly significant linear correlations with bone mineral density (BMD) for both the transverse (R2 = 0.817) and longitudinal (R2 = 0.488) directions using the 5 MHz transducer. In contrast, the correlations with density were much weaker for the 1 MHz transducer (R2 = 0.007 transverse, R2 = 0.228 longitudinal). In all cases where a significant correlation was observed, AIB was found to decrease with increasing BMD.

Implant-supported titanium prostheses following augmentation procedures: a clinical report.

BACKGROUND: This report describes a novel technique for fabricating retrievable implant-supported titanium (Ti) prostheses in patients requiring a comprehensive treatment plan involving the combined efforts of maxillofacial surgery and implant prosthodontics. METHODS: Following bone graft reconstructive surgery and implant placement prosthetic treatment was initiated by inserting ITI-Octa abutments. An impression was made, and a framework was fabricated by fusing Ti-cast frameworks to prefabricated titanium copings by laser-welding. This was followed by veneering or fabrication of a removable denture with Ti metal re-enforcement. RESULTS: Favourable clinical results have been achieved using these screw-retained Ti implant-supported restorations for patients treated with reconstructive bone graft-surgery, with clinical observation periods ranging from three to four years. CONCLUSIONS: The present observations suggest that these screw-retained implant-supported Ti prostheses may be a meaningful contribution to implant prosthodontics, facilitating retrievable restorations of optimum biocompatibility, good marginal precision and with a good esthetic result. However, controlled clinical studies are needed to establish the long-term serviceability of these Ti restorations.

Oesophageal squamous cell neoplasia in head and neck cancer patients: upregulation of COX-2 during carcinogenesis.

Patients with (previous) head and neck cancer (HNC) are at high risk for developing second squamous cell cancer of the oesophagus. The role of cyclooxygenase-2 (COX-2) in oesophageal squamous carcinogenesis has not yet been investigated in this high-risk group. Therefore, this study examined COX-2 mRNA and protein expression in oesophageal biopsies and resected tissues of 44 HNC patients. The evaluation covered 55 oesophageal tissue samples (18 invasive oesophageal squamous cell cancers, four high- and eight low-grade dysplasias, 25 normal squamous epithelia) from the 44 patients. mRNA levels of COX-2 were measured by real-time PCR using a LightCycler. COX-2 protein expression was studied immunohistochemically and graded by a staining score. COX-2 mRNA was detected in all samples, and its levels correlated positively with the immunohistochemical staining score (P<0.05). COX-2 expression was upregulated during oesophageal squamous carcinogenesis in HNC patients, that is COX-2 expression increased significantly from normal oesophageal squamous epithelium to low- and high-grade dysplasia and finally to invasive squamous cell cancer (P<0.001). Our findings suggest that COX-2 upregulation contributes to oesophageal squamous carcinogenesis in HNC patients. Prospective studies are needed to evaluate the chemopreventive potential of COX-2 inhibitors in this high-risk group.

[Clinical and molecular genetic observations on families with cherubism over three generations]. / Klinische und molekulargenetische Befunde bei Familien mit Cherubismus über 3 Generationen.

BACKGROUND: Cherubism is a rare fibro-osseous disorder that almost exclusively affects the maxilla and mandible. CASE REPORT: We report on three affected males in three generations in family A, and ten affected patients in family B. The youngest affected relative in family A also had craniosynostosis. His father and grandfather had cherubism and clubbed fingers. RESULTS AND DISCUSSION: Cherubism was mapped to region 4p16.3. Because of the associated craniosynostosis, we excluded the FGFR3 gene as a candidate gene for cherubism. The inheritance pattern is autosomal dominant with variable expression. The penetrance is 100% in males and 50-70% in females. We found incomplete penetrance in males, which does not conform with all publications.

Effect of collagen and mineral content on the high-frequency ultrasonic properties of human cancellous bone.

The technology surrounding ultrasonic bone assessment is evolving rapidly as investigators explore the utility of new ultrasonic parameters and different ultrasonic frequencies. This study had three main goals. The first was to perform in vitro measurements of the speed of sound (SOS) and normalized broadband ultrasonic attenuation (nBUA) in specimens of normal human cancellous bone using a 2.25 MHz broadband measurement system. The second was to explore the utility of a backscatter-based parameter called apparent integrated backscatter (AIB). The third goal was to investigate the roles that collagen and mineral content play in affecting each of these three ultrasonic parameters. This was accomplished by chemically treating the specimens to remove one or the other of these two important constituents of bone. Our results showed that in most cases SOS and nBUA correlated well (p < 0.05) with bone mineral density (BMD) as measured by quantitative computed tomography (QCT). In contrast, AIB did not correlate strongly with BMD. When the specimens were demineralized, decreases were produced in SOS (19-39%) and nBUA (44-58%). Changes produced in AIB were not significant except along the superoinferior direction, in which a 12% decrease was measured. When the specimens were decollagenized, decreases were produced in SOS (10-12%). In contrast, increases were produced in both nBUA (35-77%) and AIB (14-15%). From this study we conclude that high-frequency ultrasonic measurements may yield useful information about the content and organization of both collagen and mineral in cancellous bone.

Screening for oesophageal neoplasia in patients with head and neck cancer.

Due to advanced disease at the time of diagnosis the prognosis of oesophageal cancer is generally poor. As mass screening for oesophageal cancer is neither feasible nor reasonable, high-risk groups should be identified and surveilled. The aim of this study was to define the risk of oesophageal cancer in patients with (previous) head and neck cancer. A total of 148 patients with (previous) head and neck cancer were prospectively screened for oesophageal cancer by video-oesophagoscopy and random oesophageal biopsies. Even in a macroscopically normal looking oesophagus, four biopsy specimens were taken every 3 cm throughout the entire length of the squamous oesophagus. Low- or high-grade squamous cell dysplasia was detected histologically in 10 of the 148 patients (6.8%). All but one dysplasias were diagnosed synchronously with the head and neck cancers. In addition, oesophageal squamous cell carcinoma was diagnosed in 11 of the 148 patients (7.4%). Most invasive cancers (63.6%) occurred metachronously. The risk of squamous cell neoplasia of the oesophagus is high in patients with (previous) head and neck cancer. Surveillance is recommended in this high-risk group.

Mechanisms by which AC leakage currents cause complete hemodynamic collapse without inducing fibrillation.

INTRODUCTION: The first study of weak alternating current (AC) stimulation in closed chest humans showed that complete hemodynamic collapse can occur below the threshold for inducing ventricular fibrillation (VF), a heretofore unknown danger to patients. This article, and the accompanying simulation article, explore the mechanisms responsible for the collapse. METHODS AND RESULTS: A quadripolar pacing catheter was placed in the right ventricle (RV) of six dogs. The tip of the catheter (17 mm2) carried 5 seconds of AC stimulation ranging from 10 to 160 Hz and 10 to 1,000 microA. The lead II body surface ECG, femoral artery pressure, and a bipole from the proximal pair of electrodes on the RV catheter were recorded 2 seconds before, during, and 2 seconds after stimulation. Based on the blood pressure, every episode was categorized as VF, COLLAPSE without VF, extrasystolic without COLLAPSE (EFFECT), or having caused no effect (NSR). The electrical activation interval (interspike interval [ISI]) from the RV bipole was compared with the mechanical activation interval, determined from M-mode ultrasound. COLLAPSE is associated with a short ISI (NSR = 408+/-110 msec; EFFECT = 305+/-113 msec; COLLAPSE = 179+/-25 msec; P < 0.001) with a high degree of regularity (P < 0.001): coefficient of variation of ISI for COLLAPSE (0.038+/-0.069) versus VF (0.389+/-0.222), EFFECT (0.420+/-0.241), and NSR (0.016+/-0.048). Electrical activation and mechanical activation rates occurred at integer multiples of the AC stimulation period. CONCLUSION: COLLAPSE (86+/-37 microA; minimum 50 microA in two animals) occurs below the VF threshold (108+/-28 microA) by causing rapid, regular excitation.

Defibrillation and the geometry of the heart: a novel measurement with implications for defibrillation mechanisms.

We present a novel measurement for studying defibrillation mechanisms: the time course of changes in the size of the left ventricular (LV) cavity within 500 ms following defibrillation. Mechanical changes can be linked to electrical mechanisms via an understanding of excitation-contraction coupling. Eight mongrel dogs were internally defibrillated 5-50 seconds (including backup shocks) after the onset of 20 ventricular fibrillation (VF) episodes per animal. Two dimensional, short axis, LV cavity, ultrasound images were recorded at 30 frames per second just prior to inducing VF, during defibrillation and following the shock. Each frame was individually analysed to yield the LV cavity area as a function of time. Defibrillation shocks were followed by a highly reproducible phenomenon: (1) a dramatic and rapid increase in LV area, (2) a more or less prominent LV area plateau and (3) a decrease in the LV area. The peak fractional area increase ranged from 1.65 to 4.64 times larger than the baseline (LV area just prior to defibrillation), averaging 2.18 +/- 0.686. Successful shocks took significantly longer (p < 0.01) to return to 1.3 times the baseline (407 +/- 209 ms) than unsuccessful shocks (296 +/- 130 ms). Extrapolating to electrical mechanisms, our novel measurement demonstrates that defibrillation causes immediate relaxation and therefore suggests a significant role for deexcitation in defibrillation.

Ultrasonic characterization of the curing process of hydroxyapatite-modified bone cement.

Ultrasonic parameters such as velocity of sound and broad-band ultrasonic attenuation (BUA) are sensitive to changes in the viscoelastic properties of a material. Bone cement undergoes changes is these properties as it cures. By monitoring the propagation of ultrasonic pulses through a sample of curing bone cement, the curing reaction of polymethylmethacrylate-based (PMMA) bone cement was investigated for hydroxyapatite (HA) concentrations of 0, 10, and 30% (by weight). As the material hardens, the velocity of sound increases by 70%. BUA shows a large peak at the midpoint of the velocity transition. These data are used to compare the cure time and cure duration for PMMA bone cement mixed with hydroxyapatite particles. Measurements of the final sound velocity and BUA were also performed to investigate the mechanical properties of the fully cured cement, and to compare to compression testing data. This is the first time the curing process of bone cement has been investigated as a function of hydroxyapatite concentration. Results indicate that the cure time is not significantly affected by the addition of HA particles, and that both velocity of sound and BUA are sensitive to the curing process.

Primary thinning of the myocutaneous vastus lateralis flap.

To expand the indicational spectrum of the myocutaneous vastus lateralis flap, which is often too voluminous for intraoral application, primary thinning of the fat and muscle component of this microsurgical transplant was performed in 14 patients. The surgical technique includes subfascial localization of at least one myocutaneous perforating vessel of the lateral circumflex femoral artery and its dissection through the fascia, muscles and fatty tissue up to the skin. The epifascial fatty tissue is completely removed except for a 1-2 cm wide cuff around the perforating vessel. The thinning technique was used for covering 10 intraoral and 4 extraoral defects and enabled the raising of skin flaps with a thickness of 4 mm even in obese patients. The vessel pedicle length of the thinned flaps was between 12 and 16 cm; flap size varied between 4x5 and 9x15 cm and the donor sites were directly closed. In one case, there was a partial necrosis (20%), but the other flaps healed without complications. The described method allows the raising of thick myocutaneous as well as thin skin flaps from the same donor region.

Hemodynamic collapse, geometry, and the rapidly paced upper limit of ventricular vulnerability to fibrillation by T-wave stimulation.

There is an upper limit to the vulnerability (ULV) of the ventricles to fibrillation (VF) induced by T-wave stimuli. Across species, disease states, and pharmacological treatments, the ULV is correlated to the defibrillation threshold (DF50). However, one factor known to increase the ULV far above the DF50 is rapid pacing. In this article we test the hypothesis that this increase is owing to an accompanying hemodynamic collapse or geometric change. In 18 dogs, T-wave stimuli were delivered from transvenous defibrillating electrodes. The T-wave shock strength that induced VF 50% of the time (the ULV50) was measured using a 10-step Bayesian up-down protocol. T-wave stimuli were delivered after 15 paced beats at one of several rates: normal (80% of the R-R interval), rapid (the interval just fast enough to cause hemodynamic collapse), or 10 milliseconds greater than rapid (which did not cause hypotension). We measured the geometry of the left ventricle at the moment of T-wave stimulation using linear ultrasound. Rapid pacing significantly increased the ULV50 above the normal rate ULV (507 +/- 62.9 vs 379 +/- 70.6 V, P < .005, n = 18), even in the subset without hemodynamic collapse (505 +/- 84.4 vs 394 +/- 66.5 V, P < .005, n = 6). No significant geometric changes were noted between rapid (19.8 mm) and normal (20.6 mm, n = 6, P < NS) pacing, but QT interval reduction appears to correlate with the ULV50 (QT vs ULV50, r > 0, P < .01). Rapid pacing can dramatically increase the measured ULV50. The most likely cause is a concurrent change in the electrophysiology, eg, QT or APD, of the myocardium. As the only known factor to consistently alter the relationship between ULV and the DF50, rapid pacing offers a unique opportunity for the study of the link between defibrillation and ULV testing.

Anisotropy of Young's modulus of human tibial cortical bone.

The anisotropy of Young's modulus in human cortical bone was determined for all spatial directions by performing coordinate rotations of a 6 by 6 elastic stiffness matrix. The elastic stiffness coefficients were determined experimentally from ultrasonic velocity measurements on 96 samples of normal cortical bone removed from the right tibia of eight human cadavers. The following measured values were used for our analysis: c11 = 19.5 GPa, c22 = 20.1 GPa, c33 = 30.9 GPa, c44 = 5.72 GPa, c55 = 5.17 GPa, c66 = 4.05 GPa, c23 = 12.5 GPa. The remaining coefficients were determined by assuming that the specimens possessed at least an orthorhombic elastic symmetry, and further assuming that c13 = c23 c12 = c11 - 2c66. Our analysis revealed a substantial anisotropy in Young's modulus in the plane containing the long axis of the tibia, with maxima of 20.9 GPa parallel to the long axis, and minima of 11.8 GPa perpendicular to this axis. A less pronounced anisotropy was observed in the plane perpendicular to the long axis of the tibia. To display our results for the full three-dimensional anisotropy of cortical bone, a closed surface was used to represent Young's modulus in all spatial directions.