Although CA-HYP presented a slightly lower yield and higher contents of total carbohydrate and uronic acid, their composition and 13C NMR spectrum closely resembles the pectins obtained from cacao pod husks by boiling aqueous extractions (Vriesmann, Amboni, et al., 2011). It seems that, both citric acid and water, were able to remove LM pectins (DE ∼40%) probably Natural Product Library arising from the middle lamella. Fig. 4 shows the HPSEC elution profile of fraction CA-HYP. Due to the high-molar mass (1.806 × 106 g/mol), the primary peak (∼38 min) was detected

by both, the differential refractometer (RI) detector and the multiangle laser light scattering (MALLS) detector. Another peak was observed at higher elution time (>40 min), with a less intense RI signal and no MALLS detection,

indicating lower concentration and lower-molar mass (6.450 × 105 g/mol). Comparing to the pectins obtained from cacao pod husks with boiling water, CA-HYP had higher molar mass (Vriesmann, Amboni, et al., 2011). Dynamic viscoelastic properties of solutions of CA-HYP at 5 g/100 g were studied by frequency sweeps obtained at 25 °C (Fig. 5). Both elastic (G′) and viscous (G″) moduli increased with the frequency, being G′ more dependent on frequency than G″, until reach a frequency of ∼10 Hz, where the cross-over between the moduli occurs. Similar results were obtained by Vriesmann, Amboni, et al. (2011) for boiling-water extracted selleck inhibitor pectins from cacao pod husks and Min et al. (2011) for pectins from apple pomace obtained by chemical and combined physical/enzymatic treatments. However, the pectins from apple pomace at 5 g/100 g presented G″ > G′ over the range of frequency analyzed ( Min et al., 2011). These authors observed that pectins with lower DE appeared to have more elastic properties than those with higher DE ( Min et al., 2011). The results obtained for CA-HYP confirmed this trend. CA-HYP (40.3% DE) showed higher elastic properties than pectins from cacao pod husks extracted Ureohydrolase with

boiling water (42.6% DE; Vriesmann, Amboni, et al., 2011) and apple pomace pectins (58 and 69% DE; Min et al., 2011). The viscosity curve of 5 g/100 g CA-HYP aqueous solution at 25 °C (Fig. 6) showed a shear-thinning, pseudoplastic flow behavior as reported for other pectin solutions (Hwang & Kokini, 1992; Min et al., 2011; Vriesmann, Amboni, et al., 2011). Cross equation, with four parameters, can describe the general flow curve of pseudoplastic fluids (Cross, 1965). Thus, it was employed to fit the experimental data of apparent viscosity, η   (Pa s), vs. shear rate, γ˙(1/s) for CA-HYP, according to the equation: η=η∞+(η0−η∞)/[1+(γ˙/γ˙b)n], where η  0 is the zero-shear rate viscosity (Pa s), η  ∞ is the infinite-shear rate viscosity (Pa s), γ˙b is the shear rate at which the fluid changes from Newtonian to Power-law behavior (1/s) and n is the flow behavior index (−). The values found for the four parameters for the flow of CA-HYP were η  0: 7.993 Pa s; η  ∞: 0.1189 Pa s; γ˙b. 1.607 1/s and n: 0.

In a further test, we repeated the whole above analysis considering fixations within ROIs only, and fed their number to the generator of random fixations (random viewer). The previous results were confirmed, i.e., significantly smaller KLDact values for non-primate images, and significantly larger KLDact values for primate images than expected (not shown). In order to investigate the existence of regions-of-interests (ROIs), defined as areas with high GDC-0980 price density of fixation positions, we identified spatial clusters of fixations by use of the mean shift algorithm (Comaniciu and Meer, 2002 and Funkunaga and Hosteler, 1975) adapted for eye movement

data (Santella and DeCarlo, 2004). This is an automatic, entirely data-driven method that derives the number and arrangement of clusters deterministically. The algorithm starts from the set of N   fixation positions vi,j→=xi,jyi,j, with i   ∈ (1, …, N  ) being the index of the fixation positions, and j   = 1 the original fixation positions on the 2D screen. The clustering algorithm proceeds iteratively, while moving at each iteration each of the points to its new position v→i,j+1, in dependence on the weighted mean of proximity and density of points around the reference point, v→i,j+1=∑iK(Vij−Vk,j)Vk,j∑i(Vij−Vk,j) with j ≠ k. The kernel K was defined as a

2D-Gaussian with mean and Angiogenesis inhibitor variance of 0: K(v→)=e(x2+y2)σ2. σ   was the only parameter of the clustering algorithm and defined the attraction radius of the points. We varied its value and found 2.5 to yield satisfying results, i.e., the algorithm did not lead to over

fitting or to coarse clusters. We used Oxymatrine this value to perform all of our analyses. At each iteration the positions were moved into denser configurations, and the procedure was stopped after convergence. Thereby fixations were assigned to a cluster whose reference points lay within a diameter of 1° apart, referred to as experimental cluster. Robustness to extreme outliers was achieved by limiting the support of points at large distances as defined by the kernel K(v→). In order to discard outlier clusters, we additionally applied a significance test to disregard clusters containing only a very small fraction of the data that deviate from expectation of independence. As a significance test on the experimental clusters, we proceeded as follows: we assigned n random locations on the screen by drawing n pairs of uniformly distributed numbers, with n being the total number of fixations on a specific image. This random fixation map was fed into the mean shift clustering algorithm, leading to a set of simulated clusters. Repeating this procedure 100 times, we obtained two distributions: one of fixation numbers per cluster and one of cluster point density.

1 Melanoma’s metastases are usually multiple ulcerated polypoid lesions, either pigmented or amelanotic, and may present at the time of diagnosis or years later.1 Surgical interventions for symptomatic patients with melanoma metastases of find more the GI tract may be considered

for both palliation of symptoms and improvement in mortality.4 New therapeutic possibilities were recently developed, such as vemurafenib and ipilimumab, and while they still have limitations, they are the beginning of a new generation of therapies.5 Therapeutic decisions, especially in stage IV patients, should be managed by and interdisciplinary oncology team.4 The authors declare that no experiments were performed on humans or animals for this study. The authors declare that they have followed the protocols of their work centre on the publication of patient data and that all the patients included in the study received sufficient information and gave their written informed consent to participate in the study. The authors declare that no patient data appear in this article. The authors have no conflicts of interest to HIF inhibitor declare. “
“Choledocholithiasis occurs in 8–20% of patients with gallstones.1 The rate of spontaneous migration of bile duct stones through the duodenal papilla is not

well known.1 An impacted bile duct stone at duodenal papilla can be associated with either cholangitis due to the complete obstruction of the bile outflow or acute pancreatitis. Endoscopic retrograde cholangiopanteatography (ERCP) has been established as the standard treatment for impacted bile duct stones. We report a case of a patient with impacted bile duct stone who underwent needle-knife fistulotomy avoiding the papillary orifice followed by standard papillotomy for the removal of the impacted stone. A 61-year-old woman Sucrase with a past history of diabetes mellitus

type 2, hypertension and laparoscopic cholecystectomy performed one year ago, was admitted in the emergency room with epigastric pain, vomiting and fever. Physical examination showed jaundice and tenderness over the epigastrium. Significant laboratory results included 11,300 × 109/L leukocytes, C-reactive protein 6.8 mg/dL (normal value < 0.5 mg/dL), total bilirubin 3.4 mg/dL (range, 0.2–1.0), aspartate transaminase 89UI/L (range, 5–39) and alanine transaminase 206 UI/L (range, 10–49). An abdominal ultrasound showed extra-hepatic bile duct dilatation (10 mm). A CT scan showed an impacted stone at duodenal papilla. ERCP was performed and the diagnosis of an impacted bile duct stone at duodenal papilla was confirmed. The patient underwent unsuccessfully needle-knife precut papillotomy to achieve deep cannulation.

In addition, the gene(s) controlling stem solidness

was mapped based on an F2 population derived from a cross between a solid stemmed variety and a hollow stemmed one. The result will be helpful for molecular marker assisted selection (MAS) for solid stem in wheat breeding. Solid stemmed wheat line Xinongshixin (XNSX), hollow stemmed Line 3159, the F1 and F2 populations from cross XNSX/Line 3159 and Chinese Spring (CS) were planted at Changping Experimental Station, CAS, Beijing, China. Plant samples were collected from early April (three-leaf stage) Akt cancer to late June (mature stage). To evaluate stem solidness, more than 10 stems were randomly selected at post-anthesis and were cross-sectionally cut at the center of each internode. The level of pith solidness was rated

on a previously established score system [12] ranging from 1 to 5 (1 for hollow and 5 for solid). All samples were collected from main tillers. The internodes on samples were numbered consecutively from the base to the top of the stem. Sections were cut at the center of each internode and stained with either phloroglucine-HCl or Calcoflour (Sigma) according to the procedure described in our previous study [13]. The following morphological characteristics were measured and analyzed using a statistical software package attached to fluorescence microscope (Axioskop 40 with UV BIBW2992 molecular weight excitation, Protein kinase N1 ZEISS), i.e., outer and inner stem diameters, area of stem wall, radius of stem wall (RSW), width of stem wall (WOSW), area of vascular bundles (AOVB), area of transverse section (AOT), width of the mechanical tissue layer (WOMT), number of vascular bundles (NOVB), number of large and small vascular bundles (NLVB and NSVB), weight of the three lower internodes (WOL), and stem length. Carbohydrate contents (lignin and cellulose) were assayed according to the methods described previously [13], [14] and [15]. Three internodes from the bottom upwards

collected from stems were ground to fine powder in liquid nitrogen using a mortar and a pestle. Lignin content was assayed using the methods described by Kirk and Obst [16] and histochemical detection (the Wiesner reaction) following established protocols [17]. For cellulose staining, polyethylene glycol (PEG)-embedded sections (10 μm) were treated with a 0.005% aqueous solution of Calcoflour (fluorescent brightener 28, Sigma) for 2 min and then observed with a fluorescence microscope (Axioskop 40, ZEISS). Lodging resistance was ranked according to the measured resistance of stems to pushing, which was carried out on the bottom part of the stem following Kashiwagi and Ishimaru [18]. The data were analyzed by multiple ANOVA with 95% confidence limits using mean values measured for each genotype.

As the night progressed, the EEG:EMG ratios of the HDC-ΔBmal1 mice became similar to littermate controls ( Figure S4A).

Some the HDC-ΔBmal1 mice had long (up to 40 min) periods of uninterrupted waking ( Figure 3B). The total wake time, however, of HDC-ΔBmal1 selleck chemicals llc mice averaged over 24 hr was unchanged (693 ± 21 min versus 693 ± 12 min, unpaired two-tailed t test, p > 0.05), but over the night they spent more time awake than littermate control mice and less time awake during the day (night: 420 ± 16 min versus 461 ± 10 min, unpaired two-tailed t test, p < 0.05; day: 273 ± 9 min versus 231 ± 7 min, unpaired two-tailed t test, p < 0.05) ( Figure S4A). Throughout the 24 hr, during the wake periods, the HDC-ΔBmal1 mice had higher θ frequencies in the EEG than littermate controls (two-way ANOVA and post hoc Bonferroni, p < 0.05) ( Figure S4D). The amount of nonrapid eye movement (NREM) sleep was similar between HDC-ΔBmal1 and control selleck compound mice ( Figure S4B) (488 ± 11 min versus 427 ± 20 min, unpaired two-tailed t test, p > 0.05), but NREM power was lower ( Figure S4E; see next section) (two-way ANOVA and post hoc Bonferroni, ∗p < 0.05). During the day, HDC-ΔBmal1 mice had more NREM episodes than controls ( Figure 3C), but these episodes were shorter ( Figure 3D) (3.5 ± 0.3 min versus 2.4 ± 0.3 min,

unpaired two-tailed t test, ∗∗p < 0.01). The amount of REM sleep in HDC-ΔBmal1 mice compared with littermate controls was higher in the day ( Figure S4C): there were more episodes ( Figure 3E), although episode duration was unchanged ( Figure 3F) (1.7 ± 0.04 min versus 1.8 ± 0.04 min, unpaired two-tailed

t test, p > 0.05); however, REM episode duration was shorter in the HDC-ΔBmal1 mice ( Figure 3F) during the night (1.6 ± 0.04 min versus 1.4 ± 0.03 min, unpaired two-tailed t test, ∗∗p < 0.01). The daytime sleep architecture of HDC-ΔBmal1 mice differed from littermate control mice ( Figure 3G). HDC-ΔBmal1 mice had more “NREM-to-REM” (39 ± 2 versus 68 ± 2, unpaired two-tailed t test, ∗∗∗p < 0.001) and “REM-to-NREM” (29 ± 1 versus 58 ± 2, unpaired two-tailed t test, Vitamin B12 ∗∗∗p < 0.001) transitions during the day ( Figure 3G). During the night, there was no difference between genotypes in NREM-REM transitions (22 ± 3 versus 28 ± 2, unpaired two-tailed t test, p > 0.05) ( Figure 3G); however, HDC-ΔBmal1 mice had fewer wake-to-NREM transitions (29 ± 3 versus 17 ± 1, unpaired two-tailed t test, ∗∗∗p < 0.001) and vice versa (21 ± 3 versus 11 ± 1, unpaired two-tailed t test, ∗∗∗p < 0.001) ( Figure 3G), reflecting that they were awake more ( Figure 3B). Thus, sustained elevated histamine in HDC-ΔBmal1 mice changed the sleep-wake architecture. HDC-ΔBmal1 mice and littermate controls were sleep deprived for 5 hr during the start of the day [ 35].

Typical biases over land in GCM driven simulations are up to 3–4°C for temperature and 100% for precipitation. Biases are to a large degree related to errors of the large-scale circulation, SSTs and sea ice cover in the GCMs.

For surface air temperature the ensemble mean is generally better than the ensemble members. MDV3100 clinical trial In this study we focus on the assessment of atmospheric variables over the sea surface. Scenario results of the future marine environment and variables from the deeper ocean will be discussed elsewhere. We use results from RCA3, which is a state-of-the-art regional atmosphere model including a land surface model (Samuelsson et al. 2006) and a lake model – PROBE (Ljungemyr et al. 1996, Jones et al. 2004, Samuelsson et al. 2011). For the present set-up SST and sea ice conditions are prescribed for all ocean areas within the chosen model domain, including the Baltic Sea (Figure 2). Simulations with RCA3 use lateral boundary conditions from eight different GCMs (Table 1). All simulations are transient runs for 1961–2100. In addition to GCM-driven simulations, simulations with lateral boundary conditions and SST and sea ice from the ERA40 reanalysis data (Uppala et al. 2005) have also been used (Table 2). The reanalysis-driven simulations Z-VAD-FMK cover the time period 1961–2002. From August 2002 the simulations have been prolonged by using lateral boundary conditions

from the operational analysis at the European Centre for Medium range Weather Forecasts (ECMWF). Most of the RCA3 simulations

were performed with a horizontal grid resolution of 50 km. Owing to the computational burden only a few simulations could be performed with a 25 km resolution as well (Tables 1 and 2). For details of the available ensemble simulations and references to the GCMs, the reader is referred to Kjellström et al. (2011). In addition to the RCA3 simulations, briefly introduced in the previous section, six dynamical downscaling experiments with the fully coupled, atmosphere-ice-ocean-land surface model RCAO (the Rossby Centre Atmosphere Ocean model; see Döscher et al. 2002, 2010) were performed. In these experiments lateral boundary data from either ERA40 Alanine-glyoxylate transaminase (Table 2) or two GCMs, HadCM3_ref and ECHAM5 (Table 1), were used. RCAO consists of the atmospheric component RCA3 (Samuelsson et al. 2011) and the oceanic component RCO (Meier et al. 2003) with horizontal grid resolutions of 25 and 11.1 km (six nautical miles) respectively. The ocean model consists of 41 vertical layers with layer thicknesses between 3 m close to the surface and 12 m at 250 m depth, which is the maximum depth in the model. For comparison with uncoupled RCA3 simulations, runs with a horizontal resolution of 50 km for the atmosphere were also performed (Table 2). Within RCAO a recently developed river routing scheme provides the discharge from the land to the sea.

P3 and P4 do not show significant homology to any peptide with structures previously elucidated. INK 128 in vivo For these last I-Tasser server was utilized in construct models combining ab initio and threading methodologies. Models validation was realized by using C-score and TM-score parameters. C-score is based on the significance of threading template alignment and varies between −5 and 2 and positive values indicate better quality of predicted models. TM-score standards were used for measuring similarities between two structures, which are usually used to measure the accuracy of model when the native structures are known. Models with TM-score higher than 0.5 indicate a model with

correct topology. Predicted P1, P2, P3 and P4 tridimensional models were evaluated using PROCHECK for analysis of stereochemical quality. In addition RMSDs were calculated for superposition of Cα traces and backbones onto the templates structures through the program 3DSS. The peptides structures were visualized and analyzed on Delano Scientific’s PYMOL (http://pymol.sourceforge.net/).

All data were analyzed by Student’s test and ANOVA. P values below 0.05 were considered significant. Using a software designed by us to identify Selleck Caspase inhibitor antimicrobial peptide sequences in the transcriptome and genome databases, it was possible to abbreviate and find out the search for these molecules. This software was used to scan the transcriptome of the human pathogenic fungus P. brasiliensis and the human genome to find amino acids sequences that presented antimicrobial characteristics

according to algorithms previously designed to identify, among other characteristics, the presence of specific amino acids residues. Data presented here are part of a research line including the sequencing of the P. brasiliensis transcriptome focusing on further molecular drug targets identification. In this view, P. brasiliensis database was explored cAMP in order to find novel antimicrobial peptides since few is known about the presence of such compounds in this species. Nevertheless in last few years the presence of antimicrobials in pathogens has been widely described due to necessity of pathogenic fungi to develop defense mechanisms to compete and survive to the presence of other microorganisms [17] and [21]. After performing the scan on the genomic databases, some possible amino acids sequences with the desired characteristics previously defined were identified. Of these, we selected the four most promising that contained the higher algorithms score previously developed (data not shown) and also that have higher fitness to APD2 best scores for antimicrobial peptides [47], such as presence of positively charged amino acid residues, peptide length and the balance between cationic charge and hydrophobicity. They were then chemically synthesized, purified, sequences confirmed by MALD-TOF/TOF and investigated in vitro for hemocompatibility and antimicrobial activity.

This volume will be referred to as the “RO-reviewed

TES CTV,” which is used to produce the planning target volume (PTV). For the purposes of comparing the dosimetric effect of the RO modifications, a second PTV was also generated directly from the Raw TES CTV, which will be referred to as the “Raw TES PTV.” The guidelines for the creation of the PTV at this institution recommend applying 0.3–0.5 cm lateral, 0–0.3 cm anterior, and 0.5 cm superior Talazoparib margins to the CTV. No planning margins are added posteriorly or inferiorly to spare the rectum and penile bulb. Although small variations in the size of the margins were present among clinically generated PTVs, the margins applied to generate the Raw TES PTVs for this study complied with the guideline recommendations (0.3 cm lateral, 0.2 cm anterior, and 0.5 cm superior). An additional LDE225 component of this study involved the use of contours that were generated completely manually (i.e., without the presence of any preliminary contours on the image sets) by multiple blinded observers (ROs, radiation therapists, and/or individuals trained by experts). We will describe these contours and their derivative structures as “manually”

generated to distinguish them from the “RO-reviewed TES” contours, which are informed by the TES algorithm. Brachytherapy treatment plans were developed for the PTVs by a single medical physicist. These plans adhered to the standard BCCA planning algorithm, which can be generally described as following a Montelukast Sodium low-activity (0.424 U) modified peripheral loading strategy using custom-loaded, stranded seeds (RAPIDStrand; Oncura, Arlington

Heights, IL). Each plan is designed to provide 97% or higher coverage of the PTV and 99% or higher coverage of the CTV by the 100% (144 Gy) isodose, with a CTV V150 between 56% and 65% and PTV V150 between 50% and 60%. The V150 is geometrically biased to the posterolateral aspects of the target. The volume that does not reach prescription dose in planning is confined to a small region of the anterior base of the PTV whenever possible. To evaluate the TES method, two types of comparisons were carried out: volumetric and dosimetric. The volumetric comparisons aimed at evaluating the spatial agreement between Raw TES and RO-reviewed TES contours. The dosimetric comparisons were designed to investigate what the impact on coverage of the RO-reviewed PTV would have been if planning had been performed directly on the Raw TES PTV. To do this, treatment plans were originally created on Raw TES contours, while satisfying the BCCA planning goals, and subsequently superimposed on the corresponding RO-reviewed TES contours. Plans derived from Raw TES PTVs were also compared with the plans created on the manual contours of different observers on the same image set. Details of each of the evaluation methods are described in the next section. We will first define the evaluation measures used in this article.

A apresentação neurológica

surge habitualmente na 2.a ou 3.a década de vida5 e compreende os sintomas parkinsónicos e os pseudo-bulbares, Nutlin-3a in vivo nomeadamente disfagia e disartria. A apresentação psiquiátrica, sem outros sintomas associados, ocorre em cerca de 20% dos doentes, sendo a depressão a sintomatologia mais frequente6. Os anéis de Kayser-Fleischer resultam da deposição de cobre na membrana de Descemet da córnea, podem ser observados através da lâmpada de fenda e estão presentes em 50-60% dos doentes com envolvimento hepático e em 90% dos doentes com doença neurológica7. Na doença hepática de etiologia não conhecida, quando o doente apresenta ceruloplasmina < 20 mg/dL, cuprúria > 0,6 μmol/24 h e anéis de Kayser-Fleischer, pode-se

estabelecer o diagnóstico de DW, sem ser necessário recorrer a outros exames complementares de diagnóstico8, tal como se verificou no nosso caso clínico. Quando estes 3 critérios não estão presentes, torna-se necessário realizar biópsia hepática para quantificar o cobre hepático. A terapêutica farmacológica é a pedra angular no tratamento destes doentes, tendo maior eficácia se iniciada precocemente e mantida ao longo da vida. As armas terapêuticas disponíveis são os quelantes do cobre, nomeadamente a penicilamina e a trientina, e o acetato de zinco, que diminui a absorção BIRB 796 intestinal de cobre, podendo ser utilizado em associação com os quelantes. No caso Alectinib clinical trial do nosso doente, optou-se por utilizar a trientina, uma vez que este fármaco, quando administrado em doses apropriadas, tem eficácia semelhante à penicilamina e tem a vantagem de apresentar menos efeitos adversos8. Os familiares em primeiro grau de um doente com DW devem efetuar o rastreio da doença. A DW quando diagnosticada e tratada atempadamente,

geralmente apresenta bom prognóstico, não estando preconizado o rastreio para o carcinoma hepatocelular3. Os autores declaram não haver conflito de interesses. “
“A pseudolipomatose do tubo digestivo é uma entidade benigna, raramente descrita, diagnosticada durante a realização de endoscopia e cuja etiologia permanece por esclarecer. É mais frequentemente descrita no cólon com uma prevalência estimada entre 0,02 e 1,7% dos exames endoscópicos1, havendo pouco mais de 60 casos publicados2. A sua ocorrência no tubo digestivo superior é extremamente rara, existindo apenas um relato de pseudolipomatose gástrica e outro de pseudolipomatose duodenal, apesar de histologicamente não ser um achado tão raro. Esta entidade foi inicialmente descrita por Snover et al. em 19853 e caracteriza-se histologicamente pela presença de vacúolos oticamente vazios no córion, medindo entre 50 a 600 micrómetros, por vezes associado a um infiltrado inflamatório mononuclear.

76 ± 11.33%, p = 0.012 in ELD; 7.44 ± 9.43%, p < 0.001 in ALF), the increase was significantly less in the ELD group than in the ALF group (p = 0.049) ( Fig. 2). Collectively, these results suggest that ELD maintained the biomechanical properties of the femoral neck more effectively. The percentage changes in BMD, bone geometry, and biomechanical properties in the femoral shaft were compared between the ELD

group and the ALF group (Fig. 3). Cortical vBMD in the shaft decreased significantly in click here both the ELD group (− 10.13 ± 4.54%, p < 0.001) and the ALF group (− 11.85 ± 4.58%, p < 0.001) ( Fig. 3); however, the percentage decrease was significantly smaller in the ELD group than in the ALF group (p = 0.026). Although the total area increased significantly from baseline in both the ELD and ALF groups, the bone area of the femoral shaft increased significantly only in the ELD group (1.75 ± 3.24%, p < 0.001). Outer perimeter increased significantly from baseline in both treatment groups (0.92 ± 1.67%, p < 0.001 in ELD; 0.94 ± 2.22%, p < 0.001 in ALF), with no difference between the two groups. Inner perimeter increased significantly in both groups (0.76 ± 2.75%, p = 0.023 in ELD;

1.85 ± 3.52%, p < 0.001 in ALF); however, selleck the percentage increase was significantly greater in the ALF group than in the ELD group (p = 0.042). CSMI in the femoral shaft increased significantly from baseline in both the ELD and ALF groups. Thus, although there was no difference between groups with respect to this biomechanical parameter, the increase in ADAMTS5 inner perimeter, presumably due to accelerated resorption, was more effectively prevented by ELD.

A recent randomized, double-blind study to compare the effects of ELD with ALF demonstrated the superiority of ELD over the active comparator, especially with respect to non-vertebral fractures [20]. In order to gain insight into the biomechanical basis underlying this clinically verified anti-fracture action of ELD, we took a subgroup of the randomized study and used clinical MDCT scanning to compare the effects of ELD and ALF on the 3D structure of the proximal femur, focusing particularly on the cortical component and biomechanical properties. Our study not only revealed the distinct action of ELD on the cortical compartment but also provided evidence for the improvement of biomechanical properties. In the femoral neck, whereas cross-sectional cortical thickness decreased in the ALF group, it was maintained in the ELD group. Taken together with the results that the cortical perimeter increased in both the ALF and ELD groups, it is suggested that ELD was more effective than ALF in countering endocortical bone resorption, thereby maintaining cortical thickness. This is also consistent with the trend for increased CSA by ELD. Fig. 4 schematically illustrates the distinct actions of ELD and ALF on the cortical geometry and density of the femoral neck and shaft.