Osteoporosis Prediction Using Machine-Learned Optical Bone Densitometry Data.

Optical bone densitometry (OBD) has been developed for the early detection of osteoporosis. In recent years, machine learning (ML) techniques have been actively implemented for the areas of medical diagnosis and screening with the goal of improving diagnostic accuracy. The purpose of this study was to verify the feasibility of using the combination of OBD and ML techniques as a screening tool for osteoporosis. Dual energy X-ray absorptiometry (DXA) and OBD measurements were performed on 203 Thai subjects. From the OBD measurements and readily available demographic data, machine learning techniques were used to predict the T-score measured by the DXA. The T-score predicted using the Ridge regressor had a correlation of r = 0.512 with respect to the reference value. The predicted T-score also showed an AUC of 0.853 for discriminating individuals with osteoporosis. The results obtained suggest that the developed model is reliable enough to be used for screening for osteoporosis.

Development of statistical regression and artificial neural network models for estimating nitrogen, phosphorus, COD, and suspended solid concentrations in eutrophic rivers using UV-Vis spectroscopy.

River water quality monitoring is crucial for understanding water dynamics and formulating policies to conserve the water environment. In situ ultraviolet-visible (UV-Vis) spectrometry holds great potential for real-time monitoring of multiple water quality parameters. However, establishing a reliable methodology to link absorption spectra to specific water quality parameters remains challenging, particularly for eutrophic rivers under various flow and water quality conditions. To address this, a framework integrating desktop and in situ UV-Vis spectrometers was developed to establish reliable conversion models. The absorption spectra obtained from a desktop spectrometer were utilized to create models for estimating nitrate-nitrogen (NO3-N), total nitrogen (TN), chemical oxygen demand (COD), total phosphorus (TP), and suspended solids (SS). We validated these models using the absorption spectra obtained from an in situ spectrometer. Partial least squares regression (PLSR) employing selected wavelengths and principal component regression (PCR) employing all wavelengths demonstrated high accuracy in estimating NO3-N and COD, respectively. The artificial neural network (ANN) was proved suitable for predicting TN in stream water with low NH4-N concentration using all wavelengths. Due to the dominance of photo-responsive phosphorus species adsorbed onto suspended solids, PLSR and PCR methods utilizing all wavelengths effectively estimated TP and SS, respectively. The determination coefficients (R2) of all the calibrated models exceeded 0.6, and most of the normalized root mean square errors (NRMSEs) were within 0.4. Our approach shows excellent efficiency and potential in establishing reliable models monitoring nitrogen, phosphorus, COD, and SS simultaneously. This approach eliminates the need for time-consuming and uncertain in situ absorption spectrum measurements during model setup, which may be affected by fluctuating natural and anthropogenic environmental conditions.

Optical bone densitometry insensitive to skin thickness.

Skin thickness, including the adipose layer, which varies from individual to individual, affects the bone density measurement using light. In this study, we proposed a method to measure skin thickness using light and to correct the bias caused by differences in skin thickness and verified the proposed method by experiments using a phantom. We measured simulated skin of different thicknesses and bovine trabecular bone of different bone mineral densities (BMDs) using an optical system consisting of lasers of 850 and 515 nm wavelengths, lenses, and slits. Although the slope of the light intensity distribution formed on the surface of the material when irradiated by the 850 nm laser is affected by the thickness of the skin phantom. The difference of the intensity distribution peaks (δy) between the 850 and 515 nm lasers was strongly correlated with the thickness of the skin phantom. The coefficient of determination between the measurements and the BMD was improved by correcting the 850 nm laser measurements with δy. This result suggests that the method is applicable to optical bone densitometry, which is insensitive to differences in skin thickness.

Perineal herniorrhaphy with pedunculated tunica vaginalis communis in dogs: Description of the technique and clinical case series.

Background: Perineal hernia (PH) in dogs is caused by the separation of the anal septal muscles and the displacement of pelvic/abdominal organs under the perineal skin. Reconstruction of the pelvic septum by surgical repositioning is the only curative treatment. Objectives: To describe the procedure and outcomes of surgical repair using the pedunculated tunica vaginalis communis (TVC) for PH in dogs. Methods: Intact male dogs diagnosed with PH were included in this study. For surgery, each dog was positioned in the Trendelenburg position. Castration was performed with the open technique, followed by colopexy and cystopexy via laparotomy. The remaining bilateral TVCs transposed to the opening of PH were used for the perineal herniorrhaphy. Intraoperative findings, complications, and outcomes were evaluated and recorded. Results: Eight dogs [median age 10.5 years (range, 9-13 years); median body weight 4.9 kg (range, 1.6-12.3 kg)] were treated using the TVC surgical technique. Perineal herniorrhaphy with the TVC was feasible in all dogs. The median operation time was 105.5 min (range, 46-149 min) in unilateral PH, and 92 and 122 min in two dogs with bilateral PH. Short-term postoperative complications during hospitalization did not occur in six dogs, whereas the residual two dogs had a temporary local infection as a minor complication. Postoperative recurrence occurred in one dog (13%) on postoperative day 136. Conclusions: Our study suggests that the herniorrhaphy technique using the pedunculated TVC is an alternative option for the repair of PH in dogs.

Optical bone densitometry robust to variation of soft tissue using machine learning techniques: validation by Monte Carlo simulation.

SIGNIFICANCE: To achieve early detection of osteoporosis, a simple bone densitometry method using optics was proposed. However, individual differences in soft tissue structure and optical properties can cause errors in quantitative bone densitometry. Therefore, developing optical bone densitometry that is robust to soft tissue variations is important for the early detection of osteoporosis. AIM: The purpose of this study was to develop an optical bone densitometer that is insensitive to soft tissue, using Monte Carlo simulation and machine learning techniques, and to verify its feasibility. APPROACH: We propose a method to measure spatially resolved diffuse light from three directions of the biological tissue model and used machine learning techniques to predict bone density from these data. The three directions are backward, forward, and lateral to the direction of ballistic light irradiation. The method was validated using Monte Carlo simulations using synthetic biological tissue models with 1211 different random structural and optical properties. RESULTS: The results were computed after a 10-fold cross-validation. From the simulated optical data, the machine learning model predicted bone density with a coefficient of determination of 0.760. CONCLUSIONS: The optical bone densitometry method proposed in this study was found to be robust against individual differences in soft tissue.

High frequency of upper aerodigestive tract manifestations in mucous membrane pemphigoid.

OBJECTIVE: The objective of this study was to evaluate the frequency of upper aerodigestive tract involvement in patients with mucous membrane pemphigoid associated with desquamative gingivitis. SUBJECTS AND METHODS: Data from 25 patients were collected by retrospective chart review. Their upper aerodigestive had been evaluated using a conventional flexible fiberscope. Oral disease activity was quantified on the basis of the Mucous Membrane Pemphigoid Disease Area Index activity score. RESULTS: Lesions of the upper aerodigestive tract were confirmed in nine symptomatic patients (9/25, 36%), of which five (5/25, 20%) had laryngeal involvement. No lesions were seen in the asymptomatic patients on fiberscope examination. There was a statistically significant difference in the symptoms, high oral disease activity score, and linear IgA deposition on direct immunofluorescence between patients with and without upper aerodigestive tract lesions (p = .001, .001, .002, respectively). CONCLUSION: The high frequency of considerable complications highlights the importance of confirming the presence of upper aerodigestive tract involvement in patients with mucous membrane pemphigoid having desquamative gingivitis. Signs including the presence of symptoms, high oral disease activity score, or linear IgA deposition on direct immunofluorescence might indicate a higher risk of upper aerodigestive tract involvement.

Effect of Layer Directions on Internal Structures and Tensile Properties of 17-4PH Stainless Steel Parts Fabricated by Fused Deposition of Metals.

17-4PH stainless steel specimens were fabricated by fused deposition of metals (FDMet) technology, which combines 17-4PH particles with an organic binder. FDMet promises a low-cost additive manufacturing process. The present research aims to clarify the influence of layer directions in the 3D printing process on the mechanical and shrinkage properties of as-sintered and as-aged specimens. All specimens (the as-sintered and as-aged specimens printed in three layer directions) exhibited high relative density (97.5-98%). The highest ultimate strengths (880 and 1140 MPa in the as-sintered and as-aged specimens, respectively) were obtained when the layer direction was perpendicular to the tensile direction. Conversely, the specimens printed with their layer direction parallel to the tensile direction presented a low ultimate strength and low strain at breakage. The fact that the specimens with their layer direction parallel to the tensile direction presented a low ultimate strength and low strain at breakage is a usual behavior of parts obtained by means of FDM. The SEM images revealed oriented binder domains in the printed parts and oriented voids in the sintered parts. It was assumed that large binder domains in the filament were oriented perpendicular to the layer directions during the fused deposition modeling printing, and remained as oriented voids after sintering. Stress concentration in the oriented void defects was likely responsible for the poor tensile properties of these specimens.

Influence of the Layer Directions on the Properties of 316L Stainless Steel Parts Fabricated through Fused Deposition of Metals.

Metal specimens were fabricated via the fused deposition of metals (FDMet) technique with a filament composed of the 316L stainless steel particles and an organic binder. This process was adopted due to its potential as a low-cost additive manufacturing process. The objective of this study is to investigate the influence of the processing conditions-layer directions and layer thicknesses-on the mechanical and shrinkage properties of the metal components. The specimens were printed in three different layer directions. The highest ultimate strength of 453 MPa and strain at break of 48% were obtained in the specimen printed with the layer direction perpendicular to the tensile direction. On the other hand, the specimen printed in the layer direction parallel to the tensile direction exhibited poor mechanical properties. The reason for the anisotropy of the properties was investigated through systematic SEM observations. The observations revealed the presence of segregated binder domains in the filaments. It was deduced that the binder domain was oriented in the direction perpendicular to that of the layer and remained as oriented voids even after sintering. The voids oriented perpendicular to the tensile direction act as defects that could cause stress concentration, thus resulting in poor mechanical properties.

Acantholysis may precede elevation of circulating anti-desmoglein 3 antibody levels in pemphigus vulgaris presenting with desquamative gingivitis.

Pemphigus vulgaris (PV) is an autoimmune, blistering disease that affects the mucosa and skin. The current theory favors the concept that anti-desmoglein (Dsg) 3 autoimmunity is the only pathogenic event needed to induce acantholysis. However, a few cases of active PV in the oral cavity had no detectable anti-Dsg 3 antibody. The aim of this study was to evaluate the differences in clinical and laboratory findings, whether or not the anti-Dsg 3 antibodies were present. This study was based on a retrospective review of 10 PV cases. The evaluation of the circulating autoantibody titers to Dsg 3 was conducted by using enzyme-linked immunosorbent assay (ELISA). An index value of 20 or more was used as the cutoff for a positive reaction. Only five of the 10 PV cases had a positive Dsg 3 ELISA. There were no differences in clinical, cytological, histopathological, and direct immunofluorescence findings, whether or not the anti-Dsg 3 antibodies were present. Of the five patients with a negative reaction at the time of diagnosis, the Dsg 3 ELISA became positive in the follow-up period in three cases. In the remaining two cases, the Dsg 3 ELISA was consistently negative for 18 months. Dsg 3 ELISA was negative early in some PV cases. Therefore, PV acantholysis may precede the elevation of circulating anti-Dsg 3 antibody levels. The diagnosis of PV should be considered based on comprehensive clinical, histopathological, and immunofluorescent criteria.

Random Electromyostimulation Promotes Osteogenesis and the Mechanical Properties of Rat Bones.

Exercise is often recommended as a promising non-pharmacologic countermeasure to prevent osteoporosis. However, elderly osteoporotic patients generally have physical fitness difficulties preventing them from performing effective and sustainable exercise. Electromyostimulation should be one effective modality for non-pharmacological prevention of osteoporosis without any voluntary physical movements. However, successful stimulation patterns remain controversial. As suggested by our previous in vitro studies, randomized timing of stimulation could be a candidate to maximize the osteogenic effect of electromyostimulation. In this study, the effects of random stimulation to the quadriceps on osteogenesis in the femurs were investigated using rats, in comparison with a periodic stimulation pattern. In histomorphometric assessments, both stimulation patterns demonstrated increases in bone formation rate either in cortical bone at the midshaft or in trabecular bone at the femoral neck on the stimulated side. However, maximum load and strain energy to failure were enhanced only by the random stimulation, on either the stimulated or non-stimulated side. It is concluded that randomized muscle stimulation has effective osteogenic capability at the stimulation site, similar to periodic stimulation; however, its effectiveness on mechanical properties is expandable to other non-stimulated sites.

[Mechanical strength and mechano-compatibility of tissue-engineered bones].

Current artificial bones made of metals and ceramics may be replaced around a decade after implantation due to its low durability, which is brought on by a large difference from the host bone in mechanical properties, i.e., low mechano-compatibility. On the other hand, tissue engineering could be a solution with regeneration of bone tissues from stem cells in vitro. However, there are still some problems to realize exactly the same mechanical properties as those of real bone. This paper introduces the technical background of bone tissue engineering and discusses possible methods for installation of mechano-compatibility into a regenerative bone. At the end, future directions toward the realization of ideal mechano-compatible regenerative bone are proposed.

Frequency-Dependence of Mechanically Stimulated Osteoblastic Calcification in Tissue-Engineered Bone In Vitro.

The effect of mechanical stimulation on osteogenesis remains controversial, especially with respect to the loading frequency that maximizes osteogenesis. Mechanical stimulation at an optimized frequency may be beneficial for the bone tissue regeneration to promote osteoblastic calcification. The objective of this study was to investigate the frequency-dependent effect of mechanical loading on osteoblastic calcification in the tissue-engineered bones in vitro. Tissue-engineered bones were constructed by seeding rat osteoblasts into a type I collagen sponge scaffold at a cell density of 1600 or 24,000 cells/mm(3). Sinusoidal compressive deformation at the peak of 0.2% was applied to the tissue-engineered bones at 0.2, 2, 10, 20, 40, and 60 Hz for 3 min/day for 14 consecutive days. Optically-monitored calcium content started to increase on days 5-7 and reached the highest value at 2 Hz on day 14; however, no increase was observed at 0.2 Hz and in the control. Ash content measured after the mechanical stimulation also showed the highest at 2 Hz despite the differences in cell seeding density. It was concluded that mechanical stimulation at 2 Hz showed the highest promotional effect for osteogenesis in vitro among the frequencies selected in this study.

Effects of cryopreservation on the cell viability, proliferative capacity and neuronal differentiation potential of canine bone marrow stromal cells.

We investigated the cell viability, proliferative capacity and neuronal differentiation potential of canine bone marrow stromal cells (BMSCs) after cryopreservation. BMSCs were cryopreserved using cryoprotectant solutions with 10% DMSO and 10% FBS (DF group) or without DMSO and FBS (DF-free group); fresh BMSCs were used as a control. The cell viability and proliferative capacity of BMSCs were similar in the DF-free and control groups, while those in the DF group were lower. In all groups, BMSCs differentiated into neuron-like cells that stained positive against neuron markers, and the mRNA expression levels of neuron markers increased after neuronal induction. In conclusion, cryopreservation with DF-free cryoprotectant solution did not diminish the cell viability, proliferative capacity or neuronal differentiation potential of canine BMSCs.

Influence of an autologous serum-supplemented medium on the proliferation and differentiation into neurons of canine bone marrow stromal cells.

We investigated the influence of autologous serum (AS)-supplemented medium on the proliferation and differentiation into neurons of canine bone marrow stromal cells (BMSCs). Canine BMSCs were cultured using α-MEM only, α-MEM with 10% fetal bovine serum (FBS), and 5, 10 and 20% AS-supplemented α-MEM. Growth of canine BMSCs was observed in all AS groups. The proliferation capacity of canine BMSCs in the AS groups was similar to that in the FBS group. No significant differences between the FBS and AS groups were observed in the percentage of the cells that changed to the neuron-like morphology and neuron-specific enolase-positive ratio after neuronal differentiation. Canine BMSCs cultured using AS-supplemented medium were able to proliferate and showed neuronal differentiation potency.

Proliferation capacity, neuronal differentiation potency and microstructures after the differentiation of canine bone marrow stromal cells into neurons.

We examined the proliferation capacity and neuronal differentiation potency of canine bone marrow stromal cells (BMSCs). In addition, the microstructures of neuron-like cells after neuronal differentiation were observed under a scanning electron microscope. Canine BMSCs grew to confluency at 10.0 ± 2.5 days, and 3.8 ± 2.1 × 10(6) BMSCs were collected in one passage. Approximately 65% of canine BMSCs changed to neuron-like morphology after neuronal differentiation, and nearly all neuron-like cells stained positive against neuron-specific enolase. In addition, microstructures such as the cellular organelles, filaments and growth cones of these cells bore a close resemblance to those of the original mature neurons. These results suggested that canine BMSCs might be capable of differentiating into neurons.

Plasma adrenomedullin concentration in dogs with myxomatous mitral valvular disease.

Adrenomedullin (AM), a peptide identified to have vasodilating and natriuretic effects, is involved in the regulation of the cardiovascular system. To evaluate plasma AM concentration in dogs with myxomatous mitral valvular disease (MMVD), and to investigate the associations between the concentrations of plasma AM and natriuretic peptides and the echocardiographic data, we evaluated plasma AM concentrations in 31 healthy control dogs and 57 dogs with MMVD. Plasma AM concentrations in dogs with MMVD were higher than that in the control subjects. The plasma AM concentration increased in conjunction with the severity of heart failure according to the International Small Animal Cardiac Health Council (ISACHC). The AM concentrations were 25.1 ± 5.0 fmol/ml (ISACHC class Ia), 29.9 ± 11.0 fmol/ml (ISACHC class Ib), 43.4 ± 19.8 fmol/ml (ISACHC class II) and 73.5 ± 21.7 fmol/ml (ISACHC class III) and 7.5 ± 5.1 fmol/ml (control group), respectively. The receiver operating characteristic curve indicated an area of 0.93 (95% CI, 0.8801-0.9889; <0.0001), a cutoff value of 30.5 fmol/ml, a sensitivity of 87.1%, and a specificity of 82.5% for the determination of congestive heart failure. Plasma AM concentrations correlated with atrial natriuretic peptide concentrations, LA/Ao ratio, and left ventricular diameter. In conclusion, AM may be a potential diagnostic marker for canine MMVD and possibly plays a pathophysiological role in collaboration with the other neurohumoral factors such as natriuretic peptides.

Moderate joint loading reduces degenerative actions of matrix metalloproteinases in the articular cartilage of mouse ulnae.

Joint loading is a recently developed loading modality, which can enhance bone formation and accelerate healing of bone fracture. Since mechanical stimulation alters expression of matrix metalloproteinases (MMPs) in chondrocytes, a question addressed herein was, does joint loading alter actions of MMPs in the articular cartilage? We hypothesized that expression and activity of MMPs are regulated in a load-intensity-dependent manner and that moderate load scan downregulates MMPs. To test this hypothesis, a mouse elbow-loading model was employed. In the articular cartilage of an ulna, the mRNA levels of a group of MMPs as well as their degenerative activities were determined. The result revealed that elbow loading altered the expression and activities of MMPs depending on its loading intensity. Collectively, the data in this study indicate that 0.2 and 0.5 N joint loading significantly reduced the expression of multiple MMPs, that is, MMP-1, MMP-3, MMP-8, and MMP-13, and overall activities of collagenases or gelatinases in articular cartilage, while higher loads increased the expression and activity of MMP-1 and MMP-13. Furthermore, moderate loads at 1 N elevated the mRNA level of CBP/p300-interacting transactivator with ED-rich tail 2 (CITED2), but higher loads at 4 N did not induce a detectable amount of CITED2 mRNA. Since CITED2 is known to mediate the downregulation of MMP-1 and MMP-13, the result indicates that joint loading at moderate intensity reduces MMP activities through potential induction of CITED2. MMPs such as MMP-1 and MMP-13 are predominant collagenases in the pathology of osteoarthritis. Therefore, joint loading could offer an interventional regimen for maintenance of joint tissues.

Schwannoma arising from the sublingual gland.

Sublingual gland tumors, especially mesenchymal tumors, are extremely rare. We describe the first reported case of schwannoma arising from the sublingual gland with details of the histopathologic and immunohistochemical features. A 70-year-old woman developed a painless swelling on the floor of the mouth. The excised material was sublingual gland tissue with an ovoid, grayish-yellow solid tumorous mass at the cut surface. The tumor was composed of proliferated spindle-shaped tumor cells exhibiting palisading patterns. In the center of the tumor, a small salivary gland component was recognized. Immunohistochemically, the tumor cells were strongly positive for S-100 protein but negative for neurofilament protein. The Ki-67 labeling index was 4.58. The clear presence of a remnant sublingual gland lobule in the present tumor provided convincing evidence that it was a schwannoma arising from the sublingual gland and thus the first of its type to be reported.

En block resection of a large hepatocellular carcinoma involving the caudal vena cava in a dog.

A 13-year-old neutered female Shih Tzu was referred for investigation of a cranial abdominal mass. Investigations including conventional radiography, abdominal ultrasonography and computed tomography confirmed the mass in the caudate lobe of the liver. As a collateral vein originating from the caudal vena cava (CVC) communicated with the azygos vein, the CVC was ligated and transected cranial to the right renal vein and cranial to the mass under temporary occlusion of the thoracic descending aorta and posthepatic CVC. The mass combined with the CVC was excised. The mass was confirmed as hepatocellular carcinoma (HCC). This report describes the first case with successful en bloc resection of a large HCC involving the CVC in a dog.

Comparative genomic analysis of 1047 completely sequenced cDNAs from an Arabidopsis-related model halophyte, Thellungiella halophila.

BACKGROUND: Thellungiella halophila (also known as T. salsuginea) is a model halophyte with a small size, short life cycle, and small genome. Thellungiella genes exhibit a high degree of sequence identity with Arabidopsis genes (90% at the cDNA level). We previously generated a full-length enriched cDNA library of T. halophila from various tissues and from whole plants treated with salinity, chilling, freezing stress, or ABA. We determined the DNA sequences of 20 000 cDNAs at both the 5'- and 3' ends, and identified 9569 distinct genes. RESULTS: Here, we completely sequenced 1047 Thellungiella full-length cDNAs representing abiotic-stress-related genes, transcription factor genes, and protein phosphatase 2C genes. The predicted coding sequences, 5'-UTRs, and 3'-UTRs were compared with those of orthologous genes from Arabidopsis for length, sequence similarity, and structure. The 5'-UTR sequences of Thellungiella and Arabidopsis orthologs shared a significant level of similarity, although the motifs were rearranged. While examining the stress-related Thellungiella coding sequences, we found a short splicing variant of T. halophila salt overly sensitive 1 (ThSOS1), designated ThSOS1S. ThSOS1S contains the transmembrane domain of ThSOS1 but lacks the C-terminal hydrophilic region. The expression level of ThSOS1S under normal growth conditions was higher than that of ThSOS1. We also compared the expression levels of Na+-transport-system genes between Thellungiella and Arabidopsis by using full-length cDNAs from each species as probes. Several genes that play essential roles in Na+ excretion, compartmentation, and diffusion (SOS1, SOS2, NHX1, and HKT1) were expressed at higher levels in Thellungiella than in Arabidopsis. CONCLUSIONS: The full-length cDNA sequences obtained in this study will be essential for the ongoing annotation of the Thellungiella genome, especially for further improvement of gene prediction. Moreover, they will enable us to find splicing variants such as ThSOS1S (AB562331).