Increased expression and phosphorylation of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoforms in urinary exosomes in pre-eclampsia.

BACKGROUND: Glycolysis is altered in various kidney diseases, but little is known about glycolysis in pre-eclampsia, a multi-system disorder with major pathological effects on the kidney. Urinary exosomes provide a non-invasive alternative for studying changes in kidney metabolism. This study aims to characterise the expression and phosphorylation of isozymes of the key glycolytic regulatory protein, 6-phosphofructokinase-2-kinase/fructose-2,6-bisphosphatase (PFK-2/FBPase-2), in urinary exosomes of subjects with pre-eclampsia (PE), compared to normotensive non-pregnant (NC) and normotensive pregnant (NP) controls. METHODS: A cross-sectional study of NC (n = 19), NP (n = 23) and PE (n = 29) subjects was performed. Exosomes were isolated from urine samples by differential ultracentrifugation, and then analyzed by Western blot and densitometry for expression of PFK-2/FBPase-2 isozymes (PFKFB2, PFKFB3 and PFKFB4) and phosphorylation of PFKFB2 at residues Ser483 and Ser466 and PFKFB3 at Ser461. RESULTS: PFKFB2 expression was increased 4.7-fold in PE compared to NP (p < 0.001). PFKFB2 phosphorylation at Ser483 was increased 2.6-fold in PE compared to NP (p = 0.002). Expression of phosphorylated PFKFB2/PFKFB3 at Ser466/Ser461 was increased in PE, being present in 77.4% (95% CI 59.9-88.9%) of PE and 8.3% (95% CI 1.2-27.0%) of NP samples (p < 0.001). PFKFB3 was more commonly expressed in PE, detected in 90.3% (95% CI 74.3-97.4%) of PE and 8.3% (95% CI 1.2-27.0%) of NP samples (p < 0.001). PFKFB4 had a 7.2-fold increase in expression in PE compared to NP (p < 0.001). No significant differences between NP and NC groups were observed. CONCLUSION: Regulatory proteins that increase glycolysis are increased in the urinary exosomes of subjects with pre-eclampsia, suggesting that renal glycolysis may be increased in this condition.

Decreased tibial nerve movement in patients with failed back surgery syndrome and persistent leg pain.

PURPOSE: To measure and compare the total and normalised tibial nerve movements during forward bending in patients with and without failed back surgery syndrome (FBSS) and persistent leg pain following anatomically successful lumbar decompression surgery and demonstrated no psychological stress. Nerve pathomechanics may contribute to FBSS with persistent leg pain following anatomically successful lumbar decompression surgery. METHODS: Tibial nerve movement during forward bending was measured in two groups of patients following anatomically successful lumbar decompression surgery. FBSS group (N = 37) consisted of patients with persistent leg pain following lumbar surgery, and non-FBSS (N = 37) were patients with no remaining leg pain following lumbar surgery. Total and normalised tibial nerve movement at the popliteal fossa was measured by a previously validated ultrasound imaging technique and compared between the two groups, and also between the painful and non-painful leg within the FBSS group. RESULTS: Both the mean total and normalised tibial nerve movement were significantly decreased in the FBSS group in both legs when compared to the non-FBSS group (P < 0.05). The total and normalised tibial nerve movements were also more restricted in the painful leg (P < 0.05) when compared to the non-painful side within the FBSS group. CONCLUSION: This was the first study to quantify the decreased total and normalised tibial nerve mobility in FBSS patients with persistent leg pain when compared with non-FBSS patients following anatomically successful lumbar decompression surgery. Further research could investigate the efficacy of intervention, such as nerve mobilisation in this particular group of patients with failed back surgery syndrome and limited nerve mobility. These slides can be retrieved under Electronic Supplementary Material.

Realistic kinetic loading of the jaw system during single chewing cycles: a finite element study.

Although knowledge of short-range kinetic interactions between antagonistic teeth during mastication is of essential importance for ensuring interference-free fixed dental reconstructions, little information is available. In this study, the forces on and displacements of the teeth during kinetic molar biting simulating the power stroke of a chewing cycle were investigated by use of a finite-element model that included all the essential components of the human masticatory system, including an elastic food bolus. We hypothesised that the model can approximate the loading characteristics of the dentition found in previous experimental studies. The simulation was a transient analysis, that is, it considered the dynamic behaviour of the jaw. In particular, the reaction forces on the teeth and joints arose from contact, rather than nodal forces or constraints. To compute displacements of the teeth, the periodontal ligament (PDL) was modelled by use of an Ogden material model calibrated on the basis of results obtained in previous experiments. During the initial holding phase of the power stroke, bite forces were aligned with the roots of the molars until substantial deformation of the bolus occurred. The forces tilted the molars in the bucco-lingual and mesio-distal directions, but as the intrusive force increased the teeth returned to their initial configuration. The Ogden material model used for the PDL enabled accurate prediction of the displacements observed in experimental tests. In conclusion, the comprehensive kinetic finite element model reproduced the kinematic and loading characteristics of previous experimental investigations.

Improving inferential analyses predata and postdata.

The standard statistical procedure for researchers comprises a two-step process. Before data collection, researchers perform power analyses, and after data collection, they perform significance tests. Many have proffered arguments that significance tests are unsound, but that issue will not be rehashed here. It is sufficient that even for aficionados, there is the usual disclaimer that null hypothesis significance tests provide extremely limited information, thereby rendering them vulnerable to misuse. There is a much better postdata option that provides a higher grade of useful information. Based on work by Trafimow and his colleagues (for a review, see Trafimow, 2023a), it is possible to estimate probabilities of being better off or worse off, by varying degrees, depending on whether one gets the treatment or not. In turn, if the postdata goal switches from significance testing to a concern with probabilistic advantages or disadvantages, an implication is that the predata goal ought to switch accordingly. The a priori procedure, with its focus on parameter estimation, should replace conventional power analysis as a predata procedure. Therefore, the new two-step procedure should be the a priori procedure predata and estimations of probabilities of being better off, or worse off, to varying degrees, postdata. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Expression of NEDD4L and ENaC in Urinary Extracellular Vesicles in Pre-eclampsia.

OBJECTIVE: To assess changes in expression of renal epithelial sodium channel (ENaC) and NEDD4L, a ubiquitin ligase, in urinary extracellular vesicles (UEV) of pre-eclamptic women compared to normal pregnant controls. METHODS: Urine was collected from pre-eclamptic women (PE, n = 20) or during normal pregnancy (NP, n = 20). UEV were separated by differential ultracentrifugation. NEDD4L, α-ENaC and γ-ENaC were identified by immunoblotting. RESULTS: There was no difference in the expression of NEDD4L (p = 0.17) and α-ENaC (p = 0.10). PE subjects showed increased expression of γ-ENaC by 6.9-fold compared to NP (p < 0.0001). CONCLUSION: ENaC expression is upregulated in UEV of pre-eclamptic subjects but was not associated with changes in NEDD4L.

Statistical properties of bit-plane probability model and its application in supervised texture classification.

The modeling of wavelet subband histograms via the product Bernoulli distributions (PBD) has received a lot of interest and the PBD model has been applied successfully in texture image retrieval. In order to fully understand the usefulness and effectiveness of the PBD model and its associated signature, namely, the bit-plane probability (BP) signature on image processing applications, we discuss and investigate some of their statistical properties. These properties would help to clarify the sufficiency of the BP signature to characterize wavelet subbands, which, in turn, justifies its use in real time applications. We apply the BP signature on supervised texture classification problem and experimental results suggest that the weighted L(1)-norm (rather than the standard L (1)-norm) should be used for the BP signature. Comparative classification experiments show that our method outperforms the current state-of-the-art Generalized Gaussian Density approaches.

Point injection as an alternative acupuncture technique--an exploratory study of responses in healthy subjects.

INTRODUCTION: Point injection as a therapeutic technique is well documented, but its physiological effects have not been formally compared with traditional acupuncture. One aim of this study was to compare the effects of the two techniques at one acupuncture point, as a step towards understanding the mode of action of point injection and validating its clinical use. A second aim was to explore whether repeated point injection at the same site might provide a way of increasing the dose of stimulation, in the hope of identifying a dose response curve which could be an alternative strategy to placebo control in demonstrating the biological effects of acupuncture. METHODS: Sixty nine healthy subjects (age range 18-56 years, mean 29.9; 48 females) completed the study, which employed a counterbalanced experimental design with two stimulation sessions of LI4 approximately one week apart. One half of the participants received point injection first, and the other half received traditional acupuncture first. Baseline physiological data were recorded, then measurements were made before, during and after stimulation; each subject also reported needle sensation (de qi). The measures were heart rate, derived pressure rate product and mean arterial pressure. RESULTS: Although stronger sensations of de qi were reported with point injection, no significant differences were found for mean heart rate (HR), pressure rate product (PRP) and mean arterial pressure (MAP) before and after stimulation by the two techniques. No subject gender or age bias was encountered and previous exposure to acupuncture had no effect on outcome. Power spectral analysis of heart rate variability (HRV) made on data from a small subset (n=10) of this cohort also showed no significant differences in autonomic response. CONCLUSION: Point injection and traditional acupuncture seem to provoke similar physiological responses, although the greater needle sensation seen with point injection might indicate it could have more powerful clinical effects. Further studies of repeated point injection are necessary to indicate whether this technique may provide a method of increased strength of point stimulation, as an alternative to traditional needling in acupuncture research.

Weight-HbA1c-insulin-glucose model for describing disease progression of type 2 diabetes.

A previous semi-mechanistic model described changes in fasting serum insulin (FSI), fasting plasma glucose (FPG), and glycated hemoglobin (HbA1c) in patients with type 2 diabetic mellitus (T2DM) by modeling insulin sensitivity and ß-cell function. It was later suggested that change in body weight could affect insulin sensitivity, which this study evaluated in a population model to describe the disease progression of T2DM. Nonlinear mixed effects modeling was performed on data from 181 obese patients with newly diagnosed T2DM managed with diet and exercise for 67 weeks. Baseline ß-cell function and insulin sensitivity were 61% and 25% of normal, respectively. Management with diet and exercise (mean change in body weight = -4.1 kg) was associated with an increase of insulin sensitivity (30.1%) at the end of the study. Changes in insulin sensitivity were associated with a decrease of FPG (range, 7.8-7.3 mmol/L) and HbA1c (6.7-6.4%). Weight change as an effector on insulin sensitivity was successfully evaluated in a semi-mechanistic population model.

Exact inbreeding coefficients in populations with overlapping generations.

A theory is given that allows inbreeding coefficients to be calculated exactly for populations with overlapping generations. Emphasis is placed on providing equations well suited for computer iteration. Both monoecious and dioecious populations are considered and family size is not restricted to being Poisson. One-locus and two-locus inbreeding coefficients are evaluated, although the reader may omit the two-locus sections. The exact treatment is shown to be preferable to approximate treatments in that it applies to both early and late generations for all populations sizes. Inbreeding effective numbers found by the exact treatment are compared to various approximate numbers, and the approximate values are found to be generally very good.

Alteration of lysophosphatidylcholine content in low density lipoprotein after oxidative modification: relationship to endothelium dependent relaxation.

OBJECTIVE: The aim was to examine the formation of lipid peroxidation products and the alteration in phospholipid content in low density lipoprotein (LDL) after oxidative modification by CuSO4, and subsequently, to determine the ability of the modified LDL to impair endothelium dependent relaxation in rat aortic rings. METHODS: Blood samples were obtained from normal human volunteers. LDL was prepared by sequential ultracentrifugation and it was oxidatively modified in the presence of 5 microM CuSO4. Lipid peroxidation products (thiobarbituric acid reactive substances, TBARS), and alterations in electrophoretic mobility and phospholipid content were determined in normal (native) and oxidised LDL. Endothelium dependent relaxation was produced by acetylcholine (10(-8)-10(-5) M) in phenylephrine precontracted rat aortic rings. RESULTS: LDL incubated for 24 h with 5 microM CuSO4 at 20 degrees C and 37 degrees C with constant agitation displayed higher amounts of TBARS than the respective native LDL. While the amounts of TBARS in LDL modified at 20 degrees C and 37 degrees C were similar, the former condition resulted in statistically smaller changes of phospholipid contents. LDL with higher lysophosphatidylcholine content showed greater impairment of endothelium dependent relaxation in rat aortic rings than LDL with lower lysophosphatidylcholine content. CONCLUSIONS: The raised lysophosphatidylcholine level in oxidatively modified LDL was related to the ability of the LDL to impair endothelium dependent relaxation. However, lipid peroxidation products assessed by TBARS did not relate to the phospholipid changes in LDL and therefore cannot be used to predict the vascular effects of LDL after oxidative modification.

Heterogeneous growth-induced prestrain in the heart.

Even when entirely unloaded, biological structures are not stress-free, as shown by Y.C. Fung׳s seminal opening angle experiment on arteries and the left ventricle. As a result of this prestrain, subject-specific geometries extracted from medical imaging do not represent an unloaded reference configuration necessary for mechanical analysis, even if the structure is externally unloaded. Here we propose a new computational method to create physiological residual stress fields in subject-specific left ventricular geometries using the continuum theory of fictitious configurations combined with a fixed-point iteration. We also reproduced the opening angle experiment on four swine models, to characterize the range of normal opening angle values. The proposed method generates residual stress fields which can reliably reproduce the range of opening angles between 8.7±1.8 and 16.6±13.7 as measured experimentally. We demonstrate that including the effects of prestrain reduces the left ventricular stiffness by up to 40%, thus facilitating the ventricular filling, which has a significant impact on cardiac function. This method can improve the fidelity of subject-specific models to improve our understanding of cardiac diseases and to optimize treatment options.

Cavernous hemangioma of the superior mediastinum. Report of a case with electron microscopy and computerized tomography.

An unusual case of cavernous hemangioma of the superior mediastinum in a 38-year-old male is presented. Mediastinal hemangiomas occur more often in children and are usually localized in the anterior-superior compartment in all age groups. Slow expansile growth, lack of infiltration of adjacent structures and microscopically mature cellular elements clearly marked the benign nature of the lesion. Vascular mesenchymal tumors in this location must be approached with caution because of the risks of hemorrhage or local infiltration of vital structures. Electron microscopy revealed active endothelial cells, smooth muscle cells, and intercellular matrix components suggestive of smooth muscle cell origin. Computerized tomography delineated the lesion clearly and demonstrated identical densities for the mass and adjacent blood vessels.

Cross-reactivity of monovalent and polyvalent Trimeresurus antivenoms with venoms from various species of Trimeresurus (lance-headed pit viper) snake.

Trimeresurus bite is a serious medical problem in Asia. However, at present only a few monospecific Trimeresurus antivenoms are available. Investigation of the cross-neutralization capacity of three Trimeresurus antivenoms indicates that the antivenoms exhibit broad cross-reactivity. A polyvalent Trimeresurus antivenom was also found to be effective in neutralization of the haemorrhagic, necrotizing and thrombin-like activities of heterologous Trimeresurus venoms.

Cervical spine motion: radiographic study.

Knowledge of the acceptable range of motion of the cervical spine of the dog is used in the radiographic diagnosis of both developmental and degenerative diseases. A series of radiographs of mature Beagle dogs was used to identify motion within sagittal and transverse planes. Positioning of the dog's head and neck was standardized, using a restraining board, and mimicked those thought to be of value in diagnostic radiology. The range of motion was greatest between C2 and C5. Reports of severe disk degeneration in the cervical spine of the Beagle describe the most severely involved disks to be C4 through C7. Thus, a high range of motion between vertebral segments does not seem to be the cause for the severe degenerative disk disease. Dorsoventral slippage between vertebral segments was seen, but was not accurately measured. Wedging of disks was clearly identified. At the atlantoaxio-occipital region, there was a high degree of motion within the sagittal plane at the atlantoaxial and atlanto-occipital joints; the measurement can be a guideline in the radiographic diagnosis of instability due to developmental anomalies in this region. Lateral motion within the transverse plane was detected at the 2 joints; however, motion was minimal, and the measurements seemed to be less accurate because of rotation of the cervical spine. Height of the vertebral canal was consistently noted to be greater at the caudal orifice, giving some warning to the possibility of overdiagnosis in suspected instances of cervical spondylopathy.(ABSTRACT TRUNCATED AT 250 WORDS)

Ecological condition of central Australian arid-zone rivers.

Australian arid-zone rivers are known to be ecologically variable and go through "boom and bust" cycles based on highly variable and unpredictable flow regimes. They are facing increasing pressure from land and water resources development and, whilst they are considered to be still in relatively good condition, no studies have yet been carried out to verify this. Such baseline studies are crucial if we are to assess any ecological changes in response to development and management interventions. The ecological condition of four of these endorheic rivers (Georgina, Diamantina, Cooper-Thomson and Bulloo) flowing into the Lake Eyre and Bulloo Basins in central Australia was assessed using several criteria (level of human influence, habitat condition, water chemistry and aquatic macroinvertebrate composition). Using criteria based on the level of human influence, most of the sites were assessed to be relatively unimpacted (reference) condition. The most discernible and widespread impact was riparian and bank damage by stock access. However, the level of this impact was considered to be only moderate. Most aquatic macroinvertebrates found in the area are considered to be opportunistic and tolerant of a wide range of environmental conditions, but with their life histories known to be linked to flow conditions. Their trophic guild was dominated by collectors and predators. The AusRivAS modelled observed to expected values of macroinvertebrate composition indicated that there were differences in ecological condition between sites (e.g. different waterholes) and between times (e.g. seasons and years). Overall, 75% of sites were assessed to be good condition with the remainder being mildly impaired. Water chemistry of the sites was characterised by high spatial and temporal variability with low conductivity and alkaline pH, relatively high turbidity, total nitrogen and total phosphorus, and wide-ranging dissolved oxygen. Given the high variability in water quality and ecological condition within a catchment, there was little evidence of any overall difference in these factors between the catchments. However, given that the hydrology of each river system is distinctly different, one might expect some differences in ecological structure and function at finer scale. Periods of hydrological isolation (eg. to allow natural dryouts) as well as the maintenance of natural connectivity (eg. instream, overbank and floodplain wetting) are both necessary for the maintenance of ecological integrity of these systems.

Stress-whitening occurs in demineralized bone.

INTRODUCTION: The incidence of age-related bone fracture is increasing with average population age. Bone scatters more light (stress-whitens) during loading, immediately prior to failure, in a manner visually similar to polymer crazing. We wish to understand the stress-whitening process because of its possible effect on bone toughness. The goals of this investigation were a) to establish that stress-whitening is a property of the demineralized organic matrix of bone rather than only a property of mineralized tissue and that stress whitening within the demineralized bone is dependent upon both b) hydrogen bonding and, c) the orientation of loading. METHODS: Demineralized cortical bone specimens were loaded in tension to failure (0.08 strain/s). The effect of hydrogen bonding on mechanical properties and the stress-whitening process was probed by altering the Hansen's hydrogen bonding parameter (δh) of the immersing solution. RESULTS: Stress-whitening occurred in the demineralized bone. Stress-whitening was negatively correlated with δh (R(2)=0.81, p<0.0001). Stress-whitening was significantly lower (p<0.0001) in specimens loaded orthogonally compared to those loaded parallel to the long (strong) axis. CONCLUSION: The stress-whitening observed was consistent with increased Mie scattering. We suggest that the change in Mie scattering was due to collagen fibril dehydration driven by the externally applied stress. The presence of stress-whitening in demineralized bone suggests that this process may be a property of the collagenous matrix and hence may be present in other collagenous tissues rather than an emergent property of the bone composite.

Image segmentation using fuzzy region competition and spatial/frequency information.

This paper presents a multiphase fuzzy region competition model that takes into account spatial and frequency information for image segmentation. In the proposed energy functional, each region is represented by a fuzzy membership function and a data fidelity term that measures the conformity of spatial and frequency data within each region to (generalized) gaussian densities whose parameters are determined jointly with the segmentation process. Compared with the classical region competition model, our approach gives soft segmentation results via the fuzzy membership functions, and moreover, the use of frequency data provides additional region information that can improve the overall segmentation result. To efficiently solve the minimization of the energy functional, we adopt an alternate minimization procedure and make use of Chambolle's fast duality projection algorithm. We apply the proposed method to synthetic and natural textures as well as real-world natural images. Experimental results show that our proposed method has very promising segmentation performance compared with the current state-of-the-art approaches.

Statistical wavelet subband characterization based on generalized gamma density and its application in texture retrieval.

The modeling of image data by a general parametric family of statistical distributions plays an important role in many applications. In this paper, we propose to adopt the three-parameter generalized Gamma density (GGammaD) for modeling wavelet detail subband histograms and for texture image retrieval. The advantage of GGammaD over the existing generalized Gaussian density (GGD) is that it provides more flexibility to control the shape of model which is critical for practical histogram-based applications. To measure the discrepancy between GGammaDs, we use the symmetrized Kullback-Leibler distance (SKLD) and derive a closed form for the SKLD between GGammaDs. Such a distance can be computed directly and effectively via the model parameters, making our proposed scheme particularly suitable for image retrieval systems with large image database. Experimental results on the well-known databases reveal the superior performance of our proposed method compared with the current existing approaches.

Texture classification using refined histogram.

In this correspondence, we propose a novel, efficient, and effective Refined Histogram (RH) for modeling the wavelet subband detail coefficients and present a new image signature based on the RH model for supervised texture classification. Our RH makes use of a step function with exponentially increasing intervals to model the histogram of detail coefficients, and the concatenation of the RH model parameters for all wavelet subbands forms the so-called RH signature. To justify the usefulness of the RH signature, we discuss and investigate some of its statistical properties. These properties would clarify the sufficiency of the signature to characterize the wavelet subband information. In addition, we shall also present an efficient RH signature extraction algorithm based on the coefficient-counting technique, which helps to speed up the overall classification system performance. We apply the RH signature to texture classification using the well-known databases. Experimental results show that our proposed RH signature in conjunction with the use of symmetrized Kullback-Leibler divergence gives a satisfactory classification performance compared with the current state-of-the-art methods.