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Development of a spray congealing process for the preparation of insulin-loaded lipid microparticles and characterization thereof.

A spray congealing process for the preparation of protein-loaded microparticles was developed. The influence of the process parameters atomization pressure and spraying temperature on particle size and process yield was investigated by experimental design. The employed spray congealing technique enabled the production of microparticles with yields ranging from 79% to 95% and median particle sizes (d(0.5)) from 182.2 to 315 microm. Insulin lipid microparticles could be prepared without any loss of insulin during the preparation process and the protein stability was not affected by the spray congealing process as investigated by HPLC-MS analysis. The stability of insulin encapsulated in lipid microparticles under release conditions over 28 days was assessed by investigating the residual insulin content. Starting after 3 days of release, a continuous increase of desamidoinsulin in the remaining particles of up to 7.5% after 28 days was observed. An additional degradation product was detected by HPLC and HPLC-MS analysis and identified as a covalent insulin dimer by MALDI-ToF. The microparticles did not show a burst release and testing the insulin lipid microparticles in a fibrin gel chondrocyte culture revealed that the released insulin was bioactive and had a significant effect on chondrocyte extracellular matrix production.

Cartilage↗

Thermal stability, Judd-Ofelt theory analysis and spectroscopic properties of a new Er3+/Yb3+-codoped germano-tellurite glass.

The Er3+/Yb3+-codoped 70TeO2-5Li2O-10B2O3-15GeO2 glass was prepared. The thermal stability, absorption spectra, emission spectra and up-conversion spectra were measured and investigated. The Judd-Ofelt analysis based on absorption spectra was performed in order to determine the Judd-Ofelt intensity parameters Omega(t) (t = 2, 4, 6), spontaneous emission probability, radiative lifetime and branching ratios of several Er3+ transitions. It was found that this studied glass has good thermal stability, broad fluorescence full width at half maximum (FWHM), large stimulated emission cross-section and strong up-conversion emissions at about 532, 546 and 659 nm, corresponding to the 2H(11/2)-->4I(15/2), 4S(3/2)-->4I(15/2) and 4F(9/2)-->4I(15/2) transitions of Er3+, respectively under the excitation at 970 nm. The results suggest that this Er3+/Yb3+-codoped germano-tellurite glass may be a potentially useful material for developing potential amplifiers and up-conversion optical devices.

Cations, Monovalent↗

Implant stability measurements using resonance frequency analysis in the grafted maxilla: a cross-sectional pilot study.

BACKGROUND: High failure rates have been presented for implants placed in grafted bone. The bone graft-implant interface constitutes a most complex healing situation, where the time scale for osseointegration and development of implant stability currently is not known. PURPOSE: The aim of the study was to measure the stability of implants placed in grafted bone after various follow-up periods. METHODS: Implant stability measurements by means of resonance frequency analysis were performed in 10 patients previously treated with a Le Fort I osteotomy and interpositional bone grafts. The implants were placed 3 to 4 months after the grafting procedure. Sixty-seven Brånemark implants were subjected to resonance frequency analysis measurements at fixture placement and up to 5.5 years after implant surgery. Periapical radiographs were used for assessment of marginal bone levels. RESULTS: The radiographic examinations showed marginal bone loss with time during the 5.5-year follow-up. The resonance frequencies varied from 5860 to 8440 Hz. When accounting for abutment length and marginal bone level, there was a tendency of increasing resonance frequency with time. Two implants with low resonance frequencies failed during the prosthetic phase. CONCLUSION: The results indicate an increased implant stability with time, which may reflect bone formation, remodeling, and maturation at the implant interface.

Aged↗

[Biomechanical evaluation of glenohumeral stability through muscle force vector analysis. Effect of a decreased glenoid inclination in shoulders with global rotator cuff tears].

OBJECTIVES: The aim of the study was to quantify the decrease in glenohumeral stability following a global rotator cuff tear and to evaluate the effect of a decreased glenoid inclination angle through analysis of muscle force vectors in a computer model. MATERIAL AND METHODS: The lines of action of eight shoulder muscles were integrated into a standard geometric model. Muscle force magnitudes were estimated based on physiological cross-sectional area and normalized electromyographic activity. The magnitude and elevation angle of the resultant force vector was calculated at 0, 30, 60, and 90 degrees of abduction. A rotator cuff tear was simulated by reduction of the corresponding muscle force vectors. RESULTS: At 0 and 30 degrees of glenohumeral abduction a global rotator cuff tear showed a resultant force vector pointing outside the glenoid. In the computer model, decreasing the inclination angle of the glenoid by 30 degrees increased the stability in rotator cuff-deficient shoulders. CONCLUSIONS: The results of this study provide a biomechanical rationale for clinical complications of global rotator cuff tear such as superior humeral head translation. The decreased glenoid inclination simulated in the computer model may represent a biomechanical basis for the development of new operative techniques to treat global rotator cuff tears.

Biomechanical Phenomena↗

Stability and change in adult intelligence: 2. Simultaneous analysis of longitudinal means and covariance structures.

We analyzed data on psychometric intelligence from the Seattle Longitudinal Study, simultaneously estimating longitudinal factors, their covariance structure, and their mean levels. Data on five Thurstone Primary Mental Abilities subtests were available for 412 adults, ages 22-70 at first test, who were tested three times at 7-year intervals. A previous longitudinal factor analysis had shown high stability of individual differences (covariance stability) in general intelligence for three adult age groups. We extended that model to estimate factor means. All three age groups showed high levels of covariance stability, but differed sharply in their mean profiles. The young group showed increasing levels of general intelligence, the middle-aged group had stable levels of intelligence, and the old group showed salient, approximately linear, decline. The patterns of stability in middle-age, followed by mean decline and high covariance stability in old age, suggest a normative developmental transition from a stability pattern to a decline pattern of general intelligence, with the inflection point occurring somewhere around age 60.

Adult↗

Temporal stability of the Czech translation of the Satisfaction with Life Scale: test-retest data over one week.

The present study supplemented the limited 1999 psychometric data by Lewis, et al. on the Czech translation of the Satisfaction With Life Scale by examining the temporal stability of the measure over a 1-wk. period for 64 Czech undergraduate university students. Analysis indicated stability across the two administrations was very high (r=.90), and there was no significant change between Time 1 (M=23.7, SD=5.1) and Time 2 (M=24.1, SD=5.5). Short-term test-retest reliability of this Czech translation is supported.

Adult↗

The effect of platelet-rich plasma upon implant stability measured by resonance frequency analysis in the lower anterior mandibles.

Using a one-stage surgical protocol, a total of 34 Brånemark Mk-III Ti-Unite implants with a length of 13 mm and a diameter of 3.75 mm were inserted in 10 edentulous mandibles. Of these, seven patients received four and three patients two interforaminal implants. All implants were followed with repeated stability measurements by means of resonance frequency analysis at different time interval: 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 days. In quadrant III platelet-rich plasma (PRP) was instilled locally before implant placement, while no PRP was added in quadrant IV to serve as control group (split-mouth design). Results showed no statistically significant difference between the two groups. Nonetheless, both groups (PRP+control) showed a highly significant reduction of the implant stability quotient (P<0.001) between days 0 and 4. However, no difference was noted between the two groups after day 4, it may be concluded that the instillation of PRP during implant placement in the lower anterior mandible did not add additional benefit.

Aged↗

The measurement of aggression and violence in hospitalized psychiatric patients.

Aggression and violence are significant clinical problems in psychiatric inpatient units. However, research exploring violent behavior is limited by the lack of an adequate research scale. This paper reports on the development and testing of the Violence Scale (VS), a behavioral rating scale which measures aggressive and violent behavior towards self, others and property. The VS has been tested in two studies of psychiatric inpatients (N = 162) and (N = 42). Tests of reliability included internal consistency, item analysis and stability. Tests of validity included content and construct validity. The psychometric results were evaluated through the application of standard statistical criteria [Carmines, E. G. and Zeller, R. A. (1979). Reliability and Validity Assessment. Sage University Press, Beverly Hills, CA; Cronbach, L. J. (1951). Coefficient alpha and the internal structure of tests. Psychometrika 16, 197-333; Nunnally J. (1978). Psychometric Theory, McGraw-Hill, New York]. Coefficient alpha was 0.91 (study 1) and 0.68 (study 2) and stability was r = 0.79 (study 1). The items met most of the established criteria for item analysis and internal consistency. In factor analysis, the items met the criteria for loading onto the three predicted factors (others, self and property). Results of predictive model testing indicated that three of the four predicted relationships were supported. Initial testing indicates the scale is moderately stable, is internally consistent, and has evidence of initial limited construct validity.

Adult↗

Stabilization of carotid atheroma assessed by quantitative ultrasound analysis in nonhypercholesterolemic patients with coronary artery disease.

OBJECTIVES: This study examined whether intensive cholesterol-lowering therapy with statins in nonhypercholesterolemic patients is effective in improving echolucency of vulnerable plaques assessed by ultrasound with integrated backscatter (IBS) analysis. BACKGROUND: Atherosclerotic plaque stabilization is a promising clinical strategy to prevent cardiovascular events in patients with coronary artery disease (CAD). There is a correlation between coronary and carotid plaque instability, and echolucent plaques are recognized as vulnerable plaques. METHODS: Consecutive nonhypercholesterolemic patients with CAD were randomly assigned Adult Treatment Panel-III diet therapy (diet group; n = 30) or pravastatin (statin group; n = 30). Echolucent carotid plaques were monitored by measuring intima-media thickness (IMT) and echogenicity by IBS for six months. RESULTS: Total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-sensitivity C-reactive protein were significantly decreased in the statin group (from 197 +/- 15 mg/dl to 170 +/- 18 mg/dl [p < 0.001]; from 131 +/- 14 mg/dl to 99 +/- 14 mg/dl [p < 0.001]; and from 0.11 [0.04 to 0.22] mg/dl to 0.06 [0.04 to 0.11] mg/dl [p < 0.05]; respectively), whereas only total cholesterol was moderately reduced (from 193 +/- 24 mg/dl to 185 +/- 22 mg/dl [p < 0.05]) and LDL-C and triglycerides insignificantly reduced in the diet group. Significant increases of echogenicity of carotid plaques were noted in the statin group but not in the diet group (from -18.5 +/- 4.1 dB to -15.9 +/- 3.7 dB [p < 0.001] and from -18.2 +/- 4.0 dB to -18.9 +/- 3.5 dB [p = 0.13]; respectively) without significant regression of plaque-IMT values in both groups. CONCLUSIONS: Statin therapy is rapidly effective in increasing echogenicity of vulnerable plaques without regression of plaque size in nonhypercholesterolemic patients with CAD. Quantitative assessment of carotid plaque quality by ultrasound with IBS is clinically useful for monitoring atherosclerotic lesions by evaluating vulnerability of atheroma.

Atherosclerosis↗

G4STAB: a multi-input deep learning model to predict G-quadruplex thermodynamic stability based on sequence and salt concentration.

MOTIVATION: G-quadruplexes (G4s) are non-canonical nucleic acid structures formed in guanine-rich regions that modulate gene regulation and genomic stability. The thermodynamic stability of G4s directly influences their biological functions and potential as therapeutic targets. However, current quantitative frameworks for predicting G4 stability rely on predetermined structural features, limiting their effectiveness for diverse G4 topologies, and fail to account for environmental factors such as ion concentration and pH that significantly modulate G4 stability in cellular contexts. RESULTS: We present G4STAB, a multi-input deep learning neural network that accurately predicts DNA G4 melting temperatures based on sequence features, salt concentration, and pH. Trained on 2382 diverse DNA G4 sequences, our model achieves high accuracy (R&#x2002;2=0.8) without relying on predetermined G4 structural features. G4STAB successfully captures established G4 stability determinants and proposes previously unobserved sequence-stability relationships. Analysis of 391&#xa0;502 experimentally validated G4s reveals that cancer-like ionic environments alter G4 stability profiles, with a 13.5-fold increase in the number of structures exhibiting physiological melting temperatures (36-42&#xb0;C). These findings suggest systematic genomic patterns in G4 stability responses across chromosomes and gene types. AVAILABILITY AND IMPLEMENTATION: G4STAB is available at https://github.com/donn-liew/G4STAB; G4STAB web database interface is available at https://donn-liew.github.io/g4stab-web-database/.

G-Quadruplexes↗

Stability and compatibility assessment techniques for total parenteral nutrition admixtures: setting the bar according to pharmacopeial standards.

PURPOSE OF REVIEW: The stability and compatibility of total parenteral nutrition mixtures compounded for patients requiring nutritional support is paramount to their safety on intravenous infusion. The most significant pharmaceutical issues associated with mixing total parenteral nutrition formulations affecting their safety involve the stability of lipid-injectable emulsions and the compatibility of calcium and phosphate salts. Methods of analysis for stability and compatibility have varied, and the assessments have mostly been largely qualitative. RECENT FINDINGS: Although pharmacopeial standards have been primarily applicable to pharmaceutical manufacturers, recent efforts by the United States Pharmacopeia have been directed at standardizing pharmacy practices involved in the safe mixing of compounded sterile preparations. The adoption of chapter 797 entitled 'Pharmaceutical compounding - sterile preparations' on 1 January 2004 has had a dramatic impact on pharmacy practice in the United States. More recently, the United States Pharmacopeia has also proposed a new chapter 729 entitled 'Globule size distribution in lipid-injectable emulsions', setting specific limits on the sizes and concentrations of lipid droplets in the formulation, which may have implications for all-in-one mixtures. Finally, new efforts are under way to establish limits on the level of acceptable amounts of particulates intrinsically introduced by the manufacturer, and thus may have ramifications for particulates extrinsically introduced or initiated during compounding by the pharmacist. SUMMARY: With careful monitoring and the development of appropriate pharmacopeial-based specifications that limit the size and concentration of large-diameter fat globules and eliminate the possibility of dibasic calcium phosphate precipitates, improved patient outcomes may be achieved.

Drug Compounding↗

Chemical stability of lipid excipients in SLN-production of test formulations, characterisation and short-term stability.

The study investigates the chemical stability of lipids used as excipients in the production of solid lipid nanoparticles (SLN). A total of 17 SLN formulations was produced using different lipids. Most of the formulations were produced using identical binary surfactant mixtures and concentrations to study the effect of the chemical nature of the lipid on its stability in SLN. In some formulations surfactants were exchanged to study the contribution of the surfactant. The particles were characterised by photon correlation spectroscopy, laser diffractometry, zeta potential determination and differential scanning calorimetry, the latter to assess potential effects of lipid crystallinity and modifications on lipid stability. Lipid analysis was performed by gas chromatography using a sampling preparation and analysis procedure especially developed for SLN. This short-term study provides primarily information about the stability of the lipid under production conditions, that means high pressure homogenisation (cavitation) at high temperature. No degradation products couldbe detected for all lipids, the production process itself did not impair excipient stability.

Calorimetry, Differential Scanning↗

Results at 11.5 years of a series of 376 posterior stabilized HLS1 total knee replacements. Survivorship analysis, and risk factors for failure.

Of 376 cemented posterior stabilized HLS1 TKRs inserted in 329 patients (mean age 70) between 1984 and 1988, information was available on 306 (81.4%) at the third follow-up in 1998: 118 patients deceased; 163 followed up clinically (Knee Society score) and radiographically; 25 revised (15 infections; 10 mechanical failures). At a mean follow-up of 11.5 years, the mean pain score was 43/50, and the mean ROM score 21/25 (both unchanged since 1989). The function score had declined linearly, from 70/100 in 1989 to 60/100 in 1998. Forty percent had tibial radiolucencies correlating with the extent of preoperative bone wear. Polyethylene wear (seen in 35% of knees) was always < 3 mm. The implant survival rate (infections included) was 93.7% (+/- 1.4%) after 10 years. All the mechanical failures were in advanced-OA patients with ACL-deficient knees and major bony deficiencies.

Aged↗

Biomechanical comparison of the stable efficacy of two anterior plating systems.

OBJECTIVE: To compare the immediate stable efficacy and load sharing effect of two types of anterior cervical screw-plating instrumentations: the Morscher Synthes titanium locking screw-plate system and the Caspar trapezoidal screw-plate system. DESIGN: Fresh porcine cervical spines with intact, two surgery unstable models, and then reconstructed with or without screw-plating instruments were compared in three physiological loading conditions. BACKGROUND: Two markedly instrumentation systems--Morscher Synthes titanium cervical locking screw-plate and Caspar trapezoidal screw-plate systems are commonly used in management of complex cervical spine disorders. Although the biomechanical study showed that the lower cost Caspar system performed superior in extension before and after plate fatigue, the clinic evaluations of two systems were contradictory. So (1) does the titanium cervical locking plate system pay for its higher cost? and (2) what is the load sharing character of strut graft in one level corpectomy? METHODS: Eight fresh ligamentous porcine cervical spines from C3 to C7 were undergone axial compression, rotation and sagittal flexion tests. The biomechanical experiment was sequentially repeated for the intact, C5-6 discectomy, C5 corpectomy, and then stabilized by either type of plate fixation devices with or without polymethylmethacrylate bone cement grafting. Strains measured by an extensometer across the operated motion segment were used as the index of stability. RESULTS: Analysis of the strain data showed both types of anterior fixation plate systems provided adequate-restored stability for the spinal column only aided with polymethylmethacrylate construction. Statistically, there was no significant difference in biomechanical evaluation for the stability effect between much cost Morscher Synthes plate and Caspar plate system (p<0.005). The spinal disc bore as much as 75% of axial loading. While the strut graft functioned as the disc substitute and spacer, it bore more than 90% of axial loading. In high degree of flexion, the transmitted compressive load was shifted anteriorly to the screw-plate. This might unload the polymethylmethacrylate graft and resulted in the strut graft in tensile fatigue failure. CONCLUSIONS: Statistically both systems showed similar stable efficacy, however, the Morscher Synthes cervical locking plate system might provide better stable effect in higher degrees of flexion motion. The strut graft played as the major load-bearing role in axial compression and sagittal flexion, while in axial rotation, the applied torque was mainly resisted by facet joint and screw-plate system complex. RELEVANCE: The minor discrepancy of two plating systems may be due to the nature of plate geometry and design but not the material properties. Combination of bone graft and either plating systems provides adequate fusion stability under physiological loadings. The high degree flexion may cause the posterior portion of polymethylmethacrylate graft in tensile fracture and then result in polymethylmethacrylate failure in clinic observation.

Animals↗

Identification of macroprolactin in a patient with asymptomatic hyperprolactinemia as a stable PRL-IgG complex.

We characterize the molecular form of PRL in a female patient with asymptomatic, idiopathic hyperprolactinemia. Size exclusion chromatography revealed that PRL was present exclusively in the form of macroprolactin (> 200 kD mol wt). By immunoaffinity purification, Western blot analysis, and binding studies the molecule was identified as a PRL-IgG complex of extremely high stability. Sequence analysis revealed no mutations in the protein coding region of the hPRL gene using hPRL cDNA amplified from the patient's peripheral blood lymphocytes. In spite of full bioactivity in vitro, as determined by Nb2 bioassay, the complex apparently lacks bioactivity in vivo. Its high molecular weight may reduce its access to target organs in the periphery as well as centrally.

Adult↗

Phosphorylation and stabilization of ATP binding cassette transporter A1 by synthetic amphiphilic helical peptides.

To investigate structural requirement of helical apolipoprotein to phosphorylate and stabilize ATP-binding cassette transporter A1 (ABCA1), synthetic peptides (Remaley, A. T., Thomas, F., Stonik, J. A., Demosky, S. J., Bark, S. E., Neufeld, E. B., Bocharov, A. V., Vishnyakova, T. G., Patterson, A. P., Eggerman, T. L., Santamarina-Fojo, S., and Brewer, H. B. (2003) J. Lipid Res. 44, 828-836) were examined for these activities. L37pA, an L amino acid peptide that contains two class-A amphiphilic helices, and D37pA, the same peptide with all D amino acids, both removed cholesterol and phospholipid from differentiated THP-1 cells more than apolipoproteins (apos) A-I, A-II, and E. Both peptides also mediated lipid release from human fibroblasts WI-38 similar to apoA-I. L2D37pA, an L-peptide whose valine and tyrosine were replaced with D amino acids also promoted lipid release from WI-38 but less so with THP-1, whereas L3D37pA, in which alanine, lysine, and asparatic acid were replaced with D amino acids was ineffective in lipid release for both cell lines. ABCA1 protein in THP-1 and WT-38 was stabilized against proteolytic degradation by apoA-I, apoA-II, and apoE and by all the peptides tested except for L3D37pA, and ABCA1 phosphorylation closely correlated with its stabilization. The analysis of the relationship among these parameters indicated that removal of phospholipid triggers signals for phosphorylation and stabilization of ABCA1. We thus concluded that an amphiphilic helical motif is the minimum structural requirement for a protein to stabilize ABCA1 against proteolytic degradation.

ATP Binding Cassette Transporter 1↗

Clinical management of flail chest in dogs and cats: a retrospective study of 24 cases (1989-1999).

Cases of flail chest injury for 24 client-owned companion animals following various traumas were evaluated. Concurrently sustained injuries, initial emergency treatments, and definitive treatment and outcome for regimens that utilize stabilization of the flail segment were compared with cases treated with no stabilization. Flail chest was confirmed in 24 animals: 21 dogs and three cats. There was an even division (12 each) of right and left flail segments. The median number of ribs involved was three (range, two to seven). Flail segment stabilization was performed in nine, and 15 were treated with no stabilization. Statistical analysis using multiple data permutations evaluating all combinations failed to reveal a significant difference in outcome between stabilized and unstabilized cases.

Animals↗

[The effect of head position and functional status of the cervical spine on body sway in the upright posture].

In 30 subjects (16 men and 14 women) stabilometry was used to investigate the stability of posture with closed eyes and different positions of the head (backward, forward, right and left turn). Cervical spine mobility of the subjects studied was determined by vertebrogenic examination. The maximum backward extension of the head was found to reduce most markedly posture stability. Correlation analysis revealed a relationship between the functional state of the cervical spine and the degree of posture stability impairment induced by backward extension of the head, with the impairment being more pronounced in the forward-backward direction. The obtained results show that changes in the quality of proprioceptive information from the cervical spine region are also involved in determining the stability level of upright posture. The findings imply that posture with backward extension of the head can be used as a loading test for detecting ataxia of cervical origin.

Adult↗