Pre-existing osteoporosis and serum vitamin D levels in patients with distal radius fractures: are we missing something?

INTRODUCTION: Given the significant therapeutic gap for osteoporosis, this study aims to investigate the most common osteoporosis-related fracture. The analysis will also consider patients' serum vitamin D levels and the indications for basic osteoporosis diagnostic tests and osteoporosis therapy prior to fracture. MATERIALS AND METHODS: This prospective clinical trial included patients with distal radius fractures who underwent surgery at our hospital between 1 April 2021 and 7 April 2022. Blood samples were taken from all participants and existing risk factors for osteoporosis were recorded. In addition, the indication for a guideline-based osteoporosis diagnosis was assessed and the risk of another future fracture with FRAX® was calculated. This information was used to decide whether there was an indication for specific osteoporosis therapy. RESULTS: A diagnosis gap of 53% and a treatment gap of 84% were identified among the 102 patients investigated. The patients' ages ranged from 46 to 91 years, with an average vitamin D level of 57 nmol/l, which was below the recommended level of 75 nmol/l. It was noted on a monthly basis that the vitamin D level (without substitution) never exceeded the recommended value of 75 nmol/l in any month. Three-quarters of patients had indications for a baseline osteoporosis diagnosis, yet less than 50% received one. According to FRAX® data, 57% of patients had indications for specific osteoporosis treatment before experiencing the fracture. CONCLUSION: Even without a previous distal radius fracture, many patients are in need of osteoporosis diagnosis or treatment. Our research suggests that patients with distal radius fractures should have their vitamin D levels checked via a blood test and be evaluated for osteoporosis. As endogenous vitamin D levels are often inadequate, year-round vitamin D supplementation should be considered for the prevention of osteomalacia and as a basis for the treatment of osteoporosis. GERMAN CLINICAL TRIAL REGISTER ID: DRKS00028085.

Resilient back-propagation machine learning-based classification on fundus images for retinal microaneurysm detection.

BACKGROUND: The timely diagnosis of medical conditions, particularly diabetic retinopathy, relies on the identification of retinal microaneurysms. However, the commonly used retinography method poses a challenge due to the diminutive dimensions and limited differentiation of microaneurysms in images. PROBLEM STATEMENT: Automated identification of microaneurysms becomes crucial, necessitating the use of comprehensive ad-hoc processing techniques. Although fluorescein angiography enhances detectability, its invasiveness limits its suitability for routine preventative screening. OBJECTIVE: This study proposes a novel approach for detecting retinal microaneurysms using a fundus scan, leveraging circular reference-based shape features (CR-SF) and radial gradient-based texture features (RG-TF). METHODOLOGY: The proposed technique involves extracting CR-SF and RG-TF for each candidate microaneurysm, employing a robust back-propagation machine learning method for training. During testing, extracted features from test images are compared with training features to categorize microaneurysm presence. RESULTS: The experimental assessment utilized four datasets (MESSIDOR, Diaretdb1, e-ophtha-MA, and ROC), employing various measures. The proposed approach demonstrated high accuracy (98.01%), sensitivity (98.74%), specificity (97.12%), and area under the curve (91.72%). CONCLUSION: The presented approach showcases a successful method for detecting retinal microaneurysms using a fundus scan, providing promising accuracy and sensitivity. This non-invasive technique holds potential for effective screening in diabetic retinopathy and other related medical conditions.

Does access through the pronator quadratus influence pronation strength in palmar plate fixation of distal radius fractures in elderly patients?

INTRODUCTION: Palmar plate fixation of the distal radius fracture involves dissecting the pronator quadratus (PQ). This is regardless of whether the approach is radial or ulnar to the flexor carpi radialis (FCR) tendon. It is not yet clear whether and to what extent this dissection leads to a functional loss of pronation or pronation strength. The aim of this study was to investigate the functional recovery of pronation and pronation strength after dissection of the PQ without suturing. MATERIALS AND METHODS: From October 2010 to November 2011, patients aged over 65 with fracture were prospectively enrolled in this study. Fracture stabilisation was performed via the FCR approach without suturing the PQ. Follow-up examinations took place 8 weeks and 12 months postoperatively, and pronation and supination strength were analysed by means of an especially developed measuring device. RESULTS: 212 patients were initially screened and 107 were enrolled. The range of motion compared to the healthy opposite side was Ext/Flex 75/66% 8 weeks postoperatively. Pronation was 97% with a pronation strength of 59%. After 1 year, the scores improved to Ext/Flex 83/80%. Pronation recovered to 99% and pronation strength to 78%. CONCLUSION: The present study can show a recovery of pronation as well as pronation strength in a large patient population. At the same time, the pronation strength is still significantly lower 1 year after the operation than on the opposing healthy side. As the pronation strength recovers as the grip strength and is at all times on a par with the supination strength, we believe that we can continue to refrain from re-fixating the pronator quadratus.

Residual dorsal displacement following surgery in distal radial fractures: A cause for trouble?

PURPOSE: Distal radius fractures have great impact on activities of daily living of affected patients. Repeatedly, a non-anatomic restoration of the volar tilt can be observed in a minimum of 20% in postoperative X-ray control examinations. Hence, the question arises whether the achieved reduction is functionally acceptable, or whether a further attempt should be made to improve the surgical outcome. METHODS: The data presented here originate from a prospective analysis including three therapy studies on surgical treatment options for fractures of the distal radius between 2004 and 2011. For this study, the participants were divided into two groups: The first group represents the cases with non-anatomical restoration of the volar tilt with - 5° to 5°. The second group contains patients with an anatomical volar tilt between 6° and 15°. RESULTS: A total of 624 patients were screened according to the inclusion criteria. Radiological evaluation showed consolidation of all fractures. The mean volar tilt as measured in standard x-rays of the wrist was 0° and 8°, respectively. The range of wrist motion in relation of the healthy opposite side was comparable in all directions (for example comparison group 1: Ext/Flex 94/94%; group 2: Ext/Flex 93/93%). Functional assessment of postoperative midterm results employing the Castaing and Gartland & Werley scores 2.3 years after surgery did not reveal significant differences between both groups. CONCLUSION: According to the available data, a volar tilt in the range of - 5° to 5° can be tolerated intraoperatively without any risk of loss of function regarding the patient's manual abilities.

[Harvesting cancellous bone or composite corticocancellous bone grafts from the posterior iliac crest]. / Autologe Spongiosa- und trikortikale Spanentnahme aus dem hinteren Beckenkamm.

OBJECTIVE: Harvesting bone-either cancellous bone or composite corticocancellous bone grafts-from the iliac crest is an efficient method for filling or bridging bony defects commonly encountered in comminuted epimetaphyseal fractures (e.g., tibial head fractures), in nonunions or during reconstructive measures as in arthrodesis of major joints or spondylodesis, bone defects due to tumor resection or following eradication of chronic infection. INDICATIONS: All bone defects with a maximum size of 4-5 cm. CONTRAINDICATIONS: Rejection of surgery by the patient, infection or evidence of pathological bony changes in the posterior pelvic rim, inexperience of the surgeon with the procedure. SURGICAL TECHNIQUE: Incision at the posterior iliac crest and removal of a structural or cancellous bone graft of predetermined length. Depending on the bleeding tendency, a suction drain can be inserted. POSTOPERATIVE MANAGEMENT: After surgery supine positioning is favorable for wound compression to avoid bleeding as well as sufficient analgesia. Mobilization is dictated by the main operation. The pelvis is not compromised in its mechanical integrity and allows for full weight bearing on the operated side.

Utilization of gum polysaccharide of Araucaria heterophylla and Azadirachta indica for encapsulation of cyfluthrin loaded super paramagnetic iron oxide nanoparticles for mosquito larvicidal activity.

Surface engineering of super paramagnetic iron oxide nanoparticles (SPIONs) favor the tagging of any molecule or compound onto it, encapsulating them with a biopolymer make them biocompatible and favor slow release of loaded molecules. Recovery of SPIONs is easier as they obey to external magnetic field. In this study, SPIONS were used for mosquito larvicidal activity after surface engineered with oleic acid to favor the tagging of Cyfluthrin (mosquito larvicidal agent), it was then encapsulated with gum polysaccharide derived from Azadirachta indica and Araucaria heterophylla. Every stage of coreshell formation was microscopically and spectroscopically characterized. The coreshell SPIONs produced using Azadirachta indica and Araucaria heterophylla gum derived polysaccharide encapsulation were found to be the size around 80 nm. Thus, prepared coreshell SPIONs was subjected for mosquito larvicidal activity against Culex sp. The coreshell SPIONs was efficiently killing the mosquito larva and its impact was studied by percentage mortality studies.

Ordered Surface Structuring of Spherical Colloids with Binary Nanoparticle Superlattices.

Surface-patterning colloidal matter in the sub-10 nm regime generates exceptional functionality in biology and photonic and electronic materials. Techniques of artificially generating functional patterns in the small nanoscale advanced in a fascinating manner in the last several years. However, they remain often restricted to planar and noncolloidal substrates. Patterning colloidal matter in solution via bottom-up assembly of smaller subunits on larger core particles is highly challenging because it is necessary to force the subunits onto randomly moving objects. Consequently, the non-equilibrium conditions present during nanoparticle self-assembly are difficult to control to eventually achieve the desired material structures. Here, we describe the formation of surface patterns with intrinsic periodic repeats of 8.9 ± 0.9 nm and less on hard, amorphous colloidal core particles by assembling binary nanoparticle superlattices on the curved particle surface. The colloidal environment is preserved during the entire bottom-up crystallization of variable building blocks (here, monodispersed 5 nm Au and 2.4 nm Pd nanoparticles (NPs) and 230 nm SiO2 core particles) into AB13-like, binary, and isotropic superlattice domains on the amorphous cores. The three-dimensional, bottom-up assembly technique is a new tool for patterning colloidal matter in the sub-10 nm surface regime for gaining access to multicomponent metamaterials for bionanoscience, photonics, and electronics.

Locating Reactive Groups on Nanomaterials with Gold Nanoclusters: Toward a Surface Reactive Site Map.

Nanoparticles (NPs) are often functionalized with reactive groups such as amines and thiols for the subsequent conjugation of further molecules, e.g., stabilizing polymers, drugs, and proteins for targeting cells or specific diseases. In addition to the quantitative estimation of the reactive conjugation sites, their molecular positioning and nanoscale arrangement on single nanoparticles become more and more important for the tailored engineering and design of functional nanomaterials. Here, we use maleimide or sulfo-succinimidyl ester-modified 1.4 nm gold nanoclusters (AuNCs) to specifically label reactive thiol and amine groups with sub-2-nm precision on metal oxide and polymeric nanostructures. We confirm the binding of AuNCs by measuring and modeling sedimentation properties using analytical centrifugation, imaging their surface distribution and surface distances by transmission electron microscopy (TEM), and comparing the results to ensemble measurements of numbers of reactive surface groups obtained by common photometric assays. We map thiol and amine groups introduced on silica NPs (SiNPs), titania stars (Ti), silica inverse opals (SiOps), and polystyrene NPs (PS NPs). We show that the method is suitable for mapping local, clustered inhomogeneities of the reactive sites on single SiNPs introduced by masking certain areas during surface functionalization. Mapping precise positions of reactive surface groups is essential to the design and tailored ligation of multifunctional nanomaterials.

Constructing bifunctional nanoparticles for dual targeting: improved grafting and surface recognition assessment of multiple ligand nanoparticles.

Nanoparticles (NPs) functionalized with two active targeting ligands have been proposed in drug delivery for their promising capability to stimulate different pathways with one object. Due to the multivalency, the construction and analysis of the effective surface of such bifunctional nanoparticles, however, is significantly more complex than for nanoparticles bearing only one ligand. Here, we optimize construction and analysis of bifunctional NPs containing recognizable combinations of human serum albumin (HSA), transferrin (Tf), and epidermal growth factor (EGF) on fluorescent silica NPs grafted via common polyethylene glycol (PEG) linkers as a model system. Combined with an overall protein quantification, a mapping of exposed recognizable sequences using monoclonal antibodies conjugated to gold nanoparticles (AuNPs) or quantum dots (QDs) for enhanced spectroscopic and microscopic detection revealed that active protein sequences can be one to two orders of magnitude lower than overall conjugated proteins while possessing specific cellular recognition. In addition, we found that common conjugation strategies lead to a large excess of non-specifically compared to covalently bound ligands and instabilities that may impact targeting. These can be avoided by certain synthetic conditions presented here for effective exploitation of multivalent surfaces in nanomedicine.

Labeling the Structural Integrity of Nanoparticles for Advanced In Situ Tracking in Bionanotechnology.

Observing structural integrity of nanoparticles is essential in bionanotechnology but not always straightforward to measure in situ and in real-time. Fluorescent labels used for tracking intrinsically nonfluorescent nanomaterials generally do not allow simultaneous observation of integrity. Consequently, structural changes like degradation and disassembly cannot easily be followed in situ using fluorescence signals. We show that thioflavin T (ThT), a fluorophore and molecular rotor known to tag specific fibril structures in amyloids, can "label" the structural integrity of widely used and intrinsically nonfluorescent, silica nanoparticles (SiNPs). Entrapment of ThT in SiNPs controls the fluorohphore's relaxation pathway and leads to a red-shifted fluorescence spectrum providing real time information on SiNP integrity. The dynamic change of ThT fluorescence during degradation of doped SiNPs is found much higher than that of common labels fluorescein and rhodamine. Degradation kinetics of core-shell structures recorded by ThT fluorescence and light scattering prove the capability to clearly distinguish structural features during SiNPs degradation and allow obtaining degradation kinetics in vitro, in biological media, in serum, and in cells. The effect is transferable to different types of materials, here shown for ThT incorporated SiNPs with tightly tailorable sizes (9-100 nm), poly(lactic-co-glycolic acid) (PLGA) nanoparticles, poly(9-vinylcarbazole) (PVK) nanoparticles, and iron-doped-SiNPs (FeSiNPs). We thus suggest molecular rotors such as ThT as additional labels to effectively and easily sense nanoparticle structural status in situ and to enhance understanding and development of programmed nanoparticle disassembly in bionanotechnology.

Results of geriatric distal radius fractures treated by intramedullary fixation.

INTRODUCTION: Distal radius fracture are common injuries but no gold standard for their therapy exists. The aim of this study was to evaluate the quality of fracture care in distal radius fractures using an intramedullary implant (Targon DR interlocking nail). The nail had been developed to minimize the surgical exposure, increase fixation strength, to prevent tendon irritations and to allow for a fast return to activity. PATIENTS AND METHODS: Prospective study reports the result of 43 patients with an age over 70 years (range 70-91 years) treated by closed reduction and intramedullary fixation. Inclusion criteria were displaced unilateral isolated AO A or C type fractures. The Targon DR interlocking nail was used for all patients. The minimum follow up was 12 months. RESULTS: All fractures united within 2 months. At one-year follow-up the patients had a mean extension of 96.1 ± 1.5%, flexion of 91.6 ± 3.3%, pronation of 99.4 ± 0.7%, supination of 94.0 ± 2.0%, radial abduction of 98.1 ± 1.3%, ulnar deviation of 91.4 ± 3.0% and a grip strength of 91.5 ± 4.3% compared to the contralateral wrist. Pain score measured by a Visual Analogue Scale scored 0.0 ± 0.0 at rest and in activity 0.3 ± 0.3. The mean Castaing Score was good (1.06 ± 0.30) and the Gartland & Werley Score was excellent (1.50 ± 0.57). The mean radial shortening was 0.2 ± 0.1 mm and radial inclination was 3.1 ± 1.1° (range +15° to 0°). No deep soft-tissue or chronic osseous infections were observed. One patient developed a carpal tunnel syndrome. Paraesthesia or dysaesthesia of the superficial radial nerve was registered in seven patients and fully recovered in four patients. There were two cases of single screw loosening. We also found two cases of screw overlength and consecutive contact with the ulnar head, one patient underwent implant removal. Another patient developed CRPS (2.3%). We did not observe any case of hardware failure, tendon irritation or tendon rupture. CONCLUSION: In geriatric patients intramedullary interlocking nailing of displaced extraarticular or intraarticular distal radius fracture with the Targon DR nail represents a viable treatment option and alternative to the use of volar interlocking plating in terms of fracture reduction, maintenance of reduction and functional outcome.

Tuning of nanoparticle biological functionality through controlled surface chemistry and characterisation at the bioconjugated nanoparticle surface.

We have used a silica - PEG based bionanoconjugate synthetic scheme to study the subtle connection between cell receptor specific recognition and architecture of surface functionalization chemistry. Extensive physicochemical characterization of the grafted architecture is capable of capturing significant levels of detail of both the linker and grafted organization, allowing for improved reproducibility and ultimately insight into biological functionality. Our data suggest that scaffold details, propagating PEG layer architecture effects, determine not only the rate of uptake of conjugated nanoparticles into cells but also, more significantly, the specificity of pathways via which uptake occurs.

Sex steroids in Sjögren's syndrome.

The purpose of the review is to consider pathomechanisms of Sjögren's syndrome (SS), which could explain the female dominance (9:1), the most common age of onset (40-50 years) and targeting of the exocrine glands. Estrogens seem to specifically protect secretory glandular acinar cells against apoptosis whereas lack of estrogens during menopause and climacterium specifically leads to increased apoptosis of the exocrine secretory cells. Male gonads produce testosterone and convert it in exocrine glands to dihydrotesterosterone (DHT), which is anti-apoptotic and protects against acinar cell apoptosis. Estrogen-deficient women need to produce dehydroepiandrosterone (DHEA) in the adrenal glands and convert it to DHT in exocrine glands in a complex and branching reaction network in which individual enzymatic reactions are catalyzed in forward and backward directions by a myriad of different isoforms of steroidogenic enzymes. Tailoring DHT in peripheral tissues is much more complex and vulnerable in women than in men. In SS the intracrine steroidogenic enzyme machinery is deranged. These endo-/intracrine changes impair acinar remodeling due to impaired integrin α1ß1 and integrin α2ß1 expression so that the intercalated duct progenitor cells are unable to migrate to the acinar space, to differentiate to secretory acinar cells upon contact with laminin-111 and laminin-211 specifically found in the acinar basement membrane. The disarranged endo-/intracrine estrogen/androgen balance induces acinar cells to release microparticles and apoptotic bodies and to undergo apoptotis and/or anoikis. Membrane particles contain potential autoantigens recognized by T- (TCRs) and B-cell receptors (BCRs) and danger-associated molecular patterns (DAMPs) recognized by Toll-like receptors (TLRs). In membrane particles (or carrier-complexes) antigen/adjuvant complexes could stimulate professional antigen capturing, processing and presenting cells, which can initiate auto-inflammatory and autoimmune cascades, break the self-tolerance and finally lead to SS.

ExprEssence--revealing the essence of differential experimental data in the context of an interaction/regulation net-work.

BACKGROUND: Experimentalists are overwhelmed by high-throughput data and there is an urgent need to condense information into simple hypotheses. For example, large amounts of microarray and deep sequencing data are becoming available, describing a variety of experimental conditions such as gene knockout and knockdown, the effect of interventions, and the differences between tissues and cell lines. RESULTS: To address this challenge, we developed a method, implemented as a Cytoscape plugin called ExprEssence. As input we take a network of interaction, stimulation and/or inhibition links between genes/proteins, and differential data, such as gene expression data, tracking an intervention or development in time. We condense the network, highlighting those links across which the largest changes can be observed. Highlighting is based on a simple formula inspired by the law of mass action. We can interactively modify the threshold for highlighting and instantaneously visualize results. We applied ExprEssence to three scenarios describing kidney podocyte biology, pluripotency and ageing: 1) We identify putative processes involved in podocyte (de-)differentiation and validate one prediction experimentally. 2) We predict and validate the expression level of a transcription factor involved in pluripotency. 3) Finally, we generate plausible hypotheses on the role of apoptosis, cell cycle deregulation and DNA repair in ageing data obtained from the hippocampus. CONCLUSION: Reducing the size of gene/protein networks to the few links affected by large changes allows to screen for putative mechanistic relationships among the genes/proteins that are involved in adaptation to different experimental conditions, yielding important hypotheses, insights and suggestions for new experiments. We note that we do not focus on the identification of 'active subnetworks'. Instead we focus on the identification of single links (which may or may not form subnetworks), and these single links are much easier to validate experimentally than submodules. ExprEssence is available at http://sourceforge.net/projects/expressence/.