Executive functions in patients with bilateral and unilateral peripheral vestibular dysfunction.

Previous research suggests that patients with peripheral vestibular dysfunction (PVD) suffer from nonspatial cognitive problems, including executive impairments. However, previous studies that assessed executive functions are conflicting, limited to single executive components, and assessments are confounded by other cognitive functions. We compared performance in a comprehensive executive test battery in a large sample of 83 patients with several conditions of PVD (34 bilateral, 29 chronic unilateral, 20 acute unilateral) to healthy controls who were pairwise matched to patients regarding age, sex, and education. We assessed basic and complex executive functions with validated neuropsychological tests. Patients with bilateral PVD performed worse than controls in verbal initiation and working memory span, while other executive functions were preserved. Patients with chronic unilateral PVD had equal executive performance as controls. Patients with acute unilateral PVD performed worse than controls in the exact same tests as patients with bilateral PVD (verbal initiation, working memory span); however, this effect in patients with acute PVD diminished after correcting for multiple comparisons. Hearing loss and affective disorders did not influence our results. Vestibular related variables (disease duration, symptoms, dizziness handicap, deafferentation degree, and compensation) did not predict verbal initiation or working memory span in patients with bilateral PVD. The results suggest that bilateral PVD not only manifests in difficulties when solving spatial tasks but leads to more general neurocognitive deficits. This understanding is important for multidisciplinary workgroups (e.g., neurotologists, neurologists, audiologists) that are involved in diagnosing and treating patients with PVD. We recommend screening patients with PVD for executive impairments and if indicated providing them with cognitive training or psychoeducational support.

High-current galvanic vestibular stimulation impairs working memory span, but not other executive functions.

Patients with peripheral vestibular dysfunction (PVD) suffer not only from physical problems such as imbalance or vertigo but also from neuropsychological difficulties, including executive deficits. However, it is unclear whether the PVD directly causes executive problems. To examine the causal vestibular influence on executive functions, we induced either high-current (2 mA), low-current (0.8 mA), or sham current (0 mA) galvanic vestibular stimulation (GVS) in 79 healthy participants. Participants solved three tasks, measuring the core executive components (working memory, inhibition, cognitive flexibility) before and during GVS. High-current GVS impaired working memory span, but not inhibition and cognitive flexibility performance. Low-current GVS did not influence executive performance. Results indicate a causal vestibular influence on working memory span. Joint cortical areas of vestibular and working memory processing are discussed. Since high-current GVS in healthy participants serves as a model for an artificial vestibular dysfunction, our results could improve the diagnostics and therapy of patients with PVD.

Hippocampal volume in patients with bilateral and unilateral peripheral vestibular dysfunction.

Previous studies have found that peripheral vestibular dysfunction is associated with altered volumes in different brain structures, especially in the hippocampus. However, published evidence is conflicting. Based on previous findings, we compared hippocampal volume, as well as supramarginal, superior temporal, and postcentral gyrus in a sample of 55 patients with different conditions of peripheral vestibular dysfunction (bilateral, chronic unilateral, acute unilateral) to 39 age- and sex-matched healthy controls. In addition, we explored deviations in gray-matter volumes in hippocampal subfields. We also analysed correlations between morphometric data and visuo-spatial performance. Patients with vestibular dysfunction did not differ in total hippocampal volume from healthy controls. However, a reduced volume in the right presubiculum of the hippocampus and the left supramarginal gyrus was observed in patients with chronic and acute unilateral vestibular dysfunction, but not in patients with bilateral vestibular dysfunction. No association of altered volumes with visuo-spatial performance was found. An asymmetric vestibular input due to unilateral vestibular dysfunction might lead to reduced central brain volumes that are involved in vestibular processing.

Residual TRM-to-Concrete Bond after Freeze-Thaw Cycles.

In the present work, the effect of various freeze-thaw cycles (namely, 0, 10, 30, 50, 60, and 70) on the residual bond characteristics of textile reinforced mortar (TRM)-to-concrete was experimentally examined. The TRM consisted of a carbon dry fiber textile embedded in a cement-based matrix. Two mortar types were used as the matrix: a normal-weight and a lightweight one sharing the same hydraulic powders but different aggregates (limestone and pumice sand, respectively). The single-lap/single-prism set up was applied after the specimens underwent hygro-thermal treatment (according to ASTM C 666-Procedure B). Failure was due to the sleeve fibers rupturing the load aligned yarns or textile slippage from the mortar for an exposure period ranging between 0 and 60 cycles and to TRM debonding from the substrate for 70 cycles. Increasing cycles resulted in the intensification of partial interlaminar debonding phenomena and the weakening of the textile-to-matrix bond, with lightweight mortar being more prone to these effects. In the absence of a commonly accepted standardized method for the assessment of the freeze-thaw resistance of cement-based composites, the criterion for the termination of the freeze-thaw sequence was the number of cycles inferring a shift in failure mode (from fiber rupture/fiber slippage to TRM debonding from the substrate).

Experimental Investigation of the TRM-to-Masonry Bond after Exposure to Elevated Temperatures: Cementitious and Alkali-Activated Matrices of Various Densities.

Limited research has focused on the effect of high temperatures on the textile-reinforced mortar (TRM)-to-masonry bond. In this study, masonry prisms that were furnished with double-layered TRM strips were tested under shear bond conditions after their exposure to 200 °C and 400 °C for 1 h using the single-lap/single-prism setup. A total of four TRM systems were applied sharing the same type of textile -a dry AR glass fiber one- and different matrices: two cementitious matrices, namely a normal-weight (TRCNM) and a lightweight (TRCLM) one, and two counterpart alkali-activated matrices (TRAANM and TRAALM) based on metakaolin and fly ash. Specimens' exposure to elevated temperatures did not alter their failure mode which was due to the sleeve fibers' rupture along with core fibers' slippage from the mortar. The residual bond capacity of the TRM systems decreases almost linearly with increasing exposure temperature. The alkali-activated textile reinforced mortars outperformed their cement-based counterparts in terms of bond strength at every temperature. All systems retained close to 50% of their original shear bond strength after heating at 400 °C. Per the type of binder, lightweight matrices resulted in either comparable (cement-based systems) or better (alkali-activated systems) heat protection at the TRM/masonry interface.

Tissue curvature and apicobasal mechanical tension imbalance instruct cancer morphogenesis.

Tubular epithelia are a basic building block of organs and a common site of cancer occurrence1-4. During tumorigenesis, transformed cells overproliferate and epithelial architecture is disrupted. However, the biophysical parameters that underlie the adoption of abnormal tumour tissue shapes are unknown. Here we show in the pancreas of mice that the morphology of epithelial tumours is determined by the interplay of cytoskeletal changes in transformed cells and the existing tubular geometry. To analyse the morphological changes in tissue architecture during the initiation of cancer, we developed a three-dimensional whole-organ imaging technique that enables tissue analysis at single-cell resolution. Oncogenic transformation of pancreatic ducts led to two types of neoplastic growth: exophytic lesions that expanded outwards from the duct and endophytic lesions that grew inwards to the ductal lumen. Myosin activity was higher apically than basally in wild-type cells, but upon transformation this gradient was lost in both lesion types. Three-dimensional vertex model simulations and a continuum theory of epithelial mechanics, which incorporate the cytoskeletal changes observed in transformed cells, indicated that the diameter of the source epithelium instructs the morphology of growing tumours. Three-dimensional imaging revealed that-consistent with theory predictions-small pancreatic ducts produced exophytic growth, whereas large ducts deformed endophytically. Similar patterns of lesion growth were observed in tubular epithelia of the liver and lung; this finding identifies tension imbalance and tissue curvature as fundamental determinants of epithelial tumorigenesis.

Development of executive functions from childhood to adolescence in very preterm-born individuals - A longitudinal study.

Preterm-born individuals are at risk for poorer executive functions. Longitudinal studies investigating whether preterm-born individuals present persistent cognitive deficits, or a transient delay of development are scarce. We assessed developmental trajectories of executive functions (inhibition, working memory, cognitive flexibility) in 29 very preterm-born individuals (<32 weeks' gestation) and 25 term-born controls longitudinally over two time points, namely in childhood (7-12 years of age, TP1) and adolescence (13-16 years of age, TP2). Individual changes in executive functions were examined using relative difference scores (TP2 - TP1) / TP1). There was a significantly stronger improvement of inhibition (U = 477, p = .024) and cognitive flexibility (U = 312, p = .029) between childhood and adolescence in very preterm-born individuals than in term-born controls. Preterm-born individuals improved their performance in the domain of cognitive flexibility significantly more often (76%) between childhood and adolescence than controls (31%, χ2 = 8.6, p = .003). Controls worsened significantly more often (36%) in the domain of inhibition than the preterm group (14%, χ2 = 4.8, p = .028). Results indicate that healthy preterm-born individuals show prolonged development of executive functions throughout childhood up into adolescence.

Unlocked versus dynamic and static distal locked femoral nails in stable and unstable intertrochanteric fractures. A prospective study.

INTRODUCTION: Few clinical studies have analyzed the utility of distal interlocking screws in stable and unstable intertrochanteric fractures treated with intramedullary devices. We performed a prospective analysis comparing short unlocked versus short dynamic and short static distal locked intramedullary nails. MATERIALS AND METHODS: Nine level-II trauma centres were involved in the study. 240 patients over the age of 65 with a stable (AO/OTA 31-A1) or unstable intertrochanteric fracture (AO/OTA 31-A2) were prospectively investigated. The same type of nail was used in every patient. Patients were randomly divided into 3 groups according to the type of distal locking used. Intra-operative variables were examined and patients were followed clinically and radiographically at 1, 3, 6, 12 months postoperatively. All complications were recorded. RESULTS: A total of 212 patients completed 1 year of follow-up visits. In the Unlocking Group (UG) the operation time, blood loss, fluoroscopy time, total length of incision were significantly decreased compared to both the Dynamic Group (DG) and the Static Group (SG) (p < 0.05). Conversely, no reliable differences in intraoperative variables were noted between the Dynamic Group and the Static Group (p > 0.05). In terms of time of fracture union we found no differences among the three Groups (p > 0.05). Moreover, no cases of limb shortening >1 cm or varus collapse were detected in any group. The 3 Groups were similar in terms of HHS, SF-12 and Barthel index results at 1-year follow-up (p > 0.05). Finally, no significant differences were demonstrated across the three Groups in terms of major complications. CONCLUSIONS: This clinical study further confirms the hypothesis that short intramedullary nails do not need to be locked for stable and unstable intertrochanteric fractures.

Cognitive Rehabilitation in Bilateral Vestibular Patients: A Computational Perspective.

There is evidence that vestibular sensory processing affects, and is affected by, higher cognitive processes. This is highly relevant from a clinical perspective, where there is evidence for cognitive impairments in patients with peripheral vestibular deficits. The vestibular system performs complex probabilistic computations, and we claim that understanding these is important for investigating interactions between vestibular processing and cognition. Furthermore, this will aid our understanding of patients' self-motion perception and will provide useful information for clinical interventions. We propose that cognitive training is a promising way to alleviate the debilitating symptoms of patients with complete bilateral vestibular loss (BVP), who often fail to show improvement when relying solely on conventional treatment methods. We present a probabilistic model capable of processing vestibular sensory data during both passive and active self-motion. Crucially, in our model, knowledge from multiple sources, including higher-level cognition, can be used to predict head motion. This is the entry point for cognitive interventions. Despite the loss of sensory input, the processing circuitry in BVP patients is still intact, and they can still perceive self-motion when the movement is self-generated. We provide computer simulations illustrating self-motion perception of BVP patients. Cognitive training may lead to more accurate and confident predictions, which result in decreased weighting of sensory input, and thus improved self-motion perception. Using our model, we show the possible impact of cognitive interventions to help vestibular rehabilitation in patients with BVP.

The Novel Aminomethylcycline Omadacycline Has High Specificity for the Primary Tetracycline-Binding Site on the Bacterial Ribosome.

Omadacycline is an aminomethylcycline antibiotic with potent activity against many Gram-positive and Gram-negative pathogens, including strains carrying the major efflux and ribosome protection resistance determinants. This makes it a promising candidate for therapy of severe infectious diseases. Omadacycline inhibits bacterial protein biosynthesis and competes with tetracycline for binding to the ribosome. Its interactions with the 70S ribosome were, therefore, analyzed in great detail and compared with tigecycline and tetracycline. All three antibiotics are inhibited by mutations in the 16S rRNA that mediate resistance to tetracycline in Brachyspira hyodysenteriae, Helicobacter pylori, Mycoplasma hominis, and Propionibacterium acnes. Chemical probing with dimethyl sulfate and Fenton cleavage with iron(II)-complexes of the tetracycline derivatives revealed that each antibiotic interacts in an idiosyncratic manner with the ribosome. X-ray crystallography had previously revealed one primary binding site for tetracycline on the ribosome and up to five secondary sites. All tetracyclines analyzed here interact with the primary site and tetracycline also with two secondary sites. In addition, each derivative displays a unique set of non-specific interactions with the 16S rRNA.

Is distal locking with short intramedullary nails necessary in stable pertrochanteric fractures? A prospective, multicentre, randomised study.

We investigated whether a proximal femoral nail can be implanted without a distal locking screw in AO/OTA 31-A1 and 31-A2 pertrochanteric stable femur fractures. A multicentre, randomised study was conducted in six level-two trauma centres in our area (Puglia, Italy). A total of 333 patients received their allocated intervention (162 in the locking group [LG] and 171 in the unlocking group [UG]) and 266 patients were included in the final analysis at 1year. Our data showed no statistically significant difference between the two groups at 1-year follow-up for ability to walk, SF-36 questionnaire results, residual pain (visual analogue scale [VAS] score) and level of overall satisfaction. There were also no statistically significant differences between groups for mortality and length of hospital stay. Conversely, the UG was associated with shorter operation and fluoroscopy times, shorter surgical incision length, and less blood loss and residual thigh pain. Pertrochanteric stable fractures (31-A1, 31-A2) can be treated successfully with intramedullary nails without distal locking, reducing patient and clinical personnel radiation exposure and sanitary costs (surgery time and screws costs).

Biomarkers of Cytotoxic, Genotoxic and Apoptotic Effects in Cyprinus carpio Exposed to Complex Mixture of Contaminants from Hospital Effluents.

Hospital wastewater is an important source of emerging contaminants. Recent studies emphasize the importance of assessing the effects of mixtures of contaminants rather than environmental risk of their individual components, as well as the determination of intrinsic toxicity of wastewater. Mixtures of pollutants has possible interactions that have notable environmental side effects. The aim of this study is an attempt to characterize biomarkers in Cyprinus carpio related to the exposure to a complex mixture of contaminants found in hospital wastewater. Results of a particular hospital effluent show the presence of traces of heavy metals, high chlorine concentration and emerging contaminants such as non-steroidal anti-inflammatory drugs. The LC50 was of 5.49 % at 96 h. The cytotoxic, genotoxic and apoptotic biomarkers increase when fishes were exposed to wastewater (1/10 CL50) from hospital wastewater. This study emphasizes the importance of identifying and quantifying the effects of contaminants as pharmaceuticals, disinfectants and surfactants in order to design and implement an ecotoxicological plan.

Heel displaced intra-articular fractures treated with mini-calcaneal external fixator.

INTRODUCTION: Treatment of displaced heel fractures is controversial; however, ORIF is widely described in the literature to be the gold-standard. Percutaneous reduction and monolateral external fixation is gaining increasing attention because it provides a good and stable reduction, and minimises soft tissue complications due to open surgery, such as deep infections and delays in wound healing. The aim of this study was to show that the new Orthofix Calcaneal Minifixator (six pins) provides a greater stability than the four-pin version to enable a better and more stable reduction, an earlier weight-bearing (30 days) and improved functional outcomes. METHODS: A series of 69 consecutive closed heel intraarticular displaced fractures treated with the new Orthofix Calcaneal Minifixator were evaluated. Patients were assessed clinically with the Maryland Foot Score and radiologically with standard radiographs. RESULTS: The clinical results at follow-up were excellent in 37 cases (53.6%), good in 27 (39.2%), fair in two (2.9%) and poor in three (4.3%). The mean preoperative Böhler's angle was 5.2˚ (range 0-18˚) and the mean postoperative value was 28.5˚ (range 16-38˚). CONCLUSION: The excellent functional outcomes were despite some radiological images of imperfect posterior facet anatomical reduction and seemed to correlate with the use of a good and stable minimally-invasive surgical technique. This technique enabled early weight-bearing, minimised complications, respected the delicate biology of this anatomical site and restored the good heel volume and Böhler angle.

Experimental validation of an intrasubject elastic registration algorithm for dynamic-3D ultrasound images.

PURPOSE: In image-guided therapy, real-time visualization of the anatomy and adjustments in the therapy plan due to anatomical motions during the procedure is of outmost importance. 3D ultrasound has the potential to enable this real-time monitoring; however, nonrigid registration of a sequence of 3D ultrasound volumes remains to be a challenging problem. The authors present our recent results on the development of a computationally inexpensive feature-based registration algorithm for elastic alignment of dynamic-3D ultrasound images. METHODS: Our algorithm uses attribute vectors, based on the image intensity and gradient information, to perform feature-based matching in a sequence of 3D ultrasound images. Prior information from both the fixed and previous moving images is utilized to track features throughout the 3D image series. The algorithm has been compared to various publicly available registration techniques, i.e., the B-splines deformable registration, the symmetric forces Demons, and the fast free-form deformable registration method. RESULTS: Using a series of validation experiments on datasets collected from carotid artery, liver, and kidney of 20 subjects, the authors demonstrate that the feature-based, B-splines, Demons, and fast free-form deformable registration techniques can all recover volume deformations in a 3D ultrasound image series with reasonable accuracy; however, the proposed feature-based registration technique has substantial computational advantage over the other approaches. CONCLUSIONS: The proposed feature-based registration technique has the potential for real-time implementation on a computationally inexpensive platform and has the capability of recovering nonrigid deformations in tissue with reasonable accuracy.