Fast treatment of anterior shoulder dislocations with two sedation-free methods: The Davos self-reduction method and Arlt method.

Background: Various reduction techniques exist to treat traumatic shoulder dislocation, but best management remains unclear. Aims: To investigate the reduction rate of traumatic anteroinferior shoulder dislocations using two sedation-free techniques and success rates of subgroups. Methods: A single-center study was performed analysing shoulder dislocations in a two-year period. Adult patients with anteroinferior shoulder dislocation were included. Two sedation-free reduction techniques were used: the Davos self-reduction technique and the Arlt-chair technique. Two attempts were performed before sedation. All patients gave informed consent to study participation. Results: The investigated 106 patients (106 shoulder dislocations) had a mean age of 48 ± 18 years (74% male patients). The majority occurred during winter sports (76%). The overall success rate for both sedation-free reduction techniques was 82% (87 reduced shoulders, two attempts). A significantly increased success rate was found in patients without greater tuberosity fracture (86% without vs. 68% with fracture, p = 0.002) and for patients with repeated dislocation (93% vs. 80% for primary dislocation, p = 0.004). Time for reduction was 5 minutes (Davos technique) and 1 minute (Arlt-chair-technique). Associated injuries were mostly Hill Sachs lesions (78%). There was no major complication and no new-onset sensory deficit. Conclusion: Davos and Arlt reduction techniques allowed sedation-free and fast treatment for anteroinferior shoulder dislocation during winter sports.

The motor domain of the kinesin Kip2 promotes microtubule polymerization at microtubule tips.

Kinesins are microtubule-dependent motor proteins, some of which moonlight as microtubule polymerases, such as the yeast protein Kip2. Here, we show that the CLIP-170 ortholog Bik1 stabilizes Kip2 at microtubule ends where the motor domain of Kip2 promotes microtubule polymerization. Live-cell imaging and mathematical estimation of Kip2 dynamics reveal that disrupting the Kip2-Bik1 interaction aborts Kip2 dwelling at microtubule ends and abrogates its microtubule polymerization activity. Structural modeling and biochemical experiments identify a patch of positively charged residues that enables the motor domain to bind free tubulin dimers alternatively to the microtubule shaft. Neutralizing this patch abolished the ability of Kip2 to promote microtubule growth both in vivo and in vitro without affecting its ability to walk along microtubules. Our studies suggest that Kip2 utilizes Bik1 as a cofactor to track microtubule tips, where its motor domain then recruits free tubulin and catalyzes microtubule assembly.

Rethinking clinical study data: why we should respect analysis results as data.

The development and approval of new treatments generates large volumes of results, such as summaries of efficacy and safety. However, it is commonly overlooked that analyzing clinical study data also produces data in the form of results. For example, descriptive statistics and model predictions are data. Although integrating and putting findings into context is a cornerstone of scientific work, analysis results are often neglected as a data source. Results end up stored as "data products" such as PDF documents that are not machine readable or amenable to future analyses. We propose a solution to "calculate once, use many times" by combining analysis results standards with a common data model. This analysis results data model re-frames the target of analyses from static representations of the results (e.g., tables and figures) to a data model with applications in various contexts, including knowledge discovery. Further, we provide a working proof of concept detailing how to approach standardization and construct a schema to store and query analysis results.

Peliosis lienalis with atraumatic splenic rupture in a patient with chronic myelomonocytic leukemia: A case report.

INTRODUCTION: Atraumatic splenic rupture is a rare but life-threatening condition which may be associated with hematological malignancies. PRESENTATION OF CASE: We present the case of a 63-year-old male patient with a history of chronic myelomonocytic leukemia and sarcoidosis under therapy with prednisone, who suffered an atraumatic splenic rupture with hemodynamic instability. He was managed with proximal splenic artery embolization and secondary open splenectomy. On pathology the diagnosis of peliosis lienalis was established. DISCUSSION: Peliosis is a rare pathological entity, which presents with multiple blood-filled cavities within parenchymatous organs and is of unknown etiology and pathogenesis. In retrospect a rapid increase in splenomegaly and inhomogeneous parenchyma of the spleen on sonography was realized. CONCLUSION: Sonographic changes in size and parenchyma of the spleen in patients with hematological malignancies might help suspecting peliosis lienalis with impending splenic rupture and could alter clinical management towards a prophylactic splenectomy.

Long-Term Effects of Self-Administered Transcranial Direct Current Stimulation in Episodic Migraine Prevention: Results of a Randomized Controlled Trial.

BACKGROUND: Migraine is a multifactorial neurovascular disorder, which affects about 12% of the general population. In episodic migraine, the visual cortex revealed abnormal processing, most likely due to decreased preactivation level. Transcranial direct current stimulation (tDCS) is able to modify cortical excitability and might result in an alleviation of migraine occurrence if used repetitively. OBJECTIVE: To test the hypothesis that self-administered anodal tDCS over the visual cortex significantly decreases the number of monthly migraine days in episodic migraine. MATERIALS AND METHODS: The study was single-blind, randomized, and sham-controlled. Inclusion criteria were age 18-80 years and an ICHD-3 diagnosis of episodic migraine. Exclusion criteria were pregnancy, presence of a neurodegenerative disorder, a contraindication against MRI examinations, and less than two migraine days during the 28-day baseline period. Patients in whom the baseline period suggested chronic migraine were excluded. After baseline, participants applied daily either verum (anodal-1 mA to 20 min) or sham tDCS (anodal-1 mA to 30 sec) at Oz (reference Cz electrode) for 28 days. Headache diaries were used to record the number of migraine days at baseline, during the stimulation period, and during four subsequent 28-day periods. RESULTS: Twenty-eight patients were included; two were excluded after the baseline period because less than two migraine days occurred; three were excluded because their headache diaries suggested the diagnosis of chronic migraine. Twenty-three datasets were taken for further analysis. Compared to sham tDCS (n = 12), verum tDCS (n = 11) resulted in a lower number of migraine days (p = 0.010) across all follow-up periods. We found no significant change in total headache days (p = 0.165), anxiety (p = 0.884), or depression scores (p = 0.535). No serious adverse events occurred; minor side effects were similar in both groups. CONCLUSIONS: This study provides Class II evidence that self-administered anodal tDCS over the visual cortex in episodic migraine results in a significantly lower number of monthly migraine days. However, it has neither an immediate nor a long-term effect.

Gene expression dynamics during rapid organismal diversification in African cichlid fishes.

Changes in gene expression play a fundamental role in phenotypic evolution. Transcriptome evolutionary dynamics have so far mainly been compared among distantly related species and remain largely unexplored during rapid organismal diversification, in which gene regulatory changes have been suggested as particularly effective drivers of phenotypic divergence. Here we studied gene expression evolution in a model system of adaptive radiation, the cichlid fishes of African Lake Tanganyika. By comparing gene expression profiles of 6 different organs in 74 cichlid species representing all subclades of this radiation, we demonstrate that the rate of gene expression evolution varies among organs, transcriptome parts and the subclades of the radiation, indicating different strengths of selection. We found that the noncoding part of the transcriptome evolved more rapidly than the coding part, and that the gonadal transcriptomes evolved more rapidly than the somatic ones, with the exception of liver. We further show that the rate of gene expression change was not constant over the course of the radiation but accelerated at its later phase. Finally, we show that-at the per-gene level-the evolution of expression patterns is dominated by stabilizing selection.

Where Am I? Niche constraints due to morphological specialization in two Tanganyikan cichlid fish species.

Food resource specialization within novel environments is considered a common axis of diversification in adaptive radiations. Feeding specializations are often coupled with striking morphological adaptations and exemplify the relation between morphology and diet (phenotype-environment correlations), as seen in, for example, Darwin finches, Hawaiian spiders, and the cichlid fish radiations in East African lakes. The cichlids' potential to rapidly exploit and occupy a variety of different habitats has previously been attributed to the variability and adaptability of their trophic structures including the pharyngeal jaw apparatus. Here we report a reciprocal transplant experiment designed to explore the adaptability of the trophic structures in highly specialized cichlid fish species. More specifically, we forced two common but ecologically distinct cichlid species from Lake Tanganyika, Tropheus moorii (rock-dweller), and Xenotilapia boulengeri (sand-dweller), to live on their preferred as well as on an unpreferred habitat (sand and rock, respectively). We measured their overall performance on the different habitat types and explored whether adaptive phenotypic plasticity is involved in adaptation. We found that, while habitat had no effect on the performance of X. boulengeri, T. moorii performed significantly better in its preferred habitat. Despite an experimental duration of several months, we did not find a shift in the morphology of the lower pharyngeal jaw bone that would be indicative of adaptive phenotypic plasticity in this trait.

Remote control of microtubule plus-end dynamics and function from the minus-end.

In eukaryotes, the organization and function of the microtubule cytoskeleton depend on the allocation of different roles to individual microtubules. For example, many asymmetrically dividing cells differentially specify microtubule behavior at old and new centrosomes. Here we show that yeast spindle pole bodies (SPBs, yeast centrosomes) differentially control the plus-end dynamics and cargoes of their astral microtubules, remotely from the minus-end. The old SPB recruits the kinesin motor protein Kip2, which then translocates to the plus-end of the emanating microtubules, promotes their extension and delivers dynein into the bud. Kip2 recruitment at the SPB depends on Bub2 and Bfa1, and phosphorylation of cytoplasmic Kip2 prevents random lattice binding. Releasing Kip2 of its control by SPBs equalizes its distribution, the length of microtubules and dynein distribution between the mother cell and its bud. These observations reveal that microtubule organizing centers use minus to plus-end directed remote control to individualize microtubule function.

Point-Combination Transect (PCT): Incorporation of small underwater cameras to study fish communities.

Available underwater visual census (UVC) methods such as line transects or point count observations are widely used to obtain community data of underwater species assemblages, despite their known pit-falls. As interest in the community structure of aquatic life is growing, there is need for more standardized and replicable methods for acquiring underwater census data.Here, we propose a novel approach, Point-Combination Transect (PCT), which makes use of automated image recording by small digital cameras to eliminate observer and identification biases associated with available UVC methods. We conducted a pilot study at Lake Tanganyika, demonstrating the applicability of PCT on a taxonomically and phenotypically highly diverse assemblage of fishes, the Tanganyikan cichlid species-flock.We conducted 17 PCTs consisting of five GoPro cameras each and identified 22,867 individual cichlids belonging to 61 species on the recorded images. These data were then used to evaluate our method and to compare it to traditional line transect studies conducted in close proximity to our study site at Lake Tanganyika.We show that the analysis of the second hour of PCT image recordings (equivalent to 360 images per camera) leads to reliable estimates of the benthic cichlid community composition in Lake Tanganyika according to species accumulation curves, while minimizing the effect of disturbance of the fish through SCUBA divers. We further show that PCT is robust against observer biases and outperforms traditional line transect methods.

Clipping of a superior hypophyseal artery aneurysm during endoscopic transnasal removal of a Rathke cleft cyst: a case report.

The concomitant presence of an aneurysm in contact with a sellar lesion usually contraindicates a transsphenoidal approach (TSS). Clipping of an intracranial aneurysm is however possible in highly selected cases also through an endoscopic TSS approach, as long as the basic principles of cerebrovascular surgery are respected. We report thus on a case of a patient harboring a Rathke cleft cyst (RCC) and an aneurysm of the carotid artery (ICA) in close contact with the RCC. The anatomical characteristics of both lesions warranted an endoscopic TSS for removal of the RCC and clipping of the aneurysm during the same approach.

Mortality, risk factors and causes of death in Swedish patients with open tibial fractures - a nationwide study of 3, 777 patients.

BACKGROUND: Open tibial fractures are serious, complicated injuries. Previous studies suggested an increased risk of death, however, this has not been studied in large population-based settings. We aimed to analyze mortality including causes of death in all patients with open tibial fractures in Sweden. Moreover, we wanted to compare mortality rates with the Swedish population and determine whether treatment-related or demographic variables were independently associated with death. METHOD: We searched the Swedish National Hospital Discharge Register for all patients with open tibial fracture between 1998 and 2010. We collected the following variables: age, gender, length of stay, mechanism of injury and treatment rendered. We then cross-referenced the Swedish Cause of Death Register to determine the cause of death, if applicable. We compared mortality in the study population with population-based mortality data from Statistics Sweden and determined whether variables were independently associated with death using regression analysis. RESULTS: Of the 3777 open tibial fractures, 425 (11.3%) patients died. The most common causes of death for elderly patients were cardiovascular and respiratory disease. Patients aged 15-39 years succumbed to external causes (accidents, suicides or poisoning). Increasing age (OR 25.7 (95% CI 11.8-64.8) p < 0.001), length of hospital stay (HR 1.01, (95% CI 1.01-1.02,) p < 0.001), limb amputation (OR 4.8 (95% CI 1.86-11.1) p < 0.001) and cause of the accident were independently associated with an increased mortality. CONCLUSION: Patients with open tibial fractures have an increased risk of death compared with the general population in all age- and gender-groups. External causes of death are over-represented and indicate a subgroup with a risky behaviour among younger males. Elderly patients have an increased risk of dying comparable to hip fracture patients. They are at risk for cardiovascular and respiratory failure and should be treated with urgency, emphasizing the need for specialized geriatric trauma units.

Bridging intracellular scales by mechanistic computational models.

The impact of intracellular spatial organization beyond classical compartments on processes such as cell signaling is increasingly recognized. A quantitative, mechanistic understanding of cellular systems therefore needs to account for different scales in at least three coordinates: time, molecular abundances, and space. Mechanistic mathematical models may span all these scales, but corresponding multi-scale models need to resolve mechanistic details on small scales while maintaining computational tractability for larger ones. This typically results in models that combine different levels of description: from a microscopic representation of chemical reactions up to continuum dynamics in space and time. We highlight recent progress in bridging these model classes and outline current challenges in multi-scale models such as active transport and dynamic geometries.

More Than Talking About the Weekend: Content of Case-Irrelevant Communication Within the OR Team.

BACKGROUND: Case-irrelevant communication (CIC) is defined as "any conversation" irrelevant to the case. It includes small talk, but also communication related to other work issues besides the actual task. CIC during surgeries is generally seen as distracting, despite a lack of knowledge about the content of CIC and its regulation in terms of adjustments to the situation of CIC. Primary goal of the study was to evaluate CIC content; secondary goal was to evaluate whether surgical teams regulate CIC according to different concentration demands of surgical procedures. METHODS: In 125 surgeries, 1396 CIC events were observed. CIC were content coded into work-related CIC (pertaining to other tasks or work in general) and social CIC (pertaining to acquaintance talk, gossip, or private conversation). The impact of different phases and the difficulty of the surgical procedure on CIC were assessed. RESULTS: Work-related CIC were significantly more frequent (2.49 per hour, SD = 2.17) than social CIC (1.42 per hour, SD = 2.17). Across phases, frequency of work-related CIC was constant, whereas social CIC increased significantly across phases. In surgeries assessed as highly difficult by the surgeons, social CIC were observed at a lower frequency, and less work-related CIC were observed during the main phase compared to surgeries assessed as less difficult. CONCLUSION: The high proportion of work-related CIC indicates that surgical teams deal with other tasks during surgeries. Surgical teams adapt CIC according to the demands of the procedure. Hospital policies should support these adaptations rather than attempt to suppress CIC entirely.

Sequence-based prediction of permissive stretches for internal protein tagging and knockdown.

BACKGROUND: Internal tagging of proteins by inserting small functional peptides into surface accessible permissive sites has proven to be an indispensable tool for basic and applied science. Permissive sites are typically identified by transposon mutagenesis on a case-by-case basis, limiting scalability and their exploitation as a system-wide protein engineering tool. METHODS: We developed an apporach for predicting permissive stretches (PSs) in proteins based on the identification of length-variable regions (regions containing indels) in homologous proteins. RESULTS: We verify that a protein's primary structure information alone is sufficient to identify PSs. Identified PSs are predicted to be predominantly surface accessible; hence, the position of inserted peptides is likely suitable for diverse applications. We demonstrate the viability of this approach by inserting a Tobacco etch virus protease recognition site (TEV-tag) into several PSs in a wide range of proteins, from small monomeric enzymes (adenylate kinase) to large multi-subunit molecular machines (ATP synthase) and verify their functionality after insertion. We apply this method to engineer conditional protein knockdowns directly in the Escherichia coli chromosome and generate a cell-free platform with enhanced nucleotide stability. CONCLUSIONS: Functional internally tagged proteins can be rationally designed and directly chromosomally implemented. Critical for the successful design of protein knockdowns was the incorporation of surface accessibility and secondary structure predictions, as well as the design of an improved TEV-tag that enables efficient hydrolysis when inserted into the middle of a protein. This versatile and portable approach can likely be adapted for other applications, and broadly adopted. We provide guidelines for the design of internally tagged proteins in order to empower scientists with little or no protein engineering expertise to internally tag their target proteins.

Simulation in vascular access surgery training.

Rapidly growing technical developments and working time constraints call for changes in trainee formation. In reality, trainees spend fewer hours in the hospital and face more difficulties in acquiring the required qualifications in order to work independently as a specialist. Simulation-based training is a potential solution. It offers the possibility to learn basic technical skills, repeatedly perform key steps in procedures and simulate challenging scenarios in team training. Patients are not at risk and learning curves can be shortened. Advanced learners are able to train rare complications. Senior faculty member's presence is key to assess and debrief effective simulation training. In the field of vascular access surgery, simulation models are available for open as well as endovascular procedures. In this narrative review, we describe the theory of simulation, present simulation models in vascular (access) surgery, discuss the possible benefits for patient safety and the difficulties of implementing simulation in training.

Simulation in vascular access surgery.

In the last years, simulation training has become widespread in different areas of medicine due to social expectations, political accountability and professional regulation. Different types of simulators allow to improve knowledge, skills, communication and team behavior. Simulation sessions have been proven to shorten the learning curve and allow education in a safe environment. Patients on dialysis are an expanding group. They often suffer from several comorbidities and need complex surgical procedures with regard to their dialysis access. Therefore, education in evidence-based algorithms is as important as teaching of practical skills. In this chapter, we are presenting an overview of available dialysis access training modalities. We are convinced that simulation will become more important in the near future and has a substantial impact on strategies to improve aspects of patient safety.

Effect of Immunosuppression on T-Helper 2 and B-Cell Responses to Influenza Vaccination.

BACKGROUND: Influenza vaccine immunogenicity is suboptimal in immunocompromised patients. However, there are limited data on the interplay of T- and B- cell responses to vaccination with simultaneous immunosuppression. METHODS: We collected peripheral blood mononuclear cells from transplant recipients before and 1 month after seasonal influenza vaccination. Before and after vaccination, H1N1-specific T- and B-cell activation were quantified with flow cytometry. We also developed a mathematical model using T- and B-cell markers and mycophenolate mofetil (MMF) dosage. RESULTS: In the 47 patients analyzed, seroconversion to H1N1 antigen was demonstrated in 34%. H1N1-specific interleukin 4 (IL-4)-producing CD4(+) T-cell frequencies increased significantly after vaccination in 53% of patients. Prevaccine expression of H1N1-induced HLA-DR and CD86 on B cells was high in patients who seroconverted. Seroconversion against H1N1 was strongly associated with HLA-DR expression on B cells, which was dependent on the increase between prevaccine and postvaccine H1N1-specific IL-4(+)CD4(+) T cells (R(2) = 0.35). High doses of MMF (≥ 2 g/d) led to lower seroconversion rates, smaller increase in H1N1-specific IL-4(+)CD4(+) T cells, and reduced HLA-DR expression on B cells. The mathematical model incorporating a MMF-inhibited positive feedback loop between H1N1-specific IL-4(+)CD4(+) T cells and HLA-DR expression on B cells captured seroconversion with high specificity. CONCLUSIONS: Seroconversion is associated with influenza-specific T-helper 2 and B-cell activation and seems to be modulated by MMF.

Changing face of vaccination in immunocompromised hosts.

Infection prevention is a key component of care and an important determinant of clinical outcomes in a diverse population of immunocompromised hosts. Vaccination remains a fundamental preventative strategy, and clear guidelines exist for the vaccination of immunocompromised individuals and close contacts. Unfortunately, adherence to such guidelines is frequently suboptimal, with consequent missed opportunities to prevent infection. Additionally, vaccination of immunocompromised individuals is known to produce responses inferior to those observed in immunocompetent hosts. Multiple factors contribute to this finding, and developing improved vaccination strategies for those at high risk of infectious complications remains a priority of care providers. Herein, we review potential factors contributing to vaccine outcomes, focusing on host immune responses, and propose a means for applying modern, innovative systems biology technology to model critical determinants of vaccination success. With influenza vaccine in solid organ transplants used as a case in point, novel means for stratifying individuals using a host "immunophenotype" are explored, and strategies for individualizing vaccine approaches tailored to safely optimize vaccine responses in those most at risk are discussed.

A specialized ODE integrator for the efficient computation of parameter sensitivities.

BACKGROUND: Dynamic mathematical models in the form of systems of ordinary differential equations (ODEs) play an important role in systems biology. For any sufficiently complex model, the speed and accuracy of solving the ODEs by numerical integration is critical. This applies especially to systems identification problems where the parameter sensitivities must be integrated alongside the system variables. Although several very good general purpose ODE solvers exist, few of them compute the parameter sensitivities automatically. RESULTS: We present a novel integration algorithm that is based on second derivatives and contains other unique features such as improved error estimates. These features allow the integrator to take larger time steps than other methods. In practical applications, i.e. systems biology models of different sizes and behaviors, the method competes well with established integrators in solving the system equations, and it outperforms them significantly when local parameter sensitivities are evaluated. For ease-of-use, the solver is embedded in a framework that automatically generates the integrator input from an SBML description of the system of interest. CONCLUSIONS: For future applications, comparatively 'cheap' parameter sensitivities will enable advances in solving large, otherwise computationally expensive parameter estimation and optimization problems. More generally, we argue that substantially better computational performance can be achieved by exploiting characteristics specific to the problem domain; elements of our methods such as the error estimation could find broader use in other, more general numerical algorithms.

Reliability and repeatability of toe pressures measured with laser Doppler and portable and stationary photoplethysmography devices.

BACKGROUND: There are two principally different methods for measuring toe pressures (TP)-photoplethysmography (PPG) and laser Doppler (LD). PPG is based on detecting changes in the blood filling of the digital arteries and arterioles, and the LD perfusion signal is derived from the Doppler shift undergone by the emitted infrared laser light after reflection from moving particles (red blood cells). The aim of the study was to compare two PPG devices and one LD device in TP measurement. The PPG devices used were the Nicolet VasoGuard (Nicolet Vascular Inc, Madison, WI; PPG1) and Systoe (Atys Medical, France; PPG2), and the LD device was the Perimed system 5000 (Perimed, Stockholm, Sweden). MATERIALS AND METHODS: TPs were measured from 54 nonselected consecutive patients who visited the vascular surgical outpatient clinic or underwent an endovascular procedure owing to chronic lower limb ischemia. A total of 107 toes were measured. The symptoms were claudication in 51.4% (n = 55), rest pain in 4.7% (n = 5), and ulcer or gangrene in 14.0% (n = 15) of the legs. Of the measured legs, 29.9% (n = 32) were asymptomatic. Forty patients had undergone endovascular revascularization immediately before the TP measurement. The limits of agreement show the estimated range within which the differences between measurements by the two devices would fall in approximately 95% of the measurements. The approximate 95% limits of agreement were calculated as the mean difference ± 2 standard deviation and presented in the Bland-Altman scatter plots. RESULTS: For PPG1 versus LD, the mean difference between two measurements was 14 mm Hg and the limits of agreement were 38 mm Hg. In 47% of the toes, the difference was ≥10 mm Hg, and in 37% of the toes, it was ≥15 mm Hg. For PPG2 versus LD, the mean difference between the TPs was 12 mm Hg and the limits of agreement were 24 mm Hg. In 44% of the cases, the difference was ≥10 mm Hg, and in 30%, it was ≥15 mm Hg. For PPG1 versus PPG2, the mean difference between two measurements was 14 mm Hg and the limits of agreement were 24 mm Hg. In 50% of the cases, the difference between the two machines was ≥10 mm Hg, and in 33%, it was ≥15 mm Hg. Repeatability measured with LD, PPG1, and PPG2 showed that the difference between the first and second measurement was <10 mm Hg in 93%, 86%, and 78% of the cases, respectively, and <15 mm Hg in 98%, 94%, and 88% of the cases, respectively. CONCLUSIONS: TP values vary greatly depending on the device used. However, the repeatability seemed to be acceptable with LD and PPG1. We recommend using same device when circulation is repeatedly assessed in the same patient. Also, we emphasize the importance of clinical examination and low threshold for angiography and revascularization especially in diabetics with wound healing problems.