Search

Low emittance tuning at the Cornell Electron Storage Ring (CESR) test accelerator depends on precision measurement of vertical dispersion and transverse coupling. The CESR beam position monitors (BPMs) consist of four button electrodes, instrumented with electronics that allow acquisition of turn-by-turn data. The response to the beam will vary among the four electrodes due to differences in electronic gain and/or misalignment. This variation in the response of the BPM electrodes will couple real horizontal offset to apparent vertical position, and introduce spurious measurements of coupling and vertical dispersion. To alleviate this systematic effect, a beam based technique to measure the relative response of the four electrodes has been developed. With typical CESR parameters, simulations show that turn-by-turn BPM data can be used to determine electrode gains to within ∼0.1%.

Measurement of the betatron phase in the vertical and horizontal planes as well as the transverse horizontal-vertical coupling is a standard procedure now used at the Cornell Electron/Positron Storage Ring. The measurement is made by shaking the beam and observing the phase of oscillation at detectors located around the ring. The measurements allow quadrupolar errors to be corrected.

MicroRNAs (miRNAs) have been implicated in human disorders, from cancers to infectious diseases. Targeting miRNAs or their target genes with small molecules offers opportunities to modulate dysregulated cellular processes linked to diseases. Yet, predicting small molecules associated with miRNAs remains challenging due to the small size of small molecule-miRNA datasets. Herein, we develop a generalized deep learning framework, sChemNET, for predicting small molecules affecting miRNA bioactivity based on chemical structure and sequence information. sChemNET overcomes the limitation of sparse chemical information by an objective function that allows the neural network to learn chemical space from a large body of chemical structures yet unknown to affect miRNAs. We experimentally validated small molecules predicted to act on miR-451 or its targets and tested their role in erythrocyte maturation during zebrafish embryogenesis. We also tested small molecules targeting the miR-181 network and other miRNAs using in-vitro and in-vivo experiments. We demonstrate that our machine-learning framework can predict bioactive small molecules targeting miRNAs or their targets in humans and other mammalian organisms., (© 2024. The Author(s).)

Our previous research revealed a key microRNA signature that is associated with spaceflight that can be used as a biomarker and to develop countermeasure treatments to mitigate the damage caused by space radiation. Here, we expand on this work to determine the biological factors rescued by the countermeasure treatment. We performed RNA-sequencing and transcriptomic analysis on 3D microvessel cell cultures exposed to simulated deep space radiation (0.5 Gy of Galactic Cosmic Radiation) with and without the antagonists to three microRNAs: miR-16-5p, miR-125b-5p, and let-7a-5p (i.e., antagomirs). Significant reduction of inflammation and DNA double strand breaks (DSBs) activity and rescue of mitochondria functions are observed after antagomir treatment. Using data from astronaut participants in the NASA Twin Study, Inspiration4, and JAXA missions, we reveal the genes and pathways implicated in the action of these antagomirs are altered in humans. Our findings indicate a countermeasure strategy that can potentially be utilized by astronauts in spaceflight missions to mitigate space radiation damage., (© 2024. The Author(s).)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral proteins bind to host mitochondrial proteins, likely inhibiting oxidative phosphorylation (OXPHOS) and stimulating glycolysis. We analyzed mitochondrial gene expression in nasopharyngeal and autopsy tissues from patients with coronavirus disease 2019 (COVID-19). In nasopharyngeal samples with declining viral titers, the virus blocked the transcription of a subset of nuclear DNA (nDNA)-encoded mitochondrial OXPHOS genes, induced the expression of microRNA 2392, activated HIF-1α to induce glycolysis, and activated host immune defenses including the integrated stress response. In autopsy tissues from patients with COVID-19, SARS-CoV-2 was no longer present, and mitochondrial gene transcription had recovered in the lungs. However, nDNA mitochondrial gene expression remained suppressed in autopsy tissue from the heart and, to a lesser extent, kidney, and liver, whereas mitochondrial DNA transcription was induced and host-immune defense pathways were activated. During early SARS-CoV-2 infection of hamsters with peak lung viral load, mitochondrial gene expression in the lung was minimally perturbed but was down-regulated in the cerebellum and up-regulated in the striatum even though no SARS-CoV-2 was detected in the brain. During the mid-phase SARS-CoV-2 infection of mice, mitochondrial gene expression was starting to recover in mouse lungs. These data suggest that when the viral titer first peaks, there is a systemic host response followed by viral suppression of mitochondrial gene transcription and induction of glycolysis leading to the deployment of antiviral immune defenses. Even when the virus was cleared and lung mitochondrial function had recovered, mitochondrial function in the heart, kidney, liver, and lymph nodes remained impaired, potentially leading to severe COVID-19 pathology.

Background: Low energy falls (LEF) in older adults constitute a relevant cause for emergency department (ED) visits, hospital admission and in-hospital mortality. Patient-reported outcome measures containing information about patients' medical, mental and social health problems might support disposition and therapy decisions. We investigated the value of a tablet-based (self-)assessment in predicting hospital admission and in-hospital mortality., Methods: Patients 65 years or older, consecutively presenting with LEF to our level I trauma center ED (from November 2020 to March 2021), were eligible for inclusion in this prospective observational study. The primary endpoint was hospital admission; secondary endpoints were in-hospital mortality and the use of the tablet for self-reported assessment. Multivariate logistic regression models were calculated to measure the association between clinical findings and endpoints., Results: Of 618 eligible patients, 201 patients were included. The median age was 82 years (62.7% women). The hospital admission rate was 45.3% (110/201), with an in-hospital mortality rate of 3.6% (4/110). Polypharmacy (odds ratio (OR): 8.48; 95% confidence interval (95%CI) 1.21-59.37, p = 0.03), lower emergency severity index (ESI) scores (OR: 0.33; 95%CI 0.17-0.64, p = 0.001) and increasing injury severity score (ISS) (OR: 1.54; 95%CI 1.32-1.79, p < 0.001) were associated with hospital admission. The Charlson comorbidity index (CCI) was significantly associated with in-hospital mortality (OR: 2.60; 95%CI: 1.17-5.81, p = 0.03). Increasing age (OR: 0.94; 95%CI: 0.89-0.99, p = 0.03) and frailty (OR: 0.71; 95%CI: 0.51-0.99, p = 0.04) were associated with the incapability of tablet use., Conclusions: The severity of fall-related injuries and the clinical acuity are easily accessible, relevant predictors for hospital admission. Tablet-based (self-)assessment may be feasible and acceptable during ED visits and might help facilitate comprehensive geriatric assessments during ED stay.

Introduction  The surgical management that achieves minimal morbidity and mortality for patients with glomus and non-glomus tumors involving the jugular foramen (JF) region requires a comprehensive understanding of the complex anatomy, anatomic variability, and pathological anatomy of this region. Objective  The aim of this study is to propose a rational guideline to expose and preserve the lower cranial nerves (CNs) in the lateral approach of the JF. Methods  The technique utilized is the gross and microdissection of 4 fixed cadaveric heads to revise the JF's surgical anatomy and high part of the carotid sheath compared with surgical cases to understand and preserve the integrity of lower CNs. The method involves radical mastoidectomy, microdissection of the JF, facial nerve, and high neck just below the carotid canal and the JF. The CNs IX, X, XI, and XII are microscopically dissected and kept in sight up to the JF. Results  This study realized well the surgical and applied anatomy of the lower CNs with relation to the facial nerve and JF. Conclusions  The JF anatomy is complicated, and the key to safely operate on it and preserving the lower CNs is to find the posterior belly of the digastric muscle, to skeletonize the facial nerve, to remove the mastoid tip preserving the stylomastoid foramen, to skeletonize the sigmoid sinus and posterior fossa dura not only anterior but also posteroinferior to reach and drill the jugular tubercle., Competing Interests: Conflict of interests The authors have no conflict of interests to declare., (Fundação Otorrinolaringologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

We analyzed RNA sequencing data from nasal swabs used for SARS-CoV-2 testing. 13% of 317 PCR-negative samples contained over 100 reads aligned to multiple regions of the SARS-CoV-2 genome. Differential gene expression analysis compares the host gene expression in potential false-negative (FN: PCR negative, sequencing positive) samples to subjects with multiple SARS-CoV-2 viral loads. The host transcriptional response in FN samples was distinct from true negative samples (PCR & sequencing negative) and similar to low viral load samples. Gene Ontology analysis shows viral load-dependent changes in gene expression are functionally distinct; 23 common pathways include responses to viral infections and associated immune responses. GO analysis reveals FN samples had a high overlap with high viral load samples. Deconvolution of RNA-seq data shows similar cell content across viral loads. Hence, transcriptome analysis of nasal swabs provides an additional level of identifying SARS-CoV-2 infection., Competing Interests: Dr. Mason is a cofounder for Aevum (acquired by Onegevity), Biotia, BridgeOmics, Onegevity (acquired by Thorne HealthTech), as well as a current advisor, shareholder, or compensated speaker for Acuamark Diagnostics, Allen and Company, ArcBio, BGI/MGI, Bumrungrad International Hospital, Carverr, Color Genomics, Cowen, DNA Genotek, EdenRoc, Enzymetrics, Element Bio, Foresite Capital, F!nd Genomics, Genialis, GenPro, Ginger Network, Google, Homo Deus, iCareDx, JP Morgan, Illumina, Infectious Economics, Meenta, Merck, MilliporeSigma, Mirimus, Morgan Stanley, Nano-Lit, Nanostring, New England Biolabs, Nooma, Pandemic Response Lab, Promega, Pendulum Health, Poppy Health, QIAGEN, Roche, Seed, Tecan, Tempus Labs, Testing for America, Thermo Fisher, Torus, Twist Biosciences, UBS, Ursa Bio, WorldQuant, and Zymo Research., (© 2022 The Authors.)

The World Health Organization recently defined hypertension and type 2 diabetes (T2D) as modifiable comorbidities leading to dementia and Alzheimer's disease. In the United States (US), hypertension and T2D are health disparities, with higher prevalence seen for Black and Hispanic minority groups compared to the majority White population. We hypothesized that elevated prevalence of hypertension and T2D risk factors in Black and Hispanic groups may be associated with dementia disparities. We interrogated this hypothesis using a cross-sectional analysis of participant data from the All of Us (AoU) Research Program, a large observational cohort study of US residents. The specific objectives of our study were: (1) to compare the prevalence of dementia, hypertension, and T2D in the AoU cohort to previously reported prevalence values for the US population, (2) to investigate the association of hypertension, T2D, and race/ethnicity with dementia, and (3) to investigate whether race/ethnicity modify the association of hypertension and T2D with dementia. AoU participants were recruited from 2018 to 2019 as part of the initial project cohort (R2019Q4R3). Participants aged 40-80 with electronic health records and demographic data (age, sex, race, and ethnicity) were included for analysis, yielding a final cohort of 125,637 individuals. AoU participants show similar prevalence of hypertension (32.1%) and T2D (13.9%) compared to the US population (32.0% and 10.5%, respectively); however, the prevalence of dementia for AoU participants (0.44%) is an order of magnitude lower than seen for the US population (5%). AoU participants with dementia show a higher prevalence of hypertension (81.6% vs. 31.9%) and T2D (45.9% vs. 11.4%) compared to non-dementia participants. Dominance analysis of a multivariable logistic regression model with dementia as the outcome shows that hypertension, age, and T2D have the strongest associations with dementia. Hispanic was the only race/ethnicity group that showed a significant association with dementia, and the association of sex with dementia was non-significant. The association of T2D with dementia is likely explained by concurrent hypertension, since > 90% of participants with T2D also had hypertension. Black race and Hispanic ethnicity interact with hypertension, but not T2D, to increase the odds of dementia. This study underscores the utility of the AoU participant cohort to study disease prevalence and risk factors. We do notice a lower participation of aged minorities and participants with dementia, revealing an opportunity for targeted engagement. Our results indicate that targeting hypertension should be a priority for risk factor modifications to reduce dementia incidence., (© 2022. The Author(s).)

In this study, we characterize biophysical changes in NMDA receptor function in response to brief non-injurious ischemic stress (ischemic preconditioning). Electrophysiological studies show NMDA receptor function is reduced following preconditioning in cultured rat cortical neurons. This functional change is not due to changes in the reversal potential of the receptor, but an increase in desensitization. We performed concentration-response analysis of NMDA-evoked currents, and demonstrate that preconditioned neurons show a reduced potency of NMDA to evoke currents, an increase in Mg 2+ sensitivity, but no change in glycine sensitivity. Antagonists studies show a reduced inhibition of GluN2B antagonists that have an allosteric mode of action (ifenprodil and R-25-6981), but competitive antagonists at the GluR2A and 2B receptor (NVP-AMM077 and conantokin-G) appear to have similar potency to block currents. Biochemical studies show a reduction in membrane surface GluN2B subunits, and an increased co-immunoprecipitation of GluN2A with GluN2B subunits, suggestive of tri-heteromeric receptor formation. Finally, we show that blocking actin remodeling with jasplakinolide, a mechanism of rapid ischemic tolerance, prevents NMDA receptor functional changes and co-immunoprecipitation of GluN2A and 2B subunits. Together, this study shows that alterations in NMDA receptor function following preconditioning ischemia are associated with neuroprotection in rapid ischemic tolerance.

Rationale: Viral infections are complex processes based on an intricate network of molecular interactions. The infectious agent hijacks components of the cellular machinery for its profit, circumventing the natural defense mechanisms triggered by the infected cell. The successful completion of the replicative viral cycle within a cell depends on the function of viral components versus the cellular defenses. Non-coding RNAs (ncRNAs) are important cellular modulators, either promoting or preventing the progression of viral infections. Among these ncRNAs, the long non-coding RNA (lncRNA) family is especially relevant due to their intrinsic functional properties and ubiquitous biological roles. Specific lncRNAs have been recently characterized as modulators of the cellular response during infection of human host cells by single stranded RNA viruses. However, the role of host lncRNAs in the infection by human RNA coronaviruses such as SARS-CoV-2 remains uncharacterized. Methods: In the present work, we have performed a transcriptomic study of a cohort of patients with different SARS-CoV-2 viral load and analyzed the involvement of lncRNAs in supporting regulatory networks based on their interaction with RNA-binding proteins (RBPs). Results: Our results revealed the existence of a SARS-CoV-2 infection-dependent pattern of transcriptional up-regulation in which specific lncRNAs are an integral component. To determine the role of these lncRNAs, we performed a functional correlation analysis complemented with the study of the validated interactions between lncRNAs and RBPs. This combination of in silico functional association studies and experimental evidence allowed us to identify a lncRNA signature composed of six elements - NRIR, BISPR, MIR155HG, FMR1-IT1, USP30-AS1, and U62317.2 - associated with the regulation of SARS-CoV-2 infection. Conclusions: We propose a competition mechanism between the viral RNA genome and the regulatory lncRNAs in the sequestering of specific RBPs that modulates the interferon response and the regulation of RNA surveillance by nonsense-mediated decay (NMD)., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Whole transcriptome RNA-sequencing was performed to quantify RNA expression changes in whole blood samples collected from steady state sickle cell anemia (SCA) and control subjects. Pediatric SCA and control subjects were recruited from Atlanta (GA)-based hospital(s) systems and consented for RNA sequencing. RNA sequencing was performed on an Ion Torrent S5 sequencer, using the Ion Total RNA-seq v2 protocol. Data were aligned to the hg19 reference genome and analyzed in the Partek Genomics studio package (v7.0). 223 genes were differentially expressed between SCA and controls (± 1.5 fold change FDR p < 0.001) and 441 genes show differential transcript expression (± 1.5 fold FDR p < 0.001). Differentially expressed RNA are enriched for hemoglobin associated genes and ubiquitin-proteasome pathway genes. Further analysis shows higher gamma globin gene expression in SCA (33-fold HBG1 and 49-fold HBG2, both FDR p < 0.05), which did not correlate with hemoglobin F protein levels. eQTL analysis identified SNPs in novel non-coding RNA RYR2 gene as having a potential regulatory role in HBG1 and HBG2 expression levels. Gene expression correlation identified JHDM1D-AS1(KDM7A-DT), a non-coding RNA associated with angiogenesis, enhanced GATA1 and decreased JAK-STAT signaling to correlate with HBG1 and HBG2 mRNA levels. These data suggest novel regulatory mechanisms for fetal hemoglobin regulation, which may offer innovative therapeutic approaches for SCA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gee, Pearson, Buchanan-Perry, Simon, Archer and Meller.)

MicroRNAs (miRNAs) are small non-coding RNAs involved in post-transcriptional gene regulation that have a major impact on many diseases and provide an exciting avenue toward antiviral therapeutics. From patient transcriptomic data, we determined that a circulating miRNA, miR-2392, is directly involved with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) machinery during host infection. Specifically, we show that miR-2392 is key in driving downstream suppression of mitochondrial gene expression, increasing inflammation, glycolysis, and hypoxia, as well as promoting many symptoms associated with coronavirus disease 2019 (COVID-19) infection. We demonstrate that miR-2392 is present in the blood and urine of patients positive for COVID-19 but is not present in patients negative for COVID-19. These findings indicate the potential for developing a minimally invasive COVID-19 detection method. Lastly, using in vitro human and in vivo hamster models, we design a miRNA-based antiviral therapeutic that targets miR-2392, significantly reduces SARS-CoV-2 viability in hamsters, and may potentially inhibit a COVID-19 disease state in humans., Competing Interests: Declaration of interests A.C., P.N., S.V.C., and A.B. have a provisional patent based on the antiviral discovery and design. A.C., P.N., and S.S. are part of the company (Sachi Bioworks Inc.) that has filed a patent on the Nanoligomer technology., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

With the development of transcriptomic technologies, we are able to quantify precise changes in gene expression profiles from astronauts and other organisms exposed to spaceflight. Members of NASA GeneLab and GeneLab-associated analysis working groups (AWGs) have developed a consensus pipeline for analyzing short-read RNA-sequencing data from spaceflight-associated experiments. The pipeline includes quality control, read trimming, mapping, and gene quantification steps, culminating in the detection of differentially expressed genes. This data analysis pipeline and the results of its execution using data submitted to GeneLab are now all publicly available through the GeneLab database. We present here the full details and rationale for the construction of this pipeline in order to promote transparency, reproducibility, and reusability of pipeline data; to provide a template for data processing of future spaceflight-relevant datasets; and to encourage cross-analysis of data from other databases with the data available in GeneLab., Competing Interests: The authors declare no competing interests.

Spaceflight is known to impose changes on human physiology with unknown molecular etiologies. To reveal these causes, we used a multi-omics, systems biology analytical approach using biomedical profiles from fifty-nine astronauts and data from NASA's GeneLab derived from hundreds of samples flown in space to determine transcriptomic, proteomic, metabolomic, and epigenetic responses to spaceflight. Overall pathway analyses on the multi-omics datasets showed significant enrichment for mitochondrial processes, as well as innate immunity, chronic inflammation, cell cycle, circadian rhythm, and olfactory functions. Importantly, NASA's Twin Study provided a platform to confirm several of our principal findings. Evidence of altered mitochondrial function and DNA damage was also found in the urine and blood metabolic data compiled from the astronaut cohort and NASA Twin Study data, indicating mitochondrial stress as a consistent phenotype of spaceflight., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Spaceflight missions can cause immune system dysfunction in astronauts with little understanding of immune outcomes in deep space. This study assessed immune responses in mice following ground-based, simulated deep spaceflight conditions, compared with data from astronauts on International Space Station missions. For ground studies, we simulated microgravity using the hindlimb unloaded mouse model alone or in combination with acute simulated galactic cosmic rays or solar particle events irradiation. Immune profiling results revealed unique immune diversity following each experimental condition, suggesting each stressor results in distinct circulating immune responses, with clear consequences for deep spaceflight. Circulating plasma microRNA sequence analysis revealed involvement in immune system dysregulation. Furthermore, a large astronaut cohort showed elevated inflammation during low-Earth orbit missions, thereby supporting our simulated ground experiments in mice. Herein, circulating immune biomarkers are defined by distinct deep space irradiation types coupled to simulated microgravity and could be targets for future space health initiatives., Competing Interests: All authors declare no competing interests., (© 2020 The Author(s).)

Background: In the setting of complete distal biceps tendon rupture, surgical repair has become the standard of care to restore optimal elbow function, but the optimal approach and method of tendon fixation are still subjects of debate and have remained controversial for more than half a century., Purpose: To evaluate patient-reported long-term outcomes after distal biceps tendon repair using a modified double-incision technique., Study Design: Case series; Level of evidence, 4., Methods: We reviewed primary distal biceps tendon repairs after isolated tendon rupture using the modified muscle-splitting double-incision approach and transosseous suture fixation technique described by Morrey et al (1985), which had been performed at our level 1 trauma center between January 2000 and December 2013. Outcome measures included the subjective elbow value (SEV), the Oxford Elbow Score (OES) with its 3 domains (function, pain, and social-psychological), a self-performed hook test, and the 3-level version of the EuroQoL 5-dimensional instrument (EQ-5D-3L) as a measure of health status. Levels of overall satisfaction were determined by asking whether the patient would consent to the operation again. In addition, patients were asked to report any complications., Results: A total of 30 patients met the inclusion criteria, and 25 patients were available for the survey. Mean age at the time of rupture was 47 years. All patients were male. Mean follow-up was 120 months (range, 57-207 months). The follow-up rate was 83.34%. The following outcome results were obtained: SEV, 88.16% ± 25.18%; OES, 43.80 ± 10.56 out of 48 points; OES Pain, 92.50% ± 23.03%; OES Function, 92.25% ± 22.19%; OES Social-Psychological, 89% ± 23.68%; EQ-5D-3L, 0.93 ± 0.21. All patients described a negative hook test. Patient-reported complications included painless limitation in forearm rotation in 8% of patients (n = 2); reduced flexion and forearm rotation strength with and without pain in 8% (n = 2) and 4% (n = 1), respectively; synostosis after 1 year requiring revision surgery in 4% (n = 1); and transient wrist drop in 4% (n = 1). The overall complication rate was 28% (7/25), and 96% (n = 24) would consent to the operation again., Conclusion: Despite the cited approach-related morbidity, we report an excellent patient-reported long-term outcome for the double-incision distal biceps repair technique., Competing Interests: The authors declared that there are no conflicts of interest in the authorship and publication of this contribution. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2020.)

Background: Proximal humerus fractures account for 4 - 6% of all fractures and are a common result of low-energy trauma in the elderly. Concomitant neurovascular injury of the neighboring axillary artery and brachial plexus is a rarity, but has enormous impact on therapy, rehabilitation and prognosis. Diagnosis of axillary artery injury may be delayed due to its varied clinical presentation and lead to prolonged ischemia, distal necrosis and even loss of limb. Thorough clinical examination, high suspicion and identification of known predictors can be helpful in early diagnosis of this rare injury., Patients/material and Methods: We report a case of an intoxicated 76-year-old male who sustained a dislocated proximal humerus fracture, resulting in concomitant brachial plexopathy and axillary artery dissection with secondary thrombosis after a low-energy fall from standing height. Due to mistriage as a neurological emergency the somnolent patient presented under delayed circumstances at our traumatological emergency department, demonstrating pain, paleness, paralysis, paresthesia and non-palpable wrist pulses. Diagnosis was made through high suspicion after clinical examination with the aid of CT angiography. Emergent open reduction and anatomic shoulder hemiarthroplasty was performed followed by axillobrachial interposition grafting using a reversed saphenous vein graft and brachial plexus exploration., Results: The surgical treatments were uncomplicated. The affected limb remains viable at 6-week follow-up; however, active shoulder function is limited due to residual brachial plexopathy., Conclusion: Despite early diagnosis and management of this rare injury, the prognosis for functional recovery is guarded and largely dictated by the extent of neurological injury in the setting of concomitant brachial plexopathy. Brachial plexopathy is highly associated with axillary artery injury and its impact often underestimated in comparison due to its non-limb-threatening nature in the acute setting. Future studies should focus on the long-term prognosis for functional recovery in patients with this rare injury pattern., Competing Interests: The authors declare that they have no conflict of interest./Die Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Background: The aim of this study is to evaluate the correlation between the Oxford Elbow Score (OES) and Single Assessment Numeric Evaluation (SANE). To date, there has been no study investigating a correlation between this patient-reported outcome measure and SANE., Methods: Between December 2018 and February 2019, all patients who underwent consultation for elbow pathology and completed the OES and SANE were retrospectively analyzed. Pearson correlation coefficient between the OES and SANE was calculated. Variables, including age, gender, diagnosis, chief complaint for consultation, and pain level on the visual analog scale (VAS), were also collected, and a mixed effects linear regression model was used to identify predictors for higher correlation., Results: One hundred seven consultations of 86 patients were analyzed. The mean SANE and OES were 62.13% and 60.36%, respectively. Both scores correlated highly (r = 0.903). Across the OES domains, the strongest correlation was found between SANE and the OES psychosocial domain (r = 0.885). High correlations were also found between SANE and the OES function (r = 0.847) and OES pain (r = 0.804) domains. All values were statistically significant (P < .001). A moderate inverse correlation was found between SANE and VAS (r = -0.631). Aside from SANE, the VAS was identified as a significant predictor of the OES., Conclusion: SANE correlates highly with the OES. It is an easy tool for assessing the condition of the elbow joint, can be obtained without any license or payment restrictions, and should be considered as a worthwhile adjunct to currently used scores., (Copyright © 2020 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Mitochondrial fission catalyzed by dynamin-related protein 1 (Drp1) is necessary for mitochondrial biogenesis and maintenance of healthy mitochondria. However, excessive fission has been associated with multiple neurodegenerative disorders, and we recently reported that mice with smaller mitochondria are sensitized to ischemic stroke injury. Although pharmacological Drp1 inhibition has been put forward as neuroprotective, the specificity and mechanism of the inhibitor used is controversial. Here, we provide genetic evidence that Drp1 inhibition is neuroprotective. Drp1 is activated by dephosphorylation of an inhibitory phosphorylation site, Ser637. We identify Bβ2, a mitochondria-localized protein phosphatase 2A (PP2A) regulatory subunit, as a neuron-specific Drp1 activator in vivo Bβ2 KO mice of both sexes display elongated mitochondria in neurons and are protected from cerebral ischemic injury. Functionally, deletion of Bβ2 and maintained Drp1 Ser637 phosphorylation improved mitochondrial respiratory capacity, Ca 2+ homeostasis, and attenuated superoxide production in response to ischemia and excitotoxicity in vitro and ex vivo Last, deletion of Bβ2 rescued excessive stroke damage associated with dephosphorylation of Drp1 S637 and mitochondrial fission. These results indicate that the state of mitochondrial connectivity and PP2A/Bβ2-mediated dephosphorylation of Drp1 play a critical role in determining the severity of cerebral ischemic injury. Therefore, Bβ2 may represent a target for prophylactic neuroprotective therapy in populations at high risk of stroke. SIGNIFICANCE STATEMENT With recent advances in clinical practice including mechanical thrombectomy up to 24 h after the ischemic event, there is resurgent interest in neuroprotective stroke therapies. In this study, we demonstrate reduced stroke damage in the brain of mice lacking the Bβ2 regulatory subunit of protein phosphatase 2A, which we have shown previously acts as a positive regulator of the mitochondrial fission enzyme dynamin-related protein 1 (Drp1). Importantly, we provide evidence that deletion of Bβ2 can rescue excessive ischemic damage in mice lacking the mitochondrial PKA scaffold AKAP1, apparently via opposing effects on Drp1 S637 phosphorylation. These results highlight reversible phosphorylation in bidirectional regulation of Drp1 activity and identify Bβ2 as a potential pharmacological target to protect the brain from stroke injury., (Copyright © 2020 the authors.)

Background: Ionizing radiation from galactic cosmic rays (GCR) is one of the major risk factors that will impact the health of astronauts on extended missions outside the protective effects of the Earth's magnetic field. The NASA GeneLab project has detailed information on radiation exposure using animal models with curated dosimetry information for spaceflight experiments. Methods: We analyzed multiple GeneLab omics datasets associated with both ground-based and spaceflight radiation studies that included in vivo and in vitro approaches. A range of ions from protons to iron particles with doses from 0.1 to 1.0 Gy for ground studies, as well as samples flown in low Earth orbit (LEO) with total doses of 1.0 mGy to 30 mGy, were utilized. Results: From this analysis, we were able to identify distinct biological signatures associating specific ions with specific biological responses due to radiation exposure in space. For example, we discovered changes in mitochondrial function, ribosomal assembly, and immune pathways as a function of dose. Conclusions: We provided a summary of how the GeneLab's rich database of omics experiments with animal models can be used to generate novel hypotheses to better understand human health risks from GCR exposures., Competing Interests: The authors declare no conflict of interest.

We hypothesize that enhancing mitochondrial base excision repair (BER) capability in brain will reduce reperfusion-associated ischemic brain injury. Post-stroke reperfusion was modeled in mice via transient filament occlusion of the middle cerebral artery (60 min) (transient MCAO). Administration of a TAT-modified form of a DNA glycosylase (EndoIII) following reperfusion of the brain reduced resultant brain infarct volume. Protection was dose-dependent, BER enzyme specific, and regionally specific (more effective via the jugular vein). EndoIII is compatible with tissue plasminogen activator (tPA). The time window of a single dose of EndoIII effect is 3 h following reperfusion onset. These data suggest a novel approach to enhance protection of reperfused brain in the setting of revascularization procedures (thrombectomy or thrombolytic therapy) following stroke.

The tumor immune microenvironment (TIME) consists of multiple cell types that contribute to the heterogeneity and complexity of prostate cancer (PCa). In this study, we sought to understand the gene-expression signature of patients with primary prostate tumors by investigating the co-expression profiles of patient samples and their corresponding clinical outcomes, in particular "disease-free months" and "disease reoccurrence". We tested the hypothesis that the CXCL13-CXCR5 axis is co-expressed with factors supporting TIME and PCa progression. Gene expression counts, with clinical attributes from PCa patients, were acquired from TCGA. Profiles of PCa patients were used to identify key drivers that influence or regulate CXCL13-CXCR5 signaling. Weighted gene co-expression network analysis (WGCNA) was applied to identify co-expression patterns among CXCL13-CXCR5, associated genes, and key genetic drivers within the CXCL13-CXCR5 signaling pathway. The processing of downloaded data files began with quality checks using NOISeq, followed by WGCNA. Our results confirmed the quality of the TCGA transcriptome data, identified 12 co-expression networks, and demonstrated that CXCL13, CXCR5 and associated genes are members of signaling networks (modules) associated with G protein coupled receptor (GPCR) responsiveness, invasion/migration, immune checkpoint, and innate immunity. We also identified top canonical pathways and upstream regulators associated with CXCL13-CXCR5 expression and function.

Owing to the discovery of a less soluble crystalline form (form 2) of cyclosporine (CsA), risks in solubility and physical stability of these formulations need to be revisited. This work focused on understanding the solubility behavior of various CsA forms in different media, including water, castor oil, and selected cosolvent micellar systems. In water, form 2 was approximately 8-9 times less soluble than form 1 (aka. tetragonal dihydrate). In neat nonaqueous solvent, for example, castor oil, form 3 (aka. orthorhombic hydrate) was found to have the lowest solubility and therefore the most stable form. In addition, the solubility-temperature relationship of CsA is complex and solvent-dependent. In aqueous vehicles, retrograde temperature dependence of solubility was observed in aqueous vehicles, that is, the solubility of CsA decreased with temperature, which was attributed to the effect of temperature on the strength of hydrogen bonding interactions; conversely, the solubility of CsA increased with temperature in nonaqueous solvents. In addition, the solubility of these CsA forms was very sensitive to temperature. Temperature-dependent form transformation was also observed in the media studied, with faster form conversion occurring at elevated temperatures. These studies provided key information to support the risk assessment for topical ophthalmic formulation development of CsA., (Copyright © 2019 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Purpose: A crucial step of the Latarjet procedure is the fixation of the coracoid process onto the glenoid. Multiple problems associated with the fixation have been described, including lesions of the suprascapular nerve due to prominence of the screw or bicortical drilling. The purpose of the present study was to evaluate whether monocortical fixation, without perforating the posterior glenoid cortex, would provide sufficient graft stability., Methods: Coracoid transfer was performed in 14 scapula models (Sawbones ® , Composite Scapula, 4th generation). Two groups were assigned: in one group, fixation was achieved with two screws that did not perforate the posterior cortex of the glenoid neck (monocortical fixation), in the other group, fixation was achieved with perforation of the posterior cortex (bicortical fixation). The ultimate failure load and mode of failure were evaluated biomechanically., Results: Monocortical fixation was a significantly weaker construct than bicortical fixation (median failure load 221 N, interquartile range 211-297 vs. median failure load 423 N, interquartile range 273-497; p = 0.017). Failure was either due to a pullout of the screws from the socket or a fracture of the glenoid. There was no significant difference in the mode of failure between the two groups (n.s.)., Conclusion: Monocortical fixation was significantly weaker than bicortical fixation. However, bicortical drilling and overly long screws may jeopardize the suprascapular nerve. Thus, anatomic knowledge about the safe zone at the posterior rim of the glenoid is crucial. Until further research has evaluated, if the inferior stability is clinically relevant, clinicians should be cautious to use a monocortical fixation technique for the coracoid graft.

Background: Bone conduction implants based on abutment-driven acoustic transmission result in good hearing outcomes; however, skin complications impact the quality of life (QOL) and possibly the viability of the device for many patients. The transcutaneous magnetic Baha ® Attract technology was developed with the goal of minimising skin complications., Objectives: To analyse surgical, auditory and QOL outcomes for patients implanted with the Baha ® Attract., Design: Prospective multicentre cohort study., Setting: Four French tertiary referral centres., Participants: Thirty-two patients implanted with the Baha ® Attract, including 25 with conductive and mixed hearing loss and 7 with single-sided deafness., Main Outcome Measures: Postoperative follow-up involved the visual analysis of soft tissue adaptation and sound processor magnet strength measurement. The audiometric outcomes were evaluated in quiet and noise, and the QOL was assessed using three different questionnaires., Results: After 12 months of use, soft tissue was thinner, and mean magnet strength was significantly decreased (3.7-3.1, P < 0.05) relative to measures during surgery. The speech recognition threshold in quiet significantly improved compared to unaided situation (73-44 dB HL respectively, P < 0.001) as did functional gain in noise (+2.8). All QOL scores improved, and the APHAB questionnaire score correlated with the audiometric outcomes., Conclusions: The Baha ® Attract technology results in significant hearing gain and improves QOL. Skin complications were not observed, although surgeons, audiologists and patients should be aware of soft tissue evolution during the first postoperative year. The reversibility of this implant is a major advantage that allows switching to another system if hearing degrades., (© 2018 John Wiley & Sons Ltd.)

Introduction: The use of reverse shoulder arthroplasty (RSA) has increased dramatically over the last two decades, with many surgeons now indicating RSA for the acute management of displaced proximal humerus fractures (PHF) in the elderly. RSA relies on adequate deltoid muscle function to obtain a good outcome, yet no literature to date exists which discusses preoperative assessment of deltoid structure prior to RSA. The purpose of this study was to assess for preoperative fatty deltoid-degeneration in patients with displaced PHF., Materials and Methods: We reviewed the axial CT scans of 100 consecutive patients with a displaced PHF. Fatty degeneration within each of the three deltoid-heads was graded at three levels, according to Goutallier and colleagues. Fractures were classified according to Neer., Results: Seventy-nine percent of the patients were female, 75% showed 3 or 4 parts fractures. The average cross-sectional area of the posterior deltoid was greatest-representing 37%, 40% and 42% of total area at each level, respectively. Severe fatty degeneration (Stages 3 and 4) was observed in the posterior deltoid only (26%). Absence of fatty degeneration (Stage 0) was observed in < 25% of cases. The Inter-Observer-Reliability for the continuous variables proved to be high., Conclusion: Preoperative deltoid fatty degeneration is common in displaced PHF in the elderly. Because CT is commonly obtained to assess fracture morphology and for preoperative planning purposes, it is an ideal tool to assess the deltoid additionally. Future studies are warranted to determine whether preoperative fatty infiltration of the deltoid correlates with mid and long term functional outcomes when RSA is used acutely to manage a PHF., Level of Evidence: Level IV-consecutive case series.

Mild traumatic brain injury (mTBI) is a complex, neurophysiological condition that can have detrimental outcomes. Yet, to date, no objective method of diagnosis exists. Physical damage to the blood-brain-barrier and normal waste clearance via the lymphatic system may enable the detection of biomarkers of mTBI in peripheral circulation. Here we evaluate the accuracy of whole transcriptome analysis of blood to predict the clinical diagnosis of post-concussion syndrome (PCS) in a military cohort. Sixty patients with clinically diagnosed chronic concussion and controls (no history of concussion) were recruited (retrospective study design). Male patients (46) were split into a training set comprised of 20 long-term concussed (> 6 months and symptomatic) and 12 controls (no documented history of concussion). Models were validated in a testing set (control = 9, concussed = 5). RNA&#95;Seq libraries were prepared from whole blood samples for sequencing using a SOLiD5500XL sequencer and aligned to hg19 reference genome. Patterns of differential exon expression were used for diagnostic modeling using support vector machine classification, and then validated in a second patient cohort. The accuracy of RNA profiles to predict the clinical diagnosis of post-concussion syndrome patients from controls was 86% (sensitivity 80%; specificity 89%). In addition, RNA profiles reveal duration of concussion. This pilot study shows the potential utility of whole transcriptome analysis to establish the clinical diagnosis of chronic concussion syndrome.

Purpose: Various stitching techniques have been described to facilitate arthroscopic repair of rotator cuff tears. The aim of the present study was to compare the biomechanical properties of the lasso-loop, lasso-mattress and simple-cinch stitch for rotator cuff repair., Methods: Twelve infraspinatus tendons were harvested from sheep and split in half. The tendons were randomized into three different stitch configuration groups for biomechanical testing: lasso-loop, lasso-mattress and simple-cinch stitch. Each specimen was first cyclically loaded on a universal materials testing machine under force control from 5 to 30 N at 0.25 Hz for twenty cycles. Then, each specimen was loaded to failure under displacement control at a rate of 1 mm/s. Cyclic elongation, peak-to-peak displacement and ultimate tensile load were reported as mean ± standard error and compared using one way analysis of variance. The type of failure was recorded., Results: No differences in cyclic elongation (1.31 ± 0.09 mm for the simple-cinch vs. 1.49 ± 0.07 mm for the lasso-mattress vs. 1.61 ± 0.09 mm for the lasso-loop stitch, p = 0.063) or peak-to-peak displacement (0.58 ± 0.04 mm for the simple-cinch, 0.50 ± 0.03 mm for the lasso-mattress and 0.62 ± 0.06 mm for the lasso-loop stitch, p = 0.141) were seen between all tested stitch configurations. In the load-to-failure test, the simple cinch stitch (149.38 ± 11.89 N) and the lasso-mattress (149.38 ± 10.33 N) stitch demonstrated significantly higher ultimate load than the lasso-loop stitch (65.88 ± 4.75 N, p < 0.001). All stitch configurations failed with suture pull out., Conclusions: The lasso-mattress and the simple-cinch stitch showed similar biomechanical properties with significant higher tensile loads needed for failure than the lasso-loop stitch.

Study Objectives: Episodes of brief limb ischemia (remote preconditioning) in mice induce tolerance to modeled ischemic stroke (focal brain ischemia). Since stroke outcomes are in part dependent on sleep-wake history, we sought to determine if sleep is critical for the neuroprotective effect of limb ischemia., Methods: EEG/EMG recording electrodes were implanted in mice. After a 24 h baseline recording, limb ischemia was induced by tightening an elastic band around the left quadriceps for 10 minutes followed by 10 minutes of release for two cycles. Two days following remote preconditioning, a second 24 h EEG/EMG recording was completed and was immediately followed by a 60-minute suture occlusion of the middle cerebral artery (modeled ischemic stroke). This experiment was then repeated in a model of circadian and sleep abnormalities ( Bmal1 knockout [KO] mice sleep 2 h more than wild-type littermates). Brain infarction was determined by vital dye staining, and sleep was assessed by trained identification of EEG/EMG recordings., Results: Two days after limb ischemia, wild-type mice slept an additional 2.4 h. This additional sleep was primarily comprised of non-rapid eye movement (NREM) sleep during the middle of the light-phase (i.e., naps). Repeating the experiment but preventing increases in sleep after limb ischemia abolished tolerance to ischemic stroke. In Bmal1 knockout mice, remote preconditioning did not increase daily sleep nor provide tolerance to subsequent focal ischemia., Conclusions: These results suggest that sleep induced by remote preconditioning is both sufficient and necessary for its neuroprotective effects on stroke outcome., (© 2016 Associated Professional Sleep Societies, LLC.)

Background: Arthroscopic debridement represents a salvage procedure for irreparable rotator cuff tears. It is important to accurately diagnose the patient for irreparable rotator cuff tears. The diagnosis and the therapeutic options must be explained to the patient. It is mandatory that the patient understands the primary goal of the arthroscopic debridement being reduction of pain, not improving strength or function., Methods: The procedure consists of 7 distinct steps to debride the soft tissues and alleviate pain., Results: Even though there is a lack of evidence that this procedure is superior to other therapeutic options, it has shown good results in patients with the main complaint of pain., Conclusion: The results reported in some studies should, however, be interpreted with caution, taking into consideration the substantial structural damage in irreparable defects.

Background: The tissue-suture interface is described as the most vulnerable and susceptible area in the muscle-tendon-bone construction of arthroscopic rotator cuff repair. Various stitching techniques have been described to enhance the strength, fixation and stability of the repair, but technical and biomechanical challenges remain. Purpose was to examine the biomechanical properties of the simple cinch stitch in comparison to other stitches commonly used for rotator cuff repair., Methods: Infraspinatus tendons were harvested from sheep and split in half. The tendons were randomized into five different stitch configuration groups for biomechanical testing: simple stitch; horizontal stitch; FiberChain®; simple cinch stitch; and modified Mason-Allen stitch. Each specimen was first cyclically loaded on a universal materials testing machine under force control from 5 to 30N at 0.25Hz for twenty cycles. Then, each specimen was loaded to failure under displacement control at a rate of 1mm/s. Cyclic elongation, peak-to-peak displacement and ultimate tensile load were measured. The type of failure was recorded., Findings: No differences in cyclic elongation or peak-to-peak displacement were seen between stitch configurations. In the load-to-failure test, the simple cinch stitch demonstrated significantly higher ultimate load than the simple and the horizontal stitch configurations. The comparison to the FiberChain® Suture revealed no statistical significant differences. The FiberChain® Suture demonstrated significantly higher ultimate load than the simple stitch. No statistical significance could be demonstrated in comparison to the horizontal stitch or the simple cinch stitch. The ultimate tensile load of the modified Mason-Allen stitch was significantly higher than that of the other stitch configurations., Interpretation: The simple cinch stitch has an ultimate tensile load comparable to the FiberChain® suture and is superior to the simple stitch and the horizontal stitch. The major advantage of the simple cinch technique is that it is possible to perform the stitch entirely arthroscopically, without the need to perforate the tissue a second time or to use special suture materials., Study Design: Controlled laboratory study., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: The Latarjet technique is a reliable treatment option for recurrent anterior shoulder instability. However, the complication rate has been reported to be as high as 30%, with 1.6% of patients suffering a nerve injury. The all-arthroscopic Latarjet procedure has been gaining popularity, even as it has introduced its own challenges. Given that the surgeon is not able to palpate the nerves, their localization and protection can be difficult. Additionally, the use of different instruments can lead to distinct nerve injury mechanisms., Purpose: To describe the anatomic trajectory of the musculocutaneous, axillary, and suprascapular nerves in relation to the arthroscopic Latarjet approach. Using this information, guidance is provided for reducing nerve injuries during instrumentation and screw insertion., Study Design: Descriptive laboratory study., Methods: A total of 50 cadaveric shoulders from 25 whole-body specimens were examined. The specimens were placed in the beach-chair position, and the deltopectoral and dorsal approaches were used to expose the relevant structures. A subscapularis muscle split was performed between the inferior and middle thirds of the tendon. Digital caliper measurements were taken between various points of the trajectories of the nerves and surrounding anatomic landmarks. The location of the nerves relative to the split was recorded., Results: The musculocutaneous nerve lay within the split in 66% of the shoulders (n = 33); it was medial to the split in 28% (n = 14); it was found lateral to split in 2% (n = 1); and it was not identified in 4% of shoulders (n = 2). The mean length of the axillary nerve was 4.0 cm (95% CI, 3.7-4.2) from the exit of the plexus to the quadrangular space. The axillary nerve was found to be within the split in 50% of the shoulders (n = 25) and medial to the split in the remaining 50% (n = 25). The suprascapular nerve at the level of the supraspinatous fossa passed 3.3 cm (95% CI, 3.1-3.5) medial to the superior rim of the posterior glenoid. The nerve curves around the root of the spine at the spinoglenoid notch level, approximating the glenoid rim to a distance of 2.1 cm (95% CI, 2.0-2.2). Finally, the nerve runs medially again before branching out into smaller fibers to innervate the infraspinatus muscle at a distance of 2.9 cm (95% CI, 2.7-3.1) from the inferior glenoid rim. Based on these findings, there is an approximately 2 cm-wide safe zone from the edge of the glenoid rim for the insertion of graft-fixing screws., Conclusion: When performing a subscapularis split in the arthroscopic Latarjet procedure, the risk of injuries to the musculocutaneous and axillary nerves could be reduced by aiming the switching stick inserted through the posterior portal toward the lateral edge of the intended location of the split. Injuries to the suprascapular nerve could be prevented by aiming the graft-fixing screws laterally toward the edge of the glenoid rim., Clinical Relevance: This study clarifies the location of the nerves relevant to the arthroscopic Latarjet technique and provides anatomic information that could help the surgeon reduce the risk of injuries to the musculocutaneous, axillary, and suprascapular nerves., (© 2015 The Author(s).)

Objective: Molecular diagnostic medicine holds much promise to change point of care treatment. An area where additional diagnostic tools are needed is in acute stroke care, to assist in diagnosis and prognosis. Previous studies using microarray-based gene expression analysis of peripheral blood following stroke suggests this approach may be effective. Next-generation sequencing (NGS) approaches have expanded genomic analysis and are not limited to previously identified genes on a microarray chip. Here, we report on a pilot NGS study to identify gene expression and exon expression patterns for the prediction of stroke diagnosis and prognosis., Methods: We recruited 28 stroke patients and 28 age- and sex-matched hypertensive controls. RNA was extracted from 3 mL blood samples, and RNA-Seq libraries were assembled and sequenced., Results: Bioinformatical analysis of the aligned RNA data reveal exonic (30%), intronic (36%), and novel RNA components (not currently annotated: 33%). We focused our study on patients with confirmed middle cerebral artery occlusion ischemic stroke (n = 17). On the basis of our observation of differential splicing of gene transcripts, we used all exonic RNA expression rather than gene expression (combined exons) to build prediction models using support vector machine algorithms. Based on model building, these models have a high predicted accuracy rate >90% (spec. 88% sen. 92%). We further stratified outcome based on the improvement in NIHss scores at discharge; based on model building we observe a predicted 100% accuracy rate., Interpretation: NGS-based exon expression analysis approaches have a high potential for patient diagnosis and outcome prediction, with clear utility to aid in clinical patient care.

The aim was to report a rare case of isolated traumatic atlantoaxial rotatory subluxation without ligamentous injury. Management consisted of analgesia, sedation, and application of a halo skull traction device. After removing halo skull traction, full reduction and recovery were achieved without instability.

The sequencing of the human genome and technological advances in DNA sequencing have led to a revolution with respect to DNA sequencing and its potential to diagnose genetic disorders. However, requests for open access to genomic data must be balanced against the guiding principles of the Common Rule for human subject research. Unfortunately, the risks to patients involved in genomic studies are still evolving and as such may not be clear to learned and well-intentioned scientists. Central to this issue are the strategies that enable human participants in such studies to remain anonymous, or de-identified. The wealth of genomic data on the Internet in genomic data repositories and other databases has enabled de-identified data to be broken and research subjects to be identified. The security of de-identification neglects the fact that DNA itself is an identifying element. Therefore, it is questionable whether data security standards can ever truly protect the identity of a patient, under the current conditions or in the future. As Big Data methodologies advance, additional sources of data may enable the re-identification of patients enrolled in next-generation sequencing (NGS) studies. As such, it is time to re-evaluate the risks of sharing genomic data and establish new guidelines for good practices. In this commentary, I address the challenges facing federally funded investigators who need to strike a balance between compliance with federal (US) rules for human subjects and the recent requirement for open access/sharing of data from National Institute for Health (NIH)-funded studies involving human subjects.

Remote preconditioning (rPC) is the phenomenon whereby brief organ ischemia evokes an endogenous response such that a different (remote) organ is protected against subsequent, normally injurious ischemia. Experiments show rPC to be effective at evoking cardioprotection against ischemic heart injury and, more recently, neuroprotection against brain ischemia. Such is the enthusiasm for rPC that human studies have been initiated. Clinical trials suggest rPC to be safe (phase II trial) and effective in reducing stroke incidence in a population with high stroke risk. However, despite the therapeutic potential of rPC, there is a large gap in knowledge regarding the effector mechanisms of rPC and how it might be orchestrated to improve outcome after stroke. Here we provide a critical review of mechanisms that are directly attributable to rPC-induced neuroprotection in preclinical trials of rPC., (Copyright © 2015 the American Physiological Society.)

The main objective was to evaluate the bimodal self-rated benefits on auditory performance under real conditions and the quality of life in two groups of cochlear-implanted adults, with or without a contralateral hearing aid. The secondary objective was to investigate correlations between the use of a hearing aid and residual hearing on the non-implanted ear. This retrospective study was realized between 2000 and 2010 in two referral centers. A population of 183 postlingually deaf adults, implanted with a cochlear experience superior to 6 months, was selected. The Speech, Spatial, and other Qualities of Hearing Scale were administered to evaluate the auditory performances, and the Nijmegen Cochlear Implant Questionnaire to evaluate the quality of life. The population was divided into two groups: a group with unilateral cochlear implants (Cochlear Implant-alone, n = 54), and a bimodal group with a cochlear implant and a contralateral hearing aid (n = 62). Both groups were similar in terms of auditory deprivation duration, duration of cochlear implant use, and pure-tone average on the implanted ear. There was a significant difference in terms of pure-tone average on low and low-to-mid frequencies on the non-implanted ear. The scores on both questionnaires showed an improvement in the basic sound perception and quality of social activities for the bimodal group. The results suggest that the bimodal stimulation (cochlear implant and contralateral hearing aid) improved auditory perception in quiet and the quality of life domain of social activities.

Objectives: To present the option to use a Fascia Temporalis Superficialis pedicled flap for the implantation of a transcutaneous magnetic osseointegrated auditory implant in selected revision procedures., Background: Osseointegrated auditory implants represent a reliable option for patients. Skin intolerance and aesthetic issue are two clear limitations of percutaneous system. Magnetic transcutaneous devices have been developed to overcome such drawbacks. The current new experience of such a device shows that they are well tolerated in primary cases. However, switching from a previous percutaneous system raises the question of skin tolerance. Hence, previous implanted abutments with skin penetration and skin reduction are more likely cause to skin intolerance and complication., Methods: We described here the option to use a Fascia Temporalis Superficialis flap to cover the implanted magnet., Conclusion: When switching from percutaneous osseointegrated auditory implant to transcutaneous system in case of high risk of skin intolerance, this procedure may provide sufficient tissue coverage to prevent skin intolerance, pain and delayed extrusion.