Development of 68Ga-SCN-DOTA-Capsaicin as an Imaging Agent Targeting Apoptosis and Cell Cycle Arrest in Breast Cancer

Cancer Biotherapy & Radiopharmaceuticals , Vol. 0, No. 0.


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Radioembolization for Unresectable Intrahepatic Cholangiocarcinoma: Review of Safety, Response Evaluation Criteria in Solid Tumors 1.1 Imaging Response and Survival

Cancer Biotherapy & Radiopharmaceuticals , Vol. 0, No. 0.


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Increase in carbon dioxide accelerates the performance of endurance exercise in rats

Abstract

Endurance exercise generates CO₂ via aerobic metabolism; however, its role remains unclear. Exogenous CO₂ by transcutaneous delivery promotes muscle fibre-type switching to increase endurance power in skeletal muscles. Here we determined the performance of rats running in activity wheels with/without transcutaneous CO₂ exposure to clarify its effect on endurance exercise and recovery from muscle fatigue. Rats were randomised to control, training and CO₂ groups. Endurance exercise included activity-wheel running with/without transcutaneous CO₂ delivery. Running performance was measured after exercise initiation. We also analysed changes in muscle weight and muscle fibres in the tibialis anterior muscle. Running performance improved over the treatment period in the CO₂ group, with a concomitant switch in muscle fibres to slow-type. The mitochondrial DNA content and capillary density in the CO₂ group increased. CO₂ was beneficial for performance and muscle development during endurance exercise: it may enhance recovery from fatigue and support anabolic metabolism in skeletal muscles.

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Development of 68Ga-SCN-DOTA-Capsaicin as an Imaging Agent Targeting Apoptosis and Cell Cycle Arrest in Breast Cancer

Cancer Biotherapy & Radiopharmaceuticals , Vol. 0, No. 0.


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Radioembolization for Unresectable Intrahepatic Cholangiocarcinoma: Review of Safety, Response Evaluation Criteria in Solid Tumors 1.1 Imaging Response and Survival

Cancer Biotherapy & Radiopharmaceuticals , Vol. 0, No. 0.


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Molecular Characterization of Methicillin-Resistant Staphylococcus aureus Isolated from Australian Animals and Veterinarians

Microbial Drug Resistance , Vol. 0, No. 0.


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Cervical and thoracic intervertebral disc hydration increases with recumbency. a study in 101 healthy volunteers

Variation in water content and size of the lumbar intervertebral discs (IVDs) is known to occur due to recumbency and has been associated with lumbar IVD herniation risk through the impact of IVD hydration on tissue mechanical properties. It is not clear if similar changes in the cervical or thoracic IVDs occur with recumbency.

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Potential risks of using cement-augmented screws for spinal fusion in patients with low bone quality

Dramatic increases in the average life expectancy have led to increases in the variety of degenerative changes and deformities observed in the aging spine. The elderly population can present challenges for spine surgeons, not only because of increased comorbidities, but also because of the quality of their bones. Pedicle screws are the implants used most commonly in spinal surgery for fixation, but their efficacy depends directly on bone quality. While PMMA-augmented screws represent an alternative for patients with osteoporotic vertebrae, their use has raised some concerns due to the possible association between cement leakages (CLs) and other morbidities.

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Natural radionuclides in plants, soils and sediments affected by U-rich coal mining activities in Brazil

Publication date: October 2017
Source:Journal of Environmental Radioactivity, Volume 177
Author(s): Juliana Aparecida Galhardi, Rafael García-Tenorio, Daniel Marcos Bonotto, Inmaculada Díaz Francés, João Gabriel Motta
Mining activities can increase the mobility of metals by accelerating the dissolution and leaching of minerals from the rocks and tailing piles to the environment and, consequently, their availability for plants and subsequent transfer to the food chain. The weathering of minerals and the disposal of coal waste in tailing piles can accelerate the generation of acid mine drainage (AMD), which is responsible for the higher dissolution of metals in mining areas. In this context, the behavior of U, Th and K in soils and sediment, and the transfer factor (TF) of ²³⁸U, ²³⁴U and ²¹⁰Po for soybean, wheat, pine and eucalyptus cultivated around a coal mine in southern Brazil was evaluated. Alpha and gamma spectrometry were used for the measurements of the activity concentration of the radioelements. ²¹⁰Po was the radionuclide that is most accumulated in the plants, especially in the leaves. When comparing the plant species, pine showed the highest TF values for ²³⁴U (0.311 ± 0.420) for leaves, while eucalyptus showed the highest TF for ²³⁸U (0.344 ± 0.414) for leaves. In general, TF were higher for the leaves of soybean and wheat when compared to the grains, and grains of wheat showed higher TF for ²¹⁰Po and ²³⁸U than grains of soybean. Deviations from the natural U isotopic ratio were recorded at all investigated areas, indicating possible industrial and mining sources of U for the vegetables. A safety assessment of transport routes and accumulation of radionuclides in soils with a potential for cultivation is important, mainly in tropical areas contaminated with solid waste and effluents from mines and industry.

Graphical abstract

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Constraints on eQTL Fine Mapping in the Presence of Multi-site Local Regulation of Gene Expression

Expression QTL (eQTL) detection has emerged as an important tool for unraveling of the relationship between genetic risk factors and disease or clinical phenotypes. Most studies use single marker linear regression to discover primary signals, followed by sequential conditional modeling to detect secondary genetic variants affecting gene expression. However, this approach assumes that functional variants are sparsely distributed and that close linkage between them has little impact on estimation of their precise location and magnitude of effects. We describe a series of simulation studies designed to evaluate the impact of linkage disequilibrium on the fine-mapping of causal variants with typical eQTL effect sizes. In the presence of multi-site regulation, even though between 80% and 90% of modeled eSNPs associate with normally distributed traits, up to 10% of all secondary signals could be statistical artefacts, and at least 5% but up to one quarter of credible intervals of SNPs within r2>0.8 of the peak may not even include a causal site. The Bayesian methods eCAVIAR and DAP provide only modest improvement in resolution. Given the strong empirical evidence that gene expression is commonly regulated by more than one variant, we conclude that the fine-mapping of causal variants needs to be adjusted for multi-site influences, as conditional estimates can be highly biased by interference among linked sites, but ultimately experimental verification of individual effects is needed. Presumably similar conclusions apply not just to eQTL mapping, but to multi-site influences on fine mapping of most types of quantitative trait.

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A High-Density Genetic Linkage Map and QTL Fine Mapping for Body Weight in Crucian Carp (Carassius auratus) Using 2b-RAD Sequencing

A high-resolution genetic linkage map is essential for a wide range of genetics and genomics studies such as comparative genomics analysis and QTL fine mapping. Crucian carp (Carassius auratus) widely distributes in Eurasia and is an important aquaculture fish worldwide. In this study, a high-density genetic linkage map was constructed for crucian carp using 2b-RAD technology. The consensus map contains 8,487 SNP markers assigning on 50 linkage groups (LGs) and spanned 3,762.88 cM with an average marker interval of 0.44 cM and genome coverage of 98.8 %. The female map had 4,410 SNPs and spanned 3,500.42 cM (0.79 cM/marker), while the male map had 4,625 SNPs and spanned 3,346.33 cM (0.72 cM/marker). The average recombination ratio of female to male was 2.13:1, and significant male-biased recombination suppressions were observed in LG47 and LG49. Comparative genomics analysis revealed a clear 2:1 syntenic relationship between crucian carp LGs and chromosomes of zebrafish and grass carp, and a 1:1 correspondence but extensive chromosomal rearrangement between crucian carp and common carp, providing an evidence that crucian carp had experienced the fourth round of whole genome duplication (4R-WGD). Eight chromosome-wide QTL for body weight at two months after hatch were detected on five LGs, explaining 10.1-13.2% of the phenotypic variations. Potential candidate growth-related genes, such as EGF-like domain and TGF-beta, were identified within the QTL intervals. This high-density genetic map and QTL analysis supply a basis for genome evolutionary studies in cyprinid fishes, genome assembly and QTL fine mapping for complex traits in crucian carp.

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Unique Allelic eQTL Clusters in Human MHC Haplotypes

The control of gene regulation within the MHC remains poorly understood despite several eQTL studies revealing an association of MHC gene expression with independent tag-SNPs. MHC haplotype variation may exert a greater effect on gene expression phenotype than specific single variants. To explore the effect of MHC haplotype sequence diversity on gene expression phenotypes across the MHC, we examined the MHC transcriptomic landscape at haplotype-specific resolution for three prominent MHC haplotypes (A2-B46-DR9, A33-B58-DR3, and A1-B8-DR3) derived from MHC-homozygous B-lymphoblastoid cell lines. We demonstrate that MHC-wide gene expression patterns are dictated by underlying haplotypes, and identify 36 differentially expressed genes. By mapping these haplotype sequence variations to known eQTL, we provide evidence that unique allelic combinations of eQTL, embedded within haplotypes, are correlated with the level of expression of 17 genes. Interestingly, the influence of haplotype sequence on gene expression is not homogenous across the MHC. We show haplotype sequence polymorphisms within or proximate to HLA-A, HLA-C, C4A, and HLA-DRB regions exert haplotype-specific gene regulatory effects, whereas the expression of genes in other parts of the MHC region are not affected by the haplotype sequence. Overall, we demonstrate that MHC haplotypes sequence diversity can impact phenotypic outcome via the alteration of transcriptional variability, indicating that a haplotype-based approach is fundamental for the assessment of trait associations in the MHC.

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The role of low-intensity pulse ultrasound (LIPUS) on cartilage healing in knee osteoarthritis: a review

Ultrasound (US) is a therapeutic modality that has been used in the treatment of musculoskeletal conditions for decades. In recent years there has been technological advancements using Low-Intensity Pulsed Ultrasound (LIPUS) as a clinical modality. The purpose of this review was to critically examine the medical literature to determine the effects of low-intensity pulse ultrasound (LIPUS) on the chondrogenic properties of knee osteoarthritis. A literature search of three major databases (Pubmed, Scopus, EMBASE) was performed.

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Brachial Plexus Injury in a 6 Year Old Boy with 100% Displaced Proximal Humeral Metaphyseal Fracture, a Case Report

Post-traumatic brachial plexopathies can occur following displaced proximal humeral fractures, causing profound functional deficits. Described here is an unusual case of a displaced proximal humeral metaphyseal fracture in a young child. The patient underwent closed reduction and serial casting, but hand weakness and forearm sensory loss persisted. Needle EMG localized the injury to the mid/proximal arm near the fracture site, resulting in damage to the posterior and medial cords of the brachial plexus with profound involvement of the radial, ulnar, and median nerves and sparing of the axillary nerve.

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Where are the Women? The Underrepresentation of Women Physicians among Recognition Award Recipients from Medical Specialty Societies

Membership in medical societies is associated with a number of benefits to members that may include professional education, opportunities to present research, scientific and/or leadership training, networking and others. In this perspective article, the authors address the value that medical specialty society membership and inclusion have in the development of an academic physician's career and how underrepresentation of women may pose barriers to their career advancement. Because society membership itself is not likely sufficient to support the advancement of academic physicians, this report focuses on one key component of advancement that can also be used as a measure of inclusion in society activities—the representation of women physicians among recipients of recognition awards.

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Cephalad Lead Migration During a Spinal Cord Stimulation Trial: A Case Report

Spinal cord stimulation is used in the treatment of a variety of pain conditions. Lead migration is among the most common complications associated with spinal cord stimulation. While there have been reports of caudal lead migration, there have been no reports of significant cephalad lead migration during a spinal cord stimulation trial. Here we report what is potentially the first case of significant cephalad lead migration (from the initial T8 position to C2) during a spinal cord stimulation trial.

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New tests identify patterns of vestibular loss

For the last century, the caloric test of horizontal canal function has been the standard test of vestibular function and, as a result, many deficits of peripheral and central vestibular function have gone undetected. Clinicians have puzzled about patients showing what are manifestly vestibular symptoms at the bedside examination, in whom the calorics were within the normal range. The introduction of the new vestibular tests – video head impulse test of all six semicircular canals (reviewed in (Halmagyi et al., 2017) and vestibular evoked myogenic potentials (VEMP) testing of utricular and saccular function (reviewed in (Curthoys et al., 2017) has solved this puzzle.

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The Use of Intracranial Doppler as a Cause for Intraoperative Hyperthermia

No abstract available

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Effects of an Intraoperative Dexmedetomidine Bolus on the Postoperative Blood Pressure and Pain Subsequent to Craniotomy for Supratentorial Tumors

Background: Control of emergence hypertension and pain is important after craniotomy for monitoring the neurological status. This prospective double-blinded study investigated the hemodynamics after a single bolus of dexmedetomidine (DEX) infusion administered to the patient undergoing craniotomy under general anesthesia, and its effect on emergence hypertension and postsurgical pain. Methods: Adult patients scheduled for elective surgery for supratentorial tumors were randomized to receive a 10-minute intraoperative DEX infusion of 0.4 μg/kg (small dose, n=43) or 0.8 μg/kg (medium dose, n=46), or normal saline (vehicle control, n=45), ∼60 minutes before the end of anesthesia. Results: A transient increase in the blood pressure associated with DEX was observed; 53.5% and 91.3% of the patients in the small-dose and the medium-dose groups, respectively, required treatment. Emergence mean arterial pressure and heart rates were significantly lower in the DEX groups compared with the control group. Incidence rates of postoperative hypertension in the small-dose (16.3%) and the medium-dose groups (15.2%) were significantly lower relative to that of the control group (35.6%). Patients who received DEX had a lower Verbal Numerical Rating Scale (VNRS) score in the neurosurgical ICU than the control group, and postsurgical pain (VNRS≥4) was lower in the medium-dose group (41.3%) than in the control group (71.1%). No shivering was observed in the medium-dose group, which was significantly less than that of the other 2 groups. Conclusions: An intraoperative bolus of DEX risks a transient increase in mean arterial pressure, but controls emergence hypertension effectively. Dose-related reductions in postsurgical pain and shivering were observed.

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Perioperative Management of Adult Patients With External Ventricular and Lumbar Drains: Guidelines From the Society for Neuroscience in Anesthesiology and Critical Care

External ventricular drains and lumbar drains are commonly used to divert cerebrospinal fluid and to measure cerebrospinal fluid pressure. Although commonly encountered in the perioperative setting and critical for the care of neurosurgical patients, there are no guidelines regarding their management in the perioperative period. To address this gap in the literature, The Society for Neuroscience in Anesthesiology & Critical Care tasked an expert group to generate evidence-based guidelines. The document generated targets clinicians involved in perioperative care of patients with indwelling external ventricular and lumbar drains.

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Effects of Acupuncture in Anesthesia for Craniotomy: A Meta-Analysis

Background: Acupuncture treatment has been used in China for >2500 years, and at present it is used worldwide as a form of analgesia in patients with acute and chronic pain. Furthermore, acupuncture is regularly used not only as a single anesthetic technique but also as a supplement or in addition to general anesthesia (GA). Objectives: The aim of this systematic review and meta-analysis was to assess the level of evidence for the clinical use of acupuncture in addition to GA in patients undergoing craniotomy. Design: This is a systematic review of randomized controlled trials with meta-analyses. Data Sources: The literature search (PubMed, Cochrane Library, and Web of Science) yielded 56 citations, published between 1972 and March 01, 2015. No systematic review or meta-analyses on this topic matched our search criteria. Each article of any language was assessed and rated for the methodological quality of the studies, using the recommendation of the Oxford Centre for Evidence Based Medicine. Ten prospective randomized controlled clinical trials with a total of 700 patients were included. Eligibility Criteria: Included in the meta-analysis were studies that involved any craniotomy under GA compared with a combination of GA and acupuncture. Exclusion criteria were no acupuncture during surgery, no GA during surgery, only postoperative data available, animal studies, and low grade of evidence. Results: The use of acupuncture significantly reduced the amount of volatile anesthetics during surgery (P

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The Trigemino-cardiac Reflex: Is Treatment With Atropine Still Justified?

No abstract available

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Intraoperative Secondary Insults During Orthopedic Surgery in Traumatic Brain Injury

Background: Secondary insults worsen outcomes after traumatic brain injury (TBI). However, data on intraoperative secondary insults are sparse. The primary aim of this study was to examine the prevalence of intraoperative secondary insults during orthopedic surgery after moderate-severe TBI. We also examined the impact of intraoperative secondary insults on postoperative head computed tomographic scan, intracranial pressure (ICP), and escalation of care within 24 hours of surgery. Materials and Methods: We reviewed medical records of TBI patients 18 years and above with Glasgow Coma Scale score 20 mm Hg), cerebral hypotension (cerebral perfusion pressure40 mm Hg), hypocarbia (end-tidal CO2200 mg/dL), hypoglycemia (glucose38°C). Results: A total of 78 patients (41 [18 to 81] y, 68% male) met the inclusion criteria. The most common intraoperative secondary insults were systemic hypotension (60%), intracranial hypertension and cerebral hypotension (50% and 45%, respectively, in patients with ICP monitoring), hypercarbia (32%), and hypocarbia (29%). Intraoperative secondary insults were associated with worsening of head computed tomography, postoperative decrease of Glasgow Coma Scale score by ≥2, and escalation of care. After Bonferroni correction, association between cerebral hypotension and postoperative escalation of care remained significant (P

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Large-volume Epidural Blood Patch: An Alternative Technique

No abstract available

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Cerebral Gaseous Microemboli are Detectable During Continuous Venovenous Hemodialysis in Critically Ill Patients: An Observational Pilot Study

Background: Continuous venovenous hemodialysis (CVVHD) may generate microemboli that cross the pulmonary circulation and reach the brain. The aim of the present study was to quantify (load per time interval) and qualify (gaseous vs. solid) cerebral microemboli (CME), detected as high-intensity transient signals, using transcranial Doppler ultrasound. Materials and Methods: Twenty intensive care unit (ICU group) patients requiring CVVHD were examined. CME were recorded in both middle cerebral arteries for 30 minutes during CVVHD and a CVVHD-free interval. Twenty additional patients, hospitalized for orthopedic surgery, served as a non-ICU control group. Statistical analyses were performed using the Mann-Whitney U test or the Wilcoxon matched-pairs signed-rank test, followed by Bonferroni corrections for multiple comparisons. Results: In the non-ICU group, 48 (14.5-169.5) (median [range]) gaseous CME were detected. In the ICU group, the 67.5 (14.5-588.5) gaseous CME detected during the CVVHD-free interval increased 5-fold to 344.5 (59-1019) during CVVHD (P

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Bowel Preparation in Awake Craniotomy: An Overlooked Entity

No abstract available

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Effects of Prone Position and Positive End-Expiratory Pressure on Noninvasive Estimators of ICP: A Pilot Study

Background: Prone positioning and positive end-expiratory pressure can improve pulmonary gas exchange and respiratory mechanics. However, they may be associated with the development of intracranial hypertension. Intracranial pressure (ICP) can be noninvasively estimated from the sonographic measurement of the optic nerve sheath diameter (ONSD) and from the transcranial Doppler analysis of the pulsatility (ICPPI) and the diastolic component (ICPFVd) of the velocity waveform. Methods: The effect of the prone positioning and positive end-expiratory pressure on ONSD, ICPFVd, and ICPPI was assessed in a prospective study of 30 patients undergoing spine surgery. One-way repeated measures analysis of variance, fixed-effect multivariate regression models, and receiver operating characteristic analyses were used to analyze numerical data. Results: The mean values of ONSD, ICPFVd, and ICPPI significantly increased after change from supine to prone position. Receiver operating characteristic analyses demonstrated that, among the noninvasive methods, the mean ONSD measure had the greatest area under the curve signifying it is the most effective in distinguishing a hypothetical change in ICP between supine and prone positioning (0.86±0.034 [0.79 to 0.92]). A cutoff of 0.43 cm was found to be a best separator of ONSD value between supine and prone with a specificity of 75.0 and a sensitivity of 86.7. Conclusions: Noninvasive ICP estimation may be useful in patients at risk of developing intracranial hypertension who require prone positioning.

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Urinary Retention Manifesting as Excessive Venous Ooze During Cranio-Vertebral Junction Surgery

No abstract available

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Noninvasive Hemodynamic Measurements During Neurosurgical Procedures in Sitting Position

Background: Neurosurgical procedures in sitting position need advanced cardiovascular monitoring. Transesophageal echocardiography (TEE) to measure cardiac output (CO)/cardiac index (CI) and stroke volume (SV), and invasive arterial blood pressure measurements for systolic (ABPsys), diastolic (ABPdiast) and mean arterial pressure (MAP) are established monitoring technologies for these kind of procedures. A noninvasive device for continuous monitoring of blood pressure and CO based on a modified Penaz technique (volume-clamp method) was introduced recently. In the present study the noninvasive blood pressure measurements were compared with invasive arterial blood pressure monitoring, and the noninvasive CO monitoring to TEE measurements. Methods: Measurements of blood pressure and CO were performed in 35 patients before/after giving a fluid bolus and a change from supine to sitting position, start of surgery, and repositioning from sitting to supine at the end of surgery. Data pairs from the noninvasive device (Nexfin HD) versus arterial line measurements (ABPsys, ABPdiast, MAP) and versus TEE (CO, CI, SV) were compared using Bland-Altman analysis and percentage error. Results: All parameters compared (CO, CI, SV, ABPsys, ABPdiast, MAP) showed a large bias and wide limits of agreement. Percentage error was above 30% for all parameters except ABPsys. Conclusion: The noninvasive device based on a modified Penaz technique cannot replace arterial blood pressure monitoring or TEE in anesthetized patients undergoing neurosurgery in sitting position.

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Pediatric Neurosurgery. Tricks of the Trade

No abstract available

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Intraoperative and Postoperative Administration of Dexmedetomidine Reduces Anesthetic and Postoperative Analgesic Requirements in Patients Undergoing Cervical Spine Surgeries

Background: Early recovery from anesthesia and avoidance of analgesics with respiratory depressant properties are vital for maintenance of extubated airway in cervical spine surgeries. The current study investigated the role of dexmedetomidine as an anesthetic sparing agent and as a sole postoperative analgesic in these cases. Materials and Methods: Sixty adult patients undergoing cervical spine surgeries were randomized into 2 groups. Group D received intravenous dexmedetomidine infusion 0.5 μg/kg/h throughout the surgery after a loading dose of 1 μg/kg over 10 minutes. Postoperatively, dexmedetomidine infusion was continued at 0.2 μg/kg/h for 24 hours. Group C received a volume-matched bolus and infusion of 0.9% saline. Intraoperative anesthetic requirement, time to recovery, and discharge were recorded. Patients were observed for rescue analgesic requirements for 24 hours after surgery. Hemodynamic stability, sedation scores, and pain scores were assessed for 48 hours after surgery. Results: There was significant reduction in intraoperative anesthetic requirement in group D (P

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Unusual Presentation of Refractory Autonomic Dysreflexia During General Anesthesia

No abstract available

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Latent Class Analysis of Neurodevelopmental Deficit After Exposure to Anesthesia in Early Childhood

Introduction: Although some studies have reported an association between early exposure to anesthesia and surgery and long-term neurodevelopmental deficit, the clinical phenotype of children exposed to anesthesia is still unknown. Methods: Data were obtained from the Western Australian Pregnancy Cohort Study (Raine) with neuropsychological tests at age 10 years measuring language, cognition, motor function, and behavior. Latent class analysis of the tests was used to divide the cohort into mutually exclusive subclasses of neurodevelopmental deficit. Multivariable polytomous logistic regression was used to evaluate the association between exposure to surgery and anesthesia and each latent class, adjusting for demographic and medical covariates. Results: In our cohort of 1444 children, latent class analysis identified 4 subclasses: (1) Normal: few deficits (n=1135, 78.6%); (2) Language and Cognitive deficits: primarily language, cognitive, and motor deficits (n=96, 6.6%); (3) Behavioral deficits: primarily behavioral deficits, (n=151, 10.5%); and (4) Severe deficits: deficits in all neuropsychological domains (n=62, 4.3%). Language and cognitive deficit group children were more likely to have exposure before age 3 (adjusted odds ratio [aOR], 2.11; 95% confidence interval [CI], 1.17-3.81), whereas a difference in exposure was not found between Behavioral or Severe deficit children (aOR, 1.00; 95% CI, 0.58-1.73, and aOR, 0.85; 95% CI, 0.34-2.15, respectively) and Normal children. Conclusions: Our results suggest that in evaluating children exposed to surgery and anesthesia at an early age, the phenotype of interest may be children with deficits primarily in language and cognition, and not children with broad neurodevelopmental delay or primarily behavioral deficits.

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Acute Reduction in the End-Tidal Carbon Dioxide Level During Neurosurgery: Another Cause for Capnography Artifact

No abstract available

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Use of Dexmedetomidine Along With Local Infiltration Versus General Anesthesia for Burr Hole and Evacuation of Chronic Subdural Hematoma (CSDH)

Background: In neurosurgery, chronic subdural hematoma (CSDH) is a very common clinical entity. Both general anesthesia (GA) and local anesthesia with or without sedation are used for the surgical treatment of CSDH. Sedation with dexmedetomidine has been safely used for various diagnostic and therapeutic procedures. However, its effectiveness against GA has not been evaluated for surgical treatment of CSDH. We tried to compare dexmedetomidine sedation technique with the GA technique for surgical treatment of CSDH. Materials and Methods: In this prospective-randomized study, 76 patients undergoing surgery for CSDH were divided into 2 groups using computer-generated randomized tables; Dex group ([n=38]; received IV bolus of dexmedetomidine 1 mcg/kg over 10 min followed by maintenance infusion 0.5 mcg/kg/h) and GA group ([n=38; of which 4 patients were dropped out]; received endotracheal intubation with balanced anesthesia). Results: Both anesthesia techniques (Dex group; n=35/38 [92.1%] and GA group; n=34/34 [100%]) were successfully used for surgical treatment of CSDH. Significantly less time for anesthesia onset (14.2±4.2 vs. 20.5±3.4 min, P=0.001), total duration of surgery (77.1±23.9 vs. 102.7± 24.8 min, P=0.001), and recovery from anesthesia (7.4±5.9 vs. 13.2±6.5 min, P=0.004) was observed in the Dex group compared with GA group. Perioperative hemodynamic fluctuations were more common in the GA group as against the Dex group. Postoperative complications (n=2 vs. 9, P=0.021) and length of hospital stay (1.05±0.23 vs. 1.79±2.1 d, P=0.007) were significantly less in the Dex group as against the GA group. Conclusions: Dexmedetomidine sedation with local anesthesia is a safe and effective technique for burr hole and evacuation of CSDH. It is associated with significantly shorter operative time, lesser hemodynamic fluctuations, postoperative complications, and length of hospital stay, thus it is a better alternative to GA.

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Obscure Retropharyngeal Mucocutaneous Masses Associated With Acoustic Neurofibromatosis: A Source of Difficult Airway Management

No abstract available

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The Prophylactic Use of Remifentanil for Delayed Extubation After Elective Intracranial Operations: a Prospective, Randomized, Double-Blinded Trial

Background: Endotracheal extubation is a painful and stressful procedure. The authors hypothesized that the prophylactic use of remifentanil would attenuate the pain intensity and stress responses resulting from extubation in neurosurgical patients. Materials and Methods: In this prospective, randomized, double-blinded, controlled trial, 160 patients with planned delay extubation after elective intracranial operation were randomized 1:1 to receive either remifentanil or normal saline (control) before their extubation. The dose regime of remifentanil was a bolus of 0.5 μg/kg over 1 minute, followed by a continuous infusion of 0.05 μg/kg/min for 20 minutes. The primary outcome was the incidence of severe pain during the periextubation period. Secondary outcomes included changes in the pain intensity and vital signs, failing to pass an extubation evaluation after the study drug infusion, severe adverse events, postextubation complications, and clinical outcomes. Results: Two patients in the remifentanil group did not pass the extubation evaluation. The incidence of severe pain during the periextubation period was significantly lower in the remifentanil group compared with the control group (25.0% vs. 41.3%, P=0.029). Compared with the control group, the visual analog scale in the remifentanil group was significantly lower after the bolus of remifentanil (12±18 vs. 25±27, P=0.001) and immediately after extubation (19±25 vs. 34±30, P=0.001). There were no significant differences in the vital signs immediately after extubation between the 2 groups (P>0.05). Conclusions: The prophylactic use of remifentanil decreases the incidence of severe pain. Our preliminary findings merit a larger trial to clarify the effect of the prophylactic use of remifentanil on clinical outcomes and adverse events.

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Sodium butyrate protects against oxidative stress in HepG2 cells through modulating Nrf2 pathway and mitochondrial function

Abstract

Sodium butyrate (NaBu) is a by-product of microbial fermentation of dietary fiber in the gastrointestinal tract and has been shown to increase the activity of antioxidant enzymes, such as catalase or heme oxidase-1, in vivo. However, the mechanism of this effect is still unclear. This study investigated the antioxidant effect of NaBu on HepG2 cells under H₂O₂-induced oxidative stress. NaBu (0.3 mM) attenuated cell death and accumulation of reactive oxygen species and improved multiple antioxidant parameters in H₂O₂-injured HepG2 cells. NaBu inhibited glycogen synthase kinase-3 beta (GSK-3β) by increasing the p-GSK-3β (Ser9) level and promoted nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2), which increased the expression of downstream antioxidant enzymes. Together with promotion of peroxisome proliferator-activated receptor gamma coactivator 1-alpha and mitochondrial DNA copy number, NaBu modulated energy metabolism and mitochondrial function, decreasing glycolysis, increasing β-oxidation, and enhancing the tricarboxylic acid cycle and oxidative phosphorylation. NaBu increased mitochondrial manganese-superoxide dismutase and glutathione peroxidase activity. In conclusion, NaBu protected HepG2 cells against oxidative stress by modulating Nrf2 pathway activity and mitochondrial function.

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Intraosseous (IO) Lines Driver Slow Down

Do you know the two most common causes of IO driver slow down and what to do about them? Get this scenario-based video and 100 more from EMS1 Academy to learn new tactics for the personnel at your agency.

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Intraosseous (IO) Lines Driver Slow Down

Do you know the two most common causes of IO driver slow down and what to do about them? Get this scenario-based video and 100 more from EMS1 Academy to learn new tactics for the personnel at your agency.

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Intraosseous (IO) Lines Driver Slow Down

Do you know the two most common causes of IO driver slow down and what to do about them? Get this scenario-based video and 100 more from EMS1 Academy to learn new tactics for the personnel at your agency.

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In Vitro Evaluation of 188Re-HEDP: A Mechanistic View of Bone Pain Palliations

Cancer Biotherapy & Radiopharmaceuticals , Vol. 0, No. 0.


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Intraosseous (IO) Lines Driver Slow Down

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Intraosseous (IO) Lines Driver Slow Down

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Intraosseous (IO) Lines Driver Slow Down

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Intraosseous (IO) Lines Driver Slow Down

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In Vitro Evaluation of 188Re-HEDP: A Mechanistic View of Bone Pain Palliations

Cancer Biotherapy & Radiopharmaceuticals , Vol. 0, No. 0.


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The landscape of genetic diseases in Saudi Arabia based on the first 1000 diagnostic panels and exomes

Abstract

In this study, we report the experience of the only reference clinical next-generation sequencing lab in Saudi Arabia with the first 1000 families who span a wide-range of suspected Mendelian phenotypes. A total of 1019 tests were performed in the period of March 2016–December 2016 comprising 972 solo (index only), 14 duo (parents or affected siblings only), and 33 trio (index and parents). Multigene panels accounted for 672 tests, while whole exome sequencing (WES) represented the remaining 347 tests. Pathogenic or likely pathogenic variants that explain the clinical indications were identified in 34% (27% in panels and 43% in exomes), spanning 279 genes and including 165 novel variants. While recessive mutations dominated the landscape of solved cases (71% of mutations, and 97% of which are homozygous), a substantial minority (27%) were solved on the basis of dominant mutations. The highly consanguineous nature of the study population also facilitated homozygosity for many private mutations (only 32.5% of the recessive mutations are founder), as well as the first instances of recessive inheritance of previously assumed strictly dominant disorders (involving ITPR1, VAMP1, MCTP2, and TBP). Surprisingly, however, dual molecular diagnosis was only observed in 1.5% of cases. Finally, we have encountered candidate variants in 75 genes (ABHD6, ACY3, ADGRB2, ADGRG7, AGTPBP1, AHNAK2, AKAP6, ASB3, ATXN1L, C17orf62, CABP1, CCDC186, CCP110, CLSTN2, CNTN3, CNTN5, CTNNA2, CWC22, DMAP1, DMKN, DMXL1, DSCAM, DVL2, ECI1, EP400, EPB41L5, FBXL22, GAP43, GEMIN7, GIT1, GRIK4, GRSF1, GTRP1, HID1, IFNL1, KCNC4, LRRC52, MAP7D3, MCTP2, MED26, MPP7, MRPS35, MTDH, MTMR9, NECAP2, NPAT, NRAP, PAX7, PCNX, PLCH2, PLEKHF1, PTPN12, QKI, RILPL2, RIMKLA, RIMS2, RNF213, ROBO1, SEC16A, SIAH1, SIRT2, SLAIN2, SLC22A20, SMDT1, SRRT, SSTR1, ST20, SYT9, TSPAN6, UBR4, VAMP4, VPS36, WDR59, WDYHV1, and WHSC1) not previously linked to human phenotypes and these are presented to accelerate post-publication matchmaking. Two of these genes were independently mutated in more than one family with similar phenotypes, which substantiates their link to human disease (AKAP6 in intellectual disability and UBR4 in early dementia). If the novel candidate disease genes in this cohort are independently confirmed, the yield of WES will have increased to 83%, which suggests that most "negative" clinical exome tests are unsolved due to interpretation rather than technical limitations.

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London's Air Ambulance doctor describes London Bridge attack response

Dr. Chris Lambert describes extraordinary scenes as bystanders and police rushed to help injured victims.

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The social organization of Homo ergaster: Inferences from anti-predator responses in extant primates

Publication date: August 2017
Source:Journal of Human Evolution, Volume 109
Author(s): Erik P. Willems, Carel P. van Schaik
Patterns of primate socioecology have been used to suggest that the first truly savanna-dwelling hominin, Homo ergaster, lived in sizeable groups. Here, we revisit these estimates and infer additional features of the social organization of these early hominins based on anti-predator responses observed across the primate taxon. We first show that the effect of habitat on primate group size, composition, and sexual dimorphism is negligible after controlling for substrate use and phylogeny: terrestrial species live in larger groups with more and bigger males than arboreal taxa. We next hypothesize that groups can only survive in open habitats if males are able to engage in joint counter-attacks against the large carnivorans typical of such environments. To test this, we analyze reports on primate counter-attacks against known predators and find these are indeed disproportionately frequent in terrestrial taxa living in open habitats, sometimes even involving the use of tentative weapons. If we subsequently only examine the taxa that are particularly adept at this (chimpanzees and baboons), we find an effect of habitat type on group size: groups on the savanna are larger than those in the forest. We thus infer that H. ergaster lived in very large groups with many males that jointly defended the group against carnivorans, and argue that these counter-attacks will readily have turned into confrontational scavenging and cooperative hunting, allowing Homo to move into the niche of social carnivore. These two features (life in very large multi-male groups and a switch to persistent carnivory) shaped the evolution of our lineage to such an extent that the social organization of H. ergaster may already have contained many key elements characterizing modern day foragers: male bonding, incipient male–female friendships with food sharing, a tendency toward endogamy, and the presence of large communities that eventually turned into the ethno-linguistic units we can still recognize today.



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Comment on “Ecological niche of Neanderthals from Spy Cave revealed by nitrogen isotopes of individual amino acids in collagen” [J. Hum. Evol. 93 (2016) 82–90]

Publication date: Available online 8 June 2017
Source:Journal of Human Evolution
Author(s): Tamsin C. O'Connell, Matthew J. Collins




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London's Air Ambulance doctor describes London Bridge attack response

Dr. Chris Lambert describes extraordinary scenes as bystanders and police rushed to help injured victims.

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London's Air Ambulance doctor describes London Bridge attack response

Dr. Chris Lambert describes extraordinary scenes as bystanders and police rushed to help injured victims.

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London's Air Ambulance doctor describes London Bridge attack response

Dr. Chris Lambert describes extraordinary scenes as bystanders and police rushed to help injured victims.

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Growth charts for Australian children with achondroplasia

Achondroplasia is an autosomal dominant disorder, the most common genetic cause of short stature in humans. Reference curves for head circumference, weight, height, and BMI are needed in clinical practice but none exist for the Australian population. This study aimed to produce head circumference, height, weight, and BMI reference percentile curves for Australian children and adolescents with achondroplasia. Measurements of head circumference, height and weight taken at clinical visits were retrospectively extracted from the electronic medical record. Age was corrected for prematurity. Patients were excluded from head circumference analysis if they had significant neurosurgical complications and from the weight and BMI analysis when they had a clinical diagnosis of overweight. Measurements were available on 138 individuals (69 males and 69 females) taken between 1970 and 2015, with over 50% collected since 2005. A total of 3,352 data points were available. The LMS method was used to produce growth charts with estimated centiles (10, 25, 50, 75, and 90th) separately for males and females. For females birth weight was 3 kg (2.5–3.5 kg), birth length 48 cm (44–50 cm) and head circumference 37.5 cm (36–39 cm), adult height was 125 cm (116–132 cm), weight 42 kg (34–54 kg), and head circumference 58 cm (55.5–60.5 cm) all 50th centile (10–90th). For males birth weight was 3.5 kg (3–4 kg), length 49 cm (46–52 cm) and head circumference 38.5 cm (36–41 cm), adult height was 134 cm (125–141 cm), weight 41 kg (24.5–57 kg) and head circumference 61 cm (58–64 cm). The curves are similar to previously published reference data from the USA and have expected population wide variation from curves from an Argentinian population. Despite limitations of our curves for adolescents (12 years and older) due to data paucity, these Australian growth charts for children and adolescents with achondroplasia will be a useful reference in clinical practice.

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Clinical and molecular genetic characterization of two siblings with trisomy 2p24.3-pter and monosomy 5p14.3-pter

Partial trisomy 2p syndrome is occasionally associated with neural tube defects (NTDs), such as anencephaly, encephalocele, and spina bifida, in addition to common features of intellectual disability, developmental delay, and characteristic facial appearance. The 2p24 region has been reported to be associated with NTDs. Here, we report the cases of 2 siblings with trisomy 2p24.3-pter and monosomy 5p14.3-pter caused by the paternal translocation t(2;5)(p24.3;p14.3). Of the two siblings, the elder sister had spina bifida. We determined the nucleotide sequences of the chromosomal breakpoints and found that the sizes of trisomy 2p and monosomy 5p segments were 18.77 and 17.89 Mb, respectively. NTDs were present in four of seven previously reported patients with trisomy 2p and monosomy 5p as well as in one of the two patients examined in the present study. Although the monosomy 5p of the nine patients were similar in size, the two patients reported here had the smallest size of trisomy 2p. When the clinical features of the nine patients were compared to the present two patients, the elder sister had postaxial polydactyly of the left foot in addition to the characteristic facial appearance and spina bifida, indicating that these features were associated with trisomy 2p24.3-pter. To our knowledge, this is the first study on spina bifida to determine the nucleotide sequences of breakpoints for trisomy 2p24.3-pter and monosomy 5p14.3-pter. Increased gene dosages of dosage-sensitive genes or genes at the trisomy segment (2p24.3) of the presented patients could be associated with NTDs of patients with trisomy 2p.

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Clinical and molecular cytogenetic characterization of four unrelated patients carrying 2p14 microdeletions

We report the clinical and molecular cytogenetic characterization of four unrelated patients from France and Spain, carrying 2p14 microdeletions and presenting with intellectual disability and dysmorphisms. 2p14 microdeletions are very rare. Seven patients have been reported so far harboring deletions including 2p14p15 and encompassing OTX1, whose haploinsufficiency is frequently associated with genitourinary defects. To date, only one patient has been reported carrying a more proximal 2p14 microdeletion which does not include OTX1. Here, we report three further patients carrying proximal 2p14 microdeletions not including OTX1 and one patient carrying a more distal 2p14p15 microdeletion including this gene, providing new insights into the associated phenotypic spectrum. First, our study and a review of the literature showed that 3/4 patients carrying proximal 2p14 microdeletions had sensorineural hearing loss, suggesting the presence of a previously unreported deafness-causing gene in this chromosomal region. Second, one patient developed a progressive cardiomyopathy, suggesting that a cardiac follow-up should be systematically warranted even in the absence of congenital heart disease. We speculate that ACTR2 and MEIS1 might respectively play a role in the pathogenesis of the observed deafness and cardiomyopathy. Third, we observed other previously unreported features such as glaucoma, retinopathy, and mild midline abnormalities including short corpus callosum, hypospadias and anteriorly placed anus. Finally, the patient carrying a 2p14p15 deletion including OTX1 had normal kidneys and genitalia, thus confirming that OTX1 haploinsufficiency is not invariably associated with genitourinary defects. In conclusion, our study contributes significantly to delineate the phenotypic spectrum of 2p14 microdeletions.

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Whole-genome sequencing of monozygotic twins discordant for schizophrenia indicates multiple genetic risk factors for schizophrenia

Publication date: Available online 8 June 2017
Source:Journal of Genetics and Genomics
Author(s): Jinsong Tang, Yu Fan, Hong Li, Qun Xiang, Deng-Feng Zhang, Zongchang Li, Ying He, Yanhui Liao, Ya Wang, Fan He, Fengyu Zhang, Yin Yao Shugart, Chunyu Liu, Yanqing Tang, Raymond C.K. Chan, Chuan-Yue Wang, Yong-Gang Yao, Xiaogang Chen
Schizophrenia is a common disorder with a high heritability, but its genetic architecture is still elusive. We implemented whole-genome sequencing (WGS) analysis of 8 families with monozygotic (MZ) twin pairs discordant for schizophrenia to assess potential association of de novo mutations (DNMs) or inherited variants with susceptibility to schizophrenia. Eight nonsynonymous DNMs (including one splicing site) were identified and shared by twins, which were either located in previously reported schizophrenia risk genes (p.V24689I mutation in TTN, p.S2506T mutation in GCN1L1, IVS3+1G>T in DOCK1) or have a benign to damaging effect according to in silico prediction analysis. By searching the inherited rare damaging or loss-of-function (LOF) variants and common susceptible alleles from three classes of schizophrenia candidate genes, we were able to distill genetic alterations in several schizophrenia risk genes, including GAD1, PLXNA2, RELN and FEZ1. Four inherited copy number variations (CNVs; including a large deletion at 16p13.11) implicated for schizophrenia were identified in four families, respectively. Most of families carried both missense DNMs and inherited risk variants, which might suggest that DNMs, inherited rare damaging variants and common risk alleles together conferred to schizophrenia susceptibility. Our results support that schizophrenia is caused by a combination of multiple genetic factors, with each DNM/variant showing a relatively small effect size.



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Dopamine induces inhibitory effects on the circular muscle contractility of mouse distal colon via D1- and D2-like receptors

Abstract

Dopamine (DA) acts as gut motility modulator, via D1- and D2-like receptors, but its effective role is far from being clear. Since alterations of the dopaminergic system could lead to gastrointestinal dysfunctions, a characterization of the enteric dopaminergic system is mandatory. In this study, we investigated the role of DA and D1- and D2-like receptors in the contractility of the circular muscle of mouse distal colon by organ-bath technique. DA caused relaxation in carbachol-precontracted circular muscle strips, sensitive to domperidone, D2-like receptor antagonist, and mimicked by bromocriptine, D2-like receptor agonist. 7-Chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH-23390), D1-like receptor antagonist, neural toxins, L-NAME (nitric oxide (NO) synthase inhibitor), 2′-deoxy-N₆-methyl adenosine 3′,5′-diphosphate diammonium salt (MRS 2179), purinergic P2Y1 antagonist, or adrenergic antagonists were ineffective. DA also reduced the amplitude of neurally evoked cholinergic contractions. The effect was mimicked by (±)-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol hydrobromide (SKF-38393), D1-like receptor agonist and antagonized by SCH-23390, MRS 2179, or L-NAME. Western blotting analysis determined the expression of DA receptor proteins in mouse distal colon. Notably, SCH-23390 per se induced an increase in amplitude of spontaneous and neurally evoked cholinergic contractions, unaffected by neural blockers, L-NAME, MRS 2179, muscarinic, adrenergic, or D2-like receptor antagonists. Indeed, SCH-23390-induced effects were antagonized by an adenylyl cyclase blocker. In conclusion, DA inhibits colonic motility in mice via D2- and D1-like receptors, the latter reducing acetylcholine release from enteric neurons, involving nitrergic and purinergic systems. Whether constitutively active D1-like receptors, linked to adenylyl cyclase pathway, are involved in a tonic inhibitory control of colonic contractility is questioned.

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Morphology and hydro-sensory role of superficial neuromasts in schooling behaviour of yellow-eyed mullet ( Aldrichetta forsteri )

Abstract

The lateral line system is a mechanosensory organ found in all fish species and located on the skin or in subdermal canals. The basic functional units are superficial and canal neuromasts, which are involved in hydrodynamic sensing and cohesion in schooling fish. Yellow-eyed mullet (Aldrichetta forsteri) are an obligate schooling species found commonly in shallow coastal areas of New Zealand and Australia. Schooling is a fundamental part of their behavioural repertoire, yet little is known about the structure or functionality of the lateral line in this species. We used scanning electron microscopy to characterise the morphology of trunk superficial neuromasts. We then took a multi-sensory approach and conducted behavioural experiments comparing school structure in groups of fish with and without fully functioning lateral lines, under photopic and scotopic conditions. A highly developed hydro-sensing system exists on the trunk of yellow-eyed mullet consisting of superficial neuromasts containing hundreds of hair cells aligned, with respect to their most sensitive axis, in a rostrocaudal direction. Without functioning superficial neuromasts, schooling behaviour was disrupted under both photopic and scotopic conditions and the ability to detect stationary objects decreased. Results highlight the importance of this component of the lateral line system to schooling behaviour.

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The nervous and visual systems of onychophorans and tardigrades: learning about arthropod evolution from their closest relatives

Abstract

Understanding the origin and evolution of arthropods requires examining their closest outgroups, the tardigrades (water bears) and onychophorans (velvet worms). Despite the rise of molecular techniques, the phylogenetic positions of tardigrades and onychophorans in the panarthropod tree (onychophorans + tardigrades + arthropods) remain unresolved. Hence, these methods alone are currently insufficient for clarifying the panarthropod topology. Therefore, the evolution of different morphological traits, such as one of the most intriguing features of panarthropods—their nervous system—becomes essential for shedding light on the origin and evolution of arthropods and their relatives within the Panarthropoda. In this review, we summarise current knowledge of the evolution of panarthropod nervous and visual systems. In particular, we focus on the evolution of segmental ganglia, the segmental identity of brain regions, and the visual system from morphological and developmental perspectives. In so doing, we address some of the many controversies surrounding these topics, such as the homology of the onychophoran eyes to those of arthropods as well as the segmentation of the tardigrade brain. Finally, we attempt to reconstruct the most likely state of these systems in the last common ancestors of arthropods and panarthropods based on what is currently known about tardigrades and onychophorans.

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Digital innovations and emerging technologies for enhanced recovery programmes

Abstract

Enhanced recovery programmes (ERPs) are increasingly used to improve post-surgical recovery. However, compliance to various components of ERPs—a key determinant of success—remains sub-optimal. Emerging technologies have the potential to help patients and caregivers to improve compliance with ERPs.Preoperative physical condition, a major determinant of postoperative outcome, could be optimized with the use of text messages (SMS) or digital applications (Apps) designed to facilitate smoking cessation, modify physical activity, and better manage hypertension and diabetes. Several non-invasive haemodynamic monitoring techniques and decision support tools are now available to individualize perioperative fluid management, a key component of ERPs. Objective nociceptive assessment may help to rationalize the use of pain medications, including opioids. Wearable sensors designed to monitor cardio-respiratory function may help in the early detection of clinical deterioration during the postoperative recovery and to address 'failure to rescue'. Activity trackers may be useful to monitor early mobilization, another major element of ERPs. Finally, electronic checklists have been developed to ensure that none of the above-mentioned ERP elements is omitted during the surgical journey.By optimizing compliance to the multiple components of ERPs, digital innovations, non-invasive techniques and wearable sensors have the potential to magnify the clinical and economic benefits of ERPs. Among the growing number of technical innovations, studies are needed to clarify which tools and solutions have real clinical value and are cost-effective.

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Laparoscopic segmental duodenectomy for a gastrointestinal stromal tumor located in the second portion of the duodenum: A case report

Abstract

Gastrointestinal stromal tumors of the duodenum are rare. For benign tumors, premalignant lesions, or malignant potential tumors located in the second portion of the duodenum close to the papilla of Vater, pancreaticoduodenectomy is sometimes performed. A case of laparoscopic segmental duodenectomy for a gastrointestinal stromal tumor at the second portion of the duodenum is reported. The surgical procedure was performed as follows: first, the second portion of the duodenum was separated from the pancreatic head; second, the duodenum was cut off with the linear stapler after having confirmed preservation of the papilla by intraoperative endoscopy; and third, reconstruction was carried out by a side-to-side duodenojejunostomy. Laparoscopic segmental duodenectomy for duodenal gastrointestinal stromal tumors is thought to be advantageous compared with pancreaticoduodenectomy in terms of low burden and organ function preservation. The present procedure is feasible for benign or low-malignant tumors that do not infiltrate outside of the duodenal walls.

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Fla. fire, EMS departments to be equipped with body armor

Responders will receive ballistic vests and helmets tested against special threats

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Paving the way for Bartter syndrome type 3 drug discovery: a hope from basic research

Abstract

Understanding the genetic background and the molecular mechanisms of inherited kidney channelopathies is essential to definition of targeted therapeutic approaches for affected patients.

This article is protected by copyright. All rights reserved

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Specialist Endoscopists Are Associated with a Decreased Risk of Incomplete Polyp Resection During Endoscopic Mucosal Resection in the Colon

Abstract

Background

Endoscopic experience is known to correlate with outcomes of endoscopic mucosal resection (EMR), particularly complete resection of the polyp tissue. Whether specialist endoscopists can protect against incomplete polypectomy in the setting of known risk factors for incomplete resection (IR) is unknown.

Aims

We aimed to characterize how specialist endoscopists may help to mitigate the risk of IR of large sessile polyps.

Methods

This is a retrospective cohort study of patients who underwent EMR at the University of Michigan from January 1, 2006, to November 15, 2015. The primary outcome was endoscopist-reported polyp tissue remaining at the end of the initial EMR attempt. Specialist endoscopists were defined as endoscopists who receive tertiary referrals for difficult colonoscopy cases and completed at least 20 EMR colonic polyp resections over the study period.

Results

A total of 257 patients with 269 polyps were included in the study. IR occurred in 40 (16%) cases. IR was associated with polyp size ≥ 40 mm [adjusted odds ratio (aOR) 3.31, 95% confidence interval (CI) 1.38–7.93], flat/laterally spreading polyps (aOR 2.61, 95% CI 1.24–5.48), and difficulty lifting the polyp (aOR 11.0, 95% CI 2.66–45.3). A specialist endoscopist performing the initial EMR was protective against IR, even in the setting of risk factors for IR (aOR 0.13, 95% CI 0.04–0.41).

Conclusions

IR is associated with polyp size ≥ 40 mm, flat and/or laterally spreading polyps, and difficulty lifting the polyp. A specialist endoscopist initiating the EMR was protective of IR.

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Chronic Kidney Disease and H. pylori Prevalence: A Significant Association?

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Validation of Demographics, Etiology, and Risk Factors for Chronic Pancreatitis in the USA: A Report of the North American Pancreas Study (NAPS) Group

Abstract

Background/Objectives

Our aim was to validate recent epidemiologic trends and describe the distribution of TIGAR-O risk factors in chronic pancreatitis (CP) patients.

Methods

The NAPS-2 Continuation and Validation (NAPS2-CV) study prospectively enrolled 521 CP patients from 13 US centers from 2008 to 2012. CP was defined by definitive changes in imaging, endoscopy, or histology. Data were analyzed after stratification by demographic factors, physician-defined etiology, participating center, and TIGAR-O risk factors.

Results

Demographics and physician-defined etiology in the NAPS2-CV study were similar to the original NAPS2 study. Mean age was 53 years (IQR 43, 62) with 55% males and 87% white. Overall, alcohol was the single most common etiology (46%) followed by idiopathic etiology (24%). Alcohol etiology was significantly more common in males, middle-aged (35–65 years), and non-whites. Females and elderly (≥65 years) were more likely to have idiopathic etiology, while younger patients (<35 years) to have genetic etiology. Variability in etiology was noted by participating centers (e.g., alcohol etiology ranged from 27 to 67% among centers enrolling ≥25 patients). Smoking was the most commonly identified (59%) risk factor followed by alcohol (53%), idiopathic (30%), obstructive (19%), and hyperlipidemia (13%). The presence of multiple TIGAR-O risk factors was common, with 1, 2, ≥3 risk factors observed in 27.6, 47.6, and 23.6% of the cohort, respectively.

Conclusion

Our data validate the current epidemiologic trends in CP. Alcohol remains the most common physician-defined etiology, while smoking was the most commonly identified TIGAR-O risk factor. Identification of multiple risk factors suggests CP to be a complex disease.

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Late-onset ornithine transcarbamylase deficiency associated with hyperammonemia

Abstract

The urea cycle converts ammonia and produces urea. One form of urea cycle abnormality is ornithine transcarbamylase (OTC) deficiency. This hereditary disorder is associated with hyperammonemia. OTC deficiency commonly appears during neonatal and early childhood life and is rare in adults. We report a 69-year-old man who presented at the local hospital with 3-day loss of appetite, early morning vomiting, and state of confusion. Blood ammonia was 293 μg/dl. At 2–3 h after admission, the patient went into a deep coma. He was intubated and admitted immediately to the intensive care unit. Treatment, including sustained hemodialysis, failed to lower blood ammonia level. His grandchild died of OTC deficiency at 6 year of age. Computed tomography, magnetic resonance imaging and esophagogastroduodenoscopy showed no abnormalities. On admission to our hospital, he complained of vomiting and disturbance of consciousness, hyperammonemia, and normal anion gap. Genetic analysis showed A208T mutation. The deceased grandchild with OTC deficiency also had the same mutation. Long-term hemodialysis coupled with administration of l-arginine and lactulose resulted in improvement of blood ammonia level. Early diagnosis and treatment of adult-onset OTC deficiency are essential to avoid serious complications.

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Endoscopic management of biliary strictures after living donor liver transplantation

Abstract

Living donor liver transplantation (LDLT) is an effective alternative to deceased liver transplantation (DDLT) for end-stage liver disease. Although advances in surgical techniques, immunosuppressive management, and post-transplant care have improved the overall outcomes of LDLT, biliary strictures remain the major unsolved problem. Endoscopic retrograde cholangiopancreatography (ERCP) is currently considered the first-line therapy for biliary strictures following LDLT with duct-to-duct reconstruction, with percutaneous and surgical interventions reserved for patients with unsuccessful management via ERCP. Endoscopic management of biliary strictures is technically more challenging in LDLT than in DDLT because of the complexity of the biliary anastomosis, in addition to the tortuous and angulated biliary system. Placement of one or more plastic stents after balloon dilation has been the standard strategy for post-LDLT stricture, but this requires multiple stent exchange to prevent stent occlusion until stricture resolution. Inside stents might prevent duodenobiliary reflux and thus have longer stent patency, obviating the need for multiple ERCPs. Newly developed covered self-expandable metallic stents with anti-migration systems are alternatives to the placement of multiple plastic stents. With the advent of deep enteroscopy, biliary strictures in LDLT patients with Roux-en-Y hepaticojejunostomy are now treatable endoscopically. In this review, we discuss the short- and long-term outcomes of endoscopic management of post-LDLT strictures as well as recent advances in this field.

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Genetic Study of Early-onset Graves’ Disease in the Chinese Han Population

Abstract

Graves' disease (GD) is a complex autoimmune disorder in which genetic and environmental factors are both involved in the pathogenesis. Early-onset patients have a shorter exposure time to environmental factors and are, therefore, good models to help understand the genetic architecture of GD. Based on previous studies of early-onset GD, eleven single nucleotide polymorphisms (SNPs) and their related SNPs (R² > 0.6), SNPs located within a ± 1-Mb region of the FOXP3 gene, and twenty validated GD-risk SNPs were selected and screened for genotyping in 3,735 GD and 4,893 control patients to investigate whether early-onset GD is a subtype of GD with distinct susceptibility genes. Ultimately, we did not confirm the reported genetic markers of early-onset GD in our Chinese Han population but found that a GD-risk SNP located in the human leukocyte antigen class I region—rs4947296—was more strongly correlated with early-onset GD than non-early onset GD. In addition, heterogeneity analysis of GD patients suggests that it may be more reasonable to define early-onset GD as an onset age ≤ 20 years.

Graphical abstract

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Large-scale Study of Clinical and Biochemical Characteristics of Chinese Patients Diagnosed with Krabbe Disease

ABSTRACT

Krabbe disease (KD) is a rare disease caused by the deficiency of β-galactocerebrosidase. This study investigated 22 unrelated Chinese patients, including their clinical presentations, plasma psychosine levels and GALC gene mutations. We found the late-onset form of KD present in 82% of the patients in our study, which was more prevalent than in patients from other populations. Plasma psychosine levels were elevated in KD, which were correlated with the severity of clinical presentations. Sanger sequencing identified 8 novel mutations, including 7 missense mutations, p.H253Y, p.S259L, p.P318L, p.F350V, p.T428A, p.L530P, p.G586D, and 1 splicing mutation, c.1251+1G>A. Quantitative real-time PCR and multiplex ligation-dependent probe amplification identified a novel exon 12 and 14 deletion, separately. Next generation sequencing, applied at the final step, revealed 2 missense mutant alleles missed by Sanger sequencing. The most common mutation in Chinese population is p.P154H, which accounts for 20.5% of alleles. Consistent with the higher prevalence of the late-onset form of KD, missense mutations predominated in our study, different with the common mutation types in Europe and Japan. This work was the first large-scale study of Chinese KD patients describing their clinical, biochemical and genetic characteristics, which furthered our understanding of this classical neurological lysosomal storage disease.

Graphical abstract

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Genetic epidemiology of Familial Mediterranean Fever through integrative analysis of whole genome and exome sequences from Middle East and North Africa

Abstract

Familial Mediterranean fever (FMF), an autosomal recessive and rare autoinflammatory disease is caused by genetic mutations in the MEFV gene and is highly prevalent in the Mediterranean basin. Though the carrier frequency of specific disease variants in the MEFV gene has been reported from isolated studies, a comprehensive view of variants in the Mediterranean region has not been possible due to paucity of data. The recent availability of whole-genome and whole-exome datasets prompted us to study the genetic epidemiology of MEFV variants in the region. We assembled data from five datasets encompassing whole-genome and whole-exome datasets for 2115 individuals from multiple subpopulations in the region and also created a compendium for MEFV genetic variants, which were further systematically annotated as per the ACMG guidelines. Our analysis points to significant differences in allele frequencies in the subpopulations, and the carrier frequency for MEFV genetic variants in the population to be about 8%. The MEFV gene appears to be under natural selection from our analysis. To the best of our knowledge, this is the most comprehensive study and analysis of population epidemiology of MEFV gene variants in the Middle East and North African populations.

Graphical Abstract

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Comparison of propofol with midazolam in endoscopic submucosal dissection for esophageal squamous cell carcinoma: a randomized controlled trial

Abstract

Background

Interruption of sedation due to a poor response to modified neuroleptanalgesia (m-NLA) with midazolam often occurs during endoscopic submucosal dissection (ESD) for esophageal squamous cell carcinoma (ESCC) because most patients have a history of heavy alcohol intake. Recently, propofol has been used feasibly and safely during endoscopic procedures. The aim of this study was to clarify the efficacy and safety of propofol compared with that of midazolam during ESD for ESCC.

Methods

This was a single-blind, randomized controlled trial in a single center. Patients with ESCC scheduled for ESD were included in the study. Patients were randomly assigned to one of two groups: the propofol group and the midazolam group. The main outcome was the incidence of discontinuation of the procedure due to a poor response to sedation. Secondary outcomes included risk factors for a poor response to sedation.

Results

Between April 2014 and October 2015, 132 patients (n = 66 per group) who underwent ESD for ESCC were enrolled in this study. The incidence of discontinuation due to a poor response to sedation in the propofol and midazolam groups was 0% (0/66) and 37.9% (25/66), respectively (p < 0.01). Multivariate analyses revealed that use of midazolam [Odds ratio (OR), 7.61; 95% confidence interval (CI), 2.64–21.92; p < 0.01] and age (OR, 0.93; 95% CI, 0.86–0.98; p < 0.01) were risk factors for a poor response to sedation.

Conclusions

Our study indicates that, compared with midazolam, propofol is a more efficient sedative for m-NLA during ESD for ESCC.

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Lack of linear correlation between dynamic and steady-state cerebral autoregulation

Abstract

The purpose of this study was to investigate the relationship between dynamic (dCA) and steady-state cerebral autoregulation (sCA). In 28 healthy older adults, sCA was quantified by a linear regression slope of proportionate (%) changes in cerebrovascular resistance (CVR) in response to proportionate (%) changes in mean blood pressure (BP) induced by stepwise sodium nitroprusside (SNP) and phenylephrine (PhE) infusion. Cerebral blood flow (CBF) was measured at the internal carotid (ICA) and vertebral (VA) artery and cerebral blood flow velocity (CBFV) at the middle cerebral artery (MCA). With CVR = BP/CBF, Slope-CVR_ICA, Slope-CVR_VA and Slope-CVRi_MCA were derived. dCA was assessed in (1) supine rest, analysed with transfer function analysis (gain and phase) and autoregulatory index (ARI) fit from spontaneous oscillations (ARI_Baseline), (2) transient changes in BP using a bolus injection of SNP (ARI_SNP) and PhE (ARI_PhE). Comparison of sCA and dCA parameters (using Pearson's r for continuous and Spearman's ρ for ordinal parameters) demonstrated a lack of linear correlations between sCA and dCA measures. However, comparisons of parameters within dCA and within sCA were correlated. For sCA slope-CVR_VA with Slope-CVRi_MCA (r = 0.45, P < 0.03); for dCA ARI_SNP with ARI_PhE (ρ = 0.50, P = 0.03), ARI_Baseline (ρ = 0.57, P = 0.03), and Phase_LF (ρ = 0.48, P = 0.03); Gain_VLF with Gain_LF (r = 0.51, P = 0.01). Conclusions: In contrast to the commonly held assumption based on an earlier study, there were no linear correlations between sCA and dCA. As an additional observation, there was strong inter-individual variability, both in dCA and sCA, in this healthy group of elderly, in a range from low to high CA efficiency.

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The beneficial metabolic effects of insulin sensitizers are not attenuated by mitochondrial pyruvate carrier 2 hypomorphism

Abstract

Rosiglitazone and pioglitazone are thiazolidinedione (TZD) compounds that have been used clinically as insulin-sensitizing drugs and are generally believed to mediate their effects via activation of the peroxisome proliferator-activated receptor γ (PPARγ). Recent work has shown that it is possible to synthesize TZD compounds with potent insulin-sensitizing effects and markedly-diminished affinity for PPARγ. Both clinically-used TZDs and investigational PPARγ-sparing TZDs, such as MSDC-0602, interact with the mitochondrial pyruvate carrier (MPC) and inhibit its activity. Two proteins, MPC1 and MPC2, comprise the MPC complex. Herein, we used mice expressing a hypomorphic MPC2 protein missing 16 amino acids in the N terminus (Mpc2Δ16 mice) to determine the effects of these residues in mediating the insulin-sensitizing effects of TZDs in diet-induced obese mice. We found that both pioglitazone and MSDC-0602 elicited their beneficial metabolic effects, including improving glucose tolerance, attenuating hepatic steatosis, reducing adipose tissue inflammation, and stimulating adipocyte browning, in both WT and Mpc2Δ16 mice after high fat diet feeding. In addition, truncation of MPC2 failed to attenuate the interaction between TZDs and the MPC in a BRET-based assay or to affect the suppression of pyruvate-stimulated respiration in cells. Collectively, these data suggest that the interaction between TZDs and MPC2 is not affected by loss of the N-terminal 16 amino acids nor are these residues required for the insulin-sensitizing effects of these compounds.

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Academy News – June PM&R Journal

As the primary medical society for the specialty of PM&R, your Academy is focused on moving the specialty and you forward. Academy membership supports initiatives to assist our members with:

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Reliability Statistics

Measurement tools used in clinical studies need to be sufficiently reliable. Reliability means that the tool gives consistent results when administered by different people (interrater reliability) or at different time points (test-retest reliability). Statistical tests of association are not appropriate for assessing reliability—reliability statistics assess agreement rather than association. Reliability statistics include the Kappa statistic for categorical scales and the intraclass correlation coefficient (ICC) for continuous scales.

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Information for Authors

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Copyright Page

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Should This Patient With Global Aphasia After a Left Cerebral Stroke Be Admitted to Your Hospital-Based Inpatient Rehabilitation Unit?

You are the medical director of a very busy, 20-bed, general inpatient rehabilitation unit (IRU) at a community hospital. About 40% of admissions to the unit are persons with moderate and severe stroke from the geographic region, and your census runs very nearly 100% capacity, usually with a waiting list. The neurology service asks you to assess a 60-year-old man with a long history of hypertension and diabetes mellitus who is now 6 days post a large left middle cerebral artery (MCA) ischemic stroke.

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Spanish Translated Abstracts

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Editorial Board

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Table of Contents

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Effects of bright and blue light on acoustic reaction time and maximum handgrip strength in male athletes: a randomized controlled trial

Abstract

Purpose

To assess which type of evening light exposure has the greatest effect on reaction time and maximum handgrip strength. These were pre-specified secondary outcomes in a trial which primarily investigated the influence of light on cycling performance.

Methods

Seventy-four male athletes were allocated at random to either bright light (BRIGHT), monochromatic blue light (BLUE), or a control condition (CONTROL). Light exposure lasted for 60 min and started 17 h after the individual midpoint of sleep. Reaction time, handgrip strength, and melatonin levels were measured before and after the light exposure. We used analysis of covariance to compare the groups with respect to the investigated outcomes.

Results

Two participants had to be excluded retrospectively. The remaining 72 participants had a median age of 23 years. The adjusted difference in reaction time was −1 ms [95% confidence interval (CI) −8, 6] for participants in BRIGHT and 2 ms (95% CI −5, 9) for participants in BLUE, both relative to participants in CONTROL. The adjusted difference in handgrip strength was 0.9 kg (95% CI −1.5, 3.3) for participants in BRIGHT and −0.3 kg (95% CI −2.7, 2.0) for participants in BLUE, both relative to participants in CONTROL. After the light exposure, 17% of participants in BRIGHT, 22% in BLUE, and 29% in CONTROL showed melatonin concentrations of 2 pg/ml or higher.

Conclusions

The results suggest that bright light might reduce melatonin levels but neither bright nor blue light exposure in the evening seem to improve reaction time or handgrip strength in athletes.

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Prognostic factors in patients with advanced biliary tract cancer treated with first-line gemcitabine plus cisplatin: Retrospective analysis of 740 patients

Cancer Chemotherapy and Pharmacology

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Group: 504 sought life-ending drugs under new California law

AP

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Impact of weekday of esophagectomy on short-term and long-term oncological outcomes: A nationwide population-based cohort study in the Netherlands

Annals of Surgery

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Lower-income US adults haven't seen heart health gains

Reuters Health News

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Alpha-lipoic acid supplement in obesity treatment: A systematic review and meta-analysis of clinical trials

Clinical Nutrition

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Clinical efficacy and tolerability of direct-acting antivirals in elderly patients with chronic hepatitis C

European Journal of Gastroenterology & Hepatology

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Systematic review and meta-analysis of the role of metronidazole in post-haemorrhoidectomy pain relief

Colorectal Disease

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Phase II study of induction gemcitabine and S-1 followed by chemoradiotherapy and systemic chemotherapy using S-1 for locally advanced pancreatic cancer

Cancer Chemotherapy and Pharmacology

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Comparison between two population-based hepatitis B serosurveys within an 8-year interval in Shandong province, China

International Journal of Infectious Diseases

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Exercise-induced gastrointestinal syndrome-implications for health and intestinal disease

Alimentary Pharmacology and Therapeutics

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Incidence and clinical outcomes of inflammatory bowel disease in South Korea, 2011-2014: A nationwide population-based study

Digestive Diseases and Sciences

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A diagnostic accuracy meta-analysis of CT and MRI for the evaluation of small bowel Crohn disease

Academic Radiology

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Terminally ill man arrested after plotting to kill 3 doctors

AP

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Hepatitis B virus reactivation among hepatitis C patients treated with direct-acting antiviral therapies in routine clinical practice

Journal of Clinical Virology

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The cardiac glycoside oleandrin induces apoptosis in human colon cancer cells via the mitochondrial pathway

Cancer Chemotherapy and Pharmacology

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Bevacizumab for metastatic colorectal cancer: A global cost-effectiveness analysis

The Oncologist

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Molecular profiling of signet ring cell colorectal cancer provides a strong rationale for genomic targeted and immune checkpoint inhibitor therapies

British Journal of Cancer

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Repeat rifaximin for irritable bowel syndrome: No clinically significant changes in stool microbial antibiotic sensitivity

Digestive Diseases and Sciences

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Hepatitis E virus IgG seroprevalence in HIV patients and blood donors, west-central Poland

International Journal of Infectious Diseases

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Prevalence of naturally occurring protease inhibitor resistance-associated variants in hemodialysis and renal transplant patients with hepatitis C virus infection

European Journal of Gastroenterology & Hepatology

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Skeletal myofiber VEGF is required for the exercise training-induced increase in dentate gyrus neuronal precursor cells

Abstract

Exercise signals neurogenesis in the dentate gyrus of the hippocampus. This phenomenon requires vascular endothelial growth factor (VEGF) originating from outside the blood brain barrier, but no cellular source has been identified. Thus, we hypothesized that VEGF produced by skeletal myofibers plays a role in regulating hippocampal neuronal precursor cell proliferation following exercise training. This was tested in adult conditional skeletal myofiber-specific VEGF gene-ablated mice (VEGF^HSA-/−) by providing VEGF^HSA-/− and non-ablated (VEGF^f/f) littermates with running wheels for 14 days. Following this training period, hippocampal cerebral blood flow (CBF) was measured by functional magnetic resonance imaging (fMRI) and neuronal precursor cells (BrDU+/Nestin+) were detected by immunofluorescence. The VEGF^f/f trained group showed improvements in both speed and endurance capacity in acute treadmill running tests (P < 0.05). The VEGF^HSA-/− group did not. The number of proliferating neuronal precursor cells was increased with training in VEGF^f/f (P < 0.05) but not in VEGF^HSA-/− mice. Endothelial cell (CD31+) number did not change in this region with exercise training or skeletal myofiber VEGF gene deletion. However, resting blood flow through the hippocampal region was lower in VEGF^HSA-/− mice, both untrained and trained, than untrained VEGF^f/f mice (P < 0.05). An acute hypoxic challenge decreased CBF (P < 0.05) in untrained VEGF^f/f, untrained VEGF^HSA-/−, and trained VEGF^HSA-/−, but not trained VEGF^f/f mice. VEGF^f/f, but not VEGF^HSA-/− mice, were able to acutely run on a treadmill at an intensity sufficient to increase hippocampus VEGF levels. These data suggest that VEGF expressed by skeletal myofibers may directly or indirectly regulate both hippocampal blood flow and neurogenesis.

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Context Matters: Team and Organizational Factors Associated with Reach of Evidence-Based Psychotherapies for PTSD in the Veterans Health Administration

Abstract

Evidence-based psychotherapies for PTSD are often underused. The objective of this mixed-method study was to identify organizational and clinic factors that promote high levels of reach of evidence-based psychotherapies for PTSD 10 years into their dissemination throughout the Veterans Health Administration. We conducted 96 individual interviews with staff from ten outpatient PTSD teams at nine sites that differed in reach of evidence-based psychotherapies for PTSD. Major themes associated with reach included clinic mission, clinic leader and staff engagement, clinic operations, staff perceptions, and the practice environment. Strategies to improve reach of evidence-based psychotherapies should attend to organizational and team-level factors.

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