Trans-spinal direct current stimulation modulates migration and proliferation of adult newly-born spinal cells in mice

Direct current electrical fields have been shown to be a major factor in the regulation of cell proliferation, differentiation, migration, and survival, as well as in the maturation of dividing cells during development. During adulthood, spinal cord cells are continuously produced in both animals and humans, and they hold great potential for neural restoration following spinal cord injury. While the effects of direct current electrical fields on adult-born spinal cells cultured ex vivo have recently been reported, the effects of direct current electrical fields on adult-born spinal cells in vivo have not been characterized. Here, we provide convincing findings that a therapeutic form of trans-spinal direct current stimulation (tsDCS) effects the migration and proliferation of adult-born spinal cells in mice. Specifically, cathodal-tsDCS attracted the adult-born spinal cells, while anodal-tsDCS repulsed them. In addition, both tsDCS polarities caused a significant increase in cell number. Regarding the potential mechanisms involved, both cathodal- and anodal-tsDCS caused significant increases in expression of brain-derived neurotrophic factor (BDNF), while expression of nerve growth factor (NGF) increased and decreased, respectively. In the spinal cord, both anodal and cathodal tsDCS increased blood flow. Since blood flow and angiogenesis are associated with the proliferation of neural stem cells, increased blood flow may represent a major factor in the modulation of newly-born spinal cells by tsDCS. Consequently, we propose that the method and novel findings presented in the current study have the potential to facilitate cellular, molecular, and/or bioengineering strategies to repair injured spinal cords.

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A LED-based phosphorimeter for measurement of microcirculatory oxygen pressure

Quantitative measurements of microcirculatory and tissue oxygenation are of prime importance in experimental research. Non-invasive time-resolved quenching of phosphorescence has given further insight into the fundamental mechanisms of oxygen transport to healthy tissues and in models of disease. Phosphorimeters are devices dedicated to the study of phosphorescence quenching. The experimental applications of phosphorimeters range from measuring a specific oxygen partial pressure (PO₂) in cellular organelles such as mitochondria, finding values of PO₂ distributed over an organ or capillaries, to measuring microcirculatory PO₂ changes simultaneously in several organ systems. Most of the current phosphorimeters use flash lamps as a light excitation source. However, a major drawback of flash lamps is their inherent plasma glow that persists for tens of microseconds after the primary discharge. This complex distributed excitation pattern generated by the flash lamp can lead to inaccurate PO₂ readings unless a deconvolution analysis is performed. Using light-emitting diode (LED), a rectangular shaped light pulse can be generated that provides a more uniformly distributed excitation signal. This study presents the design and calibration process of an LED-based phosphorimeter (LED-P). The in vitro calibration of the LED-P using Palladium(II)-meso-tetra(4-carboxyphenyl)-porphyrin (Pd-TCCP) as a phosphorescent dye is presented. The pH and temperature were altered to assess whether the decay times of the Pd-TCCP measured by the LED-P were significantly influenced. An in vivo validation experiment was undertaken to measure renal cortical PO₂ in a rat subjected to hypoxic ventilation conditions and ischemia/reperfusion. The benefits of using LEDs as a light excitation source are presented.

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Adjustments with running speed reveal neuromuscular adaptations during landing associated with high mileage running training

It remains to be determined whether running training influences the amplitude of lower limb muscle activations prior to and during the first half of stance, and whether such changes are associated with joint stiffness regulation and usage of stored energy from tendons. Therefore, the aim of this study was to investigate neuromuscular and movement adaptations before and during landing in response to running training across a range of speeds. Two groups of high mileage (HM; >45 km/wk, n=13) and low mileage (LM; <15 km/wk, n=13) runners ran at four speeds (2.5-5.5 m•s^-1) while lower limb mechanics and electromyography of the thigh muscles were collected. There were few differences in pre-landing activation levels, but HM runners displayed lower activations of the Rectus Femoris, Vastus Medialis and Semitendinosus muscles post-landing, and these differences increased with running speed. HM runners also demonstrated higher initial knee stiffness during the impact phase compared to LM runners which was associated with an earlier peak knee flexion velocity, and both were relatively unchanged by running speed. In contrast, LM runners had higher knee stiffness during the slightly later weight acceptance phase and the disparity was amplified with increases in speed. It was concluded that initial knee joint stiffness might predominantly be governed by tendon stiffness rather than muscular activations before landing. Estimated elastic work about the ankle was found to be higher in the HM runners which might play a role in reducing weight acceptance phase muscle activation levels and improve muscle activation efficiency with running training.

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Coupling of EIT with computational lung modeling for predicting patient-specific ventilatory responses

Providing personalised optimal mechanical ventilation for patients with acute or chronic respiratory failure is still a challenge within a clinical setting for each case anew. In this article, we integrate electrical impedance tomography (EIT) monitoring into a powerful patient-specific computational lung model to create an approach for personalising protective ventilatory treatment. The underlying computational lung model is able to predict global quantities e.g., tracheal flow and tidal volume, as well as local tissue aeration and strains for any ventilation manoeuvre. A novel "virtual EIT" module is added to our computational lung model and allows to simulate EIT voltage patterns based on the patient's thorax geometry and the results of our numerically predicted tissue aeration. Similar algorithms are used for reconstructing images from simulated and actually clinically measured EIT voltages allowing an exact comparison of the two data sets with high temporal resolution. As clinically measured EIT images are not used to calibrate the computational model, they can be utilised to validate its predictive capability. The performance of this coupling approach has been tested in an example patient with acute respiratory distress syndrome (ARDS). The method shows good agreement between computationally predicted and clinically measured airflow data and EIT images. These results encourage using the proposed framework for numerically predicting patient-specific responses to certain therapeutic measures before applying them to an actual patient and, on the long run, even finding patient-specific optimal ventilation protocols assisted by computational modeling.

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The effects of voluntary exercise and prazosin on capillary rarefaction and metabolism in streptozotocin-induced diabetic male rats

Type-1 diabetes mellitus (T1D) causes impairments within the skeletal muscle microvasculature. Both regular exercise and prazosin have been shown to improve skeletal muscle capillarization and metabolism in healthy rats, through distinct angiogenic mechanisms. The aim of this study was to evaluate the independent and additive effects of voluntary exercise and prazosin treatment on capillary-to-fiber ratio (C:F) in streptozotocin (STZ)-treated diabetic rats. STZ (65mg/kg) was intraperitoneally administered to male Sprague-Dawley rats (n=36) to induce diabetes, with healthy, non-diabetic, sedentary rats (n=10) as controls. The STZ-treated rats were then divided into sedentary (SED) or exercising (EX, 24h access to running wheels) groups and then further subdivided into prazosin (Praz) or water (H₂O) treatment groups: non-diabetic-SED-H₂O, STZ-SED-H₂O, STZ-EX-H₂O, STZ-SED-Praz, and STZ-EX-Praz. After 3 weeks, untreated diabetes significantly reduced the C:F in tibialis anterior (TA) and soleus muscles in the STZ-SED-H₂O animals (both P<0.05). Voluntary exercise and prazosin treatment independently resulted in a normalization of C:F within the TA (1.86±0.12 & 2.04±0.03 vs 1.71±0.09, P<0.05) and the soleus (2.36±0.07 & 2.68±0.14 vs 2.13±0.12, P<0.05). The combined STZ-EX-Praz group resulted in the highest C:F within the TA (2.26±0.07, P<0.05). Voluntary exercise volume was negatively correlated with fed blood glucose levels (r²=-0.7015, P<0.01), and when combined with prazosin, caused further enhanced non-fasted glucose (P<0.01). Exercise and prazosin reduced circulating non-esterified fatty acids (NEFAs) more than either stimulus alone (P<0.05). These results suggest that the distinct stimulation of angiogenesis, with both regular exercise and prazosin treatment, causes a cooperative improvement in the microvascular complications associated with T1D.

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Are there sex differences in the capillary blood volume and diffusing capacity response to exercise?

Previous work suggests that women may exhibit a greater respiratory limitation to exercise compared to height-matched men. Diffusion capacity (DL_CO) increases with incremental exercise, and the smaller lungs of women may limit membrane diffusing capacity (Dm) and pulmonary capillary blood volume (Vc) in response to the increased oxygen demand. We hypothesized that females would have a lower DL_CO, DL_CO relative to cardiac output (DLCO/Q), Dm, Vc, and pulmonary transit time, secondary to lower Vc at peak exercise. Sixteen females (112±12% predicted relative VO_2peak), and sixteen males (118±22% predicted relative VO_2peak) were matched for height and weight. Hemoglobin-corrected diffusing capacity (DL_CO), Vc, and Dm were determined via the multiple-F_IO₂ DL_CO technique at rest, and during incremental exercise up to 90% of VO_2peak. Both groups increased DL_CO, Vc, and Dm with exercise intensity, but women had 20% lower DLCO (p<0.001), 18% lower Vc (p=0.002), 22% lower Dm (p<0.001) compared to men across all workloads, and neither group exhibited a plateau in Vc. When expressed relative to alveolar volume (V_A), the between-sex difference was eliminated. The drop in DL_CO/Q was proportionally less in women than men, and mean pulmonary transit time did not drop below 0.3s in either group. Women demonstrate consistently lower DL_CO, Vc, and Dm compared to height-matched men during exercise; however, these differences disappear when corrected for lung size. These results suggest that after accounting for differences in lung volume, there is no intrinsic sex difference in the diffusing capacity, capillary blood volume or diffusion membrane response to exercise.

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Recovery of central and peripheral neuromuscular fatigue after exercise

Sustained physical exercise leads to a reduced capacity to produce voluntary force that typically outlasts the exercise bout. This "fatigue" can be due both to impaired muscle function, termed "peripheral fatigue", and a reduction in the capacity of the central nervous system to activate muscles, termed "central fatigue". In this mini-review we consider the factors that determine the recovery of voluntary force generating capacity after various types of exercise. After brief, high-intensity exercise there is typically a rapid restitution of force that is due to recovery of central fatigue (typically within 2min) and aspects of peripheral fatigue associated with excitation-contraction coupling and re-perfusion of muscles (typically within 3-5 min). Complete recovery of muscle function may be incomplete for some hours, however, due to prolonged impairment in intracellular Ca²⁺ release or sensitivity. After low-intensity exercise of long duration, voluntary force typically shows rapid, partial, recovery within the first few minutes, due largely to recovery of the central, neural component. However, this ability to voluntarily activate muscles may not recover completely within 30 minutes after exercise. Recovery of peripheral fatigue contributes comparatively little to the fast initial force restitution, and is typically incomplete for at least 20-30 minutes. Work remains to identify what factors underlie the prolonged central fatigue that usually accompanies long-duration single joint and locomotor exercise, and to document how the time-course of neuromuscular recovery is affected by exercise intensity and duration in locomotor exercise. Such information could be useful to enhance rehabilitation and sports performance.

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Suite of Clinically Relevant Functional Assays to Address Therapeutic Efficacy and Disease Mechanism in the Dystrophic mdx Mouse

Duchenne muscular dystrophy (DMD) is a progressive primary myodegenerative disease caused by a genetic deficiency of the 427 KD cytoskeletal protein dystrophin. Despite its single-gene etiology, DMD's complex pathogenesis remains poorly understood, complicating the extrapolation from results of preclinical studies in genetic homologues to the design of informative clinical trials. Here we describe novel phenotypic assays which when applied to the mdx mouse resemble recently used primary endpoints for DMD clinical trials. A common feature of these physiological assays is the precise tracking and analysis of volitional movement, thereby optimizing the relevance to clinical tests. Unexpectedly, the measurable biological distinction between dystrophic and control mice at early time points in the disease process is better resolved with these tests than with the majority of previously used, labor-intensive studies of individual muscle function performed ex vivo. The most extreme example, the abrupt loss of volitional movement following a novel, standardized grip test, distinguishes control 100% (60.9 ± 12.1 units of activity) from mdx 6% (3.5 ± 2.2 units of activity) mice in groups of 12 with a p value of p<0.0001. By coupling force transduction, high precision motion tracking, and respiratory measurements we have achieved a suite of integrative physiological tests that provide novel insights regarding normal and pathological responses to muscular exertion. The findings have both mechanistic and translational implications of potential significance to the fields of basic myology and neuromuscular therapeutics.

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Acute intermittent hypoxia in rats activates muscle proteolytic pathways through a glucocorticoid-dependent mechanism

Although it is well known that chronic hypoxia induces muscle wasting, the effects of intermit-tent hypoxia on skeletal muscle protein metabolism remains unclear. We hypothesized that acute intermittent hypoxia (AIH), a challenge that activates the hypothalamic-pituitary-adrenal axis, would alter muscle protein homeostasis through a glucocorticoid-dependent mechanism. Three-week-old rats were submitted to adrenalectomy (ADX) and exposed to 8 h of AIH (6% O2 for 40s at 9 min intervals). Animals were sacrificed and the soleus and extensor digitorum longus (EDL) muscles were harvested and incubated in vitro for measurements of protein turn-over. AIH increased plasma levels of corticosterone and induced insulin resistance as estimated by the insulin tolerance test, and lower rates of muscle glucose oxidation and the HOMA index. In both soleus and EDL muscles, rates of overall proteolysis increased after AIH. This rise was accompanied by an increased proteolytic activities of Ubiquitin(Ub)-proteasome system (UPS), lysosomal and Ca²⁺-dependent pathways. Furthermore, AIH increased Ub-protein conjugates, and gene expression of atrogin-1 and MuRF-1, two key Ub-protein ligases involved in muscle atrophy. In parallel, AIH increased the mRNA expression of the autophagy-related genes LC3b and GABARAPl1. In vitro rates of protein synthesis in skeletal muscles did not differ between AIH and control rats. ADX completely blocked the insulin resistance in hypoxic rats and the AIH-induced activation of proteolytic pathways and atrogenes expression in both soleus and EDL muscles. These results demonstrate that AIH induces insulin resistance in association with activation of the UPS, autophagic-lysosomal process and Ca²⁺-dependent proteolysis through a glucocorticoid-dependent mechanism

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Metabolic adaptations in skeletal muscle after 84 days bed rest with and without concurrent flywheel resistance exercise

As metabolic changes in human skeletal muscle after long-term (simulated) spaceflight are not well understood, this study examined the effects of long-term microgravity, with and without concurrent resistance exercise on skeletal muscle oxidative and glycolytic capacity. Twenty-one men were subjected to 84 days head-down tilt bed rest with (BRE; n=9) or without (BR; n=12) concurrent flywheel resistance exercise. Activity and gene expression of glycogen synthase, glycogen phosphorylase (GPh), hexokinase, phosphofructokinase-1 (PFK-1) and citrate synthase (CS), as well as gene expression of succinate dehydrogenase (SDH), vascular endothelial growth factor (VEFG), peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1α) and myostatin, were analysed in samples from m. vastus lateralis collected before and after bed rest. Activity and gene expression of enzymes controlling oxidative metabolism (CS, SDH) decreased in BR, but were partially maintained in BRE. Activity of enzymes regulating anaerobic glycolysis (GPh, PFK-1) was unchanged in BR. Resistance exercise increased the activity of GPh. PGC-1α and VEGF expression decreased in both BR and BRE. Myostatin increased in BR, but decreased in BRE, after bed rest. The analyses of these unique samples indicate that long-term microgravity induces marked alterations in the oxidative, but not the glycolytic, energy system. The proposed flywheel resistance exercise was effective in counteracting some of the metabolic alterations triggered by 84-d bed rest. Given the disparity between gene expression vs. enzyme activity in several key metabolic markers, post-transcriptional mechanisms should be explored to fully evaluate metabolic adaptations to long-term microgravity with/without exercise countermeasures in human skeletal muscle.

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Tendon collagen synthesis declines with immobilization in elderly humans: no effect of anti-inflammatory medication

Background: Non-steroidal anti-inflammatory drugs (NSAID) are used as pain killers during periods of unloading caused by traumatic occurrences or diseases. However, it is unknown how the tendon protein turnover and mechanical properties responds to unloading and subsequent loading in elderly humans, and especially whether NSAIDs affect tendon adaptation during such periods. Thus, we studied the influence of NSAID upon the human patellar tendon protein synthesis and mechanical properties during immobilization and subsequent rehabilitating resistance training. Methods: 19 men (60-80 yrs, range) were randomly assigned to NSAID (Ibuprofen 1200 mg/d, Ibu) or placebo (Plc). One lower limb was immobilized in a cast for two weeks and retrained for six weeks. Tendon collagen protein synthesis, expression of gene related to collagen turnover and remodeling, size, signal intensity (from magnetic resonance imaging), and mechanical properties were investigated. Results: Tendon collagen synthesis decreased (p<0.001), whereas tendon size and mechanical properties were generally unchanged with immobilization, and NSAID treatment did not influence this. Matrix metalloproteinase-2 mRNA tended to increase (p<0.1) after immobilization in both groups, whereas scleraxis mRNA decreased with inactivity in the Plc group only (p<0.05). Conclusion: In elderly human tendons, collagen protein synthesis decreased after two weeks of immobilization, whereas tendon stiffness and modulus were only marginally reduced, and NSAID had no influence upon this. This indicates an importance of mechanical loading for maintenance of tendon collagen turnover. However, reduced collagen production induced by short-term unloading may only marginally affect tendon mechanical properties in elderly individuals.

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Assessing fear learning via conditioned respiratory amplitude responses

Abstract

Respiratory physiology is influenced by cognitive processes. It has been suggested that some cognitive states may be inferred from respiration amplitude responses (RAR) after external events. Here, we investigate whether RAR allow assessment of fear memory in cued fear conditioning, an experimental model of aversive learning. To this end, we built on a previously developed psychophysiological model (PsPM) of RAR, which regards interpolated RAR time series as the output of a linear time invariant system. We first establish that average RAR after CS+ and CS− are different. We then develop the response function of fear-conditioned RAR, to be used in our PsPM. This PsPM is inverted to yield estimates of cognitive input into the respiratory system. We analyze five validation experiments involving fear acquisition and retention, delay and trace conditioning, short and medium CS-US intervals, and data acquired with bellows and MRI-compatible pressure chest belts. In all experiments, CS+ and CS− are distinguished by their estimated cognitive inputs, and the sensitivity of this distinction is higher for model-based estimates than for peak scoring of RAR. Comparing these data with skin conductance responses (SCR) and heart period responses (HPR), we find that, on average, RAR performs similar to SCR in distinguishing CS+ and CS−, but is less sensitive than HPR. Overall, our work provides a novel and robust tool to investigate fear memory in humans that may allow wide and straightforward application to diverse experimental contexts.

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Cautiously Caffeinated: Does Caffeine Modulate Inhibitory, Impulsive, or Risky Behavior?

Journal of Caffeine Research , Vol. 0, No. 0.


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Rigor and Replication: Towards Improved Best Practices in Human Electrophysiology Research

Publication date: Available online 8 December 2016
Source:International Journal of Psychophysiology
Author(s): Michael J. Larson, Jason S. Moser




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Cautiously Caffeinated: Does Caffeine Modulate Inhibitory, Impulsive, or Risky Behavior?

Journal of Caffeine Research , Vol. 0, No. 0.


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The CCAAT-binding complex (CBC) in Aspergillus species

Publication date: Available online 8 December 2016
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Peter Hortschansky, Hubertus Haas, Eva M. Huber, Michael Groll, Axel A. Brakhage
BackgroundThe CCAAT binding complex (CBC), consisting of a heterotrimeric core structure is highly conserved in eukaryotes and constitutes an important general transcriptional regulator.Scope of the review.In this review we discuss the scientific history and the current state of knowledge of the multiple gene regulatory functions, protein motifs and structure of the CBC in fungi with a special focus on Aspergillus species.Major conclusions and general significance.Initially identified as a transcriptional activator of respiration in Saccharomyces cerevisiae, in other fungal species the CBC was found to be involved in highly diverse pathways but a general rational for its involvement was missing. Subsequently, the CBC was found to sense reactive oxygen species through oxidative modifications of cysteine residues in order to mediate redox regulation. Moreover, via interaction with the iron-sensing bZIP transcription factor HapX, the CBC was shown to mediate adaptation to both iron starvation and iron excess. Due to the control of various pathways in primary and secondary metabolism the CBC is of crucial importance for fungal virulence in both animal and plant hosts as well as antifungal resistance. Consequently, CBC-mediated control affects biological processes that are of high interest in biotechnology, agriculture and infection medicine.



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Plant NF-Y transcription factors: key players in plant-microbe interactions, root development and adaptation to stress

Publication date: Available online 8 December 2016
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): María Eugenia Zanetti, Carolina Rípodas, Andreas Niebel
NF-Ys are heterotrimeric transcription factors composed by the NF-YA, NF-YB and NF-YC subunits. In plants, NF-Y subunits are encoded by multigene families whose members show structural and functional diversifications. An increasing number of NF-Y genes has been shown to play key roles during different stages of root nodule and arbuscular mycorrhizal symbiosis, as well as during the interaction of plants with pathogenic microorganisms. Individual members of the NF-YA and NF-YB families have also been implicated in the development of primary and lateral roots. In addition, different members of the NF-YA and NF-YB gene families from mono- and di-cotyledonous plants have been involved in plant responses to water and nutrient scarcity. This review presents the most relevant and striking results concerning these NF-Y subunits. A phylogenetic analysis of the functionally characterized NF-Y genes revealed that, across plant species, NF-Y proteins functioning in the same biological process tend to belong to common phylogenetic groups. Finally, we discuss the forthcoming challenges of plant NF-Y research, including the detailed dissection of expression patterns, the elucidation of functional specificities as well as the characterization of the potential NF-Y-mediated epigenetic mechanisms by which they control the expression of their target genes.



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Posture-Dependent Corticomotor Excitability Differs Between the Transferred Biceps in Individuals With Tetraplegia and the Biceps of Nonimpaired Individuals

Background. Following biceps transfer to enable elbow extension in individuals with tetraplegia, motor re-education may be facilitated by greater corticomotor excitability. Arm posture modulates corticomotor excitability of the nonimpaired biceps. If arm posture also modulates excitability of the transferred biceps, posture may aid in motor re-education. Objective. Our objective was to determine whether multi-joint arm posture affects corticomotor excitability of the transferred biceps similar to the nonimpaired biceps. We also aimed to determine whether corticomotor excitability of the transferred biceps is related to elbow extension strength and muscle length. Methods. Corticomotor excitability was assessed in 7 arms of individuals with tetraplegia and biceps transfer using transcranial magnetic stimulation and compared to biceps excitability of nonimpaired individuals. Single-pulse transcranial magnetic stimulation was delivered to the motor cortex with the arm in functional postures at rest. Motor-evoked potential amplitude was recorded via surface electromyography. Elbow moment was recorded during maximum isometric extension trials, and muscle length was estimated using a biomechanical model. Results. Arm posture modulated corticomotor excitability of the transferred biceps differently than the nonimpaired biceps. Elbow extension strength was positively related and muscle length was unrelated, respectively, to motor-evoked potential amplitude across the arms with biceps transfer. Conclusions. Corticomotor excitability of the transferred biceps is modulated by arm posture and may contribute to strength outcomes after tendon transfer. Future work should determine whether modulating corticomotor excitability via posture promotes motor re-education during the rehabilitative period following surgery.

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Corpus Callosum Structural Integrity Is Associated With Postural Control Improvement in Persons With Multiple Sclerosis Who Have Minimal Disability

Background. Improvement of postural control in persons with multiple sclerosis (PwMS) is an important target for neurorehabilitation. Although PwMS are able to improve postural performance with training, the neural underpinnings of these improvements are poorly understood. Objective. To understand the neural underpinnings of postural motor learning in PwMS. Methods. Supraspinal white matter structural connectivity in PwMS was correlated with improvements in postural performance (balancing on an oscillating surface over 25 trials) and retention of improvements (24 hours later). Results. Improvement in postural performance was directly correlated to microstructural integrity of white matter tracts, measured as radial diffusivity, in the corpus callosum, posterior parieto-sensorimotor fibers and the brainstem in PwMS. Within the corpus callosum, the genu and midbody (fibers connecting the prefrontal and primary motor cortices, respectively) were most strongly correlated to improvements in postural control. Twenty-four-hour retention was not correlated to radial diffusivity. Conclusion. PwMS who exhibited poorer white matter tract integrity connecting the cortical hemispheres via the corpus callosum showed the most difficulty learning to control balance on an unstable surface. Prediction of improvements in postural control through training (ie, motor learning) via structural imaging of the brain may allow for identification of individuals who are particularly well suited for postural rehabilitation interventions.

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Totally laparoscopic total gastrectomy using the overlap method; early outcomes of 50 consecutive cases

Abstract

Background

Construction of an esophagojejunostomy is still a challenging procedure in totally laparoscopic total gastrectomy (TLTG), and there is no standard anastomosing method. The aims of this study were to describe our TLTG with the overlap method using a linear stapler and report surgical outcomes.

Methods

From January 2015 to April 2016, 50 patients underwent TLTG using the overlap method for gastric cancer. The procedures were performed by a single surgeon, and the patients' medical records were reviewed. Their clinicopathologic characteristics, operation time, date of flatus, hospital stay, morbidity, and mortality were analyzed.

Results

The median age and body mass index were 56 years and 23.5, respectively. Stage 1A tumors were the most common. Mean operating time was 144.6 min, and no cases required changing to open laparotomy during surgery. On average, flatus occurred 3.5 days after surgery, and patients were discharged 6.8 days after surgery. No patient experienced anastomosis leakage, stricture, duodenal stump leakage, luminal bleeding, pancreatic fistula, or wound problems. There were two cases of intra-abdominal bleeding that required additional surgery. Intra-abdominal fluid collection and mechanical ileus occurred in two patients, respectively, and were successfully managed with conservative treatment.

Conclusions

We reported favorable surgical outcomes of TLTG using the overlap method. It is a feasible and safe option for treatment of gastric cancer.

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Laparo-endoscopic versus open recurrent inguinal hernia repair: should we follow the guidelines?

Abstract

Introduction

On the basis of six meta-analyses, the guidelines of the European Hernia Society (EHS) recommend laparo-endoscopic recurrent repair following previous open inguinal hernia operation and, likewise, open repair following previous laparo-endoscopic operation. So far no data are available on implementation of the guidelines or for comparison of outcomes. Besides, there are no studies for comparison of outcomes for compliance versus non-compliance with the guidelines.

Patients and methods

In total, 4812 patients with elective unilateral recurrent inguinal hernia repair in men were enrolled between September 1, 2009, and September 17, 2014, in the Herniamed Registry. Only patients with 1-year follow-up were included.

Results

Out of the 2482 laparo-endoscopic recurrent repair operations 90.5% of patients, and out of the 2330 open recurrent repair procedures only 38.5% of patients, were operated on in accordance with the guidelines of the EHS. Besides, on compliance with the guidelines multivariable analysis demonstrated for laparo-endoscopic recurrent repair a significantly lower risk of pain at rest (OR 0.643 [0.476; 0.868]; p = 0.004) and pain on exertion (OR 0.679 [0.537; 0.857]; p = 0.001). Comparison of laparo-endoscopic and open recurrent repair in settings of compliance versus non-compliance with the guidelines showed a higher incidence of perioperative complications and re-recurrences for recurrent repairs that did not comply with the guidelines.

Conclusion

The EHS guidelines for recurrent inguinal hernia repair are not yet being observed to the extent required. Non-compliance with the guidelines is associated with higher perioperative complication rates and higher risk of re-recurrence. Even on compliance with the guidelines, the risk of pain at rest and pain on exertion is higher after open recurrent repair than after laparo-endoscopic repair.

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Robotic approaches for the rehabilitation of upper limb recovery after stroke: a systematic review and meta-analysis.

This systematic review with a meta-analysis of studies was carried out to evaluate the effectiveness of robotic training (RT) and conventional training (CT) in improving the motor recovery of paretic upper limbs in stroke patients. Numerous electronic databases were searched from January 2000 to May 2016. Finally, 13 randomized-controlled trials fulfilled the inclusion criteria and were included in the three meta-analyses. The first meta-analysis carried out for those studies using RT for stroke patients indicated a significant improvement in the RT groups. The second meta-analysis suggested that the upper limb function (measured by Fugl-Meyer test) was significantly improved when RT was used with CT compared with CT alone. The third meta-analysis noted a significant difference in motor recovery between the CT-only and RT groups (RT only or RT combined with CT) in the chronic stages of stroke, but not in the acute or subacute stages. However, the RT group also showed a higher Fugl-Meyer score in patients at both the acute and the subacute stage. RT appeared to have positive outcomes to enhance motor recovery of the paralyzed upper limb. Robotic devices were believed to provide more assistance to patients to help support the weight of the upper limb; thus, active movement training can begin in the early rehabilitation stage. These novel devices may also help those chronic patients to achieve better rehabilitation goals. As a summary, RT could be used in addition to CT to help both therapists and patients in the management of the paralyzed upper limb. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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Passion for leisure activity contributes to pain experiences during rehabilitation.

The primary aim of this study was to determine whether the levels of obsessive passion (OP) and harmonious passion for a suspended leisure activity contribute to pain catastrophizing and pain intensity in patients undergoing the rehabilitation process. The secondary aim was to examine whether the levels of passion associated with a maintained leisure activity offset the contribution of having a leisure activity suspended to pain intensity and catastrophizing. Ninety-one outpatients from functional rehabilitation units (Mage=37, SD=13.44 years) completed measures of pain catastrophizing, pain intensity, and passion about valued leisure activities (one they were prevented from practicing and one they remained able to practice). Correlation analysis showed that the level of OP for a suspended valued leisure activity was positively associated with pain catastrophizing and pain intensity. Results showed that pain catastrophizing mediated the relationship between this level of passion and pain intensity. The levels of harmonious passion and OP for a maintained valued leisure activity did not offset the contribution of OP for a suspended leisure activity to pain-related outcomes. When prevented from practicing a valued leisure activity, only OP contributes to the prediction of pain catastrophizing and pain intensity. The contribution of pain catastrophizing provides a potential explanation for why the level of OP for a suspended leisure activity is related to pain intensity ratings. The benefits of maintaining a valued leisure activity during rehabilitation do not seem sufficient to counterbalance the maladaptive effects of being prevented from the practice of a previous/another valued leisure activity. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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Does sensory transcutaneous electrical stimulation prevent pneumonia in the acute stage of stroke? A preliminary study.

Acute stroke patients with dysphagia are at risk of developing pulmonary infection, which increases the risk of death. Therefore, optimal management of dysphagia is essential; however, available evidence supporting the effectiveness of dysphagia treatments is limited. Surface electrical stimulation (e-stim) has been developed as a new treatment modality for dysphagia. In this study, we investigated the efficacy of surface sensory e-stim therapy in preventing pulmonary infection in 53 acute stroke patients with dysphagia. The risk of pulmonary infection was significantly decreased in the general dysphagia/surface e-stim combination therapy group. We considered that surface e-stim therapy can impact dysphagia treatment in acute stroke patients, particularly in preventing pulmonary infection. Future large and randomized studies are needed to evaluate the effects of surface sensory e-stim therapy on acute stroke patients. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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Alpha1-antitrypsin restores colonic epithelial permeability in irritable bowel syndrome with diarrhea

2016-12-08T17-06-24Z
Source: Journal of Molecular Pathophysiology
Julien Boyer, Marie-Hélène Vivinus-Nébot, Valérie Verhasselt, Thierry Piche, Meri K Tulic.



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Solving the puzzle: what is behind our forefathers’ anti-inflammatory remedies?

2016-12-08T15-46-06Z
Source: Journal of Intercultural Ethnopharmacology
Javier Rodriguez Villanueva, Jorge Martín Esteban, Laura Rodríguez Villanueva.
Inflammation is a ubiquitous host response in charge of restoring normal tissue structure and function but is a double-edged sword, as the uncontrolled or excessive process can lead to the injury of host cells, chronic inflammation, chronic diseases and also neoplastic transformation. Throughout history, a wide range of species have been claimed to have anti-inflammatory effects worldwide. Among them, Angelica sinensis, Tropaeolum majus, Castilleja tenuiflora, Biophytum umbraculum, to name just a few, have attracted the scientific and general public attention in the last years. Efforts have been made to assess their relevance through a scientific method. However, inflammation is a complex interdependent process, and phytomedicines are complex mixtures of compounds with multiple mechanisms of biological actions, which restricts systematic explanation. For this purpose, the omics techniques could prove extremely useful. They provide tools for interpreting and integrating results from both the classical medical tradition and modern science. As a result, the concept of network pharmacology applied to phytomedicines emerged. All of this is a step toward personalized therapy.


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The adjuvant use of calcium fructoborate and borax with etanercept in patients with rheumatoid arthritis: Pilot study

2016-12-08T15-46-06Z
Source: Journal of Intercultural Ethnopharmacology
Saad Abdulrahman Hussain, Sattar Jabir Abood, Faiq Isho Gorial.
Objective: The present study was designed to evaluate the effects calcium fructoborate (CFB) and sodium tetraborate (NTB) as supplements in Iraqi patients with active RA maintained on Etanercept. Materials and Methods: A double blind randomized placebo-controlled clinical trial with 60 days treatment period was carried out at Baghdad Teaching Hospital, Medical City, Baghdad, Iraq. Eighty RA patients were randomized into 3 groups to receive either 220 mg/day calcium fructoborate, 55 mg/day sodium tetraborate in capsule dosage form (equivalent to 6 mg elemental Boron), or placebo formula once daily. Only 72 patients completed the study. All patients were clinically evaluated utilizing DAS28-ESR, SDAI-CRP and CDAI scores at baseline and at the end of the study. Venous blood was obtained at baseline and after 60 days, and utilized for the measurement of erythrocyte sedimentation rate (ESR), hemoglobin (Hb), in addition to evaluation of C-reactive protein (hsCRP), TNF-α, interleukin-1α (IL-1α) and IL-6. Results: After 60 days, both types of boron significantly improve the clinical scores, in association with significant decrease in the serum levels of ESR, hsCRP, IL-1α, IL-6, and TNF-α with remarkable superiority for CFB over NTB, compared to baseline and placebo-treated group. Conclusion: The use of boron, as adjuvant with etanercept, have potentiated therapeutic outcomes in RA patients, and may be a new strategy to improve treatment and avoid the problems associated with biologics utilized in RA treatment.


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Primary Adrenal Lymphoma Infiltrating in to Pancreas: A Rare Cause of Adrenomegaly

2016-12-08T15-21-13Z
Source: Journal of Interdisciplinary Histopathology
Lovelesh Kumar Nigam, Kamal V Kanodia, Aruna V Vanikar, Rashmi D Patel, Kamlesh S Suthar, Syed J Rizvi.
Primary adrenal lymphoma is a rare entity and may be suspected in patients having bilateral adrenal masses, with/without lymphadenopathy, and with/without adrenal insufficiency. We report a rare case of a 45-year-old man who presented with pain in the abdomen, with no signs of adrenal insufficiency and bilateral adrenal masses on imaging. Light microscopy findings with immunohistochemistry and flow cytometry confirmed the diagnosis of diffuse large B-cell lymphoma. The patient was offered cyclophosphamide, adriamycin, vincristine, and prednisolone chemotherapy regimen and doing well till the last follow-up.


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The Significance of BerEp4 and Cytokeratin 19 Expressions in Epithelial Tumors of Kidney and Renal Pelvis

2016-12-08T15-21-13Z
Source: Journal of Interdisciplinary Histopathology
Ayhan Ozcan, Ibrahim Yavan, Melih Kilinc, Sami Uguz, Sukru Ozaydin.
Objective: The differential diagnosis in the epithelial tumors of kidney and renal pelvis can be problematic due to their overlapping morphologic features. This is much more complicated in some conditions, such as renal oncocytoma (RO) vs chromophobe renal cell carcinoma (ChRCC) and renal cell carcinoma (RCC) vs urothelial carcinoma of renal pelvis (UC-RP). The purpose of this study was to assess potential contributions of BerEP4 and cytokeratin 19 (CK19) expressions in the differential diagnosis of these challenging cases. Methods: A total 57 cases consisted of 11 chromophobe (ChRCC), 18 clear cell (CCRCC), 12 papillary (PRCC), and 2 unclassified RCCs, 1 multilocular cystic renal cell neoplasm (MCRCN) with low malignant potential, 7 UC-RP, and 6 renal oncocytomas (RO) were stained against BerEp4 and CK19 antibodies using automated immunostainer. Results: All ROs demonstrated membranous BerEP4 expression, but no CK19 expression. Unlike ROs, most ChRCCs exhibited diffuse and strong CK19 expression, but no or focal and weak BerEP4 expression. This distinctive opposite expression pattern was highlighted in hybrid oncocytic chromophobe tumor (HOCT). CCRCCs showed highly variable expression patterns for both markers. PRCC type 1 tumors demonstrated diffuse and strong BerEp4 and CK19 expressions. PRCC type 2 exhibited BerEP4 and CK19 expressions, but their expressions were focal and weaker than for PRCC type 1. MCRCN demonstrated diffuse and strong BerEP4 expression, but no expression for CK19 unlike cystic CCRCC, which is strongly positive for both markers. Epithelioid cells in unclassified RCC showed strong CK19 and weak BerEP4 expression, whereas spindle cells in the tumor did not express CK19 and BerEp4 or exhibited scattered and weak expressions. UC-RP showed diffuse and strong CK19 expression, but no or scattered BerEP4expression was seen in the tumor. We also evaluated CK19 and BerEP4 expression in non-neoplastic adjacent kidney and renal pelvis. Conclusion: This study revealed that 1) BerEP4 and CK19 exhibit variable and distinctive immunoprofiles in epithelial tumors of kidney and renal pelvis, 2) an immunoprofile of BerEP4 (+)/CK19 (-) favors RO in contrast to an opposite profile for ChRCC, 3) The heterogeneous expressions of BerEP4 and CK19 in low grade RCC with eosinophilic cytoplasm favors HOCT, 4) PRCC type 1 strongly express both biomarkers, and 5) although RCC subtypes express CK19 in a variable proportion and intensity, diffuse and strong CK19 expression favors UC-RP.


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Modelling of atorvastatin pharmacokinetics and the identification of the effect of a BCRP polymorphism in the Japanese population

Aim: Ethnicity plays a modulating role in atorvastatin pharmacokinetics (PK), with Asian patients reported to have higher exposure compared with Caucasians. Therefore, it is difficult to safely extrapolate atorvastatin PK data and models across ethnic groups. This work aims to develop a population PK model for atorvastatin and its pharmacologically active metabolites specifically for the Japanese population. Subsequently, it aimed to identify genetic polymorphisms affecting atorvastatin PK in this population. Methods: Atorvastatin acid (ATA) and ortho-hydroxy-atorvastatin acid (o-OH-ATA) plasma concentrations, clinical/demographic characteristics and genotypes for 18 (3, 3, 1, 1, 7, 2 and 1 in the ABCB1, ABCG2, CYP3A4, CYP3A5, SLCO1B1, SLCO2B1 and PPARA genes, respectively) genetic polymorphisms were collected from 27 Japanese individuals (taking 10 mg atorvastatin once daily) and analysed using a population PK modelling approach. Results: The population PK model developed (one-compartment for ATA linked through metabolite formation to an additional compartment describing the disposition of o-OH-ATA) accurately described the observed data and the associated population variability. Our analysis suggested that patients carrying one variant allele for the rs2622604 polymorphism (ABCG2) show a 55% (95% confidence interval: 16–131%) increase in atorvastatin oral bioavailability relative to the value in individuals without the variant allele. Conclusion: The current work reports the identification in the Japanese population of a BCRP polymorphism, not previously associated with the PK of any statin, that markedly increases ATA and o-OH-ATA exposure. The model developed may be of clinical importance to guide dosing recommendations tailored specifically for the Japanese.

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Genome-wide association study of paliperidone efficacy

Objective: Clinical response to the atypical antipsychotic paliperidone is known to vary among schizophrenic patients. We carried out a genome-wide association study to identify common genetic variants predictive of paliperidone efficacy. Methods: We leveraged a collection of 1390 samples from individuals of European ancestry enrolled in 12 clinical studies investigating the efficacy of the extended-release tablet paliperidone ER (n1=490) and the once-monthly injection paliperidone palmitate (n2=550 and n3=350). We carried out a genome-wide association study using a general linear model (GLM) analysis on three separate cohorts, followed by meta-analysis and using a mixed linear model analysis on all samples. The variations in response explained by each single nucleotide polymorphism (h2SNP) were estimated. Results: No SNP passed genome-wide significance in the GLM-based analyses with suggestive signals from rs56240334 [P=7.97×10−8 for change in the Clinical Global Impression Scale-Severity (CGI-S); P=8.72×10−7 for change in the total Positive and Negative Syndrome Scale (PANSS)] in the intron of ADCK1. The mixed linear model-based association P-values for rs56240334 were consistent with the results from GLM-based analyses and the association with change in CGI-S (P=4.26×10−8) reached genome-wide significance (i.e. P

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Concordance between actual and pharmacogenetic predicted desvenlafaxine dose needed to achieve remission in major depressive disorder: a 10-week open-label study

Background: Pharmacogenetic-based dosing support tools have been developed to personalize antidepressant-prescribing practice. However, the clinical validity of these tools has not been adequately tested, particularly for specific antidepressants. Objective: To examine the concordance between the actual dose and a polygene pharmacogenetic predicted dose of desvenlafaxine needed to achieve symptom remission. Materials and methods: A 10-week, open-label, prospective trial of desvenlafaxine among Caucasian adults with major depressive disorder (n=119) was conducted. Dose was clinically adjusted and at the completion of the trial, the clinical dose needed to achieve remission was compared with the predicted dose needed to achieve remission. Results: Among remitters (n=95), there was a strong concordance (Kendall's τ-b=0.84, P=0.0001; Cohen's κ=0.82, P=0.0001) between the actual and the predicted dose need to achieve symptom remission, showing high sensitivity (≥85%), specificity (≥86%), and accuracy (≥89%) of the tool. Conclusion: Findings provide initial evidence for the clinical validity of a polygene pharmacogenetic-based tool for desvenlafaxine dosing.

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The influence of living donor SHROOM3 and ABCB1 genetic variants on renal function after kidney transplantation

Objective: A genome-wide association study has identified several gene polymorphisms associated with loss of renal function. The effect of these variants on renal function in kidney transplant recipients receiving immunosuppressive treatment is unknown. Materials and methods: A cohort of 189 kidney transplant recipients and their living donors were recruited from West China Hospital of Sichuan University, on whom we assessed the association of five single nucleotide polymorphisms with renal function after kidney transplantation. Results: Glomerular filtration rate estimated by serum creatinine was significantly higher in recipients carrying allograft with the A allele at rs17319721 in SHROOM3 (shroom family member 3) than those in the group with the GG genotype from month 1 to month 6 after transplantation (P=0.020). Covariate adjustment analysis showed that the variant at rs17319721 in SHROOM3 was an independent risk factor for renal dysfunction after the first month after transplantation (P=0.022). The estimated glomerular filtration rate was the lowest in recipients with allograft carrying both the A allele at rs17319721 in SHROOM3 and the CC genotype at rs1045642 in ABCB1 (P

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PharmGKB summary: ivacaftor pathway, pharmacokinetics/pharmacodynamics

No abstract available

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Relationship between normal preoperative white blood cell count and major adverse events after endovascular repair for abdominal aortic aneurysm: results of a pilot study

To examine the association between preoperative white blood cell (WBC) count within the reference range and major adverse events (MAEs) following endovascular repair of abdominal aortic aneurysms (AAA).

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Association of MMP-9 C-1562T polymorphism with risk of Henoch-Schönlein purpura nephritis in children of southeast China

Abstract

Henoch-Schönlein purpura nephritis (HSPN) is the most prevalent vasculitis in childhood worldwide. Although the etiology of HSPN is not yet fully elucidated, it is believed to be closely related with infections and genetic predispositions. In this study, a cohort of children from southeast China, including 108 healthy controls and 184 patients were involved in. We scanned the promoter region and the whole gene for genetic variations. A C/T transition located in the promoter region of MMP-9 gene, C-1562T was identified. Subjects were genotyped by using SNaPshot sequencing and the frequencies of CC, CT and TT genotypes were 43, 33 and 24% in patients and 53, 37 and 10% in healthy controls. Allele distribution was found to be in Hardy–Weinberg equilibrium (P = 0.17). Association analysis revealed that the polymorphism was significantly related with HSPN risk (P < 0.05) and T allele was shown to be a risk factor (P = 0.003, odds ratio (OR) 1.63, 95% confidence interval (CI) 1.13–2.34). Additionally, we measured the serum MMP-9 concentration and quantified the mRNA expression. Results showed that an elevated protein level was observed in patients compared with controls in both ELISA (P = 0.0029, 136.5 μg/L vs. 103.9 μg/L) and Western blot assays. Furthermore, we also detected 1.93-fold increase in the mRNA transcription in patients carrying homozygous TT genotype, indicating enhanced promoter activity caused by the polymorphism. Based on the incidence risk, a cut-off value of serum MMP-9 served as HSPN diagnosis was suggested at 155 μg/L. Conclusively, our findings suggested that MMP-9 polymorphism was significantly associated with HSPN susceptibility, and C-1562T T allele contributed to HSPN development.

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Inside EMS Podcast: Why scene safety needs to be more than an EMS mantra

Download this podcast on iTunes, SoundCloud or via RSS feed

​​In this Inside EMS Podcast episode, co-hosts Chris Cebollero and Kelly Grayson discuss the top EMS news articles from the week, including how an IV infiltration led to a $700,000 negligence award, what EMS leaders need to know about public health and how a 17-year-old EMT student, who was shot while aiding a shooting victim, was able to meet the doctor who treated him on scene.

Kelly also talks about his new book, "En Route: A Paramedic's Stories of Life, Death, and Everything in Between."

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Association between day and time of admission to critical care and acute hospital outcome for unplanned admissions to adult general critical care units: cohort study exploring the 'weekend effect

Background. We aimed to identify any association between day and time of admission to critical care and acute hospital outcome.

Methods. We conducted a cohort study using prospectively collected data from the national clinical audit of adult critical care. We included 195 428 unplanned admissions from 212 adult general critical care units in England, Wales and Northern Ireland, between April 1, 2013 and March 31, 2015 in the analysis.

Results. Hourly admission rates for unplanned admissions varied more than three-fold during the 24 h cycle. Overall acute hospital mortality was 26.8%. Before adjustment, acute hospital mortality was similar between weekends and weekdays but was significantly lower for admissions at night compared with the daytime (–3.4%, –3.8 to –3.0%; P<0.001). After adjustment for casemix, there remained no difference between weekends and weekdays (–0.0%, –0.4 to +0.3%; P=0.87) or between nighttime and daytime (–0.2%, –0.5 to +0.1%; P=0.21). Delays in admission were reported for 4.3% of admissions and were slightly more common during weekdays than weekends and in the daytime than at night. Delayed admission was associated with a small increase in acute hospital mortality, but adjusting for this did not affect the estimates of the effect of day and time of admission.

Conclusions. The day of week and time of admission have no influence on patient mortality for unplanned admissions to adult general critical care units within the UK. Ways to improve critical care and hospital systems to minimize delays in admission and potentially improve outcomes need to be ascertained in future research.

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London Ambulance Service chief announces retirement

London Ambulance Service

 

LONDON — The London Ambulance Service announced Wednesday that executive chief Dr. Fionna Moore will retire from her position at the end of the year. 

 

Dr. Moore, 67, plans to ease her way into retirement by spending three days a week doing clinical shifts with the service and in emergency medicine. 

 

"I took on the chief executive role intending to do it for two years, to stabilize the Service at what was a challenging time," Dr. Moore said. "I always wanted time at the end of my career to step back from management responsibilities and focus on my first passion, the clinical care of patients."

 

Dr. Moore has worked for the London Ambulance Service for over 40 years, where she was medical director for 18 years and chief executive for two.

 

Dr. Moore was awarded an MBE in the Queen's birthday honors in 2013 for services to the NHS and the emergency services.

 

"Her leadership has helped steer the service through a challenging period and in the last two years she has overseen one of the biggest recruitment drives in NHS history, the development of the advanced paramedic practitioners programme, an improved fleet and focused on the personal development and recognition for everyone who works for the Service," NHS Chairman Heather Lawrence said. 

 

As medical director, Dr. Moore led a transformation in patient care, from a doubling of cardiac arrest survival rates in just four years, to the service being at the center of the development of specialist stroke, trauma and heart attack centers – and she was appointed London's first Trauma Director in 2009.

 

"We have seen a 63 percent reduction in mortality from trauma in London and where we led the way, the rest of the country has followed," Dr. Moore said. 

 

NHS Improvement London regional director Steve Russell paid tribute to Dr. Moore and thanked her for the "professional dedication and personal commitment" she has made to the London Ambulance Service over the past 20 years.

 

"For two decades, Dr Moore has devoted herself to London Ambulance Service, first as a clinician and most recently as chief executive. Her willingness to step into the chief executive role at a time of significant challenge for the organization demonstrates her commitment to the Service," Russell said.

 

"It's been a huge privilege to work alongside so many dedicated, committed and wonderful people for so many years. I am immensely proud of the work everyone at the Service does and the progress we have made to improve our care to patients over the last 20 years," Dr. Moore said.

 

The board and NHS Improvement will now seek to appoint a new permanent chief executive for the Service. In the meantime, Andrew Grimshaw, Director of Finance, will act as interim Chief Executive.

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Factors Associated with Medication Non-adherence in Patients with End-Stage Liver Disease

Abstract

Background

Low medication adherence is known to contribute to worse health outcomes in the general population.

Aim

We aimed to evaluate the medication regimen and determine the adherence levels among patients with end-stage liver disease.

Methods

We measured adherence in patients awaiting liver transplantation at a single center using the 8-item Morisky Medication Adherence Scale (MMAS-8), with a score <8 classified as low adherence. Medication regimen complexity was assessed using the Medication Regimen Complexity Index (MRCI) tool. Factors associated with low adherence were identified by logistic regression.

Results

Of 181 patients, 33% were female, median age was 62, and model for end-stage liver disease (MELD) score was 13. The median (IQR) number of medications was 10 (7–13), and the MRCI was 19 (13–27). In total, 54 (30%) were high adherers, and 127 (70%) were low adherers. In total, 42% reported sometimes forgetting to take their medication and 22% reported intermittent adherence within the past 2 weeks. The most common reasons for low adherence were: forgetfulness (27%) and side effects (14%). Compared to high adherence, low adherence was associated with higher number of medications, medication complexity, and diabetes, but lower rates of hepatocellular carcinoma and self-perceived health. In univariable logistic regression, total medication number (OR 1.08), MRCI (OR 1.04), diabetes (OR 2.38), HCC (OR 0.38), and lower self-perceived health (OR 1.37), were statistically significant factors associated with non-adherence. In multivariate analysis, only medication number without supplements (OR 1.14) remained significantly associated with medication non-adherence.

Conclusion

A majority of patients awaiting liver transplantation demonstrated low medication adherence. Total number of medications and regimen complexity were strong correlates of low adherence. Our data underscores the need for chronic liver disease management programs to improve medication adherence in this vulnerable population.

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Erratum to: Identification of a Novel Binding Protein of FAT10: Eukaryotic Translation Elongation Factor 1A1

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High Percentage of IBD Patients with Indefinite Fecal Calprotectin Levels: Additional Value of a Combination Score

Abstract

Background and Aim

Monitoring mucosal inflammation in inflammatory bowel disease (IBD) is of major importance to prevent complications and improve long-term disease outcome. The correlation of clinical activity indices with endoscopic disease activity is, however, moderate. Fecal calprotectin (FC) is a better predictor of mucosal inflammation, but values between 100 and 250 µg/g are difficult to interpret in clinical practice. We aimed to evaluate the occurrence of indefinite FC levels in a real-life IBD cohort and study the additional value of a combination of biochemical markers and clinical activity indices.

Methods

In total, 148 Crohn's disease (CD) and 80 ulcerative colitis (UC) patients visiting the outpatient clinic were enrolled. FC, clinical disease activity scored by the Harvey–Bradshaw index or Simple Clinical Colitis Activity Index, and C-reactive protein (CRP) were assessed. In a subset of patients, endoscopic activity was scored by the simple endoscopic score-Crohn's disease and Mayo endoscopic subscore. Clinical activity index, CRP, and FC were integrated in a combination score and compared with endoscopy.

Results

Indefinite FC values were present in 24% of CD and 15% of UC. In the cohort of patients with endoscopy scores available, the combination score predicted endoscopic disease activity in CD with a sensitivity of 83% and specificity of 69% [positive predictive value (PPV) 58%, negative predictive value (NPV) 89%]. In UC, this was 88 and 75% (PPV 93%, NPV 60%).

Conclusions

A combination of FC with clinical activity indices or CRP may aid in classifying patients with indefinite disease activity according to FC alone.

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Tumor Necrosis Factor Alpha Inhibitors Did Not Influence Postoperative Morbidity After Elective Surgical Resections in Crohn’s Disease

Abstract

Background

The real impact of anti-tumor necrosis alpha (TNF) therapy in postoperative complications after intestinal resections in Crohn's disease (CD) still needs to be determined.

Aims

To compare the postoperative complication rates after elective intestinal resections in CD patients, with or without previous exposure to anti-TNF therapy.

Methods

This was a retrospective and observational study, with elective intestinal resections for CD (emergency procedures were excluded). Patients were allocated in two groups according to preoperative anti-TNF status. Surgical and medical complications were analyzed and subsequently compared between the groups.

Results

A total of 123 patients were included (71 with and 52 without preoperative anti-TNF). The groups were considered homogeneous, except for perianal CD, previous azathioprine, and stomas. There was no significant difference between the groups regarding overall surgical complications (32.69% in anti-TNF− vs. 39.44% in anti-TNF+ patients, p = 0.457) or overall medical complications (21.15 vs. 21.13%, respectively, p = 1.000). In univariate analysis, previous steroids, perianal CD, and stomas were considered risk factors for surgical complications, and previous steroids and hypoalbuminemia for medical complications. In multivariate analysis, previous steroids were associated with higher rates of surgical and medical complications, while hypoalbuminemia was associated with higher medical complication rates.

Conclusions

There was no influence of the previous use of anti-TNF agents in postoperative surgical and medical complication rates in elective intestinal resections for CD. Previous steroids and hypoalbuminemia were associated with higher complication rates. This was the first case series of the literature describing outcomes in exclusively elective operations.

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Telephone-Based Mindfulness Therapy Intervention for Patients with Chronic Pancreatitis

Abstract

Background

Patients with chronic pancreatitis (CP) have substantially impaired quality of life (QOL) both physically and mentally. Mindfulness therapy is a form of treatment that has been shown to be beneficial in many medical conditions but has not been evaluated in the CP patient population.

Aims

The aims of this study were (1) to test the feasibility and usability of a novel telephone-based mindfulness therapy service for patients with CP and (2) to determine whether there was any effect on CP quality of life.

Methods

We recruited ten patients with suspected or confirmed CP and five controls who were asked to utilize our telephone-based mindfulness therapy service daily for 28 days. Feasibility of the service was defined as the fraction of subjects with a ≥50% compliance rate. Usability was assessed using a System Usability Scale (SUS). QOL was evaluated using the SF-36 questionnaire and the Pancreatitis Quality of Life Instrument (PANQOLI). Paired t tests were used to compare the SF-36 and PANQOLI pre- and post-intervention.

Results

There was an overall compliance rate of 67%. The mean SUS score for all participants was 79.3, above the average published score of 68. Results showed a significant improvement in the SF-36 Mental Component Summary scores after 28 days of mindfulness therapy for patients with CP, t(9) = 2.48, p = 0.035. There was also a significant improvement in the mean total PANQOLI scores in CP patients, t(9) = 2.41, p = 0.04, most notably in the social domain.

Conclusion

Our telephone-based mindfulness therapy service represents a feasible and easily usable treatment adjunct for patients with CP, which may provide benefit in QOL by improving mental health-related domains.

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RI woman thanks paramedic for saving her life

By EMS1 Staff

SCITUATE, R.I. — Seven weeks after a woman was seriously injured in a horseback riding incident, she has credited paramedics with saving her life. 

Sandy Kelley suffered 10 broken ribs and a collapsed lung after she was knocked off her horse and hit a fence Oct. 17. Doctors said a volunteer paramedic likely saved Kelley's life, reported the Valley Breeze. 

"That was very lucky," Kelley said. "There must have been an angel on my shoulder."

Kelley's husband immediately called 911, and paramedic Joseph Krewko and Mike Conti arrived to the scene. Krewko works as a volunteer per diem in Scituate, but works full-time for the Fall River Fire Department.

While Kelley was being transported by ambulance to the hospital, Krewko performed a thoracostomy. Kelley spent 11 days in the hospital, eight of which were in the ICU.

After the incident, doctors told Kelley she was lucky a paramedic happened to be on-call and responded; there are four different volunteer fire and rescue departments in Scituate.

"You wouldn't get a [paramedic] every single time," Krewko said. "It's a toss-up of who's going to come to your house."

Kelley brought coffee and donuts to Krewko and Conti at their station last week to thank them for saving her life. They took a selfie together. 

Kelley said she doesn't remember much during the ambulance ride to the hospital. She did say the incident "does make you look at life differently. You value every day, every friend. Everybody has been wonderful."

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EMS Artwork: Emotional toll on dispatchers

Artist's image shows a behind-the-scenes look at how some calls can be difficult to walk away from

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EMS Artwork: Emotional toll on dispatchers

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5 things EMS providers should know about seeking mental health treatment

By Bob Sullivan and Shauna Sullivan

EMS providers face a number of challenges that compromise mental health and well-being. These include both acute stress after critical incidents, and chronic stress associated with day-to-day EMS work. Mental health treatment, in the form of therapy and/or medication, can help improve wellness on and off the job.

Here are five things to consider about whether mental health treatment may be helpful for you, how to find the best match with a mental health provider and the options available to pay for mental health care and medications.

1. Receiving mental health treatment does not mean something is wrong with you.
While traumatic stress after critical incidents has gotten a lot of attention recently, there are many other factors that predispose EMS providers to mental health problems and substance abuse. Mood fluctuations associated with sleep deprivation, challenges to healthy eating and fitness, low wages, overtime, conflict with coworkers and unsupportive management over time can lead to symptoms of anxiety and depression.

An NAEMT survey showed that respondents overwhelmingly wanted mental health care to recover from traumatic incidents, to maintain mental health, cope with stress and prevent developing PTSD, anxiety or depression [1]. However, the report also states that the stigma of mental illness and fear of being perceived as weak deters many respondents from seeking treatment. Only about half of respondents reported that they feel comfortable even talking about mental health with colleagues [1].

It does not have to be that way. Mental health treatment can be viewed as an adjunct to diet, exercise, hobbies and other healthy coping strategies to manage the unique challenges associated with EMS work. Seeing a mental health therapist or taking medication for anxiety is really no different from seeing a physical therapist or taking medication for hypertension.

Many people believe that mental health treatment is only necessary for people with significant mental health problems, but this is not true. Talk therapy can provide practical solutions for everyday stress management and work life balance, whether you have a diagnosed mental health issue or only feel symptoms occasionally.

2. Therapists and medication prescribers are the main options for mental health treatment.
Mental health professionals generally fall into two categories — those who provide talk therapy and those who prescribe medications. Some people see only one type of mental health professional and some people see both types; which one to start with depends on your preference. A therapist may refer a client to a prescriber, or vice versa, and the prescriber and therapist can collaborate on how to best meet the patient's treatment goals.

Mental health therapists have a doctorate or master's degree, and include psychologists, mental health counselors, clinical social workers and pastoral counselors. While the educational backgrounds are different, all may function in similar roles, and all may specialize in particular populations or conditions.

Medications for symptoms of anxiety and depression are prescribed by psychiatrists, who are physicians trained in mental health disorders. Nurse practitioners and physician assistants may also specialize in prescribing medications for mental health conditions, and some primary care physicians prescribe psychotropic medications as well.

3. Look for a mental health provider who matches your personality and situation.
Several NAEMT survey respondents who received mental health treatment expressed frustration that their provider did not understand the demands of EMS work, and that they would have preferred to see someone with a background working with EMS providers. Consider these resources to find a mental health practitioner who may be a good fit for you.

One referral source is The Code Green Campaign, whose website includes a state-by-state list of mental health providers with experience serving first responders. Other websites with reviews of health care providers include mental health practitioners, and describe areas of specialty.

For people who are comfortable talking to coworkers and friends about mental health, word of mouth can be a good referral source for a therapist or prescriber. Many individual mental health providers also have websites or blogs that describe their treatment philosophy, and populations and conditions that they are comfortable seeing.

Once the search is narrowed, it is a good idea to call the mental health provider before making an appointment. Ask about their experience with people who work in EMS and with people who have your symptoms. See if their initial analysis of your situation gels with your own self-assessment. Also ask if their appointment hours will fit your work schedule.

Many respondents to the NAEMT survey expressed reluctance to seek mental health treatment because of concerns about confidentiality [1]. Information shared during a treatment session is protected by HIPAA, but there are exceptions, such as release because of a court order. A mental health practitioner can describe exactly what information can and cannot be shared before any sensitive issues are discussed.

4. Payment for mental health services may be covered by an employer, health insurance or made directly to a provider.
Many EMS services offer employee assistance programs, which includes confidential, short-term mental health counseling. This may be a good option if you are having difficulty with a particular event or life change, such as a traumatic call or divorce. EAPs are also a way to try therapy before making a financial investment in it. A disadvantage to EAPs is that treatment is usually limited to five or six sessions, and there are few therapists to choose from. Several NAEMT survey respondents stated the short-duration of EAP provided therapy was not enough time and that they had difficulty relating to the therapist they saw through the EAP [1].

You can also look for treatment through your health insurance plan, which has a list of mental health providers who are covered. Out of pocket costs depend on the plan's copay and deductible. Mental health providers also can be paid directly, which eliminates strings attached to treatment covered by an employer or insurance. This is the most expensive option, but some providers offer a sliding scale or a discount to emergency services personnel.

The cost of mental health treatment deters many people from seeking help. While this is a challenge for many EMS providers, think of the cost as an investment in overall wellness that may help prevent missed days of work, financial setbacks and medical problems in the future.

5. After selecting a mental health provider, feeling a strong connection with them is key to successful treatment.
While many NAEMT survey respondents stated they preferred to see a therapist who specialize in treating first responders, a good therapist can relate to their client even if they do not have a background in the work that they do. Several studies in psychology literature report that the "therapeutic alliance" between a therapist and their client is a strong predictor of success, even more so than the provider's education background or treatment approach [2]. A good therapist can develop a bond with their client, earn their trust, work with them to achieve goals and understand their factors that impede change.

A personality mismatch with one mental health provider does not mean that any future mental health treatment will be unhelpful. The first few sessions with a mental health practitioner are like a probationary period with an employer; if you do not feel a connection, try meeting with another one.

Seeing a mental health professional can be a valuable way to manage stress and maintain wellness. Think about whether mental health treatment may be right for you, and look for a provider who best meets your personality, situation and budget.

About the authors:
Shauna Sullivan, LCSW, LLC is a licensed clinical social worker providing therapy to individuals and families. She has special interest in eradicating stigma and advocating for those affected by mental illness. Shauna owns a private practice in Wilmington, Delaware, and can be reached at her blog, Take on Mental Health.

Bob Sullivan, MS, NRP, is a paramedic instructor at Delaware Technical Community College. He has been in EMS since 1999, and has worked as a paramedic in private, fire-based, volunteer, and municipal EMS services. Contact Bob at his blog, The EMS Patient Perspective.

References
1. 2016 NAEMT National Survey on Mental Health Services, retrieved from: http://ift.tt/2havEJr"sfvrsn=4

2. Ardito R & Rabellino D. Therapeutic Alliance and Outcome of Psychotherapy: Historical Excursus, Measurements, and Prospects for Research. Frontiers in Psychology. 2011; 2:270. doi: 10.3389/fpsyg.2011.00270

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