Increased urinary lysophosphatidic acid in mouse with subtotal nephrectomy: potential involvement in chronic kidney disease

Abstract

Increased incidence of chronic kidney disease (CKD) with consecutive progression to end-stage renal disease represents a significant burden to healthcare systems. Renal tubulointerstitial fibrosis (TIF) is a classical hallmark of CKD and is well correlated with the loss of renal function. The bioactive lysophospholipid lysophosphatidic acid (LPA), acting through specific G-protein-coupled receptors, was previously shown to be involved in TIF development in a mouse model of unilateral ureteral obstruction. Here, we study the role of LPA in a mouse subjected to subtotal nephrectomy (SNx), a more chronic and progressive model of CKD. Five months after surgical nephron reduction, SNx mice showed massive albuminuria, extensive TIF, and glomerular hypertrophy when compared to sham-operated animals. Urinary and plasma levels of LPA were analyzed using liquid chromatography tandem mass spectrometry. LPA was significantly increased in SNx urine, not in plasma, and was significantly correlated with albuminuria and TIF. Moreover, SNx mice showed significant downregulation in the renal expression of lipid phosphate phosphohydrolases (LPP1, 2, and 3) that might be involved in reduced LPA bioavailability through dephosphorylation. We concluded that SNx increases urinary LPA through a mechanism that could involve co-excretion of plasma LPA with albumin associated with a reduction of its catabolism in the kidney. Because of the previously demonstrated profibrotic activity of LPA, the association of urinary LPA with TIF suggests the potential involvement of LPA in the development of advanced CKD in the SNx mouse model. Targeting LPA metabolism might represent an interesting approach in CKD treatment.

http://ift.tt/2cxLtZE

Erratum to: Modeling Alexander disease with patient iPSCs reveals cellular and molecular pathology of astrocytes

http://ift.tt/2ckIJz4

Genetic markers as therapeutic target in rheumatoid arthritis: A game changer in clinical therapy?

Abstract

Rheumatoid arthritis (RA) is a chronic, inflammatory, multi-systemic autoimmune disease unremitted by genetic and environmental factors. The factors are crucial but inadequate in the development of disease; however, these factors can be representative of potential therapeutic targets and response to clinical therapy. Insights into the contribution of genetic risk factors are currently in progress with studies querying the genetic variation, their role in gene expression of coding and non-coding genes and other mechanisms of disease. In this review, we describe the significance of genetic markers architecture of RA through genome-wide association studies and meta-analysis studies. Further, it also reveals the mechanism of disease pathogenesis investigated through the mutual findings of functional and genetic studies of individual RA-associated genes, which includes HLA-DRB1, HLA-DQB1, HLA-DPB1, PADI4, PTPN22, TRAF1-C5, STAT4 and C5orf30. However, the genetic background of RA remains to be clearly depicted. Prospective efforts of the post-genomic and functional genomic period can travel toward real possible assessment of the genetic effect on RA. The discovery of novel genes associated with the disease can be appropriate in identifying potential biomarkers, which could assist in early diagnosis and aggressive treatment.

http://ift.tt/2d5fY8h

Advanced computational workflow for the multi-scale modeling of the bone metabolic processes

Abstract

Multi-scale modeling of the musculoskeletal system plays an essential role in the deep understanding of complex mechanisms underlying the biological phenomena and processes such as bone metabolic processes. Current multi-scale models suffer from the isolation of sub-models at each anatomical scale. The objective of this present work was to develop a new fully integrated computational workflow for simulating bone metabolic processes at multi-scale levels. Organ-level model employs multi-body dynamics to estimate body boundary and loading conditions from body kinematics. Tissue-level model uses finite element method to estimate the tissue deformation and mechanical loading under body loading conditions. Finally, cell-level model includes bone remodeling mechanism through an agent-based simulation under tissue loading. A case study on the bone remodeling process located on the human jaw was performed and presented. The developed multi-scale model of the human jaw was validated using the literature-based data at each anatomical level. Simulation outcomes fall within the literature-based ranges of values for estimated muscle force, tissue loading and cell dynamics during bone remodeling process. This study opens perspectives for accurately simulating bone metabolic processes using a fully integrated computational workflow leading to a better understanding of the musculoskeletal system function from multiple length scales as well as to provide new informative data for clinical decision support and industrial applications.

http://ift.tt/2d1Adrp

PCA-based artifact removal algorithm for stroke detection using UWB radar imaging

Abstract

Stroke patients should be dispatched at the highest level of care available in the shortest time. In this context, a transportable system in specialized ambulances, able to evaluate the presence of an acute brain lesion in a short time interval (i.e., few minutes), could shorten delay of treatment. UWB radar imaging is an emerging diagnostic branch that has great potential for the implementation of a transportable and low-cost device. Transportability, low cost and short response time pose challenges to the signal processing algorithms of the backscattered signals as they should guarantee good performance with a reasonably low number of antennas and low computational complexity, tightly related to the response time of the device. The paper shows that a PCA-based preprocessing algorithm can: (1) achieve good performance already with a computationally simple beamforming algorithm; (2) outperform state-of-the-art preprocessing algorithms; (3) enable a further improvement in the performance (and/or decrease in the number of antennas) by using a multistatic approach with just a modest increase in computational complexity. This is an important result toward the implementation of such a diagnostic device that could play an important role in emergency scenario.

http://ift.tt/2ctKs2J

Optic disc detection in retinal fundus images using gravitational law-based edge detection

Abstract

Diabetic retinopathy is one of the primary causes of vision loss worldwide. Early detection of the condition is critical for providing adequate treatment of this ailment to prevent vision loss. This detection is achieved by processing retinal fundus images. A key step in detecting diabetic retinopathy is identifying the optic disc in these images. The optic disc is similar in color and contrast to the exudates that indicate diabetic retinopathy. Hence, the optic disc has to be removed from the fundus image before exudates can be detected. Detecting the optic disc is also required in algorithms used for blood vessel segmentation in fundus images. Therefore, there is a need for approaches that accurately and quickly detect optic disc. This paper proposes a simple, deterministic, and time-efficient approach for optic disc detection by adapting an edge detection algorithm inspired by the gravitational law. Our method introduces novel pre- and post-detection steps that aim to increase the accuracy of the adapted detection method. In addition, a candidate selection technique is proposed to decrease the number of missed optic discs. The proposed methodology was found to have a detection rate of 100, 97.75, 92.90, and 95 % for DRIVE, DiaRet, DMED, and STARE datasets, respectively, which is comparatively better than existing optic disc detection schemes. Experimental results showed an average running time of 0.40 s per image, which is significantly lower than available methods published in the literature.

http://ift.tt/2d1zl5Y

An enhanced random walk algorithm for delineation of head and neck cancers in PET studies

Abstract

An algorithm for delineating complex head and neck cancers in positron emission tomography (PET) images is presented in this article. An enhanced random walk (RW) algorithm with automatic seed detection is proposed and used to make the segmentation process feasible in the event of inhomogeneous lesions with bifurcations. In addition, an adaptive probability threshold and a k-means based clustering technique have been integrated in the proposed enhanced RW algorithm. The new threshold is capable of following the intensity changes between adjacent slices along the whole cancer volume, leading to an operator-independent algorithm. Validation experiments were first conducted on phantom studies: High Dice similarity coefficients, high true positive volume fractions, and low Hausdorff distance confirm the accuracy of the proposed method. Subsequently, forty head and neck lesions were segmented in order to evaluate the clinical feasibility of the proposed approach against the most common segmentation algorithms. Experimental results show that the proposed algorithm is more accurate and robust than the most common algorithms in the literature. Finally, the proposed method also shows real-time performance, addressing the physician's requirements in a radiotherapy environment.

http://ift.tt/2ctLr2W

Emerging Trends in the Etiology, Prevention, and Treatment of Gastrointestinal Anastomotic Leakage

Abstract

Anastomotic leaks represent one of the most alarming complications following any gastrointestinal anastomosis due to the substantial effects on post-operative morbidity and mortality of the patient with long-lasting effects on the functional and oncologic outcomes. There is a lack of consensus related to the definition of an anastomotic leak, with a variety of options for prevention and management. A number of patient-related and technical risk factors have been found to be associated with the development of an anastomotic leak and have inspired the development of various preventative measures and technologies. The International Multispecialty Anastomotic Leak Global Improvement Exchange group was convened to establish a consensus on the definition of an anastomotic leak as well as to discuss the various diagnostic, preventative, and management measures currently available.

http://ift.tt/2cdStHS

Minimally invasive mitral valve surgery through a right mini-thoracotomy

Abstract

Since its introduction in the mid-1990s, minimally invasive mitral valve surgery (MIMVS) has been shown to be a feasible alternative to a conventional full-sternotomy approach, and several studies have reported excellent clinical outcomes with low perioperative morbidity and mortality. As a result, MIMVS is being increasingly employed as a routine procedure worldwide. On the other hand, several issues have been raised, including complications specific to this technique and its steep learning curve, while there are also concerns regarding the durability of a mitral valve repair through a limited access. In this study, the current status and future perspectives of MIMVS were examined.

http://ift.tt/2cGmJvX

How females of chirping and trilling field crickets integrate the ‘what’ and ‘where’ of male acoustic signals during decision making

Abstract

In crickets acoustic communication serves mate selection. Female crickets have to perceive and integrate male cues relevant for mate choice while confronted with several different signals in an acoustically diverse background. Overall female decisions are based on the attractiveness of the temporal pattern (informative about the 'what') and on signal intensity (informative about the 'where') of male calling songs. Here, we investigated how the relevant cues for mate choice are integrated during the decision process by females of five different species of chirping and trilling field crickets. Using a behavioral design, female preferences in no-choice and choice situations for male calling songs differing in pulse rate, modulation depth, intensities, chirp/trill arrangements and temporal shifts were examined. Sensory processing underlying decisions in female field crickets is rather similar as combined evidence suggested that incoming song patterns were analyzed separately by bilaterally paired networks for pattern attractiveness and pattern intensity. A downstream gain control mechanism leads to a weighting of the intensity cue by pattern attractiveness. While remarkable differences between species were observed with respect to specific processing steps, closely related species exhibited more similar preferences than did more distantly related species.

http://ift.tt/2d6YgE0

Prevalence and risk factors for patent Toxocara infections in cats and cat owners’ attitude towards deworming

Abstract

The prevalence of and risk factors for shedding Toxocara eggs in cats older than 6 months were determined by examining 670 faecal samples collected in 4 cross-sectional studies in the Netherlands. Additionally, cat owners provided information on their attitude towards routine deworming. Samples were examined using the centrifugal sedimentation flotation method. Overall Toxocara prevalence was 7.2 %. Multivariable logistic regression analysis revealed that young age and living in rural areas were significant risk factors for shedding Toxocara eggs. Moreover, the more time a cat was allowed to roam outdoors, the higher was its risk to shed Toxocara as compared to cats with no outdoor access at all. For 199 cats (81.6 % of cats subjected to a deworming regimen) owners provided the reason for treatment. The main reason for routine deworming (80.4 %) concerned the cat's health and only 10.6 % of the cats were treated for public health reasons. Moreover, the generally advocated four-times-a-year deworming advice was applied on only 24.5 % of cats. We concluded that free roaming is a key factor in the acquisition of patent Toxocara infections leading to the environmental contamination with Toxocara eggs. Additionally, the knowledge of cat owners is still insufficient to expect them to make sound decisions on routine deworming.

http://ift.tt/2ctEHBR

Pneumatosis intestinalis during chemotherapy with nilotinib in a patient with chronic myeloid leukemia who tested positive for anti-topoisomerase I antibodies

Abstract

A 55-year-old man with several comorbidities including idiopathic interstitial pneumonia under long-term corticosteroid therapy, longstanding myocardial infarction, chronic heart failure, paroxysmal atrial fibrillation, gastro-esophageal reflux disease, constipation, and history of paralytic ileus, was diagnosed with chronic myelogenous leukemia (CML) in the chronic phase. He also tested positive for anti-topoisomerase I antibodies without clinical diagnosis of any connective tissue disease, including systemic sclerosis. Approximately 5 months after the initiation of nilotinib for CML, he developed upper abdominal distension with intermitting abdominal pain, and based on abdominal computed tomography findings, a diagnosis of pneumatosis intestinalis (PI) was made. Five courses of hyperbaric oxygen therapy quickly eliminated the PI and related symptoms without the cessation of nilotinib and, thereafter, additional oral prokinetic agents and non-absorbable antibiotics ensured the non-recurrence of PI. At 6 and 18 months after commencing nilotinib therapy, major and complete molecular response were achieved, respectively. It is suspected that both gastrointestinal hypokinesis related to the presence of anti-topoisomerase I antibodies and mucosal permeability due to corticosteroid therapy had existed. Thus, subsequent administration of nilotinib may have triggered PI by depressing gastrointestinal motility via the inhibition of c-kit.

http://ift.tt/2cMOGWA

The role of dendritic cells in cancer

Abstract

Though present in low numbers, dendritic cells (DCs) are recognized as major players in the control of cancer by adaptive immunity. The roles of cytotoxic CD8⁺ T-cells and Th1 helper CD4⁺ T-cells are well-documented in murine models of cancer and associated with a profound prognostic impact when infiltrating human tumors, but less information is known about how these T-cells gain access to the tumor or how they are primed to become tumor-specific. Here, we highlight recent findings that demonstrate a vital role of CD103⁺ DCs, which have been shown to be experts in cross-priming and the induction of anti-tumor immunity. We also focus on two different mediators that impair the function of tumor-associated DCs: prostaglandin E₂ and β-catenin. Both of these mediators seem to be important for the exclusion of T-cells in the tumor microenvironment and may represent key pathways to target in optimized treatment regimens against cancer.

http://ift.tt/2cQ60rU

Personalized medicine: evidence of normativity in its quantitative definition of health

Abstract

Systems medicine, which is based on computational modelling of biological systems, is emerging as an increasingly prominent part of the personalized medicine movement. It is often promoted as 'P4 medicine' (predictive, preventive, personalized, and participatory). In this article, we test promises made by some of its proponents that systems medicine will be able to develop a scientific, quantitative metric for wellness that will eliminate the purported vagueness, ambiguity, and incompleteness—that is, normativity—of previous health definitions. We do so by examining the most concrete and relevant evidence for such a metric available: a patent that describes a systems medicine method for assessing health and disease. We find that although systems medicine is promoted as heralding an era of transformative scientific objectivity, its definition of health seems at present still normatively based. As such, we argue that it will be open to influence from various stakeholders and that its purported objectivity may conceal important scientific, philosophical, and political issues. We also argue that this is an example of a general trend within biomedicine to create overly hopeful visions and expectations for the future.

http://ift.tt/2cvgJM3

The causal explanatory functions of medical diagnoses

Abstract

Diagnoses in medicine are often taken to serve as explanations of patients' symptoms and signs. This article examines how they do so. I begin by arguing that although some instances of diagnostic explanation can be formulated as covering law arguments, they are explanatory neither in virtue of their argumentative structures nor in virtue of general regularities between diagnoses and clinical presentations. I then consider the theory that medical diagnoses explain symptoms and signs by identifying their actual causes in particular cases. While I take this to be largely correct, I argue that for a diagnosis to function as a satisfactory causal explanation of a patient's symptoms and signs, it also needs to be supplemented by understanding the mechanisms by which the identified cause produces the symptoms and signs. This mechanistic understanding comes not from the diagnosis itself, but rather from the theoretical framework within which the physician operates.

http://ift.tt/2cx4Hyf

A Review of HIV-Specific Patient-Reported Outcome Measures

Abstract

The use of patient-reported outcome (PRO) measures to provide added feedback to health providers is receiving interest as a means of improving clinical care and patient outcomes, and contributing to more patient-centered care. In human immunodeficiency virus (HIV), while PROs are used in research, their application in clinical practice has been limited despite their potential utility. PRO selection is an important consideration when contemplating their use. As past reviews of PROs in HIV have focused on particular areas (e.g. disability, satisfaction with care), a more comprehensive review could better inform on the available instruments and their scope. This article reviews HIV-specific PROs to produce an inventory and to identify the central concepts targeted over time. Seven databases were searched (HAPI, MEDLINE, PsychINFO, PubMed, EMBASE, CINAHL, Google Scholar), generating 14,794 records for evaluation. From these records, 117 HIV-specific PROs were identified and categorized based on a content analysis of their targeted concept: Health-Related Quality of Life (23; 20 %), ART and Adherence-Related Views and Experiences (19; 16 %), Healthcare-Related Views and Experiences (15; 13 %), Psychological Challenges (12; 10 %), Symptoms (12; 10 %), Psychological Resources (10; 9 %), HIV Self-Management and Self-Care (8; 7 %), HIV-Related Stigma (8; 7 %), Body and Facial Appearance (4; 3 %), Social Support (3; 3 %), Sexual and Reproductive Health (2; 2 %), and Disability (1; 1 %). This review highlights the variety and evolution of HIV-specific PROs, with the arrival of seven categories of PROs only after the advent of highly-active antiretroviral therapy. Our inventory also offers a useful resource. However, the interest of further HIV-specific PRO development should be explored in sexual health, which received little independent attention.

http://ift.tt/2ck56V2

Physiology of the fasciculation potentials in amyotrophic lateral sclerosis: which motor units fasciculate?

Abstract

We set out to study whether in amyotrophic lateral sclerosis (ALS) fasciculation potentials (FPs) arise from the most excitable motor units (MUs). We studied 70 patients with ALS and 18 subjects with benign fasciculation syndrome (BFS). Of the 56 eligible ALS patients, 31 had signs of reinnervation in the right first dorsal interosseous muscle selected for study, and 25 did not. Two needle electrodes were placed in different MUs in each studied muscle. We defined the most excitable MU as that first activated by minimal voluntary contraction. In muscles without reinnervation, the recording site with most frequent FPs had a higher probability of showing the first recruited MU (p < 0.001). No significant difference was found in other patients or in BFS subjects. In very early affected muscles, fasciculating MUs are the most likely to be recruited volitionally. This probably represents hyperexcitability at lower motor neuronal level.

http://ift.tt/2cPvxBu

Bedingungsfaktoren psychopharmakologischer Behandlung bei leichter oder mittelgradiger Intelligenzminderung

Zusammenfassung

Hintergrund

In den letzten Jahren wurde wiederholt Kritik an der psychiatrisch-psychotherapeutischen Versorgung von Menschen mit Intelligenzminderung (IM) geäußert. Die Anzahl diesbezüglich vorgelegter Studien ist allerdings bislang sehr begrenzt.

Ziel der Arbeit

Ziel der vorliegenden Arbeit war die Ermittlung von Bedingungsfaktoren psychiatrisch-psychotherapeutischer und speziell psychopharmakologischer Behandlung von Menschen mit leichter oder mittelgradiger IM.

Material und Methoden

In die Auswertungen gingen die Daten von 417 Menschen mit leichter oder mittelgradiger IM ein, die im Rahmen der MEMENTA-Studie in drei Versorgungsregionen in Deutschland rekrutiert wurden. Mit Teilstichproben wurden Regressionsanalysen durchgeführt, um Prädiktoren psychiatrisch-psychotherapeutischer (n = 282) sowie psychopharmakologischer (n = 351) Behandlung zu identifizieren.

Ergebnisse

Das Vorliegen einer psychischen Störung und beobachtetes Problemverhalten erhöhten die Wahrscheinlichkeit einer psychiatrisch-psychotherapeutischen und einer psychopharmakologischen Behandlung. Menschen mit IM, die in einem Wohnheim lebten, wurden unabhängig von klinischen Merkmalen mit größerer Wahrscheinlichkeit psychopharmakologisch und mit Antipsychotika behandelt.

Diskussion

Die Ergebnisse deuten darauf hin, dass Menschen mit IM, die in einem Wohnheim leben, auch in Deutschland nicht immer leitlinienkonform psychopharmakologisch behandelt werden.

http://ift.tt/2cv3drS

Self-efficacy and sleep problems

Abstract

The present pilot study investigates the relationship between general self-efficacy (GSE) and sleep behavior in school-age children (between 5 and 10 years). Children with chronic insomnia (n = 54) had significantly lower GSE scores (p < 0.001) compared to a sample of healthy school-age children (n = 54) matched concerning age (M = 7.5 years) and gender (59.3 % boys, 40.7 % girls). In general, higher sleep disturbance scores were associated with lower GSE (r _s = −0.37, p < 0.001). The highest negative correlations with GSE were found for frequent night wakings (r _s = −0.38, p < 0.001), sleep anxiety (r _s = −0.35, p < 0.001), and sleep onset delay (r _s = −0.30, p < 0.01). In a multiple stepwise regression model, frequency of night wakings (ß = −0.33, p < 0.01) and sleep onset delay (ß = −0.26, p < 0.01) predicted GSE scores of children; sleep parameters accounted for 20 % of the variance in GSE scores. All in all, the present findings provide evidence for an association between GSE and sleep behavior, which are in line with previous results in other age groups and concerning other psychological constructs, e. g., depression and anxiety. Future studies should further investigate this topic in order to improve effective intervention programs for children.

http://ift.tt/2cCPVpg

Was hustet und juckt da im Dunkeln?

Zusammenfassung

Sowohl Asthma, atopische Dermatitis und allergische Rhinitis zeigen eine ausgeprägte zirkadiane Rhythmik mit einem Beschwerdemaximum in der Nacht. Die damit einhergehende Schlaffragmentation führt dazu, dass die betroffenen Kinder häufig unter Tagesschläfrigkeit und einer relevanten Beeinträchtigung der Lebensqualität leiden. Aufgrund der diagnostischen Lücke zur objektiven Erfassung werden nächtliche Asthmasymptome und allergieinduzierte Schlafstörungen in ihrer Häufigkeit deutlich unterschätzt. Daher sollten bei der Langzeitbetreuung von Patienten mit Asthma, atopischer Dermatitis oder allergischer Rhinitis die strukturierte Erfassung schlafbezogener Beschwerden, sowie die regelmäßige Messung von Schlafqualität und Tagesschläfrigkeit zur Routine gehören. Umgekehrt müssen die sehr häufigen Erkrankungen des atopischen Formenkreises bei der (primär somnologischen) Abklärung von Tagesschläfrigkeit im Kindes- und Jugendalter differenzialdiagnostisch mit in Betracht gezogen werden. Da Asthma und das obstruktive Schlafapnoesyndrom oft gemeinsam auftreten, sollte bei Diagnosestellung der einen Erkrankung auch gezielt nach der jeweils anderen gesucht werden.

http://ift.tt/2cPHRoj

Alpträume und nächtliche Atemnot bei einer 12-jährigen Patientin

Zusammenfassung

Vorgestellt wird der Fall eines 12-jährigen Mädchens, das wegen nächtlicher Hyperventilationssituationen mit Zittern der Hände in der Notaufnahme vorstellig wurde. Die Eltern berichteten Einschlafprobleme seit zwei Jahren und nächtliche Albträume, verbunden mit Atemnot, von zunehmender Intensität und Häufigkeit seit zwei Monaten. Tagsüber verspüre das Mädchen keine Atemnot. Die stationäre Diagnostik einschließlich laborchemischer, kardiologischer, pulmonaler und neurologischer Abklärung ergab keinerlei auffällige Befunde. Die Diagnostik im Schlaflabor ergab eine unauffällige Schlafregulierung und keine Hinweise auf epilepsietypische Potenziale im EEG oder Atmungsregulationsstörungen. Allerdings wurden in beiden Nächten keine der beschriebenen Ereignisse aufgezeichnet. Erst im Rahmen eines kontinuierlichen EEG-Monitorings zeigte sich ein fokal beginnender tonischer Anfall, welcher rasch sekundär generalisierte und in klonische Bewegungen überging. Es wurde die Diagnose einer Frontallappenepilepsie gestellt. Der Fall belegt, dass eine unauffällige EEG- und polysomnographische Diagnostik eine schlafbezogene Epilepsie nicht sicher ausschließen können, wenn das Ereignis selbst nicht aufgezeichnet wird. Bei unklarer Anamnese und zunehmender Klinik sind daher ein interdisziplinärer Ansatz und eine genaue Differenzialdiagnostik wichtig.

http://ift.tt/2cCQYoY

An implantable ENG detector with in-system velocity selective recording (VSR) capability

Abstract

Detection and classification of electroneurogram (ENG) signals in the peripheral nervous system can be achieved by velocity selective recording (VSR) using multi-electrode arrays. This paper describes an implantable VSR-based ENG recording system representing a significant development in the field since it is the first system of its type that can record naturally evoked ENG and be interfaced wirelessly using a low data rate transcutaneous link. The system consists of two CMOS ASICs one of which is placed close to the multi-electrode cuff array (MEC), whilst the other is mounted close to the wireless link. The digital ASIC provides the signal processing required to detect selectively ENG signals based on velocity. The design makes use of an original architecture that is suitable for implantation and reduces the required data rate for transmission to units placed outside the body. Complete measured electrical data from samples of the ASICs are presented that show that the system has the capability to record signals of amplitude as low as 0.5 μV, which is adequate for the recording of naturally evoked ENG. In addition, measurements of electrically evoked ENG from the explanted sciatic nerves of Xenopus Laevis frogs are presented.

http://ift.tt/2cPntRz

The Utility of Preoperative Frailty Assessment

Abstract

Purpose of review

The geriatric patient population represents an ever increasing proportion of a surgeon's practice spectrum. With this comes the need to understand the factors largely impacting the geriatric surgical population. One of these factors is frailty. At first glance frailty appears as a simple concept. However, a review of the literature reveals a plethora of definitions, quantification endeavors, and theories attempting to delineate its principle attributes.

Recent findings

Despite the variety of theories, the literature supports a strong link between frailty and poor surgical outcomes. While this link is strong, the exact utility of frailty in preoperative assessments is still being appreciated both in the general surgery setting and in its subspecialties.

Summary

In this review we first discuss the background and defining attributes of frailty and their relation to concepts closely associated with frailty such as resilience, multi-morbidity, and accelerating factors of aging. Understanding the prominent defining features and close associations allows for a greater appreciation of frailty's clinical impact on the geriatric perioperative surgical assessment. Ultimately, when including frailty in the geriatric surgical assessment its consideration allows for modification in the preoperative, intraoperative, and postoperative setting with the overall goal of improving surgical outcomes in the geriatric population.

http://ift.tt/2cF9YS5

Preclinical evaluation of posterior spine stabilization devices: can we compare in vitro and in vivo loads on the instrumentation?

Abstract

Purpose

To discuss whether the standard test method for preclinical evaluation of posterior spine stabilization devices with an anterior support correctly describes the effect of two short-segment posterior stabilization techniques frequently used in clinical practice for the treatment of traumatic, degenerative and iatrogenic instabilities.

Methods

A finite element study compared a validated instrumented L2–L4 segment undergoing standing, upper body flexion and extension to ISO 12189 standards model under a compressive load. A bridge instrumentation, with screws only at cranial and caudal levels, and a full stabilization, using screws at every level, are considered for both conditions. The internal loads on the spinal rod and the stress values on the implant are analysed in detail.

Results

Using ISO model and a bridge stabilization construct allow to overstress the pedicle screw more than a full stabilization with respect to the corresponding L2–L4 segment undergoing upper body flexion, while the stress on the spinal rod is comparable. Choosing softer/stiffer springs would involve higher/lower loads on every component.

Conclusions

ISO model predicts the effects of using both a full and a bridge posterior instrumentation. The study justifies the use of both conditions during in vitro reliability tests to achieve meaningful results easy to compare to clinically relevant loading modes and known in vivo failure modes.

http://ift.tt/2cCY91U

Genetic differences on intracranial versus spinal cord ependymal tumors: a meta-analysis of genetic researches

Abstract

Purpose

Although ependymomas occur in both the brain and the spine, the prognosis is quite varied by tumor location. Spinal ependymomas usually follow a relatively benign course with more favorable prognosis than that of the intracranial ependymomas. The aim of this study is to evaluate the genetic differences between spinal ependymomas and their intracranial counterparts using a meta-analysis.

Methods

We searched PubMed, Embase, Web of Science, and the Cochrane library. Comparative or single arm genetic studies that enrolled patients with both intracranial and spinal ependymoma were included. The frequency of genetic aberration was calculated in each group. We calculated the odds ratio (OR) with 95 % confidence intervals (CIs) for direct comparative studies and the logit event rate (LER) and 95 % CI for single arm studies.

Results

Twenty-five studies comprising of 380 spinal ependymomas and 964 intracranial ependymomas were compared to determine the association of the genetic differences of ependymomas at different locations. There were 25 comparable genetic aberrations between spinal and intracranial ependymomas. Among the genes, the NF2 mutation was significantly associated with the spinal ependymomas rather than with the intracranial ependymomas (spinal tumor: LER −0.750, 95 % CI −1.233 to −0.266, intracranial tumor: LER −3.080, 95 % CI −3.983 to −2.177). Intracranial ependymomas were found to be significantly associated with EPB41L3 deletion (OR 0.34; 95 % CI 0.14–0.80) and HIC1 methylation (OR 0.12; 95 % CI 0.02–0.68).

Conclusion

The genetic aberrations of spinal ependymomas are quite different from those of intracranial ependymomas. The difference in prognosis of ependymoma by location may be associated with genetic difference. A more detailed understanding of them may enable the development of targeted therapy and the estimation of prognosis.

http://ift.tt/2d3YhFX

Improvement of sensory function after sequestrectomy for lumbar disc herniation: a prospective clinical study using quantitative sensory testing

Abstract

Background

Previous studies have investigated sensory recovery in patients with lumbar disc herniation using rather subjective methods. There have been no reports on changes of sensory function in patients suffering from a preoperative sensory deficit using quantitative sensory testing (QST). The aims of this prospective study were (1) to assess the recovery of preoperative sensory dysfunction after lumbar sequestrectomy and (2) to quantify the strength of relationship between a sensory deficit and the patient's quality of life.

Methods

We applied the QST protocol of the German Research Network on Neuropathic Pain (DFNS) in fifty-two patients with a single lumbar disc herniation confirmed on MRI treated by lumbar sequestrectomy. Further evaluation included a detailed medical history, a physical examination, numeric rating scale for leg, EQ-5D questionnaire, and thermometer.

Results

Disc surgery resulted in a significant reduction of leg pain and a significant gain of quality of life. Thermal, mechanical, and vibration perception thresholds showed an obvious side-to-side difference preoperatively (p < 0.005). An early recovery of mechanical and vibration perception thresholds was detected, whereas cold perception needed more than 6 months to recover (p < 0.05). Quality of life was independent from perception thresholds, but correlated significantly with pain reduction.

Conclusion

Our data clearly show that there is a subjective and quantifiable improvement in sensory dysfunction postoperatively. The current data suggest that a sensory dysfunction does not influence a patient's quality of life.

http://ift.tt/2cCWTw7

New section in EJNMMI and Annals of Nuclear Medicine

http://ift.tt/2cCAzRg

One year of nuclear cardiology in Europe

http://ift.tt/2cPqDqY

Indole production provides limited benefit to Escherichia coli during co-culture with Enterococcus faecalis

Abstract

Escherichia coli lives in the gastrointestinal tract and elsewhere, where it coexists within a mixed population. Indole production enables E. coli to grow with other gram-negative bacteria as indole inhibits N-acyl-homoserine lactone (AHL) quorum regulation. We investigated whether E. coli indole production enhanced competition with gram-positive Enterococcus faecalis, wherein quorum signaling is mediated by small peptides. During planktonic co-culture with E. faecalis, the fitness and population density of E. coli tnaA mutants (unable to produce indole) equaled or surpassed that of E. coli wt. During biofilm growth, the fitness of both populations of E. coli stabilized around 100 %, whereas the fitness of E. faecalis declined over time to 85–90 %, suggesting that biofilm and planktonic populations have different competition strategies. Media supplementation with indole removed the competitive advantage of E. coli tnaA in planktonic populations but enhanced it in biofilm populations. E. coli wt and tnaA showed similar growth in Luria–Bertani (LB) broth. However, E. coli growth was inhibited in the presence of filter-sterilized spent LB from E. faecalis, with inhibition being enhanced by indole. Similarly, there was also an inhibition of E. faecalis growth by proteinaceous components (likely bacteriocins) from spent culture media from both E. coli strains. We conclude that E. coli indole production is not a universal competition strategy, but rather works against gram-negative, AHL-producing bacteria.

http://ift.tt/2cCusMS

Nonalcoholic fatty liver disease in Asia: emerging perspectives

Abstract

As in the West, nonalcoholic fatty liver disease (NAFLD) is the commonest chronic liver disease in Asia, with a prevalence higher than 40 % in some countries. The risk factors for NAFLD development are similar to those in Western countries, including increased body mass index, diabetes, insulin resistance, and metabolic syndrome. NAFLD in Asians is associated with different extrahepatic manifestations involving the cardiovascular, gastrointestinal, and renal systems. A considerable proportion of Asians with NAFLD are described as having "lean" NAFLD. Present in approximately 20 % of the Asian population, lean NAFLD is closely linked with insulin resistance, diabetes, and other metabolic complications, but its association with disease progression to nonalcoholic steatohepatitis and cirrhosis remains to be defined. There is emerging evidence of the interactions of NAFLD with hepatitis B virus and hepatitis C virus infection in Asia. Unlike in Western countries, NAFLD constitutes only a minority of cirrhosis and hepatocellular carcinoma cases in Asia. Possible explanations are the lower prevalence of obesity and the overwhelming problem of viral hepatitis in Asia. With aging of the obesity cohort in Asia, NAFLD-related liver complications are expected to increase.

http://ift.tt/2cUljyB

Long-term mid-facial growth of patients with a unilateral complete cleft of lip, alveolus and palate treated by two-stage palatoplasty: cephalometric analysis

Abstract

Objectives

The aim of this study is to evaluate long-term facial growth in adults previously treated for an isolated unilateral complete cleft lip, alveolus and palate by two-stage palatoplasty.

Materials and methods

Unilateral cleft lip and palate (UCLP) patients of 17 years and older treated by two-stage palatoplasty were invited for long-term follow-up. During follow-up, lateral cephalograms were obtained (n = 52). Medical history was acquired from their medical files. Outcome was compared to previously published normal values and the Eurocleft study.

Results

Soft and hard palate closure were performed at the age of 8 (SD 5.9) months and 3 (SD 2.2) years, respectively. The mean maxillary and mandibular angle (SNA, SNB) were 74.9° (SD 4.2) and 75.8° (SD 3.8). Maxillary and maxillomandibular relationships (SNA, ANB) were comparable to all Eurocleft Centres, except for Centre D. We observed a significantly steeper upper interincisor angle compared to the Eurocleft Centres.

Conclusions

This study describes the long-term craniofacial morphology in adults treated for a UCLP with hard palate closure at a mean age of 3 years. The mean maxillary angle SNA and mandibular angle SNPg were comparable to previous studies both applying early and delayed hard palate closure. The observed upper incisor proclination is likely caused by orthodontic overcorrection in response to the unfavourable jaw relationships. No clear growth benefit of this protocol could be demonstrated.

Clinical relevance

The present study shows the long-term craniofacial morphology of UCLP adults after the Utrecht treatment protocol which includes two-stage palate closure.

http://ift.tt/2d3OdNc

A Phase 1 Study of Arginase Inhibitor CB-1158 in Combination With Immune Checkpoint Therapy in Solid Tumors

Conditions:   Metastatic Cancer;   Solid Tumors;   Non-small Cell Lung Cancer;   Colo-Rectal Cancer;   Gastric Cancer;   Renal Cell Carcinoma;   Squamous-cell Carcinomas of the Head and Neck
Interventions:   Drug: CB-1158;   Drug: Nivolumab
Sponsor:   Calithera Biosciences, Inc
Recruiting - verified September 2016

http://ift.tt/2cTQz0G

Photobiomodulation reduces abdominal adipose tissue inflammatory infiltrate of diet-induced obese and hyperglycemic mice

Systemic inflammation is closely related to the development of insulin resistance and type-2 diabetes, since the activation of pro-inflammatory pathways leads to inhibition of insulin signaling. Although photobiomodulation (PBM) has proven beneficial effects on the treatment of inflammatory disorders, the phototherapeutic approach to manage the chronic inflammatory component of obesity and hyperglycemia had never been explored. In this work, obese and hyperglycemic mice are treated with PBM, and their body mass, glycemia and inflammatory infiltrate of abdominal adipose tissue are evaluated. During four weeks, irradiated animals are exposed to six irradiation sessions using an 843 nm LED (5.7 J cm^–2 at 19 mW cm^–2 per session). Non-irradiated control animals display inflammatory areas almost five times greater than the treated group (p < 0.001). This result on inflammatory infiltrate may have caused impacts on the significant lower blood glucose level from irradiated animals (p = 0.04), twenty-four hours after the last irradiation session.

Infra-red light application to adipose tissue reduces its inflammation and may be considered as a therapy to manage obesity-related diseases.

http://ift.tt/2cE5FGK

Nutritional Strategies in the Management of Adult Patients with Inflammatory Bowel Disease: Dietary Considerations from Active Disease to Disease Remission

Abstract

Inflammatory bowel disease (IBD) is a group of chronic, lifelong, and relapsing illnesses, such as ulcerative colitis and Crohn's disease, which involve the gastrointestinal tract. There is no cure for these diseases, but combined pharmacological and nutritional therapy can induce remission and maintain clinical remission. Malnutrition and nutritional deficiencies among IBD patients result in poor clinical outcomes such as growth failure, reduced response to pharmacotherapy, increased risk for sepsis, and mortality. The aim of this review is to highlight the consequences of malnutrition in the management of IBD and describe nutritional interventions to facilitate induction of remission as well as maintenance; we will also discuss alternative delivery methods to improve nutritional status preoperatively.

http://ift.tt/2cKXCLP

IJMS, Vol. 17, Pages 1570: Biology, Pest Status, Microbiome and Control of Kudzu Bug (Hemiptera: Heteroptera: Plataspidae): A New Invasive Pest in the U.S.

Soybean is an important food crop, and insect integrated pest management (IPM) is critical to the sustainability of this production system. In recent years, the introduction into the United States of the kudzu bug currently identified as Megacopta cribraria (F.), poses a threat to soybean production. The kudzu bug was first discovered in the state of Georgia, U.S. in 2009 and since then has spread to most of the southeastern states. Because it was not found in the North American subcontinent before this time, much of our knowledge of this insect comes from research done in its native habitat. However, since the U.S. introduction, studies have been undertaken to improve our understanding of the kudzu bug basic biology, microbiome, migration patterns, host selection and management in its expanding new range. Researchers are not only looking at developing IPM strategies for the kudzu bug in soybean, but also at its unique relationship with symbiotic bacteria. Adult females deposit bacterial packets with their eggs, and the neonates feed on these packets to acquire the bacteria, Candidatus Ishikawaella capsulata. The kudzu bug should be an informative model to study the co-evolution of insect function and behavior with that of a single bacteria species. We review kudzu bug trapping and survey methods, the development of bioassays for insecticide susceptibility, insecticide efficacy, host preferences, impact of the pest on urban environments, population expansion, and the occurrence of natural enemies. The identity of the kudzu bug in the U.S. is not clear. We propose that the kudzu bug currently accepted as M. cribraria in the U.S. is actually Megacopta punctatissima, with more work needed to confirm this hypothesis.

http://ift.tt/2cKPICa

IJMS, Vol. 17, Pages 1566: The Role of Galectin-1 in Cancer Progression, and Synthetic Multivalent Systems for the Study of Galectin-1

This review discusses the role of galectin-1 in the tumor microenvironment. First, the structure and function of galectin-1 are discussed. Galectin-1, a member of the galectin family of lectins, is a functionally dimeric galactoside-binding protein. Although galectin-1 has both intracellular and extracellular functions, the defining carbohydrate-binding role occurs extracellularly. In this review, the extracellular roles of galectin-1 in cancer processes are discussed. In particular, the importance of multivalent interactions in galectin-1 mediated cellular processes is reviewed. Multivalent interactions involving galectin-1 in cellular adhesion, mobility and invasion, tumor-induced angiogenesis, and apoptosis are presented. Although the mechanisms of action of galectin-1 in these processes are still not well understood, the overexpression of galectin-1 in cancer progression indicates that the role of galectin-1 is significant. To conclude this review, synthetic frameworks that have been used to modulate galectin-1 processes are reviewed. Small molecule oligomers of carbohydrates, carbohydrate-functionalized pseudopolyrotaxanes, cyclodextrins, calixarenes, and glycodendrimers are presented. These synthetic multivalent systems serve as important tools for studying galectin-1 mediated cancer cellular functions.

http://ift.tt/2cTxHih

Modulation of Postnatal Neurogenesis by Perinatal Asphyxia: Effect of D 1 and D 2 Dopamine Receptor Agonists

Abstract

Perinatal asphyxia (PA) is associated to delayed cell death, affecting neurocircuitries of basal ganglia and hippocampus, and long-term neuropsychiatric disabilities. Several compensatory mechanisms have been suggested to take place, including cell proliferation and neurogenesis. There is evidence that PA can increase postnatal neurogenesis in hippocampus and subventricular zone (SVZ), modulated by dopamine, by still unclear mechanisms. We have studied here the effect of selective dopamine receptor agonists on cell death, cell proliferation and neurogenesis in organotypic cultures from control and asphyxia-exposed rats. Hippocampus and SVZ sampled at 1–3 postnatal days were cultured for 20–21 days. At day in vitro (DIV) 19, cultures were treated either with SKF38393 (10 and 100 µM, a D₁ agonist), quinpirole (10 µM, a D₂ agonist) or sulpiride (10 μM, a D₂ antagonist) + quinpirole (10 μM) and BrdU (10 μM, a mitosis marker) for 24 h. At DIV 20–21, cultures were processed for immunocytochemistry for microtubule-associated protein-2 (MAP-2, a neuronal marker), and BrdU, evaluated by confocal microscopy. Some cultures were analysed for cell viability at DIV 20–21 (LIVE/DEAD kit). PA increased cell death, cell proliferation and neurogenesis in hippocampus and SVZ cultures. The increase in cell death, but not in cell proliferation, was inhibited by both SKF38393 and quinpirole treatment. Neurogenesis was increased by quinpirole, but only in hippocampus, in cultures from both asphyxia-exposed and control-animals, effect that was antagonised by sulpiride, leading to the conclusion that dopamine modulates neurogenesis in hippocampus, mainly via D₂ receptors.

http://ift.tt/2ccEKRH