Πέμπτη, 5 Οκτωβρίου 2017

Neurocognitive performances of visuospatial attention and the correlations with metabolic and inflammatory biomarkers in adults with obesity

Abstract

The purposes of the present study were to explore the neurophysiological mechanism of visuospatial attention deficits in the adults with obesity, and to examine the relationships between neurocognitive (neuropsychological and neurophysiological) performances and the biochemical markers. Thirty adults with obesity and 30 healthy-weight controls, categorized by body mass index and %fat as measured with dual-energy X-ray absorptiometry, completed a fasting blood draw and performed a visuospatial attention paradigm with concomitant electrophysiological recording. The obese group showed slower reaction times and smaller P3 amplitudes when performing the cognitive task. Even when controlling for the co-variable of cardiorespiratory fitness, the results still remained. In addition, the serum levels of insulin, glucose, leptin, and C-reactive protein (CRP) were significantly higher in the obese group relative to the control group, but not those of IL-6, IL-1ß, and TNF-α. Partial correlations adjusting for cardiorespiratory fitness showed that leptin and CRP concentrations in the obese group were negatively associated with poorer neurophysiological (i.e. P3 amplitude) performance. However, the regression analysis showed that only leptin was the sole predictor of P3 amplitude in the obese group. These findings indicate that the individuals with obesity exhibited neurocognitive deficits when performing the visuospatial attention task, and serum leptin levels could be one of the influential factors.

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The highs and lows of programmed cardiovascular disease by developmental hypoxia: studies in the chicken embryo

Abstract

It is now established that adverse conditions during pregnancy can trigger a fetal origin of cardiovascular dysfunction and/or increase the risk of heart disease in later life. Sub-optimal environmental conditions during early life that may promote the development of cardiovascular dysfunction in the offspring include alterations in fetal oxygenation and nutrition as well as fetal exposure to stress hormones, such as glucocorticoids. There has been growing interest in identifying the partial contributions of each of these stressors to programming of cardiovascular dysfunction. However, in humans and in many animal models this is difficult, as the challenges cannot be disentangled. By using the chicken embryo as an animal model, science has been able to circumvent a number of problems. In contrast to mammals, in the chicken embryo the effects on the developing cardiovascular system of changes in oxygenation, nutrition or stress hormones can be isolated and determined directly, independent of changes in the maternal or placental physiology. In this review, we summarise studies that have exploited the chicken embryo model to determine the effects on prenatal growth, cardiovascular development and pituitary-adrenal function of isolated chronic developmental hypoxia.

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PIEZO2 as the anomalous mechanotransducer channel in auditory hair cells

Abstract

Throughout post-natal maturation of the mouse inner ear, cochlear hair cells display at least two types of mechanically-gated ion channel: normal mechanotransducer (MT) channels at the tips of the stereocilia, activated by tension in inter-ciliary tip links; and anomalous mechanosensitive (MS) channels on the top surface of the cells. The anomalous MS channels are responsible for the reverse-polarity current that appears in mutants in which normal transduction is lost. They are also seen in wild-type hair cells around birth, appearing two days earlier than normal MT channels, and being down-regulated with the emergence of the normal channels. We review the evidence that the normal and anomalous channels are distinct channel types, which includes differences in localization, susceptibility to pharmacological agents, single-channel conductance and Ca2+ permeability. The dichotomy is reinforced by the observation that the anomalous current is absent in cochlear cells of Piezo2-null mice, even though the normal MT current persists. The anomalous current is suppressed by high intracellular Ca2+, suggesting that influx of the divalent via more Ca2+-permeable normal MT channels inhibits the anomalous channels, thus explaining the temporal relationship between the two. Piezo2-null mice have largely normal hearing, exhibiting up to 20 dB elevation in threshold in the acoustic brainstem response, so raising questions about the significance of PIEZO2 in the cochlea. Since the anomalous current declines with post-natal age, PIEZO2 may contribute to hair cell development, but it does not underlie the normal MT current. Its role in the development of hearing is not understood.

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Chronic beta2-adrenoceptor agonist treatment alters muscle proteome and functional adaptations induced by high intensity training in young men

Abstract

Although the effects of training have been studied for decades, data on muscle proteome signature remodelling induced by high intensity training in relation to functional changes in humans remains incomplete. Likewise, β2-agonists are frequently used to counteract exercise-induced bronchoconstriction, but the effects β2-agonist treatment on muscle remodelling and adaptations to training are unknown. In a placebo-controlled parallel study, we randomized 21 trained men to four weeks of high intensity training with (HIT + β2A) or without (HIT) daily inhalation of β2-agonist (terbutaline, 4 mg d−1). Of 486 proteins identified by mass-spectrometry proteomics of muscle biopsies sampled before and after the intervention, 32 and 85 were changing (FDR ≤ 5%) with the intervention in HIT and HIT + β2A. Proteome signature changes were different in HIT and HIT + β2A (P = 0.005), wherein β2-agonist caused a repression of 25 proteins in HIT + β2A compared to HIT, and an upregulation of 7 proteins compared to HIT. β2-agonist repressed or even downregulated training-induced enrichment of pathways related to oxidative phosphorylation and glycogen metabolism, but upregulated pathways related to histone trimethylation and the nucleosome. Muscle contractile phenotype changed differently in HIT and HIT + β2A (P ≤ 0.001), with a fast-to-slow twitch transition in HIT and a slow-to-fast twitch transition in HIT + β2A. β2-agonist attenuated training-induced enhancements in maximal oxygen consumption (P ≤ 0.01) and exercise performance (11.6 vs. 6.1%, P ≤ 0.05) in HIT + β2A compared to HIT. These findings indicate that daily β2-agonist treatment attenuates the beneficial effects of high intensity training on exercise performance and oxidative capacity, and causes remodelling of muscle proteome signature towards a fast-twitch phenotype.

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Phosphodiesterase-5 inhibition preserves exercise onset vasodilator kinetics when NOS activity is reduced

BBackground: Nitric oxide (NO) mediated vasodilation contributes to the rapid rise in muscle blood flow at exercise onset. This occurs via increased cyclic guanosine monophosphate (cGMP), which is catabolized by phosphodiesterase-5 (PDE-5). Whether PDE-5 limits exercise vasodilation onset kinetics is unknown. We hypothesized the time-course of exercise vasodilation would be: 1) accelerated during PDE-5 inhibition (sildenafil citrate, SDF), 2) decelerated during NO synthase inhibition (L-NG-monomethyl arginine, L-NMMA), 3) effect of SDF on vasodilation onset kinetics would be attenuated with concurrent L-NMMA. Methods: Data from 29 healthy adults were analyzed. Individuals completed 5-min of moderate intensity forearm exercise under control conditions and during: 1) oral SDF (n = 8), 2) intra-arterial L-NMMA (n = 15), or 3) combined SDF + L-NMMA (n = 6). Forearm blood flow (FBF; Doppler ultrasound of the brachial artery) and mean brachial artery blood pressure (MAP) was measured continuously. Forearm vascular conductance (FVC, FBF ÷ MAP) was curve-fit with a monoexponential model and vasodilation onset kinetics were assessed by mean response time (MRT, time to achieve 63% of steady state). Results: SDF had no effect on MRT (p=0.90). NOS inhibition increased MRT (p=0.01). MRT during SDF+L-NMMA was not different from control exercise (p=0.76). Conclusion: PDE-5 inhibition alone has no effect on rapid onset vasodilation. Whereas NOS inhibition decelerates vasodilator kinetics, when combined with SDF, vasodilator kinetics do not differ from control. These data suggest NO-independent activation of cGMP occurs at exercise onset; thus PDE-5 inhibition may improve vasodilation in pathologies where NO bioavailability is impaired.



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Brown adipocytes postnatally arise through both differentiation from progenitors and conversion from white adipocytes in Syrian hamster

To investigate the postnatal development of brown adipose tissue (BAT) in Syrian hamsters, we histologically examined interscapular fat tissue from 5 to 16-day-old pups, focusing on how brown adipocytes arise. Interscapular fat of 5-day-old hamsters mainly consisted of white adipocytes containing large unilocular lipid droplets, as observed in typical white adipose tissue (WAT). On day 7, clusters of small, proliferative nonadipocytes with a strong immunoreactivity for Ki67 appeared near the edge of the interscapular fat tissue. The area of the Ki67-positive regions expanded to approximately 50% of the total tissue area by day 10. The interscapular fat showed the typical BAT feature by day 16. A brown adipocyte-specific marker, uncoupling protein 1 was clearly detected on day 10 and thereafter, while not detected on day 7. During conversion of interscapular fat from WAT to BAT, unilocular adipocytes completely and rapidly disappeared without obvious apoptosis. Dual immunofluorescence staining for Ki67 and monocarboxylate transporter 1 (MCT1), another selective marker for brown adipocytes, revealed that most of the proliferating cells were of the brown adipocyte lineage. Electron microscopic examination showed that some of the white adipocytes contained small lipid droplets in addition to the large droplet, and expressed MCT1 as do progenitor and mature brown adipocytes, implying a direct conversion from white to brown adipocytes. These results suggest that BAT of Syrian hamsters develops postnatally through two different pathways: the proliferation and differentiation of brown adipocyte progenitors, and the conversion of unilocular adipocytes to multilocular brown adipocytes.



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MyoVision: Software for Automated High-Content Analysis of Skeletal Muscle Immunohistochemistry

Analysis of skeletal muscle cross sections is an important experimental technique in muscle biology. Many aspects of immunohistochemistry and fluorescence microscopy can now be automated but most image quantification techniques still require extensive human input, slowing progress and introducing the possibility of user-bias. MyoVision is a new software package that was developed to overcome these limitations. The software improves upon previously reported automatic techniques and analyzes images without requiring significant human input and correction. When compared to data derived by manual quantification, MyoVision achieves an accuracy of ≥94% for basic measurements such as fiber number, fiber type distribution, fiber cross sectional area, and myonuclear number. Scientists can download the software free from www.MyoVision.org and use it to automate the analysis of their own experimental data. This will improve the efficiency and consistency of the analysis of muscle cross sections and help to reduce the burden of routine image quantification in muscle biology.



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Exercise training improves blood flow to contracting skeletal muscle of older men via enhanced cGMP signaling

Physical activity has the potential to offset age-related impairments in the regulation of blood flow and O2 delivery to the exercising muscles; however, the mechanisms underlying this effect of physical activity remain poorly understood. The present study examined the role of cGMP in training-induced adaptations in the regulation of skeletal muscle blood flow and oxidative metabolism during exercise in aging humans. We measured leg hemodynamics and oxidative metabolism during exercise engaging the knee-extensor muscles in young (n=15, 25 ± 1 years) and older (n=15, 72 ± 1 years) subjects before and after a period of aerobic high-intensity exercise training. To determine the role of cGMP signaling, pharmacological inhibition of phosphodiesterase 5 (PDE5) was performed. Before training, inhibition of PDE5 increased (P<0.05) skeletal muscle blood flow and VO2 during moderate-intensity exercise in the older group; however, these effects of PDE5 inhibition were not detected after training. These findings suggest a role for enhanced cGMP signaling in the training-induced improvement of regulation of blood flow in contracting skeletal muscle of older men.



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Role of bronchodilation and pattern of breathing in increasing expiratory flow during progressive hypercapnia in chronic obstructive pulmonary disease.

Hypercapnia (HC) in-vitro relaxes airway smooth muscle; in-vivo it increases respiratory effort, tidal expiratory flows (V'exp), and, by decreasing inspiratory duration (Ti), increases elastic recoil pressure (Pel) via lung visco-elasticity; however, its effect on airway resistance is uncertain. We examined the contributions of bronchodilation, Ti and expiratory effort to increasing V'exp with progressive HC in 10 COPD subjects, mean FEV1 53% predicted. Lung volumes (Vl), V'exp, esophageal pressure (Pes), Ti and end tidal PCO2 (PetCO2) were measured during 6 tidal breaths followed by an inspiratory capacity (IC), breathing air and at 3 levels of HC. V'exp and V' with sub-maximal forced vital capacities breathing air (V'sFVC) were compared. Pulmonary resistance (Rl) was measured from the Pes-V' relationship. Results: V'exp and Pes at end expiratory lung volume (EELV) + 0.3 tidal volume (V'(0.3Vt) and Pes(0.3Vt), respectively), Ti and Rl correlated with PetCO2 (p <0.001 for all) and were independent of tiotropium. PetCO2, Ti and Pes (0.3Vt) predicted the increasing V'(0.3Vt)/V'sFVC(0.3Vt) (multiple regression analysis (MRA); p=0.001, 0.004 and 0.023 respectively). At PetCO2 ≥ 50 Torr, V'(0.3Vt)/V'sFVC (0.3Vt) exceeded unity in 30 of 36 measurements and was predicted by PetCO2 and Pes(0.3Vt) (MRA: p=0.02 and 0.025 respectively). Rl decreased at PetCO2 45 torr (p <0.05) and did not change with further HC. IC and Vl(0.3Vt) did not change with HC. We conclude that in COPD HC increases V'exp due to bronchodilation, increased Pel secondary to decreasing Ti, and increased expiratory effort all promoting lung emptying and a stable EELV.



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Effects of Exercise Training on Calf Muscle Oxygen Extraction and Blood Flow in Patients with Peripheral Artery Disease

We employed near-infrared optical techniques, diffuse correlation spectroscopy (DCS) and frequency-domain near-infrared spectroscopy (FD-NIRS), to test the hypothesis that supervised exercise training increases skeletal muscle microvascular blood flow and oxygen extraction in patients with peripheral artery disease (PAD) who experience claudication. PAD patients (n=64) were randomly assigned to exercise and control groups. Patients in the exercise group received three months of supervised exercise training. Calf muscle blood flow and oxygen extraction were optically monitored before, during, and after performance of a graded treadmill protocol at baseline and at three months in both groups. Additionally, measurements of the ankle-brachial index (ABI) and peak walking time (PWT) to maximal claudication were made during each patient visit. Supervised exercise training was found to increase the maximal calf muscle blood flow and oxygen extraction levels during treadmill exercise by 29%(13%,50%) and 8%(1%,12%), respectively (p<0.001; median (25th percentile, 75th percentile)). These improvements across the exercise group population were significantly higher than corresponding changes in the control group (p<0.004). Exercise training also increased PWT by 49% (18%, 101%), (p = 0.01). However, within statistical error, the ABI, the resting calf muscle blood flow and oxygen extraction, and the recovery half-time for hemoglobin/myoglobin desaturation following cessation of maximal exercise, were not altered by exercise training. The concurrent monitoring of both blood flow and oxygen extraction with the hybrid DCS/FD-NIRS instrument revealed enhanced muscle oxidative metabolism during physical activity from exercise training, which could be an underlying mechanism for the observed improvement in PWT.



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Active exercise on immobilization-induced contractured rat knees develops arthrogenic joint contracture with pathological changes

This study investigated the effects of treadmill walking during remobilization on range of motion (ROM) and histopathology in rat knee joints, which were immobilized for three weeks in a flexed position. After fixator removal, rats were divided into a no-intervention (RM) group and a group forced to walk on a treadmill daily at 12 m/min for 60 min (WALK group). Passive knee extension ROMs were measured before (m-ROM) and after (a-ROM) knee flexor myotomy on the first and last day of a seven-day remobilization period, with m-ROM mainly reflecting myogenic factors and a-ROM reflecting arthrogenic factors. Knee joints were histologically analyzed and gene expression of inflammatory or fibrosis-related mediators in the posterior joint capsule were examined. m-ROM and a-ROM restrictions were established after immobilization. m-ROM significantly increased following the remobilization period both in RM and WALK groups compared with that of immobilized (IM) group. Conversely, a-ROM decreased following the remobilization period in both RM and WALK groups compared with that of IM group. Importantly, a-ROM was smaller in WALK group than RM group. Remobilization without intervention induced inflammatory and fibrotic reactions in the posterior joint capsule after one and seven days. Treadmill walking promoted these reactions and also increased the expression of fibrosis-related TGF-β1 and collagen type I and III genes. While free movement after immobilization improved myogenic contracture, arthrogenic contracture worsened. Treadmill walking further aggravated arthrogenic contracture through amplified inflammatory and fibrotic reactions. Thus, active exercise immediately after immobilization may not improve immobilization-induced joint contracture.



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Resistance training and exercise tolerance during high-intensity exercise: moving beyond just running economy and muscle strength

No abstract is required



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Treatment Advances in Spinal Muscular Atrophy

Abstract

Purpose of Review

Spinal muscular atrophy (SMA) is a genetic disorder of motor neurons in the anterior horns of the spinal cord and brainstem that results in muscle atrophy and weakness. SMA is an autosomal recessive disease linked to deletions of the SMN1 gene on chromosome 5q. Humans have a duplicate gene (SMN2) whose product can mitigate disease severity, leading to the variability in severity and age of onset of disease, and is therefore a target for drug development.

Recent Findings

Advances in preclinical and clinical trials have paved the way for novel therapeutic options for SMA patients, including many currently in clinical trials. In 2016, the first treatment for SMA has been approved in the USA, an antisense oligonucleotide that increases full-length protein product derived from SMN2.

Summary

The approval of a first treatment for SMA and the rapid advances in clinical trials provide the prospect for multiple approaches to disease modification. There are several other promising therapeutics in different stages of development, based on approaches such as neuroprotection, or gene therapy.



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Autism spectrum disorder and Li-Fraumeni syndrome: purely coincidental or mechanistically associated?

Abstract

Background

Autism spectrum disorders (ASDs) are neurodevelopmental disorders with impaired social interactions and communication and restrictive, repetitive patterns of behaviors, interests, and activities. A recent epidemiological study suggests that children with ASD might have an increased cancer risk.

Case presentation

The 14.5-year-old boy, previously diagnosed with ASD, was referred with persistent bone pain. Diagnostic work-up confirmed diagnosis of acute lymphoblastic leukemia (ALL); cytogenetic analysis revealed low hypodiploid karyotype with a mutation (c.733G>A, p.Gly245Ser, rs28934575) in TP53 in the leukemic blasts. By Sanger sequencing, the presence of this mutation in the germline was subsequently confirmed and, thus, diagnosis of Li-Fraumeni syndrome (LFS) was made. His family history was remarkable with two siblings with intellectual disability and a mother who has died of premenopausal breast cancer.

Conclusions

Some of the oncogenes and tumor suppressor genes causing cancer susceptibility syndromes overlap with those involved in autism. This functional overlap between autism and cancer is novel and particularly compelling. The surprising coincidence of LFS and ASD in our patient raises the question whether this is purely coincidental or mechanistically associated.



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On the distribution and inventories of radionuclides in dated sediments around the Swedish coast

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Publication date: Available online 4 October 2017
Source:Journal of Environmental Radioactivity
Author(s): Grzegorz Olszewski, Pål Andersson, Patric Lindahl, Mats Eriksson
The activity concentrations and distribution of 137Cs, 238Pu, 239+240Pu, 241Am, and 210Pb was determined by the analysis of six sediment cores from the Baltic Sea and Kattegat. The chronology of the sediment cores has been used to evaluate the origin and time trend of the radionuclide sources in these sediments. The sediment cores were dated with a 210Pb model and the results were validated with fallout peaks, assumed to originate from the global nuclear weapons testing and the Chernobyl accident. Source identification, using the isotopic and radionuclide activity ratios, showed that the Chernobyl accident is the main source of 137Cs in the Baltic Sea; for 239+240Pu and 241Am the dominant source was shown to be fallout from nuclear weapons tests. For 238Pu and 241Am the Chernobyl accident had a significant impact on the direct fallout into the Baltic Proper, with up to a 65% contribution in the sediment slices dated to 1986. In these sediment slices the maximum activity ratios of 238Pu/239+240Pu and 241Am/239+240Pu were 0.314 ± 0.008 and 1.29 ± 0.06, respectively. The ratios clearly deviate from the corresponding ratios for global nuclear weapons fallout (around 0.028 and 0.54, respectively). Calculated inventories were 63–175 Bq·m−2 for 239+240Pu, 2.8–7.8 for 238Pu Bq·m−2 and 0.92–44.4 kBq·m−2 for 137Cs. Different fallout patterns for 137Cs and plutonium isotopes from the Chernobyl accident were confirmed through depth profiles analyses. The maximum inventory of 137Cs was observed in the Bothnian Sea, while Chernobyl-derived plutonium was found to be mostly present in Northern Baltic Proper. The radionuclides distribution in the depth profiles shows how contaminated water affects the sediment as it passes sampling stations according to the current circulation pattern in the Baltic Sea. Additionally, the effect of increased activity concentrations from of river discharges in the most contaminated area in the Bothnian Sea was observed.



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Does Eid-ad-Adha affect the transmission of Zoonotic diseases?

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Hamed Ebrahimzadeh Leylabadlo, Hossein Samadi Kafil, Abbas Nikmaram

Annals of Tropical Medicine and Public Health 2017 10(4):1064-1065



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Targeting global elimination of rabies by 2030: Stakeholders' consensus

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Saurabh RamBihariLal Shrivastava, Prateek Saurabh Shrivastava, Jegadeesh Ramasamy

Annals of Tropical Medicine and Public Health 2017 10(4):779-780



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What's going on antibiotic resistance? What could be done for the reduction of risk?

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Ali Mehrabi Tavana

Annals of Tropical Medicine and Public Health 2017 10(4):785-786



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Displaying solidarity and compassion to meet the needs of the refugee population in European region

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Saurabh R Shrivastava, Prateek S Shrivastava, Jegadeesh Ramasamy

Annals of Tropical Medicine and Public Health 2017 10(4):787-788



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Osteoporosis: The present concern on screening and nonmedication management

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Sora Yasri, Viroj Wiwanitkit

Annals of Tropical Medicine and Public Health 2017 10(4):1087-1089



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Meeting the sexual and reproductive health needs of the neglected population groups in Bhutan

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Saurabh R Shrivastava, Prateek S Shrivastava, Jegadeesh Ramasamy

Annals of Tropical Medicine and Public Health 2017 10(4):791-792



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New guidelines released to ensure transparency and enhance credibility of the reported health estimates: World Health Organization

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Saurabh R Shrivastava, Prateek S Shrivastava, Jegadeesh Ramasamy

Annals of Tropical Medicine and Public Health 2017 10(4):793-794



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Salmonella typhi bacteriuria, predispositions and complications: Two case reports and review of literature

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Reetika Dawar, Sanjiv Jasuja, Firdaus Imdadi, Nitin P Ghonge

Annals of Tropical Medicine and Public Health 2017 10(4):1058-1060

Salmonella typhi infection presents most commonly as typhoid fever and infrequently as extraintestinal localized infections of bone, joints, soft tissues, spleen, endocardium, pulmonary, hepatobiliary, genital and urinary systems. Urinary tract infection ( UTI) is rare and clinical presentation is indistinguishable from UTIs due to other etiological agents or may even be asymptomatic. We report two cases of patients with chronic kidney disease with UTI due to S. typhi. Renal cyst, nephrolithiasis, and urethral strictures were the concomitant findings in one case and renal tubular acidosis with nephrocalcinosis in the other. In patients with relapses and a chronic course with coexisting functional or structural abnormalities of the urinary tract system, the suspicion of Salmonella as one of the probable causative agents should be kept in mind so as to ensure appropriate and adequate therapy. Furthermore, in the presence of long-standing hypokalemia, one should investigate for renal abnormalities and vice versa.

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Offering integrated package of services to counter stigma associated with HIV

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Saurabh R Shrivastava, Prateek S Shrivastava, Jegadeesh Ramasamy

Annals of Tropical Medicine and Public Health 2017 10(4):795-796



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Wandering dog should not be the reservoir host for opisthorchiasis in highly endemic area, Thailand

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Viroj Wiwanitkit

Annals of Tropical Medicine and Public Health 2017 10(4):1068-1068



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Responding to the public health challenge of obstetric fistula in developing nations: A preventable cause of physical and social disability

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Saurabh R Shrivastava, Prateek S Shrivastava, Jegadeesh Ramasamy

Annals of Tropical Medicine and Public Health 2017 10(4):797-798



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Skin lesion from a traditional Cambodian treatment “koah kshal”: An example of clinical manifestation relating to local public health system

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Sora Yasri, Viroj Wiwanitkit

Annals of Tropical Medicine and Public Health 2017 10(4):1076-1076



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Responding to the sensitive issue of sexual health by improving awareness and sexual education

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Saurabh R Shrivastava, Prateek S Shrivastava, Jegadeesh Ramasamy

Annals of Tropical Medicine and Public Health 2017 10(4):799-800



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Uptake Characteristics and Kinetics of Inorganic and Organic Phosphorus by Ceratophyllum demersum

Abstract

Submersed macrophytes take an unreplaceable role in stabilization of aquatic ecological system and purification of eutrophic water. It is becoming the focus of purifying water bodies around the world. This study investigated the inorganic and organic phosphorus (P) uptake characteristics in different P levels by Ceratophyllum demersum and P uptake kinetics of Ceratophyllum demersum through using ion depletion method. The results showed that the average daily P uptake by Ceratophyllum demersum increased significantly during the 30-day experimental period. P uptake abilities by Ceratophyllum demersum in different inorganic P (KH2PO4) levels were obviously enhanced with the increasing P concentration. Moreover, Ceratophyllum demersum could uptake and utilize β-glycerophosphate as P source no matter whether the systems were sterilized or not, which indicates that there was no microorganism dependence on the uptake of β-glycerophosphate by Ceratophyllum demersum. However, almost no P uptake was detected when using phytic acid as another kind of organic P source. The uptake ability of β-glycerophosphate P by Ceratophyllum demersum was much higher than that of inorganic P at the P level of 10 mg/L. The P uptake kinetics parameters were calculated according to the experimental data. The maximum absorption rate (I max) of P by Ceratophyllum demersum was 54.94 μg P/g(dry weight)·h and the Michaelis constant (K m) was 1.754 mg/L, which showed that the I max of P by Ceratophyllum demersum was relatively low when compared with other emergent aquatic plants and the affinity of P with Ceratophyllum demersum was rather weak. Owing to its endurance to high P concentration and the excellent purifying capacity, Ceratophyllum demersum still can be used to control eutrophication of water bodies.



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Utility of adult-based ultrasound malignancy risk stratifications in pediatric thyroid nodules

Abstract

Background

Individual ultrasound (US) features have limited ability to distinguish benign from malignant thyroid nodules. Adult-based systems have been developed to integrate the sonographic features in an effort to improve diagnostic accuracy. None, however, has been validated in children, in whom the likelihood of malignancy is 2–5 times higher than adults.

Objective

To assess the performance of two adult-based sonographic (US) stratification methods for assessment of thyroid nodules in children.

Materials and methods

This retrospective study comprised 124 children who underwent thyroid US. Three radiologists reviewed the US data using the American Thyroid Association (ATA) and the Thyroid Image Reporting and Data System (TI-RADS). Radiologists’ accuracy and agreement was assessed. The reference standard was histopathology/cytology or 2-year follow-up of clinical outcome for nonoperative cases.

Results

We assessed 71 benign and 52 malignant nodules and excluded 1 nodule. Using the ATA pattern descriptions, 80% of malignant nodules were classified as “high” 36/52 (69%) or “intermediate” 6/52 (11%) likelihood of malignancy. A total of 20/71 (28%) benign nodules were also classified within these two categories. Using the TI-RADS, malignant nodules were classified as 2, 3, 4a, 4b, 4c and 5, with rate of malignancy of 0%, 0%, 7/52 (13.5%), 7/52 (13.5%), 32/52 (61.5%) and 6/52 (11.5%), respectively. Benign nodules were also classified in the 4a (26/71; 36.6%), 4b (17/71; 24%), 4c (14/71; 19.7%) and 5 (1/71; 1.4%) categories. The positive and negative predictive values were 68.0% and 87.5% for ATA, and 71.7% and 80.0% for TI-RADS.

Conclusion

We validated the use of ATA and TI-RADS methods in children and showed that they have test characteristics similar to those in adults, although neither is independently sufficient to discriminate nodules’ likelihood of malignancy.



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Nitric Oxide (Donor/Induced) in Chemosensitization, Volume 1. 1st Edition



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Ethical Challenges in Oncology. 1st Edition



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Announcements



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Applications of Mass Spectrometry Imaging to Cancer, Volume 134. 1st Edition



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Cancer Disparities, Volume 133. 1st Edition



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Ecology and Evolution of Cancer. 1st Edition



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Handbook of Supportive and Palliative Radiation Oncology



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Congenital and Acquired Bone Marrow Failure. 1st Edition



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Thyroid Cancer and Nuclear Accidents. 1st Edition



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Patient-Derived Mouse Models of Cancer. Patient-Derived Orthotopic Xenografts (PDOX)



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Molecular Approach to Cancer Management. 1st Edition



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Translational Advances in Gynecologic Cancers. 1st Edition



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Differential Prognostic Value of Metabolic Heterogeneity of Primary Tumor and Metastatic Lymph Nodes in Patients with Pharyngeal Cancer

Background/Aim: We aimed to explore the prognostic value of metabolic heterogeneity of 18F-FDG uptake in chemoradiotherapy-treated pharyngeal cancer patients. Patients and Methods: This study included 52 consecutive patients with pharyngeal cancer who underwent 18F-FDG PET/CT before definitive chemoradiotherapy. The heterogeneity factor (HF) was defined as the derivative (dV/dT) of a volume-threshold function for primary tumors and metastatic lymph nodes. The relationships between clinical parameters and HFs of primary tumors (pHF) and metastatic lymph nodes (nHF) were analyzed. Results: The pHF (range=1.367 - –0.027; median=–0.152) was significantly correlated with the maximum standardized uptake value, metabolic tumor volume, and total lesion glycolysis. Induction chemotherapy response was not correlated with HF, whereas response to radiotherapy was significantly better in patients with high pHF (low heterogeneity). Consistently, the 2-year locoregional recurrence-free survival was significantly better in patients with high pHF (82.9% for pHF>–0.152 vs. 30.5% for pHF<–0.152, log-rank p=0.009). The nHF (range=–1.067 - –0.039; median=-0.160) was not correlated with response to radiotherapy and locoregional recurrences. Conclusion: pHF, but not nHF, was a significant predictor of response to radiotherapy and locoregional recurrence in pharyngeal cancer. Thus, HF use can prevent unnecessary treatment and surgical delays.



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Gastric Spindle Cell Neuroendocrine Tumor Mimicking Gastrointestinal Stromal Tumor: Unique Morphology and Diagnostic Pitfall

Gastric neuroendocrine tumors (GNETs) with spindle cell morphology are extremely rare. We present a case of a 49-year-old female patient with a history of systemic lupus erythematosus, Sjogren's syndrome, and gastroesophageal reflux disease. She was initially thought to have a spindle cell gastrointestinal stromal tumor per histological studies of the fundic polypectomy samples. Immunohistochemically, the tumor cells were negative for CD117, and CD34, but positive for chromogranin, synaptophysin, and CD56 with a 6% Ki-67 index, consistent with a spindle cell-type well differentiated neuroendocrine tumor, World Health Organization (WHO) Grade 2. To the best of our knowledge, this is the first case report of a gastric spindle cell neuroendocrine tumor in the English literature.



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Book Reviews



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miR-223 and Stathmin-1 Expression in Non-tumor Liver Tissue of Patients with Hepatocellular Carcinoma

Aim: Overexpression of stathmin (STMN1) has been reported for several tumor entities. STMN1 expression correlated with the detection of mutant p53, also suggesting loss-of-function-dependent mechanisms for its accumulation in hepatocellular carcinoma (HCC) cells. On the other hand, miR-223 has been identified as one of the most down-regulated miRNAs in HCC, and its expression was shown to be negatively correlated with STMN1 expression. The aim of this study was to investigate the clinical significance of STMN1 and miRNA-223 expression. Patients and Methods: Fifty-six consecutive patients with HCC who underwent curative hepatectomy as initial treatment were enrolled. They were divided into two groups based on the STMN1 expression level: high (n=36) and low (n=20) gene-expression groups. We compared the clinicopathological factors between the groups with high and low expression in non-tumor tissues. Thirty out of 56 patients were also divided into groups with high (n=15) and low (n=15) miR-223 expression and compared the clinicopathological factors between the two groups. Results: There were no significant differences in patient background between high and low STMN1 expression groups. The incidence of multicentric (MC) recurrence in the high-expression group was significantly higher than in the low-expression group and high STMN1 expression was shown to be an independent risk factor for MC recurrence. There were also no significant differences in patient background between high and low miR-223 expression groups; however, the disease-free survival rate in the group with low expression was significantly worse. Furthermore, MC-related miRNAs identified by miRNA microarray clearly clustered patients into MC recurrence and non-recurrence groups. Conclusion: Both gene and miRNA expression profiles in non-tumor liver tissues could predict the risk for MC recurrence. Such molecular information may be useful in enabling better decision making for patients with HCC.



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Surgical Resection and Outcome of Synchronous and Metachronous Primary Lung Cancer in Breast Cancer Patients

Background/Aim: Women with breast cancer are at increased risk of subsequent primary malignancies, specifically lung cancer. The aim of this study was to report the frequency of lung cancer in patients with breast cancer, and patients' characteristics and surgical outcomes. Patients and Methods: We investigated 1,066 consecutive female patients undergoing surgical resection for breast cancer and 666 undergoing surgical resection for lung cancer. Results: Lung cancer with breast cancer was observed in 14 patients (1.3% of breast cancer and 2.1% of lung cancer cases; mean age=65 years), and 3/14 (21.4%) patients were smokers. Sixteen lung cancer lesions in 14 patients were adenocarcinomas and one was squamous cell carcinoma. All 14 patients were alive at the time of this report; 4/14 (28.6%) patients had recurrent breast cancer and 1/14 (7.1%) had recurrent lung cancer. In synchronous cases, 5/6 (83.3%) patients received concomitant surgery for both breast cancer and lung cancer. Patients' postoperative courses were uneventful. In metachronous cases, eight patients had lung cancer a mean of 33 months after breast cancer surgery. All eight patients received adjuvant therapies and 4/8 (50%) patients received adjuvant therapies for recurrent breast cancer, including chemotherapy, radiotherapy, hormonal therapy, and anti-HER2 therapy. All patients had early-stage lung adenocarcinoma and underwent surgical resection. Conclusion: Concomitant surgery for synchronous lung and breast cancer was feasible and safe. In metachronous cases, lung cancers tended to be detected within 3 years after surgery for breast cancer. Careful follow-up for postoperative breast cancer may contribute to the detection of early-stage lung cancer.



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The Association Between Chemotherapy Immediately Before Nivolumab and Outcomes Thereafter

Background/Aim: We investigated whether the efficacy and type of pre-nivolumab chemotherapy influence outcomes in non-small cell lung cancer patients following nivolumab treatment. Patients and Methods: In this multicenter study, 199 patients treated with nivolumab were retrospectively reviewed. We analyzed the relationships between the clinical response to nivolumab and to chemotherapy administered immediately beforehand. Results: Patients who achieved objective responses to pretreatments showed higher disease control rates with nivolumab than patients who did not (64% vs. 47%, p=0.03), as did those who achieved disease control with pretreatments (62% vs. 35%, p<0.001). Bevacizumab-pretreated patients tended to show better objective response rates with nivolumab (27% vs. 13%, p=0.06); the objective response rate to nivolumab was significantly higher in bevacizumab-pretreated patients who showed clinical responses (42% vs. 9.1%, p=0.02). Conclusion: Achievement of a clinical response to chemotherapy immediately before nivolumab, particularly when combined with bevacizumab, increases the likelihood of disease control post-nivolumab.



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Predictive Factors for Poor Progression-free Survival in Patients with Non-small Cell Lung Cancer Treated with Nivolumab

Background: Nivolumab has shown promising effects in patients with non-small-cell lung cancer (NSCLC) as a second- or later-line treatment. This study aimed to identify patients who would not experience any benefit from nivolumab treatment. Materials and Methods: In this study, data for 201 patients treated with nivolumab during 17 December 2015 to 31 July 2016 at three respiratory medical centers in Japan were retrospectively reviewed. We collected clinical data at the time of nivolumab treatment commencement. We investigated the relationship between progression-free survival (PFS) and patient characteristics. Results: In both univariate and multivariate analysis, performance status (PS) score ≥2, steroid use at baseline and lactate dehydrogenase (LDH) level >240 IU/l were significantly associated with poor PFS (all p<0.05). Conclusion: PS score ≥2, steroid use at baseline and a high LDH level were predictive of poor PFS in patients with NSCLC treated with nivolumab. Careful monitoring is recommended for treating such patients with nivolumab (UMIN-ID: UMIN000025908).



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A Proposal for Progression-Free Survival Assessment in Patients with Early Progressive Cancer

Background/Aim: Progression-free survival (PFS), which is evaluated in oncology clinical trials, is determined based on tumor progression evaluated according to an assessment schedule. There is possibly a bias in median PFS and hazard ratio (HR) for PFS depending on the assessment schedule referring to randomized controlled trials (RCTs) in patients with metastatic colorectal cancer. Materials and Methods: We re-analyzed the PFS in the FTD/TPI phase 2 trial by changing the assessment schedule. To assess biases in median PFS and HR for PFS resulting from different assessment schedules, we performed a computational simulation. Results: The reanalysis of FTD/TPI phase 2 trial and the simulation results showed that there were biases in median PFS and HR for PFS. Conclusion: In RCTs for early progressive cancer, median PFS is dependent on the assessment schedule; however, HR for PFS can be assessed without clinically-meaningful differences between assessment schedules, regardless of biomarker assumptions.



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Correction to: Functional and quality of life outcomes after partial glossectomy: a multi-institutional longitudinal study of the head and neck research network



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Anti-inflammatory Effects of Enhanced Recovery Programs on Early-Stage Colorectal Cancer Surgery

Abstract

Background

Postoperative ileus (POI) is observed in 20–30% of patients undergoing colorectal cancer surgery, despite enhanced recovery programs (ERPs). Cyclooxygenase (COX)-2 is identified as a key enzyme in POI, but other arachidonic acid pathway enzymes have received little attention despite their potential as selective targets to prevent POI. The objectives were to compare the expression of arachidonic acid metabolism (AAM) enzymes (1) between patients who underwent colorectal cancer surgery and followed an ERP or not (NERP), (2) and between ERP patients who experimented POI or not and (3) to determine the ability of antagonists of these pathways to modulate contractile activity of colonic muscle.

Methods

This was a translational study. Main outcome measures were gastrointestinal motility recovery data, mRNA expressions of key enzymes involved in AAM (RT-qPCR) and ex vivo motility values of the circular colon muscle. Twenty-eight prospectively included ERP patients were compared to eleven retrospectively included NERP patients that underwent colorectal cancer surgery.

Results

ERP reduced colonic mucosal COX-2, microsomal prostaglandin E synthase (mPGES1) and hematopoietic prostaglandin D synthase (HPGDS) mRNA expression. mPGES1 and HPGDS mRNA expression were significantly associated with ERP compliance (respectively, r2 = 0.25, p = 0.002 and r2 = 0.6, p < 0.001). In muscularis propria, HPGDS mRNA expression was correlated with GI motility recovery (p = 0.002). The pharmacological inhibition of mPGES1 increased spontaneous ex vivo contractile activity in circular muscle (p = 0.03).

Conclusion

The effects of ERP on GI recovery are correlated with the compliance of ERP and could be mediated at least in part by mPGES1, HPGDS and COX-2. Furthermore, mPGES1 shows promise as a therapeutic target to further reduce POI duration among ERP patients.



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Clinical and Radiological Discrimination of Solitary Pulmonary Lesions in Colorectal Cancer Patients

Abstract

Objectives

The lung is one of the most common organs of metastasis from colorectal cancer (CRC), and we have encountered lung cancer patients with a history of CRC. There have been few studies regarding methods used to discriminate between primary lung cancer (PLC) and pulmonary metastasis from CRC (PM-CRC) based only on preoperative findings. We retrospectively investigated predictive factors discriminating between these lesions in patients with a history of CRC.

Methods

Between 2006 and 2015, 117 patients with a history of CRC (44 patients with 47 PLC and 73 patients with 102 PM-CRC) underwent subsequent or concurrent resection of pulmonary lesions. We compared the clinical and radiological characteristics of 100 patients with solitary lesions (43 PLC and 57 PM-CRC). Using univariate and multivariate analyses, we examined predictive factors for discrimination of these two lesions.

Results

All tumors with findings of ground-glass opacity (GGO) were PLC (n = 19). In a multivariate analysis of 81 radiologically solid tumors, two factors were found to be significant independent predictors of PLC: a history of stage I CRC and presence of pleural indentation. All tumors in 26 patients with either GGO or both a stage I CRC history and pleural indentation were PLC, while most tumors in patients without all three factors were PM-CRC (43/44; 97.7%).

Conclusions

The presence or absence of GGO, pathological CRC stage, and pleural indentation could be useful factors to distinguish between PLC and PM-CRC.



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MOG antibody seropositivity in a patient with encephalitis: beyond the classical syndrome

The presence of circulating anti-myelin oligodendrocyte glycoprotein antibodies (MOG-Abs) has been described in sera of patients with different inflammatory conditions of the central nervous system. In adults ...

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Clinical vignettes inadequate to assess impact of implicit bias: concerning limitations of a systematic review

Abstract

We are writing in response to Dehon et al's article “A Systematic Review of the Impact of Physician Implicit Racial Bias on Clinical Decision Making”1 in the August 2017 issue of Academic Emergency Medicine. As members of SAEM's Academy of Diversity and Inclusion in Emergency Medicine, we believe it is imperative to pursue research on the impact of bias and discrimination on clinical practice and healthcare outcomes. While we commend Dr. Dehon and her colleagues for their effort to assess the impact of implicit bias on clinical decision-making, we do not think that the evidence reviewed supports the breadth of their conclusions.

This article is protected by copyright. All rights reserved.



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Study Identifies Crucial Characteristic of High-Risk HPV

By comparing the genomes of women infected with a high-risk type of human papillomavirus (HPV), researchers have found that a precise DNA sequence of a viral gene is associated with cervical cancer.



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Sap From Garden Plants Can Burn Eyes

Gardeners caring for plants in the Euphorbia genus should be careful about handling the toxic sap, according to a new report.
Reuters Health Information

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Is Age a Risk Factor for Lymph Node Positivity in Melanoma?

Certain patients with thin melanomas aren't recommended for sentinel lymph node biopsy, but a study suggests that they should be.
Medscape Dermatology

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Immediate Biopsy for Suspicious Oral Lesions, Says ADA

Biopsy and histologic assessment of suspicious mucosal lesions in the mouth continue to be the cornerstone for early cancer detection recommended by the American Dental Association.
Medscape Medical News

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Anxiety and Fear of Recurrence Despite a Good Prognosis: An Interview Study with Differentiated Thyroid Cancer Patients

Thyroid , Vol. 0, No. 0.


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MiR-203a-3p suppresses cell proliferation and metastasis through inhibiting LASP1 in nasopharyngeal carcinoma

miR-203a-3p was reported as a tumor suppressor and disregulated in many malignancies including nasopharyngeal carcinoma (NPC). However, its function in tumor growth and metastasis in NPC has rarely been reported.

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An Interesting Case of Pyoderma Gangrenosum with Immature Hystiocytoid Neutrophils

Abstract

We present a unique case of a 36-year-old male who developed more than twenty Pyoderma gangrenosum ulcers demonstrating on histopathology a dense inflammatory infiltrate composed of histiocytoid mononuclear immature cells with a strong positivity for myeloperoxidase and Leder stain, suggesting a myeloid lineage in the absence of a concomitant myeloproliferative disorder. Histiocytoid Sweet syndrome is now recognized as a histological subtype of Sweet syndrome. Although Pyoderma gangrenosum and Sweet syndrome belong to the spectrum of neutrophilic diseases, to the best of our knowledge, this is the first case of a “Histiocytoid Pyoderma gangrenosum” encompassing immature granulocytes in the absence of leukemia cutis.



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Adult reference intervals for IgG subclasses with Siemens immunonephelometric assays in Chinese population

To determine the adult reference intervals for the Siemens IgG subclass reagents.

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Plastic Surgery Videos Need Strict Ethics Standards, Doctors Argue

Some plastic surgeons have gained large social media followings by sharing theatrical videos of surgery with entertainment, rather than education, in mind. Now experts are proposing ethics guidelines to ensure that the content of plastic surgery videos on social media isn’t harmful to patients.
Reuters Health Information

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Las Vegas Faced a Massacre. Did It Have Enough Trauma Centers?

Hospitals view adding trauma care as a potential profit tool, but experts say more centers do not necessarily improve the system’s ability to respond to a mass casualty event.
Kaiser Health News

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Stopping Long-term Aspirin Linked to CV-Event Spike

The elevated risk appeared shortly after patients stopped aspirin and did not appear to diminish over time, the investigators report.
Medscape Medical News

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Reaction to 'Old' Tattoo Ink Mimics Lymphoma

An unusual case of tattoo pigment hypersensitivity caused widespread lymphadenopathy 15 years later, but without a skin reaction.
Medscape Medical News

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Abnormal intrinsic brain functional network dynamics in Parkinson’s disease

Abstract
Parkinson’s disease is a neurodegenerative disorder characterized by nigrostriatal dopamine depletion. Previous studies measuring spontaneous brain activity using resting state functional magnetic resonance imaging have reported abnormal changes in broadly distributed whole-brain networks. Although resting state functional connectivity, estimating temporal correlations between brain regions, is measured with the assumption that intrinsic fluctuations throughout the scan are stable, dynamic changes of functional connectivity have recently been suggested to reflect aspects of functional capacity of neural systems, and thus may serve as biomarkers of disease. The present work is the first study to investigate the dynamic functional connectivity in patients with Parkinson’s disease, with a focus on the temporal properties of functional connectivity states as well as the variability of network topological organization using resting state functional magnetic resonance imaging. Thirty-one Parkinson’s disease patients and 23 healthy controls were studied using group spatial independent component analysis, a sliding windows approach, and graph-theory methods. The dynamic functional connectivity analyses suggested two discrete connectivity configurations: a more frequent, sparsely connected within-network state (State I) and a less frequent, more strongly interconnected between-network state (State II). In patients with Parkinson’s disease, the occurrence of the sparsely connected State I dropped by 12.62%, while the expression of the more strongly interconnected State II increased by the same amount. This was consistent with the altered temporal properties of the dynamic functional connectivity characterized by a shortening of the dwell time of State I and by a proportional increase of the dwell time pattern in State II. These changes are suggestive of a reduction in functional segregation among networks and are correlated with the clinical severity of Parkinson’s disease symptoms. Additionally, there was a higher variability in the network global efficiency, suggesting an abnormal global integration of the brain networks. The altered functional segregation and abnormal global integration in brain networks confirmed the vulnerability of functional connectivity networks in Parkinson’s disease.

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Oncology Research Program



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NCCN News



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Bladder Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in Oncology

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Bladder Cancer focuses on systemic therapy for muscle-invasive urothelial bladder cancer, as substantial revisions were made in the 2017 updates, such as new recommendations for nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab. The complete version of the NCCN Guidelines for Bladder Cancer addresses additional aspects of the management of bladder cancer, including non–muscle-invasive urothelial bladder cancer and nonurothelial histologies, as well as staging, evaluation, and follow-up.



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Serving "a la CAR-T": Value-Based Pricing and Gene Therapy



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Distress and Financial Distress in Adults With Cancer: An Age-Based Analysis

Background: Although financial distress is commonly recognized in patients with cancer, it may be more prevalent in younger adults. This study sought to evaluate disparities in overall and financial distress in patients with cancer as a function of age. Methods: This was a single-center cross-sectional study of patients with solid malignancies requiring cancer therapy. The patient questionnaire included demographics, financial concerns, and measures of overall and financial distress. Data analyses compared patients in 3 age groups: young (<50 years), middle-aged (50–64 years), and elderly (≥65 years). Results: The cohort included 119 patients (median age, 62 years; 52% female; 84% white; 100% insured; 36% income ≥$75,000). Significant financial concerns included paying rent/mortgage (P=.003) and buying food (P=.032). Impact of Event Scale (IES) results revealed significant distress in 73% young, 64% middle-aged, and 44% elderly patients. The mean Distress Thermometer (DT) score was 6.1 (standard deviation [SD], 2.9) for young patients, 5.4 (SD, 2.6) for middle-aged, and 4.4 (SD, 3.3) for elderly patients. Young patients were more likely than elderly patients to have a higher IES distress score (P=.016) and DT score (P=.048). The mean InCharge score was lowest (indicating greatest financial distress) in the young group and progressed with age: 5.0 (SD, 1.9), 5.7 (SD, 2.7), and 7.4 (SD, 1.9), respectively (P<.001). Multivariable analyses revealed that the relationship between financial distress and overall distress was strongest in the middle-age group; as the DT increased by 1 point, the InCharge scores decreased by 0.52 (P<.001). Conclusions: Overall and financial distress are more common in young and middle-aged patients with cancer. There are several factors, including employment, insurance, access to paid sick leave, children, and education, that affect younger and middle-aged adults and are less of a potential stressor for elderly individuals.



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Implementation Framework for NCCN Guidelines



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Urothelial Carcinoma of the Bladder and the Rise of Immunotherapy

With the advent of platinum-based chemotherapy, survival rates for metastatic urothelial carcinoma have plateaued, giving way to the modern immunotherapy paradigm. Although immunotherapy as an effective treatment dates back to the live, attenuated bacillus Calmette-Guérin vaccine, the recent impact of immune checkpoint inhibitors targeting programmed death/programmed death-ligand 1 (PD-1/PD-L1) coupled with the promise of both anti–cytotoxic T-lymphocyte–associated protein 4 (CTLA-4) antibodies and indoleamine-2, 3-dioxygenase-1 (IDO-1) inhibitors have provided a resurgence. To date, pembrolizumab, a PD-1 inhibitor, has been granted full FDA approval based on its high antitumor activity, tolerability, and efficacy, with notable prolonged durable responses in the second-line setting. Nivolumab (a PD-1 inhibitor) and atezolizumab, durvalumab, and avelumab (PD-L1 inhibitors) have also gained accelerated drug approval in the second-line setting. In addition, atezolizumab and pembrolizumab have been approved for platinum-ineligible patients in the first-line setting. Effective 2-drug combinations reported include nivolumab plus the CTLA-4 antibody ipilimumab and pembrolizumab plus the IDO-1 inhibitor epacadostat. Further expansion of immunotherapy will hinge in part on the ability to define responders versus nonresponders through the use of biomarkers like PD-L1 or mutational load. Clinical trials with immunotherapy for metastatic disease as single agents or in combination are ongoing. This review explores the rise of immunotherapy and presents the current treatments and challenges posed with development of biomarkers, and provides a summary of ongoing phase III clinical trials.



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To the Editor: Predictive Markers and Precision Medicine



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Pathologic Complete Response After Neoadjuvant Chemotherapy and Long-Term Outcomes Among Young Women With Breast Cancer

Purpose: Breast cancer in young women is associated with an aggressive tumor biology and higher risk of recurrence. Pathologic complete response (pCR) after neoadjuvant therapy has been shown to be a surrogate marker for disease-free survival (DFS) and overall survival (OS), but the association between pCR and survival outcomes in young women with breast cancer is not well described. Methods: This study included women aged ≤40 years at diagnosis who received neoadjuvant chemotherapy (NAC) for stage II–III invasive breast cancer between 1998 and 2014 at Massachusetts General Hospital. Outcomes were compared between patients who achieved pCR (ypT0/is, ypN0) and those with residual disease. Results: A total of 170 young women were included in the analytical data set, of which 53 (31.2%) achieved pCR after NAC. The 5-year DFS rate for patients with and without pCR was 91% versus 60%, respectively (P<.01), and the OS rate was 95% versus 75%, respectively (P<.01). Among patients with pCR, no difference was seen in OS irrespective of baseline clinical stage (P=.6), but among patients with residual disease after NAC, a significant difference in OS based on baseline clinical stage was observed (P<.001). Conclusions: Our results suggest pCR after NAC is strongly associated with significantly improved DFS and OS in young women with breast cancer, and perhaps even more so than baseline stage. However, the significantly higher mortality for patients who did not attain pCR highlights the need for better therapies, and the neoadjuvant trial design could potentially serve as an efficient method for rapid triage and escalation/de-escalation of therapies to improve outcomes for young women with breast cancer.



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EGFR-Mutant Non-Small Cell Lung Cancer in the Era of Precision Medicine: Importance of Germline EGFR T790M Testing

With the rapid development of precision medicine, next-generation sequencing (NGS) has provided the ability to uncode tumors at the DNA level. Identifying EGFR mutations and other molecular changes has become more crucial in the management of non–small cell lung cancer (NSCLC) than ever before. Although the histologic subtypes in patients with advanced NSCLC remain valid in determining treatment options, the detection of specific molecular signatures such as de novo T790M with sensitizing EGFR mutations could be more useful than the histologic subtype itself. Germline T790M mutation should be suspected and tested for when multiple biopsies show de novo T790M mutations or when de novo T790M is found in patients with a family history of lung cancer. This case report presents a 60-year-old woman with bilateral NSCLC with 3 different distinct histologic diagnoses. Evaluating the molecular profile using NGS completely changed the diagnosis, prognosis, and management of this rare presentation of NSCLC.



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A Population-Based Assessment of Emergency Department Observation Status for Older Adults With Cancer

Background: Hospitals' use of observation status for patients with cancer presenting to the emergency department (ED) is not well understood. This model of care delivery may be a viable alternative to inpatient admission for patients with cancer presenting with certain conditions. Our objective was to assess the use of observation status among Medicare beneficiaries with and without cancer. Methods: Population-based SEER-Medicare data were used to assess differences in the use of observation status between Medicare beneficiaries aged ≥66 years with and without cancer using a matched analysis (n=151,183 per cohort). We assessed the ratio of observation unit use to inpatient admission, between cancer and noncancer cohorts, and for patients diagnosed with breast, colon, lung, and prostate cancers. Poisson regression models were used to calculate observation rate estimates and 95% CIs while adjusting for selected patient characteristics. Results: When considering the volume of hospitalizations, observation status is used less frequently among beneficiaries with cancer than those without (43 vs 69 observation status visits per 1,000 inpatient admissions, respectively). The estimated observation rate per 1,000 inpatient admissions was higher for beneficiaries aged <75 years versus those aged ≥75 years, those with a Charlson comorbidity index of 0 vs 1 or ≥2, and those without a prior hospitalization versus those with ≥1 prior hospitalizations. Patients with breast and prostate cancers had higher adjusted and unadjusted observation rates per 1,000 inpatient admissions compared with those with colon and lung cancers. Conclusions: Observation status is used proportionately less for beneficiaries with cancer than those without. There may be opportunities to develop standards for ED staff to manage certain conditions for patients with cancer in observation status, and to reserve hospital resources for those who need it most.



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NCCN Guidelines Insights: Myeloproliferative Neoplasms, Version 2.2018

Myeloproliferative neoplasms (MPNs) are a group of heterogeneous disorders of the hematopoietic system that include myelofibrosis (MF), polycythemia vera (PV), and essential thrombocythemia (ET). PV and ET are characterized by significant thrombohemorrhagic complications and a high risk of transformation to MF and acute myeloid leukemia. The diagnosis and management of PV and ET has evolved since the identification of mutations implicated in their pathogenesis. These NCCN Guideline Insights discuss the recommendations outlined in the NCCN Guidelines for the risk stratification, treatment, and special considerations for the management of PV and ET.



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Clinical Significance of Histologic Variants of Bladder Cancer

Pathologists have identified many "histologic variants" of bladder cancer (BCA): histologic patterns that differ from conventional urothelial carcinoma (transitional cell carcinoma). Several of these are biologically aggressive, and their identification may aid in clinical decision-making. This article reviews several histologic variants and their value in deciding management of cT1 disease and predicting response to neoadjuvant chemotherapy (NAC). Diagnostic issues are also addressed, such as interobserver variability among pathologists. For example, although stage cT1 conventional urothelial carcinoma is usually managed conservatively, cT1 micropapillary carcinoma has high mortality following conservative management, and early cystectomy may reduce mortality. Similarly, plasmacytoid and small cell cancers are remarkably aggressive, and those diagnosed as stage cT1 at transurethral resection are likely understaged; conservative management thus greatly risks undertreatment. As an example of response, NAC dramatically reduces mortality in patients with small cell BCA, and is thus the standard of care, even in stage cT1 disease. Although identification of histologic variants may inform on optimal management, diagnostic issues challenge their incorporation into clinical practice. For example, interobserver reproducibility is only moderate for the diagnosis of micropapillary BCA. Studies have identified specific histologic issues underlying this diagnostic irreproducibility, and ongoing work aims to remedy this issue. In summary, histologic variants are emerging as potentially useful biomarkers in the management of BCA. Although issues remain unresolved, pathologists and treating physicians will benefit from understanding these variants and their prognostic and therapeutic implications.



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The Senior Toronto Oncology Panel (STOP) Study: Research Participation for Older Adults With Cancer and Caregivers

Background: Patient engagement in research may lead to better-designed studies and improved health outcomes. The objectives of this study were to identify the research priorities of older adults with cancer (OAWCs) and their caregivers and examine how to engage these individuals in research teams and what supports are needed. Methods: We conducted 3 public meetings and 7 focus groups to delineate research priorities and the supports needed to facilitate integration of OAWCs and their caregivers on research teams. Results: A total of 33 older adults and 19 caregivers attended a public meeting and 27 older adults and 17 caregivers participated in a focus group. Most of the OAWCs and their caregivers had never participated in research before. Three themes were identified from the focus groups: (1) motivation to be on a team; (2) ability to make meaningful contributions; and (3) logistical considerations to facilitate engagement. Most participants were motivated to be a research team member and be involved in all steps of research if it could benefit them or future patients and caregivers. OAWCs and their caregivers were highly motivated to improve outcomes. Required logistics included flexibility regarding time and location, accessibility to computer technology, transportation support, materials worded in lay language, and attending/having short training sessions, as well as the presence of peer support. Conclusions: OAWCs and their caregivers are very motivated and willing to participate in research and to be research team members. Logistics and the social aspects of being on a team are important.



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Admission or Observation? Population Health Is Here



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Development, Validation, and Dissemination of a Breast Cancer Recurrence Detection and Timing Informatics Algorithm

Abstract
Background
This study developed, validated, and disseminated a generalizable informatics algorithm for detecting breast cancer recurrence and timing using a gold standard measure of recurrence coupled with data derived from a readily available common data model that pools health insurance claims and electronic health records data.
Methods
The algorithm has two parts: to detect the presence of recurrence and to estimate the timing of recurrence. The primary data source was the Cancer Research Network Virtual Data Warehouse (VDW). Sixteen potential indicators of recurrence were considered for model development. The final recurrence detection and timing models were determined, respectively, by maximizing the area under the ROC curve (AUROC) and minimizing average absolute error. Detection and timing algorithms were validated using VDW data in comparison with a gold standard recurrence capture from a third site in which recurrences were validated through chart review. Performance of this algorithm, stratified by stage at diagnosis, was compared with other published algorithms. All statistical tests were two-sided.
Results
Detection model AUROCs were 0.939 (95% confidence interval [CI] = 0.917 to 0.955) in the training data set (n = 3370) and 0.956 (95% CI = 0.944 to 0.971) and 0.900 (95% CI = 0.872 to 0.928), respectively, in the two validation data sets (n = 3370 and 3961, respectively). Timing models yielded average absolute prediction errors of 12.6% (95% CI = 10.5% to 14.5%) in the training data and 11.7% (95% CI = 9.9% to 13.5%) and 10.8% (95% CI = 9.6% to 12.2%) in the validation data sets, respectively, and were statistically significantly lower by 12.6% (95% CI = 8.8% to 16.5%, P < .001) than those estimated using previously reported timing algorithms. Similar covariates were included in both detection and timing algorithms but differed substantially from previous studies.
Conclusions
Valid and reliable detection of recurrence using data derived from electronic medical records and insurance claims is feasible. These tools will enable extensive, novel research on quality, effectiveness, and outcomes for breast cancer patients and those who develop recurrence.

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Tumor localization may change the type of adjuvant treatment in gastric cancer



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Reply to Tumor localization may change the type of adjuvant treatment in gastric cancer



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Antibiotic therapy, supportive treatment and management of immunomodulation-inflammation response in community acquired pneumonia: review of recommendations

Community-acquired pneumonia is a common and serious disease, with high rates of morbidity and mortality. Management and treatment of community-acquired pneumonia are described in three main documents: the 200...

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Reconstruction of a near total ear amputation with a neurosensorial radial forearm free flap prelaminated with porous polyethylene implant and delay procedure

When an auricular defect is caused by high-energy trauma that causes damage to the surrounding tissues, the patient may be not a candidate for reconstruction with local flaps and free tissue transfer may be necessary. Here we present a case of total auricular reconstruction in a 27 year-old man who had total loss of the left ear and traumatized temporal skin and fascia. A radial forearm flap prelaminated by a porous polyethylene implant was employed. A “printed” ear made of silicone, based on the patient's CT-scan of the contralateral ear, was used for intraoperative molding of the future reconstruction. Prolonged prelamination time and surgical delay (three months) were performed to reduce edema, distortion and loss of definition of the framework after revascularization. After subsequent integration and neovascularization of the added tissue, the prelaminated flap was transferred. Flap reinnervation was also performed by direct coaption of the great auricular nerve to the lateral antebrachial cutaneous nerve. The flap fully survived and there were no complications in the early postoperative period. Between 3 and 6 months, the patient returned to normal ranges in terms of warmth and cold, and recovered the discriminative facial sensibility. After one year the auricular reconstruction was intact and satisfactory aesthetic results were achieved. This method may offer a satisfactory solution for a difficult problem and may be considered for acquired total ear defects.



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miR-200c-3p spreads invasive capacity in human oral squamous cell carcinoma microenvironment

Abstract

Oral squamous cell carcinoma (OSCC) constitutes over 90% of all cancers in the oral cavity. The prognosis for patients with invasive OSCC is poor; therefore, it is important to understand the molecular mechanisms of invasion and subsequent metastasis not only to prevent cancer progression but also to detect new therapeutic targets against OSCC. Recently, extracellular vesicles—particularly exosomes—have been recognized as intercellular communicators in the tumor microenvironment. As exosomic cargo, deregulated microRNAs (miRNAs) can shape the surrounding microenvironment in a cancer-dependent manner. Previous studies have shown inconsistent results regarding miR-200c-3p expression levels in OSCC cell lines, tissues, or serum—likely because of the heterogeneous characters of the specimen materials. For this reason, single-cell clone analyses are necessary to effectively assess the role of exosome-derived miRNAs on cells within the tumor microenvironment. The present study utilized integrated microarray profiling to compare exosome-derived miRNA and exosome-treated cell-derived mRNA expression. Data were acquired from noninvasive SQUU-A and highly invasive SQUU-B tongue cancer cell clones derived from a single patient to determine candidate miRNAs that promote OSCC invasion. Matrigel invasion assays confirmed that hsa-miR-200c-3p was a key pro-invasion factor among six miRNA candidates. Consistently, silencing of the miR-200c-3p targets, CHD9 and WRN, significantly accelerated the invasive potential of SQUU-A cells. Thus, our data indicate that miR-200c-3p in exosomes derived from a highly invasive OSCC line can induce a similar phenotype in non-invasive counterparts. This article is protected by copyright. All rights reserved



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Biography—Hidenori Inohara



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Preface



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Serum tau and neurological outcome in cardiac arrest

Abstract

Objective: To test serum tau as a predictor of neurological outcome after cardiac arrest.

Methods: We measured the neuronal protein tau in serum at 24, 48, and 72 h after cardiac arrest in 689 patients in the prospective international Target Temperature Management trial. The main outcome was poor neurological outcome, defined as Cerebral Performance Category 3-5 at 6 months.

Results: Increased tau was associated with poor outcome at 6 months after cardiac arrest (median 38.5 [IQR 5.7-245] ng/L in poor versus 1.5 [0.7-2.4] ng/L in good outcome, for tau at 72 h, p<0.0001). Tau improved prediction of poor outcome compared to using clinical information (p<0.0001). Tau cut-offs had low false positive rates (FPR) for good outcome while retaining high sensitivity for poor outcome. For example, tau at 72 h had FPR 2% (95% CI 1-4%) with sensitivity 66% (95% CI 61-70%). Tau had higher accuracy than serum NSE (the area under the receiver operating characteristic curve was 0.91 for tau versus 0.86 for NSE at 72 hours, p=0.00024). During follow-up (up to 956 days), tau was significantly associated with overall survival. The accuracy to predict outcome by serum tau was equally high for patients randomized to 33°C and 36°C targeted temperature after cardiac arrest.

Interpretation: Serum tau is a promising novel biomarker for prediction of neurological outcome in patients with cardiac arrest. It may be significantly better than serum NSE, which is recommended in guidelines and currently used in clinical practice in several countries to predict outcome after cardiac arrest. This article is protected by copyright. All rights reserved.



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Pooled analysis of the HLA-DRB1 by smoking interaction in Parkinson's disease

ABSTRACT

Objective: Inflammatory response plays an important role in Parkinson's disease (PD). Previous studies have reported an association between human leukocyte antigen (HLA)-DRB1 and the risk of PD. There has also been growing interest in investigating whether inflammation-related genes interact with environmental factors such as smoking to influence PD risk. We performed a pooled analysis of the interaction between HLA-DRB1 and smoking in PD in three population-based case-control studies from Denmark and France.

Methods: We included 2,056 cases and 2,723 controls from three PD studies (Denmark, France) that obtained information on smoking through interviews. Genotyping of the rs660895 polymorphism in the HLA-DRB1 region was based on saliva or blood DNA samples. To assess interactions, we used logistic regression with product terms between rs660895 and smoking. We performed random-effects meta-analysis of marginal associations and interactions.

Results: Both carrying rs660895-G (AG vs. AA: OR= 0.81; GG vs. AA: OR= 0.56; p-trend=0.003) and ever smoking (OR=0.56, p<0.001) were inversely associated with PD. A multiplicative interaction was observed between rs660895 and smoking using codominant, additive (interaction parameter=1.37, p=0.005), and dominant (interaction parameter=1.54, p=0.001) genetic models without any heterogeneity (I2=0.0%): the inverse association of rs660895-(AG+GG) with PD seen in never smokers (OR=0.64, p<0.001) disappeared among ever smokers (OR=1.00, p=0.99). Similar interactions were observed when we investigated light and heavy smokers separately.

Interpretation: Our study provides the first evidence that smoking modifies the previously reported inverse association of rs660895-G with PD, and suggests that smoking and HLA-DRB1 are involved in common pathways, possibly related to neuroinflammation. This article is protected by copyright. All rights reserved.



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Mechanical and hypoxia stress can cause chondrocytes apoptosis through over-activation of endoplasmic reticulum stress

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Publication date: December 2017
Source:Archives of Oral Biology, Volume 84
Author(s): Ziwei Huang, Min Zhou, Qian Wang, Mengjiao Zhu, Sheng Chen, Huang Li
ObjectiveTo examine the role of mechanical force and hypoxia on chondrocytes apoptosis and osteoarthritis (OA)-liked pathological change on mandibular cartilage through over-activation of endoplasmic reticulum stress (ERS).MethodsWe used two in vitro models to examine the effect of mechanical force and hypoxia on chondrocytes apoptosis separately. The mandibular condylar chondrocytes were obtained from three-week-old male Sprague–Dawley rats. Flexcell 5000T apparatus was used to produce mechanical forces (12%, 0.5Hz, 24h vs 20%, 0.5Hz, 24h) on chondrocytes. For hypoxia experiment, the concentration of O2 was down regulated to 5% or 1%. Cell apoptosis rates were quantified by annexin V and propidium iodide (PI) double staining and FACS analysis. Quantitative real-time PCR and western blot were performed to evaluate the activation of ERS and cellular hypoxia. Then we used a mechanical stress loading rat model to verify the involvement of ERS in OA-liked mandibular cartilage pathological change. Histological changes in mandibular condylar cartilage were assessed via hematoxylin & eosin (HE) staining. Immunohistochemistry of GRP78, GRP94, HIF-1α, and HIF-2α were performed to evaluate activation of the ERS and existence of hypoxia. Apoptotic cells were detected by the TUNEL method.ResultsTunicamycin, 20% mechanical forces and hypoxia (1% O2) all significantly increased chondrocytes apoptosis rates and expression of ERS markers (GRP78, GRP94 and Caspase 12). However, 12% mechanical forces can only increase the apoptotic sensitivity of chondrocytes. Mechanical stress resulted in OA-liked pathological change on rat mandibular condylar cartilage which included thinning cartilage and bone erosion. The number of apoptotic cells increased. ERS and hypoxia markers expressions were also enhanced. Salubrinal, an ERS inhibitor, can reverse these effects in vitro and in vivo through the down-regulation of ERS markers and hypoxia markers.ConclusionWe confirmed that mechanical stress and local hypoxia both contributed to the chondrocytes apoptosis. Mechanical stress can cause OA-like pathological change in rat mandibular condylar cartilage via ERS activation and hypoxia existed in the meantime. Both mechanical forces and hypoxia can induce ERS and cause chondrocytes apoptosis only if the stimulate was in higher level. Salubrinal can protect chondrocytes from apoptosis, and relieve OA-liked pathological change on mandibular condylar cartilage under mechanical stress stimulation.



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Father’s Role in Preconception Health

Abstract

As part of the federal multi-agency conference on Paternal Involvement in Pregnancy Outcomes, the existing Fatherhood paradigm was expanded to include a new focus on Men's Preconception Health. This concept grew out of the women's preconception health movement and the maternal and child health (MCH) life course perspective, as well as pioneering research from the child development, public health data and family planning fields. It encourages a new examination of how men's preconception health impacts both reproductive outcomes and men's own subsequent health and development. This essay introduces the concept of men's preconception health and health care; examines its historical development; notes the challenges of its inclusion into fatherhood and reproductive health programs; and situates it within a longer men's reproductive health life course. We then briefly explore six ways men's preconception health and health care can have positive direct and indirect impacts—planned and wanted pregnancies (family planning); enhanced paternal biologic and genetic contributions; improved reproductive health biology for women; improved reproductive health practices and outcomes for women; improved capacity for parenthood and fatherhood (psychological development); and enhanced male health through access to primary health care. Research on men's preconception health and health care is very limited and siloed. We propose a research agenda to advance this topic in three broad domains: increasing the basic epidemiology and risk factor knowledge base; implementing and evaluating men's preconception health/fatherhood interventions (addressing clinical health care, psychological resiliency/maturation, and social determinants of health); and fostering more fatherhood health policy and advocacy research.



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The Occipital Artery as an Alternative Donor for Low-Flow Bypass to Anterior Circulation After Internal Carotid Artery Occlusion Failure prior to Exenteration for an Atypical Cavernous Sinus Meningioma

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Publication date: January 2018
Source:World Neurosurgery, Volume 109
Author(s): Shunya Hanakita, Stéphanie Lenck, Moujahed Labidi, Kentaro Watanabe, Damien Bresson, Sébastien Froelich
BackgroundIn skull base tumors involving the cavernous sinus, indications for aggressive resection are sparse and must be carefully examined because of their invasiveness. With careful evaluation, techniques including internal carotid artery sacrifice with or without extracranial-intracranial bypass may still be an option in some cases. Moreover, previous surgery with the sacrifice of potential donor vessels requires adjusting the revascularization strategy. We describe an occipital artery–middle cerebral artery bypass before skull base tumor resection.Case DescriptionA 47-year-old woman with a recurrent cavernous sinus meningioma was referred to our department. Because of tumor recurrence after radiotherapy and its rapid progression, radical resection, including part of the cavernous sinus, was planned. A balloon test occlusion was performed and showed good tolerance. An endovascular internal carotid artery occlusion was performed. The patient eventually experienced motor deficits and aphasia after surgery. Therefore, bypass surgery using an occipital artery–middle cerebral artery anastomosis was performed. The patient showed no exacerbation of symptoms after bypass surgery and subsequently underwent tumor resection.ConclusionsThe reliability of balloon test occlusion in the management of giant aneurysms may not be similarly applicable to skull base tumors. If hypoperfusion symptoms occur after occlusion of the internal carotid artery, a surgical revascularization procedure should be considered because of the risk of ischemic stroke following tumor resection. For patients whose superficial temporal artery is not available, the occipital artery can be a valuable alternative donor for low-flow bypass.



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Intraoperative Visualization of a Spinal Arachnoid Cyst Using Pyoktanin Blue

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Publication date: January 2018
Source:World Neurosurgery, Volume 109
Author(s): Soichiro Takamiya, Toshitaka Seki, Kazuyoshi Yamazaki, Toru Sasamori, Kiyohiro Houkin
BackgroundSpinal arachnoid cysts (SACs) are filled with cerebrospinal fluid, and they include the arachnoid membrane, making it difficult to distinguish the walls of the cyst from the arachnoid membrane and excise the cyst as a lump. Here we report a technique for the intraoperative visualization of SACs, involving the use of pyoktanin blue.MethodsFour patients with spinal intradural arachnoid cysts underwent total excision of the cysts between October 2016 and April 2017. In 1 case, magnetic resonance imaging revealed the cyst clearly, but in the other cases, the cysts were unclear. All cysts were injected with 1% pyoktanin blue (Wako Pure Chemical Industries, Osaka, Japan) diluted 500 times with physiological saline before excision. When it was difficult to distinguish the cyst from the normal arachnoid membrane, 1% pyoktanin blue diluted 1000 times with physiological saline was injected into both the cyst and the subarachnoid space, and the spread of the stain was observed.ResultsThe cysts were better visualized after pyoktanin blue injection than before injection. When it was difficult to distinguish the cyst from the normal arachnoid space, pyoktanin blue injection was useful for judging the cyst space. There were no perioperative complications, and the patients' symptoms improved partially or completely after treatment.ConclusionsOur technique of pyoktanin blue injection into SACs could make their excision easy and safe.



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Accuracy of Pedicle Screw Insertion Among 3 Image-Guided Navigation Systems: Systematic Review and Meta-Analysis

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Publication date: January 2018
Source:World Neurosurgery, Volume 109
Author(s): Jin Peng Du, Yong Fan, Qi Ning Wu, Dai Hua Wang, Jing Zhang, Ding Jun Hao
BackgroundMany retrospective studies of pedicle screw placement have revealed that intraoperative navigation systems provide higher accuracy rates and safety than do free-hand techniques. The accuracy of various image-guided navigation systems has been studied; however, differences have not been well defined due to the lack of adequate evidence-based comparative studies.ObjectiveA meta-analysis was conducted to focus on the variation in pedicle screw insertion among 3 navigation systems: a 3-dimensional fluoroscopy-based navigation system (3D FluoroNav), a 2-dimensional fluoroscopy-based navigation system (2D FluoroNav), and a conventional computed tomography navigation system (CT Nav).MethodsWe screened for comparative studies on different pedicle screw insertion navigation systems published through January 2017 using the Cochrane Library, Ovid, Web of Science, PubMed, and EMBASE databases.ResultsFrom 125 papers that were identified, 10 articles were finally chosen. The present comparative study included 8 retrospective clinical studies, 1 prospective clinical trial, and 1 randomized controlled cadaveric study. The prevalence rate of pedicle violation in the 3D FluoroNav group was significantly lower than the rates of the 2D FluoroNav group (relative risk [RR] 95%, confidence interval [CI]: 0.16–0.61, P < 0.01) and the CT Nav group (RR 95%, CI: 0.42–0.90, P = 0.01), and the rate of the CT Nav group was significantly lower than that of the 2D FluoroNav group (RR 95%, CI: 0.29–0.81, P < 0.01).ConclusionSignificant differences exist among CT Nav, 3D FluoroNav, and 2D FluoroNav. Our review suggests that 3D FluoroNav may be superior to the other 2 methods in reducing pedicle violation and that clinicians should consider 3D FluoroNav as a better choice.



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Pleomorphic fibroma of the skin with MDM2 immunoreactivity: a potential diagnostic pitfall

Abstract

Pleomorphic fibroma is a rare benign cutaneous neoplasm characterized by spindle-shaped cells and multinucleated giant cells scattered throughout collagenous stroma. These morphologic features can lead to diagnostic confusion, including atypical lipomatous tumor as one consideration. In contrast to atypical lipomatous tumor, previous studies have found pleomorphic fibroma to be negative for MDM2 immunohistochemical staining and MDM2 gene amplification. Here, we present a case of pleomorphic fibroma of skin with nuclear MDM2 immunoreactivity in the absence of MDM2 gene amplification, underscoring the superiority of fluorescence in situ hybridization as a diagnostic test in this differential diagnosis. The RB1 locus is also explored for differential diagnosis with pleomorphic / spindle cell lipoma and related entities.



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Consensus Contouring Guidelines for Post-Operative Completely Resected Cavity Stereotactic Radiosurgery (SRS) for Brain Metastases

Publication date: Available online 4 October 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Hany Soliman, Mark Ruschin, Lilyana Angelov, Paul D. Brown, Veronica L.S. Chiang, John P. Kirkpatrick, Simon S. Lo, Anita Mahajan, Kevin S. Oh, Jason P. Sheehan, Scott G. Soltys, Arjun Sahgal
PurposeCavity stereotactic radiosurgery (SRS) is an emerging treatment option after surgical resection of brain metastases. No guidelines for contouring the surgical cavity volume have been reported. The aim of this study was to propose contouring guidelines based on consensus contours generated by 10 international experts.MethodsTen post-operative completely resected cases with varying clinical scenarios and locations within the brain were selected. For each case, 10 experts independently contoured the surgical cavity clinical target volume (CTV). All the contours were analyzed and agreement was calculated using the Simultaneous Truth and Performance Level Estimation (STAPLE) with the kappa statistic. A follow-up survey was also completed by each investigator in order to summarize their contouring rationale based on a number of different clinical scenarios. Both the results from the survey and consensus STAPLE contours were summarized to establish contouring guidelines.ResultsThere was a high level of agreement between the expert CTV contours (mean sensitivity=0.75, mean specificity=0.98), and the mean kappa was 0.65. The agreement was statistically significant at p<0.001 for all cases. Based on these results and analyses of the survey answers, recommendations for CTV include: fusion of the pre-operative MRI to aid in volume delineation, contouring the entire surgical tract regardless of the preoperative location of the tumor, the CTV should be extended 5-10mm along the dura overlying the bone flap to account for microscopic disease extension in cases with preoperative dural contact, and a margin of up to 5mm into the adjacent sinus is sufficient when there is pre-operative venous sinus contact.ConclusionsConsensus contouring guidelines for post-operative completely resected cavity SRS treatment were established based on expert contours and clinical practice. However, in the absence of clinical data supporting the recommendations in this paper, these guidelines serve as a baseline for further study and refinement.



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