Editorial board

Publication date: February 2018
Source:The Journal of Steroid Biochemistry and Molecular Biology, Volume 176





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Comparative Profiling of Adrenal Steroids in Maternal and Umbilical Cord Blood

Publication date: Available online 28 November 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Simon Travers, Laetitia Martinerie, Pascal Boileau, Qiong-Yao Xue, Marc Lombès, Eric Pussard
Fetal steroidome in late pregnancy receives multiple contributions from both maternal and fetal adrenals as well as from placenta. Depressed glucocorticoid levels have been reported in fetal blood at birth, yet studies on mineralocorticoid pathways are sparse. To investigate biosynthesis pathways at birth, adrenal steroids profiles were established in paired mothers and neonates. Forty-six paired healthy term newborns and their mothers from the Aldo cohort were assessed. Steroidomic profiles of mineralocorticoids, glucocorticoids and adrenal androgens were established from umbilical cord and maternal blood at birth using a highly sensitive and specific LC-MS/MS methodology. As compared to maternal blood, umbilical cord blood exhibited high levels of steroids precursors (progesterone and 11-deoxycorticosterone) contrasting with a collapse in corticosterone levels. Consecutively, 18-hydroxycorticosterone and aldosterone levels were also depressed in neonates. Similarly, umbilical cord blood levels of both 17-hydroxyprogesterone and 11-deoxycortisol were higher while cortisol levels sharply decreased. The product-to-substrate ratios evaluating the 11-hydroxylation step (corticosterone/11-deoxycorticosterone and cortisol/11-deoxycortisol) fell for both pathways. As expected, cortisone and 11-dehydrocorticosterone levels exceed those of cortisol and corticosterone in umbilical cord blood reflecting the strong placental 11-β-hydroxysteroid-dehydrogenase type 2 (11βHSD2) activity. Dehydroepiandrosterone-sulphate levels are higher in neonates, while both androstenedione and testosterone levels sharply fell. No significant difference in steroid levels could be observed according the gender except higher testosterone concentrations in umbilical cord of boys. Moreover, a strong and negative relationship between testosterone and progesterone levels was recorded in umbilical cord of boys. These adrenal steroidomic profiling demonstrate a deficit in mineralocorticoids (aldosterone, 18-hydroxycorticosterone and corticosterone) and glucocorticoids (cortisol) in term neonates, reflecting either a relative defect in 11-hydroxylase activity or more likely the strong placental 11-β-HSD2 activity. Collectively, these findings should be taken into account for a better understanding of regulatory interactions between placenta and fetal adrenal.



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Steroidogenic enzymes, their products and sex steroid receptors during testis development and spermatogenesis in the domestic cat (Felis catus)

Publication date: Available online 28 November 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Beate C. Braun, Minami W. Okuyama, Karin Müller, Martin Dehnhard, Katarina Jewgenow
In the present study we comprehensively characterize intratesticular sex steroid production, metabolism and receptors in the domestic cat to elucidate the role of testosterone, estradiol and progesterone in testis development, steroid synthesis and spermatogenesis. There is a great demand for new concepts of fertility control in domestic (feral) cats and wild felids. The acquired knowledge will help to understand the regulation of spermatogenesis in felids, and may reveal new target points for male contraception.Progesterone and androgens are produced throughout all stages of testicular development; their synthesizing enzymes are mainly expressed in Leydig cells, and to a much lesser extent also in tubular cells. Aromatase (CYP19A1), the estrogen synthesizing enzyme, is only present in the tubuli and is first detectable in spermatocytes and round spermatids at puberty. As shown by elevated expression of the enzymes steroid 5-α-reductase type 1 (SRD5A) and aldo-keto-reductase family 1 member C3 (AKR1C3), the capacity to metabolize particular steroids increases during testis development. Apparently, this refers to a decreasing intra-testicular testosterone concentration per mg tissue with increasing testis weight during postpuberty. The increasing potential of sulfation of E2 by estrogen sulfotransferase (SULT1E1) with ongoing development might be responsible for the low level of unconjugated intratesticular estradiol in all stages of development probably due to facilitated excretion of conjugated estrogens.For the first time, expression of the progesterone membrane receptor components 1 and 2 (PGRMC1, PGRMC2) was studied in mammalian testis tissue. Both of these and also the progesterone receptor (PGR) are expressed depending on the developmental stage and cell type, suggesting an important regulatory role of progesterone in the testis. Androgen receptor (AR) is present in almost all cell types except for some spermatogenic cells. The co-localization of aromatase with estrogen receptor alpha (ESR1) in spermatocytes and round spermatids of domestic cat testis indicates an auto-/paracrine function of estrogen in spermatogenesis. In summary, the testis of the domestic cat is an important source of sex steroids. All of them could act within the testis but additionally, at least androgens and estrogens are likely secreted by the testis, partly as conjugated steroids.



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DIABETES INDUCES MITOCHONDRIAL DYSFUNCTION AND ALTERS CHOLESTEROL HOMEOSTASIS AND NEUROSTEROIDOGENESIS IN THE RAT CEREBRAL CORTEX

Publication date: Available online 26 November 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Simone Romano, Nico Mitro, Silvia Giatti, Silvia Diviccaro, Marzia Pesaresi, Roberto Spezzano, Matteo Audano, Luis Miguel Garcia-Segura, Donatella Caruso, Roberto Cosimo Melcangi
The nervous system synthesizes and metabolizes steroids (i.e., neurosteroidogenesis). Recent observations indicate that neurosteroidogenesis is affected by different nervous pathologies. Among these, long-term type 1 diabetes, together with other functional and biochemical changes, has been shown to alter neuroactive steroid levels in the nervous system. Using an experimental model of type 1 diabetes (i.e., streptozotocin injection) we here show that the levels of these molecules are already decreased in the rat cerebral cortex after one month of the initiation of the pathology. Moreover, decreased levels of free cholesterol, together with alterations in the expression of molecules involved in cholesterol biosynthesis, bioavailability, trafficking and metabolism were detected in the rat cerebral cortex after one month of diabetes. Furthermore, mitochondrial functionality was also affected in the cerebral cortex and consequently may also contribute to the decrease in neuroactive steroid levels. Altogether, these results indicate that neurosteroidogenesis is an early target for the effect of type 1 diabetes in the cerebral cortex.



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Characterization of equine GST A3-3 as a steroid isomerase

Publication date: Available online 24 November 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Helena Lindström, Shawna M. Peer, Nancy H. Ing, Bengt Mannervik
Glutathione transferases (GSTs) comprise a superfamily of enzymes prominently involved in detoxication by making toxic electrophiles more polar and therefore more easily excretable. However some GSTs have developed alternative functions. Thus, a member of the Alpha class GSTs in pig and human tissues is involved in steroid hormone biosynthesis, catalyzing the obligatory double-bond isomerization of Δ⁵-androstene-3,17-dione to Δ⁴-androstene-3,17-dione and of Δ⁵-pregnene-3,20-dione to Δ⁴-pregnene-3,20-dione on the biosynthetic pathways to testosterone and progesterone. The human GST A3-3 is the most efficient steroid double-bond isomerase known so far in mammals. The current work extends discoveries of GST enzymes that act in the steroidogenic pathways in large mammals. The mRNA encoding the steroid isomerase GST A3-3 was cloned from testis of the horse (Equus ferus caballus). The concentrations of GSTA3 mRNA were highest in hormone-producing organs such as ovary, testis and adrenal gland. EcaGST A3-3 produced in E. coli has been characterized and shown to have highly efficient steroid double-bond isomerase activity, exceeding its activities with conventional GST substrates. The enzyme now ranks as one of the most efficient steroid isomerases known in mammals and approaches the activity of the bacterial ketosteroid isomerase, one of the most efficient enzymes of all categories known today. The high efficiency and the tissue distribution of EcaGST A3-3 support the view that the enzyme plays a physiologically significant role in the biosynthesis of steroid hormones.

Graphical abstract

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Highlights from the 20th Workshop on Vitamin D in Orlando, Mar. 28–31, 2017

Publication date: Available online 24 November 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Martin Hewison, James C. Fleet, Marie B. Demay, Sylvia Christakos, Roger Bouillon, JoEllen Welsh, John H. White




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EFFLUX TRANSPORT of ESTROGEN GLUCURONIDES by HUMAN MRP2, MRP3, MRP4 and BCRP

Publication date: Available online 22 November 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Erkka Järvinen, Feng Deng, Heidi Kidron, Moshe Finel
Estrone, estradiol and estriol are endogenous human estrogens that are rapidly conjugated with glucuronic acid in both intestinal and hepatic epithelial cells. The resulting glucuronides, estrone-3-glucuronide (E1-G), estradiol-3- and 17-glucuronides (E2-3G and E2-17G), as well as estriol-3- and 16-glucuronides (E3-3G and E3-16G) are found in human plasma and urine. Unlike E2-17G, the efflux transport of other estrogen glucuronides by human transporters has not yet been investigated comprehensively. We have studied the transport of E1-G, E2-3G, E3-3G, E3-16G and estrone-3-sulfate (E1-S), another important estrogen conjugate, using the vesicular transport assay with recombinant human MRP2, MRP3, MRP4, MDR1 and BCRP that were expressed in insect cells. The transport screening assays revealed that whereas E1-S was a good and specific substrate for BCRP, the less transporter-specific conjugates, E1-G and E2-3G, were still transported by BCRP at 10-fold higher rates than E1-S. BCRP also transported E3-16G at higher rates than the studied MRPs, while it transported E3-3G at lower rates than MRP3. MRP2 exhibited lower or equal transport rates of E1-G, E2-3G, E3-3G and E3-16G in comparison to MRP3 and BCRP in the screening assays, mainly due to its high Km values, between 180 and 790μM. MRP3 transported all the tested glucuronides at rather similar rates, at Km values below 20μM, but lower Vmax values than other transporters. In the case of E3-3G, MRP3 was the most active transporter in the screening assay. MRP4 transported only E3-16G at considerable rates, while none of the tested estrogen conjugates was transported by MDR1 at higher rates than control vesicles. These new results, in combination with previously reported in vivo human data, stimulate our understanding on the substrate specificity and role of efflux transporters in disposition of estrogen glucuronides in humans.

Graphical abstract

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Impact of vitamin D on pregnancy-related disorders and on offspring outcome

Publication date: Available online 21 November 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Karoline von Websky, Ahmed Abdallah Hasan, Christoph Reichetzeder, Oleg Tsuprykov, Berthold Hocher
Observational studies from all over the world continue to find high prevalence rates of vitamin D insufficiency and deficiency in many populations, including pregnant women. Beyond its classical function as a regulator of calcium and phosphate metabolism, vitamin D elicits numerous effects in the human body. Current evidence highlights a vital role of vitamin D in mammalian gestation. During pregnancy, adaptations in maternal vitamin D metabolism lead to a physiologic increase of vitamin D levels, mainly because of an increased renal production, although other potential sources like the placenta are being discussed. A sufficient supply of mother and child with calcium and vitamin D during pregnancy ensures a healthy bone development of the fetus, whereas lack of either of these nutrients can lead to the development of rickets in the child. Moreover, vitamin D insufficiency during pregnancy has consistently been associated with adverse maternal and neonatal pregnancy outcomes. In multitudinous studies, low maternal vitamin D status was associated with a higher risk for preeclampsia, gestational diabetes mellitus and other gestational diseases. Likewise, several negative consequences for the fetus have been reported, including fetal growth restriction, increased risk of preterm birth and a changed susceptibility for later-life diseases. However, study results are diverging and causality has not been proven so far. Meta-analyses on the relationship between maternal vitamin D status and pregnancy outcomes revealed a wide heterogeneity of studied populations and the applied methodology in vitamin D assessment. Until today, clinical guidelines for supplementation cannot be based on high-quality evidence and it is not clear if the required intake for pregnant women differs from non-pregnant women. Long-term safety data of vitamin D supplementation in pregnant women has not been established and overdosing of vitamin D might have unfavorable effects, especially in mothers and newborns with mutations of genes involved in vitamin D metabolism. Reliable data from large observational and interventional randomized control trials are urgently needed as a basis for any detailed and safe recommendations for supplementation in the general population and, most importantly, in pregnant women. This is of utmost importance, as ensuring a sufficient vitamin D-supply of mother and child implies a great potential for the prevention of birth complications and development of diseases.



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Transition from androgenic to neurosteroidal action of 5α-androstane-3α, 17β-diol through the type A γ-aminobutyric acid receptor in prostate cancer progression

Publication date: Available online 15 November 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Ding Xia, Doan V. Lai, Weijuan Wu, Zachary D. Webb, Qing Yang, Lichao Zhao, Zhongxin Yu, Jessica E. Thorpe, Bryan C. Disch, Michael A. Ihnat, Muralidharan Jayaraman, Danny N. Dhanasekaran, Kelly L. Stratton, Michael S. Cookson, Kar-Ming Fung, Hsueh-Kung Lin
Androgen ablation is the standard of care prescribed to patients with advanced or metastatic prostate cancer (PCa) to slow down disease progression. Unfortunately, a majority of PCa patients under androgen ablation progress to castration-resistant prostate cancer (CRPC). Several mechanisms including alternative intra-prostatic androgen production and androgen-independent androgen receptor (AR) activation have been proposed for CRPC progression. Aldo-keto reductase family 1 member C3 (AKR1C3), a multi-functional steroid metabolizing enzyme, is specifically expressed in the cytoplasm of PCa cells; and positive immunoreactivity of the type A γ-aminobutyric acid receptor (GABAAR), an ionotropic receptor and ligand-gated ion channel, is detected on the membrane of PCa cells. We studied a total of 72 radical prostatectomy cases by immunohistochemistry, and identified that 21 cases exhibited positive immunoreactivities for both AKR1C3 and GABAAR. In the dual positive cancer cases, AKR1C3 and GABAAR subunit α1 were either expressed in the same cells or in neighboring cells. Among several possible substrates, AKR1C3 reduces 5α-dihydrotesterone (DHT) to form 5α-androstane-3α, 17β-diol (3α-diol). 3α-diol is a neurosteroid that acts as a positive allosteric modulator of the GABAAR in the central nervous system (CNS). We examined the hypothesis that 3α-diol-regulated pathological effects in the prostate are GABAAR-dependent, but are independent of the AR. In GABAAR-positive, AR-negative human PCa PC-3 cells, 3α-diol significantly stimulated cell growth in culture and the in ovo chorioallantoic membrane (CAM) xenograft model. 3α-diol also up-regulated expression of the epidermal growth factor (EGF) family of growth factors and activation of EGF receptor (EGFR) and Src as measured by quantitative polymerase chain reaction and immunoblotting, respectively. Inclusion of GABAAR antagonists reversed 3α-diol-stimulated tumor cell growth, expression of EGF family members, and activation of EGFR and Src to the level observed in untreated cells. Results from the present study suggest that 3α-diol may act as an alternative intra-prostatic neurosteroid that activates AR-independent PCa progression. The involvement of AKR1C3-mediated steroid metabolisms in modulating GABAAR activation and promoting PCa progression requires continued studies.

Graphical abstract

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Medikamentöse Therapie neuroendokriner Neoplasien des Gastrointestinaltrakts

Zusammenfassung

Hintergrund

Neuroendokrine Neoplasien (NEN) des Verdauungstrakts stellen eine seltene und heterogene Gruppe von Tumorerkrankungen dar. Dies erschwert die Vorgabe einheitlicher Therapieschemata.

Ziel

Die aktuelle Datenlage zur medikamentösen Therapie gastrointestinaler NEN soll dargestellt werden.

Methoden

Diskussion publizierter Studien und Expertenempfehlungen zur medikamentösen Therapie von gastroenteropankreatischen neuroendokrinen Neoplasien (GEP-NEN)

Ergebnisse

Wichtigstes therapeutisches Prinzip ist die komplette chirurgische Tumorentfernung. Ist diese nicht möglich, erfolgt die Therapie in der Regel multimodal und multidisziplinär und orientiert sich an der Tumorentität, dem individuellen Spontanverlauf sowie der Beschwerdesymptomatik. Bei Vorliegen eines spezifischen klinischen Hormonsyndroms sind langwirksame Somatostatinanaloga (SSA) die Therapie der Wahl. Sie stellen auch die Grundlage der antiproliferativen Therapie gut differenzierter gastroenteropankreatischer neuroendokriner Tumoren (GEP-NET) dar. Bei ausreichender Somatostatinrezeptor-Expression des Tumors steht als systemische Therapieoption die Peptidradiorezeptortherapie (PRRT) zur Verfügung. Bei gering differenzierten neuroendokrinen Karzinomen und NET des Pankreas stellen Platin- bzw. Streptozotocin-basierte Chemotherapien eine wichtige Therapieoption dar. Der Multityrosinkinaseinhibitor Sunitinib und der mTOR-Inhibitor Everolimus sind für die Behandlung pankreatischer NET zugelassen, Everolimus zudem auch für gastrointestinale NEN.

Schlussfolgerungen

Zur Behandlung von GEP-NEN stehen eine Reihe effektiver therapeutischer Optionen zur Verfügung. Die Entscheidung für ein Therapiekonzept sollte individuell im Rahmen eines in der Behandlung dieser Tumoren erfahrenen interdisziplinären Tumorboards festgelegt werden.

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BranchAnalysis2D/3D automates morphometry analyses of branching structures

Publication date: 15 January 2018
Source:Journal of Neuroscience Methods, Volume 294
Author(s): Aditya Srinivasan, Jesús Muñoz-Estrada, Justin R. Bourgeois, Julia W. Nalwalk, Kevin M. Pumiglia, Volney L. Sheen, Russell J. Ferland
BackgroundMorphometric analyses of biological features have become increasingly common in recent years with such analyses being subject to a large degree of observer bias, variability, and time consumption. While commercial software packages exist to perform these analyses, they are expensive, require extensive user training, and are usually dependent on the observer tracing the morphology.New methodTo address these issues, we have developed a broadly applicable, no-cost ImageJ plugin we call 'BranchAnalysis2D/3D', to perform morphometric analyses of structures with branching morphologies, such as neuronal dendritic spines, vascular morphology, and primary cilia.ResultsOur BranchAnalysis2D/3D algorithm allows for rapid quantification of the length and thickness of branching morphologies, independent of user tracing, in both 2D and 3D data sets.Comparison with existing methodsWe validated the performance of BranchAnalysis2D/3D against pre-existing software packages using trained human observers and images from brain and retina. We found that the BranchAnalysis2D/3D algorithm outputs results similar to available software (i.e., Metamorph, AngioTool, Neurolucida), while allowing faster analysis times and unbiased quantification.ConclusionsBranchAnalysis2D/3D allows inexperienced observers to output results like a trained observer but more efficiently, thereby increasing the consistency, speed, and reliability of morphometric analyses.



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Enhancement of the mechanical and thermal properties of injection-molded polylactide parts by the addition of acrylated epoxidized soybean oil

Publication date: 15 February 2018
Source:Materials & Design, Volume 140
Author(s): L. Quiles-Carrillo, S. Duart, N. Montanes, S. Torres-Giner, R. Balart
This work reports the effect of acrylated epoxidized soybean oil (AESO) addition on the mechanical, thermal, and thermomechanical properties of polylactide (PLA) parts obtained by injection molding. To this end, AESO, a chemically multi-functionalized vegetable oil, was incorporated into PLA during melt processing. The PLA parts with AESO contents in the 2.5–7.5wt% range showed a remarkable enhancement in both elongation at break and impact-absorbed energy while their tensile and flexural strength as well as thermomechanical properties were maintained or slightly improved. Additionally, the AESO-containing PLA parts presented higher thermal stability and lower crystallinity. The improvement achieved was ascribed to a dual effect of plasticization in combination with a chain-extension and/or cross-linking process of the PLA chains by the highly reactive acrylate and epoxy groups present in AESO. The use of AESO thus represents an environmentally friendly solution to obtain toughened PLA materials of high interest in, for instance, rigid packaging, automotive or building and construction applications.

Graphical abstract

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A novel multiscale silver paste for die bonding on bare copper by low-temperature pressure-free sintering in air

Publication date: 15 February 2018
Source:Materials & Design, Volume 140
Author(s): Jie Li, Xin Li, Lei Wang, Yun-Hui Mei, Guo-Quan Lu
Nanosilver sintering is expected to overcome the limitation of relatively high production cost and become widely available for the die bonding of power electronics. A potential application of nanosilver sintering is bare copper bonding, where replacing substrates with auxiliary silver or other plating that can damage bonding would be advantageous. Here, we introduce a novel multiscale silver paste containing both nanoparticles (20–100nm) and microparticles (1–5μm) for the bonding of high-power chips on a bare copper substrate by pressure-free sintering in air. The energy potential difference generated in the surface force field was critical in the formation of sintering necks between the nano and microparticles, which, together with other microparticles, formed the high-density sintered structure. Despite the development of a copper oxide film, the interfacial bonding was comparable to or higher than the sintering force due to the high surface energy of porous sintered structure and easy diffusion of nanoparticles occurred. A processing temperature of 265°C was considered optimal for bare copper joint (shear strength: 53MPa, transient thermal impedance: 0.132°C/W) considering the trade-off between achieving excellent mechanical and thermal properties while minimizing oxidation.

Graphical abstract

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Thermal properties of graphene/metal composites with aligned graphene

Publication date: 15 February 2018
Source:Materials & Design, Volume 140
Author(s): Ke Chu, Xiao-hu Wang, Yu-biao Li, Da-jian Huang, Zhong-rong Geng, Xi-long Zhao, Hong Liu, Hu Zhang
Graphene holds great potential in metal matrix composites for thermal management due to its excellent thermal properties. However, the graphene/metal composites possessing both high thermal conductivity (TC) and low coefficient of thermal expansion (CTE) have not yet been realized. Herein, we reported an efficient strategy to achieve a high alignment of graphene nanosheets (GNSs) in GNS/Cu composites through a vacuum filtration method followed by spark plasma sintering. Because of the highly aligned GNSs and laminated structure, the GNS/Cu composites exhibited notably anisotropic thermal properties. Intriguingly, the composites showed a reversed anisotropic behavior between TC and CTE as a function of GNS fraction, in which the in-plane TC was substantially higher than through-plane TC, whereas oppositely the through-plane CTE displayed a larger drop than in-plane CTE. Promisingly, the composite with 30vol% GNSs delivered a high in-plane TC of 458W/mK and a low through-plane CTE of 6.2ppm/K, corresponding to a 35% TC enhancement and a 64% CTE reduction compared to pure Cu, respectively. The present GNS/Cu composites with high in-plane TC and low through-plane CTE are promising candidates for specific thermal management applications that require an efficient in-plane heat dissipation but a good through-plane dimensional stability.

Graphical abstract

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Primary cutaneous mucoepidermal carcinoma

Mucoepidermal carcinoma (MEC) is a tumour having mixed components of mucus secreting and epidermoid cells. Salivary glands are the the most common site of origin. Primary cutaneous MEC is a rare presentation. We report a primary cutaneous MEC in a 98-year-old woman presenting a noduloulcerative lesion over the dorsum of the nose. Histopathology of the tumour showed nests of epidermoid cells with glandular differentiation and mucin production. The diagnosis was confirmed by immunohistochemistry.

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Systemic thrombolysis in a patient with massive pulmonary embolism and recent glioblastoma multiforme resection

While trials of systemic thrombolysis for submassive and massive pulmonary embolism (PE) report intracranial haemorrhage (ICH) rates of 2%–3%, the risk of ICH in patients with recent brain surgery or intracranial neoplasm is unknown since these patients were excluded from these trials. We report a case of massive PE treated with systemic thrombolysis in a patient with recent neurosurgery for an intracranial neoplasm. We discuss the risks and benefits of systemic thrombolysis for massive PE in the context of previous case reports, prior cohort studies and trials, and current guidelines. There may be times when the immediate risk of death from massive PE outweighs the risk of ICH from systemic thrombolysis, even when guideline-listed major contraindications exist. This case provides an example of how the haemodynamic benefit of systemic thrombolysis outweighed the impact of ICH in a patient who had undergone recent neurosurgical resection of a glioblastoma multiforme tumour.

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Lyric hearing aid: a rare cause of benign necrotising otitis externa/external ear canal cholesteatoma

An 80-year-old Caucasian man presented with an incidental and asymptomatic lesion in his right ear thought to be secondary to his use of hearing aids for presbycusis. He used Lyric hearing aids, designed for 24 hours-a-day use for 4 months at a time and had no other previous otological problems. He underwent a bony meatoplasty and vascular flap reconstruction via a retroauricular approach to remove the lesion for histological analysis and regrafting of the area. The lesion was confirmed on histopathology as an ear canal cholesteatoma.

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Follicular bronchiolitis in an HIV-infected individual on combination antiretroviral therapy with low CD4+ cell count but sustained viral suppression

A 36-year-old Danish man, living in Asia, was diagnosed with Pneumocystis pneumonia (PCP) and HIV in 2013 (CD4+ count: 6 cells/µL; viral load: 518 000 copies/mL). He initiated combination antiretroviral therapy. Later that year, he was also diagnosed with granulomatosis with polyangiitis and was treated with prednisolone. Despite complete viral suppression and increasing CD4+ count (162 cells/µL), he was readmitted with PCP in April 2015. Subsequently, he returned to Denmark (CD4+ count: 80 cells/µL, viral suppression). Over the following months, he developed progressive dyspnoea. Lung function tests demonstrated severely reduced lung capacity with an obstructive pattern and a moderately reduced diffusion capacity. High resolution computer tomography revealed minor areas with tree-in-bud pattern and no signs of air trapping on expiratory views. Lung biopsy showed lymphocytic infiltration surrounding the bronchioles with sparing of the alveolar septa. He was diagnosed with follicular bronchiolitis. The patient spontaneously recovered along with an improvement of the immune system.

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Yawning—its anatomy, chemistry, role, and pathological considerations

Publication date: Available online 29 November 2017
Source:Progress in Neurobiology
Author(s): Heinz Krestel, Claudio L. Bassetti, Olivier Walusinski
Yawning is a clinical sign of the activity of various supra- and infratentorial brain regions including the putative brainstem motor pattern, hypothalamic paraventricular nucleus, probably the insula and limbic structures that are interconnected via a fiber network. This interaction can be seen in analogy to other cerebral functions arising from a network or zone such as language. Within this network, yawning fulfills its function in a stereotype, reflex-like manner; a phylogenetically old function, preserved across species barriers, with the purpose of arousal, communication, and maybe other functions including respiration. Abnormal yawning with ≥3 yawns/15min. without obvious cause arises from lesions of brain areas involved in the yawning zone, its trajectories causing a disconnection syndrome, or from alteration of network activity by physical or metabolic etiologies including medication.



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Implementing near real-time vaccine safety surveillance using the Clinical Practice Research Datalink (CPRD)

Publication date: 14 December 2017
Source:Vaccine, Volume 35, Issue 49, Part B
Author(s): Andreia Leite, Sara L. Thomas, Nick J. Andrews
IntroductionNear real-time vaccine safety surveillance (NRTVSS) using electronic health records is increasingly used to rapidly detect vaccine safety signals. NRTVSS has not been fully implemented in the UK. We assessed the feasibility of implementing this surveillance using the UK Clinical Practice Research Datalink (CPRD).MethodsWe selected seasonal influenza vaccine/Guillain-Barré Syndrome (GBS) as an example of a rare outcome and measles-mumps-rubella (MMR) vaccine/febrile seizures as a positive control. For influenza/GBS we implemented a system for the 2013/2014 and 2014/2015 influenza seasons; for MMR/seizures the surveillance period was July 2014–June 2015. We used the continuous Poisson-based maximized sequential probability ratio test (PMaxSPRT), comparing observed-to-expected events, for both pairs. We calculated an age-sex-adjusted rate using 5years of historic data and used this rate to calculate the expected number of events in pre-specified post-vaccination risk-window (GBS: 0–42days, seizures: 6–21days). For MMR/seizures we also implemented the system using the Binominal-based maximized sequential probability ratio test (BMaxSPRT). For this, we compared seizures in the risk-window (6–21days) to a control window (0–5 and 22–32days). Delays in recording outcomes influence the data available, so we adjusted the expected number of events using a historical distribution of delays in recording GBS/febrile seizures. Analyses were run using data up to each CPRD monthly release. We also performed power calculations for detecting increases in relative risk (RR) from 1.5 to 10.ResultsFor influenza/GBS we implemented a system in both seasons with no signal. Power to detect a signal was >80% for RR≥4. For MMR/seizures we were able to identify a signal with PMaxSPRT but not with BMaxSPRT. Power≥80% for RR≥2.5 for both tests.ConclusionCPRD is a potential data source to implement NRTVSS to exclude large increases in the risk of rare outcomes after seasonal influenza and lower increases in risk for more frequent outcomes.



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Editorial Board/Aims and Scope

Publication date: 14 December 2017
Source:Vaccine, Volume 35, Issue 49, Part B





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Attitudes about vaccines to prevent Ebola virus disease in Guinea at the end of a large Ebola epidemic: Results of a national household survey

Publication date: 14 December 2017
Source:Vaccine, Volume 35, Issue 49, Part B
Author(s): Kathleen L. Irwin, Mohamed F. Jalloh, Jamaica Corker, Barry Alpha Mahmoud, Susan J. Robinson, Wenshu Li, Nyuma E. James, Musa Sellu, Mohammad B. Jalloh, Alpha Ahmadou Diallo, LaRee Tracy, Rana Hajjeh, Amanda VanSteelandt, Rebecca Bunnell, Lise Martel, Pratima L. Raghunathan, Barbara Marston
IntroductionIn 2014–2016, an Ebola epidemic devastated Guinea; more than 3800 cases and 2500 deaths were reported to the World Health Organization. In August 2015, as the epidemic waned and clinical trials of an experimental, Ebola vaccine continued in Guinea and neighboring Sierra Leone, we conducted a national household survey about Ebola-related knowledge, attitudes, and practices (KAP) and opinions about "hypothetical" Ebola vaccines.MethodsUsing cluster-randomized sampling, we selected participants aged 15+ years old in Guinea's 8 administrative regions, which had varied cumulative case counts. The questionnaire assessed socio-demographic characteristics, experiences during the epidemic, Ebola-related KAP, and Ebola vaccine attitudes. To assess the potential for Ebola vaccine introduction in Guinea, we examined the association between vaccine attitudes and participants' characteristics using categorical and multivariable analyses.ResultsOf 6699 persons invited to participate, 94% responded to at least 1 Ebola vaccine question. Most agreed that vaccines were needed to fight the epidemic (85.8%) and that their family would accept safe, effective Ebola vaccines if they became available in Guinea (84.2%). These measures of interest and acceptability were significantly more common among participants who were male, wealthier, more educated, and lived with young children who had received routine vaccines. Interest and acceptability were also significantly higher among participants who understood Ebola transmission modes, had witnessed Ebola response teams, knew Ebola-affected persons, believed Ebola was not always fatal, and would access Ebola treatment centers. In multivariable analyses of the majority of participants living with young children, interest and acceptability were significantly higher among those living with vaccinated children than among those living with unvaccinated children.DiscussionThe high acceptability of hypothetical vaccines indicates strong potential for introducing Ebola vaccines across Guinea. Strategies to build public confidence in use of Ebola vaccines should highlight any similarities with safe, effective vaccines routinely used in Guinea.



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Ethics, pregnancy, and ZIKV vaccine research & development

Publication date: 14 December 2017
Source:Vaccine, Volume 35, Issue 49, Part B
Author(s): The Ethics Working Group on ZIKV Research and PregnancyRuth R.FadenCarleigh B.KrubinerAnne D.LyerlyMargaret O.LittleAllisonAugustRichard H.BeigiAnna P.DurbinRuth A.KarronNancy E.KassFlorenciaLunaRicardoPalaciosAlexander RobertoPreciosoCarlaSaenzJeanne S.SheffieldBeatrizThoméCorresponding author.




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Randomized Split-face, Controlled Comparison of Treatment with 1565 nm Non-ablative Fractional Laser for Enlarged Facial Pores

Abstract

Enlarged pores are common cosmetic concerns¹. Though non-ablative fractional lasers (NAFLs) have been used reducing enlarged facial pores, a prospective, split-face, controlled study with objective assessment is still in blank. 1,565 nm NAFL (M22 ^™ ResurFX^™, Lumenis^® Ltd, Yokneam, Israel), proved effective on skin elasticity and stretch marks², was further aimed to assess for its safety and efficacy on enlarged facial pores.

This article is protected by copyright. All rights reserved.

http://ift.tt/2AI236J

Randomized Split-face, Controlled Comparison of Treatment with 1565 nm Non-ablative Fractional Laser for Enlarged Facial Pores

Abstract

Enlarged pores are common cosmetic concerns¹. Though non-ablative fractional lasers (NAFLs) have been used reducing enlarged facial pores, a prospective, split-face, controlled study with objective assessment is still in blank. 1,565 nm NAFL (M22 ^™ ResurFX^™, Lumenis^® Ltd, Yokneam, Israel), proved effective on skin elasticity and stretch marks², was further aimed to assess for its safety and efficacy on enlarged facial pores.

This article is protected by copyright. All rights reserved.

http://ift.tt/2AI236J

Anti-tumour necrosis factor-α antibodies and B cell homeostasis in human inflammatory bowel diseases

Publication date: January 2018
Source:International Immunopharmacology, Volume 54
Author(s): Caterina Defendenti, Fabiola Atzeni, Sergio Malandrin, Sandro Ardizzone, Piero Luigi Almasio, Simone Saibeni, Cristina Bezzio, Simona Bollani, Raffaele Salerno, Paolo Declich, Zoe Sarno, Savino Bruno, Rossella Talotta, Piercarlo Sarzi-Puttini
BackgroundThe expression of CD70 on T cells is greatly enhanced by antigen-presenting cell (APC)-associated signals, such as tumour necrosis factor(TNF)-α, which is constitutionally high in patients with inflammatory bowel disease (IBD). Experimentally, the chronic activation of CD27 as a result of the constitutive expression of CD70 leads to the demise of B cells in bone marrow (BM) and the secondary lymphoid organs. The aim of this study was to assess the number and phenotype of circulating B cell in untreated IBD patients and their counterparts treated with biological anti-TNF drugs.MethodsThe study involved 13 untreated IBD patients, 36 IBD patients treated with biological drugs, and 10 healthy controls. The B cell phenotypes were assessed by means of flow cytometry using monoclonal antibodies specific for CD20, CD19, CD3, CD27 and CD43. In order to evaluate B cell development in bone marrow and peripheral B cell activation, we identified four B cell subsets: hematogones (HBs: CD20⁺19⁺3⁻27⁻43⁺), memory B cells (MBs: CD20⁺19⁺3⁻27⁺43⁻), pre-plasmablasts (PPBs: CD20⁺19⁺3⁻27⁺43⁺), and plasmablasts (PBs: CD20⁻19⁺3⁻27⁺43⁺).ResultsThe total number of B cells in the untreated patients was three times lower than that in the patients treated with biological drug (p<0.001), and half that in the healthy controls (p=0.03). The between-group differences (including the healthy donors) were statistically significant in the case of HBs and MBs, but not in the case of PPBs and PBs. Only one treated patient showed a transiently large increase in PPBs. There were statistically significant differences in all of the parameters between the untreated patients and those receiving biological therapy, and in some cases between the untreated patients and healthy controls, but never between the controls and the treated patients. Four non-responders to anti-TNF therapy had a smaller number of total circulating B cells than the untreated patients.ConclusionsAnti-TNF drugs disinhibit B cell production in IBD patients, but maintain the constant homeostasis of circulating B cells. The presence of individual variations may allow the activity of anti-TNF drugs to be monitored by studying B cell subgroups.



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Chemical characterization of PM 2.5 collected from a rural coastal island of the Bay of Bengal (Bhola, Bangladesh)

Abstract

This work focuses on the chemical characterization of fine aerosol particles (PM_2.5) collected from a rural remote island of the Bay of Bengal (Bhola, Bangladesh) from April to August, 2013. PM_2.5 particle-loaded filters were analyzed for organic carbon (OC), elemental carbon (EC), water-soluble ions, and selected saccharides (levoglucosan, mannosan, galactosan, arabitol, and mannitol). The average PM_2.5 mass was 15.0 ± 6.9 μg m⁻³. Organic carbon and elemental carbon comprised roughly half of the analyzed components. Organic carbon was the predominant contributor to total carbon (TC) and accounting for about 28% of PM_2.5 mass. Secondary organic carbon (SOC) was inferred to be ~ 26% of OC. The sum of ions comprised ~ 27% of PM_2.5 mass. The contribution of sea salt aerosol was smaller than expected for a sea-near site (17%), and very high chloride depletion was observed (78%). NssSO₄²⁻ was a dominant ionic component with an average concentration of 2.0 μg m⁻³ followed by Na⁺, NH₄⁺, and nssCa²⁺. The average concentration of arabitol and mannitol was 0.11 and 0.14 μg m⁻³, respectively, while levoglucosan and its stereoisomers (mannosan and galactosan) were bellow detection limit. NH₄⁺/SO₄²⁻ equivalent ratio was 0.30 ± 0.13 indicating that secondary inorganic aerosol is not the main source of SO₄²⁻. Enrichment factor (EF) analysis showed that SO₄²⁻ and NO₃⁻ were enriched in atmospheric particles compared to sea aerosol and soil indicating their anthropogenic origin. Higher OC/EC ratio (3.70 ± 0.88) was a good indicator of the secondary organic compounds formation. Other ratios (OC/EC, K⁺/EC, nssSO₄²⁻/EC) and correlation analysis suggested mixed sources for carbonaceous components. Arabitol and mannitol both showed strong correlation with EC having R ² value 0.89 and 0.95, respectively. Air mass trajectories analysis showed that concentrations of soil and anthropogenic species were lower for air masses originating from the sea (May–August) and were higher when air came from land (April).

http://ift.tt/2ngPJED

The extent of surgery for benign parotid pathology and its influence on complications: A prospective cohort analysis

Publication date: Available online 29 November 2017
Source:American Journal of Otolaryngology
Author(s): Wai Keat Wong, Subhaschandra Shetty
BackgroundThe surgical management of benign parotid tumors is aimed at complete extirpation of the mass with preservation of facial nerve function. There is a relative paucity of literature pertaining to complications after benign parotid surgery and related risk factors. We aim to critically review the outcomes following treatment of benign parotid pathology when surgery entailed either complete superficial parotidectomy (CSP), partial superficial parotidectomy (PSP) or extracapsular dissection (ECD).Material and methodsThis is a review of prospectively collected data of all parotidectomies performed between June 2006 to June 2016 for histologically-proven benign pathology of the parotid. Median follow-up time was 31.6weeks.ResultsA total of 101 parotidectomies were carried out on 97 patients (40 CSP, 56 PSP and 5 ECD). Pleomorphic adenoma (48.4%) and Warthin tumors (32.7%) were the most common pathologies. Temporary facial weakness occurred after 7 operations (6.9%). Facial weakness was permanent in 4 cases (3.9%). The rates of sialocele and salivary fistula were 4.9% and 0.9%, respectively. Only one patient (0.9%) developed Frey Syndrome postoperatively. No significant associations between extent of parotid surgery and postoperative facial nerve dysfunction (p=0.674) or wound complications (p=0.433) were observed. Univariate analyses for potential contributing factors such as advanced age, smoking status, tumor location or histology did not demonstrate any increased risk with developing postoperative complications.ConclusionPartial superficial parotidectomy was associated with low rates of morbidity to the facial nerve and surgical wound. The results were comparable to complete superficial parotidectomy. We recommend offering patient partial superficial parotidectomy where appropriate and this is in line with the current trend of minimising surgical dissection, thereby potentially decreasing the risk of short-term and long-term complications.



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Acute Chest Syndrome: An Ongoing Challenge for Physicians Caring for Children with Sickle Cell Disease

Pediatric Allergy, Immunology, and Pulmonology , Vol. 0, No. 0.


http://ift.tt/2zBqZZj

Diet, Lung Function, and Asthma Exacerbations in Puerto Rican Children

Pediatric Allergy, Immunology, and Pulmonology , Vol. 0, No. 0.


http://ift.tt/2neFT63

Neutrophil–Lymphocyte Ratio in Children with Recurrent Wheezing

Pediatric Allergy, Immunology, and Pulmonology , Vol. 0, No. 0.


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Developing a Mobile Health Intervention for Low-Income, Urban Caregivers of Children with Asthma: A Pilot Study

Pediatric Allergy, Immunology, and Pulmonology , Vol. 0, No. 0.


http://ift.tt/2neNuSk

Acute Chest Syndrome: An Ongoing Challenge for Physicians Caring for Children with Sickle Cell Disease

Pediatric Allergy, Immunology, and Pulmonology , Vol. 0, No. 0.


http://ift.tt/2zBqZZj

Diet, Lung Function, and Asthma Exacerbations in Puerto Rican Children

Pediatric Allergy, Immunology, and Pulmonology , Vol. 0, No. 0.


http://ift.tt/2neFT63

Neutrophil–Lymphocyte Ratio in Children with Recurrent Wheezing

Pediatric Allergy, Immunology, and Pulmonology , Vol. 0, No. 0.


http://ift.tt/2zCVQF7

Developing a Mobile Health Intervention for Low-Income, Urban Caregivers of Children with Asthma: A Pilot Study

Pediatric Allergy, Immunology, and Pulmonology , Vol. 0, No. 0.


http://ift.tt/2neNuSk

Epidemiology, biology and therapy of Merkel cell carcinoma: conclusions from the EU project IMMOMEC

Abstract

Merkel cell carcinoma (MCC) is a highly aggressive, often lethal neuroendocrine cancer. Its carcinogenesis may be either caused by the clonal integration of the Merkel cell polyomavirus into the host genome or by UV-induced mutations. Notably, virally-encoded oncoproteins and UV-induced mutations affect comparable signaling pathways such as RB restriction of cell cycle progression or p53 inactivation. Despite its low incidence, MCC recently received much attention based on its exquisite immunogenicity and the resulting major success of immune modulating therapies. Here, we summarize current knowledge on epidemiology, biology and therapy of MCC as conclusion of the project 'Immune Modulating strategies for treatment of Merkel Cell Carcinoma', which was funded over a 5-year period by the European Commission to investigate innovative immunotherapies for MCC.

http://ift.tt/2zQ3kbN

Quantitative Measurements Versus Receiver Operating Characteristics and Visual Grading Regression in CT Images Reconstructed with Iterative Reconstruction

Publication date: Available online 29 November 2017
Source:Academic Radiology
Author(s): Kristin Jensen, Hilde Kjernlie Andersen, Örjan Smedby, Bjørn Helge Østerås, Anette Aarsnes, Anders Tingberg, Erik Fosse, Anne Catrine Martinsen
Rationale and ObjectivesThis study aimed to evaluate the correlation of quantitative measurements with visual grading regression (VGR) and receiver operating characteristics (ROC) analysis in computed tomography (CT) images reconstructed with iterative reconstruction.Materials and MethodsCT scans on a liver phantom were performed on CT scanners from GE, Philips, and Toshiba at three dose levels. Images were reconstructed with filtered back projection (FBP) and hybrid iterative techniques (ASiR, iDose, and AIDR 3D of different strengths). Images were visually assessed by five readers using a four- and five-grade ordinal scale for liver low contrast lesions and for 10 image quality criteria. The results were analyzed with ROC and VGR. Standard deviation, signal-to-noise ratios, and contrast-to-noise ratios were measured in the images.ResultsAll data were compared to FBP. The results of the quantitative measurements were improved for all algorithms. ROC analysis showed improved lesion detection with ASiR and AIDR and decreased lesion detection with iDose. VGR found improved noise properties for all algorithms, increased sharpness with iDose and AIDR, and decreased artifacts from the spine with AIDR, whereas iDose increased the artifacts from the spine. The contrast in the spine decreased with ASiR and iDose.ConclusionsImproved quantitative measurements in images reconstructed with iterative reconstruction compared to FBP are not equivalent to improved diagnostic image accuracy.



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Prognostic Factors for Survival After Transarterial Chemoembolization Combined with Sorafenib in the Treatment of BCLC Stage B and C Hepatocellular Carcinomas

Publication date: Available online 29 November 2017
Source:Academic Radiology
Author(s): Jia-yan Ni, Jian Kong, Hong-liang Sun, Yao-ting Chen, Jiang-hong Luo, Wei-dong Wang, Dong Chen, Xiong-ying Jiang, Lin-feng Xu
Rationale and ObjectiveThe objective of this study was to analyze prognostic factors for survival after transarterial chemoembolization (TACE) combined with sorafenib for hepatocellular carcinoma (HCC) of Barcelona Clinic Liver Cancer (BCLC) stages B and C.Materials and MethodsClinical data of 198 patients with BCLC stage B and C HCCs who underwent TACE combined with sorafenib between June 2012 and January 2017 were retrospectively collected and analyzed. Survival curves were detected using log-rank test. Univariate analysis was performed using log-rank test with respect to 11 prognostic factors potentially affecting survival. All statistically significant prognostic factors identified by univariate analysis were entered into a Cox proportion hazards regression model to identify independent predictors of survival. P values were two-sided and P < 0.05 was considered statistically significant.ResultsBy the end of this study, the median follow-up duration was 43.6 months. The median overall survival (OS) of the patients was 21.0 months (95% confidence interval [CI]: 16.94–25.05), and the 1-, 2-, 3- and 5-year OS rates were 72%, 43%, 28%, and 4%, respectively. Tumor size (χ² = 33.607, P < 0.0001), tumor number (χ² = 4.084, P = 0.043), Child-Pugh class (χ² = 33.187, P < 0.0001), BCLC stage (χ² = 50.224, P < 0.0001), portal vein tumor thrombus (χ² = 88.905, P < 0.0001), Eastern Cooperative Oncology Group (ECOG) performance status (χ² = 98.007, P < 0.0001), extrahepatic spread (χ² = 34.980, P < 0.0001), TACE times (χ² = 8.350, P = 0.015), and sorafenib treatment strategy (χ² = 81.593, P < 0.0001) were found to be significantly associated with OS by univariate analysis. Multivariate analysis showed that BCLC stage (95% CI: 1.133–3.982, P = 0.019), extrahepatic spread (95% CI: 1.136–2.774, P = 0.012), and sorafenib treatment duration (95% CI: 0.352–0.574, P = 0.000) were independent prognostic factors associated with OS. There were no serious treatment-related adverse events.ConclusionsThis study showed that extrahepatic spread was a risk factor, and sorafenib treatment and superior BCLC stage were protective factors. Therefore, the study indicated that TACE combined with sorafenib was an effective and safe treatment for patients with BCLC stage B HCC without extrahepatic spread.



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The Study of Clear Cell Renal Cell Carcinoma with MR Diffusion Kurtosis Tensor Imaging and Its Histopathologic Correlation

Publication date: Available online 29 November 2017
Source:Academic Radiology
Author(s): Guangyu Wu, Zizhou Zhao, Qiuying Yao, Wen Kong, Jianrong Xu, Jin Zhang, Guiqin Liu, Yongming Dai
Rationale and ObjectivesThe objective of this study was to compare the performance of diffusion kurtosis tensor imaging and diffusion-weighted imaging in the characterization of clear cell renal cell carcinoma (ccRCC) and their correlations with tumor histopathology.Materials and MethodsNinety-one patients diagnosed with ccRCC who underwent diffusion kurtosis tensor imaging were included in this study. Fractional anisotropy, mean diffusivity, radial diffusivity, axial diffusivity, mean kurtosis (MK), radial kurtosis (Krad), and axial kurtosis (Kax) data were produced. A nuclear grade of 1–4 (G1–4) was assigned for each case based on the Fuhrman grading system, whereas tumor histopathology was characterized by the nuclear-to-cytoplasm ratio, the cell nuclei count, and the cell volume fraction.ResultsAll of the metric values except for Kax and fractional anisotropy could be used to discriminate G1 vs G3, G1 vs G4, G2 vs G3, and G2 vs G4, whereas MK and Kax could be used to discriminate G3 vs G4 (P < 0.05). Moreover, the MK and Krad values exhibited better performance in differentiating G2 from G3 (P < 0.04 compared to the other metrics). The nuclear-to-cytoplasm ratio was positively correlated with the MK, Krad, and Kax values (P < 0.001) and negatively correlated with the mean diffusivity, radial diffusivity, and axial diffusivity values (P < 0.001), whereas the cell volume fraction and the cell nuclei count did not correlate with any metric examined.ConclusionThe kurtosis metrics were superior to the diffusion metrics in grading ccRCC.



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High-risk Plaque and Calcification Detected by Coronary CT Angiography to Predict Future Cardiovascular Events After Percutaneous Coronary Intervention

Publication date: Available online 29 November 2017
Source:Academic Radiology
Author(s): Nobuo Tomizawa, Kodai Yamamoto, Shinichi Inoh, Takeshi Nojo, Sunao Nakamura
Rationale and ObjectivesThe purpose of this study was to investigate whether high-risk plaque (HRP) and calcium assessed by coronary computed tomography (CT) could predict future cardiovascular events after second-generation drug-eluting stent (DES) placement.Materials and MethodsWe analyzed 317 patients from December 2012 to April 2015 who underwent coronary CT followed by DES placement. HRP was defined as a plaque with positive remodeling and low attenuation or a plaque with a napkin-ring sign. Coronary calcium was assessed by Agatston score (AS). Patients were divided into three groups: low risk, HRP negative and AS <400; intermediate risk, HRP positive and AS ≥400; high risk, HRP positive and AS ≥400. The primary end point was a composite of all-cause mortality, myocardial infarction, fatal arrhythmia, or repeated revascularization. Kaplan-Meier analysis was used to estimate the distribution of time to events.ResultsA total of 74 events (23%) occurred during a median follow-up of 25.8 months. Patients with primary end points had HRP more frequently (70% vs 51%, P = 0.003) and were more calcified (AS, 471 [interquartile range, 143–1614] vs 289 [interquartile range, 63–787]; P = 0.01) than patients without primary end points. The frequency of primary end point increased significantly in the intermediate- and high-risk patients (P = 0.0011). Multivariate analysis showed that the hazard ratio of the intermediate- and high-risk groups was 1.91 (95% confidence interval, 1.04–3.77; P = 0.037) and 2.66 (95% confidence interval, 1.27–5.73; P = 0.009), respectively.ConclusionPlaque and calcification analysis by coronary CT could predict future cardiovascular events after second-generation DES placement.



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Which Preschool Children With Specific Language Impairment Receive Language Intervention?

Purpose

Potential biases in service provision for preschool children with specific language impairment (SLI) were explored.

Method

In Study 1, children with SLI receiving treatment (SLI-T) and those with SLI not receiving treatment (SLI-NT) were compared on demographic characteristics and developmental abilities. Study 2 recruited children with articulation disorders receiving treatment (ARTIC-T) to determine if knowing service provision status influenced the results of Study 1.

Results

In Study 1, the SLI-T group was rated by teachers as having poorer executive functioning than children in the SLIT-NT group, and the SLI-T group also came from families whose mothers had more education. These 2 variables alone predicted SLI-T and SLI-NT group membership with 84% accuracy. In Study 2, the ARTIC-T group were perceived as having comparable executive functioning to the SLI-NT group and better than the SLI-T group, indicating that teachers' knowledge of service provision did not influence their ratings of children's executive functioning.

Discussion

Preschool children with SLI, whose mothers have higher education levels and whose teachers perceive them as having poorer executive functioning, are more likely to receive intervention. Recognizing service delivery biases is critical for improving early provision of intervention for this population.

http://article/doi/10.1044/2017_LSHSS-17-0024/2665177/Which-Preschool-Children-With-Specific-Language

Errata

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Errata

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Errata

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Irinotecan and Oxaliplatin Might Provide Equal Benefit as Adjuvant Chemotherapy for Patients with Resectable Synchronous Colon Cancer and Liver-confined Metastases: A Nationwide Database Study

Background: Although irinotecan and oxaliplatin are both standard treatments for advanced colon cancer, it remains unknown whether either is effective for patients with resectable synchronous colon cancer and liver-confined metastasis (SCCLM) after curative surgery. Patients and Methods: A population-based cohort of patients diagnosed with de novo SCCLM between 2004 and 2009 was established by searching the database of the Taiwan Cancer Registry and the National Health Insurance Research Database of Taiwan. Patients who underwent curative surgery as their first therapy followed by chemotherapy doublets were classified into the irinotecan group or oxaliplatin group accordingly. Patients who received radiotherapy or did not receive chemotherapy doublets were excluded. Results: We included 6,533 patients with de novo stage IV colon cancer. Three hundred and nine of them received chemotherapy doublets after surgery; 77 patients received irinotecan and 232 patients received oxaliplatin as adjuvant chemotherapy. The patients in both groups exhibited similar overall survival (median: not reached vs. 40.8 months, p=0.151) and time to the next line of treatment (median: 16.5 vs. 14.3 months, p=0.349) in both univariate and multivariate analyses. Additionally, patients with resectable SCCLM had significantly shorter median overall survival than patients with stage III colon cancer who underwent curative surgery and subsequent adjuvant chemotherapy, but longer median overall survival than patients with de novo stage IV colon cancer who underwent surgery only at the primary site followed by standard systemic chemotherapy (p<0.001). Conclusion: Irinotecan and oxaliplatin exhibited similar efficacy in patients who underwent curative surgery for resectable SCCLM.

http://ift.tt/2kaPXfe

Robotic-assisted Transperitoneal Infrarenal Para-aortic Lymphadenectomy for Gynecological Malignancies: Comparison with a Laparoscopic Approach

Background/Aim: We evaluated the clinical feasibility and surgical outcomes of robotic-assisted transperitoneal infrarenal para-aortic lymphadenectomy (TIPAL) in patients with gynecological malignancies. Patients and Methods: The perioperative outcomes in 90 patients with gynecological malignancies who underwent laparoscopic (n=43) or robotic-assisted (n=47) TIPAL were compared retrospectively. Results: The operative time for pelvic and total lymphadenectomy were significantly shorter in the robotic-assisted approach, whereas the time for infrarenal para-aortic lymphadenectomy did not differ statistically. In contrast, the number of infrarenal para-aortic lymph nodes was significantly higher in the robotic-assisted approach. We compared the time per retrieved lymph node in both approaches, and those for pelvic, infrarenal para-aortic, and total lymphadenectomy were significantly shorter in the robotic-assisted approach. Conclusion: In our study, the robotic-assisted TIPAL took less time to retrieve a lymph node than the laparoscopic approach. The robotic-assisted approach for TIPAL is feasible for the staging and treatment of patients with gynecological malignancies.

http://ift.tt/2BxEOJJ

Anastomotic Leakage Using Linear Stapling Device with Pre-attached Bioabsorbable Polyglycolic Acid Felt After Laparoscopic Anterior Resection

Aim: Many studies have evaluated the risk factors for anastomotic leakage after laparoscopic anterior resection. In this study in order to increase the tightness of anastomoses and prevent bleeding from their staple lines, a linear stapler with pre-attached bioabsorbable polyglycolic acid (PGA) felt was used for rectal transection, and the short-term surgical outcomes were evaluated. Patients and Methods: A prospective registry of 62 patients with rectosigmoidal or rectal carcinoma who initially underwent laparoscopic anterior resection using PGA felt for rectal transection was reviewed. Results: The overall frequency of anastomotic leakage was 1.6% (1/62), and none of the patients developed postoperative staple line bleeding or other adverse events related to the use of PGA felt. Conclusion: The frequency of anastomotic leakage was relatively low, and therefore the use of a linear stapler with pre-attached bioabsorbable PGA felt might reduce the risk of adverse events related to anastomosis, especially anastomotic leakage.

http://ift.tt/2k9RHWg

Association Between PD-L1 Expression and Metabolic Activity on 18F-FDG PET/CT in Patients with Small-sized Lung Cancer

Aim: We evaluated the metabolic characteristics of small-sized lung cancer using ¹⁸F-fluorodeoxyglucose positron-emission tomography/computed tomography (¹⁸F-FDG PET/CT) with regard to programmed cell death ligand 1 (PD-L1) expression. Materials and Methods: PD-L1 expression was evaluated by immunohistochemistry with the antibody clone SP142 in 263 patients with surgically resected primary small-sized lung cancer. Specimens with <5% tumor membrane staining were considered negative. We examined the association between the frequency of PD-L1 expression and the maximum standardized uptake value (SUVmax) in preoperative ¹⁸F-FDG PET/CT. Results: Among patients with non-small cell lung cancer (NSCLC), the SUVmax was significantly higher in those with PD-L1 expression than in those without (p<0.0001). However, there was no correlation between SUVmax and PD-L1 expression in patients with neuroendocrine tumors (p=0.9638). Multivariate analysis revealed that smoking and a high SUVmax were independent predictors of PD-L1 expression. Conclusion: PD-L1 expression was related to high glucose metabolism in small-sized NSCLC.

http://ift.tt/2BxqYXG

A Glissonean Approach with Individual Isolation During Right Hemi-Hepatectomy After Portal Vein Embolization

Background/Aim: Although the Glissonean approach in hemi-hepatectomy is a very useful technique, right hemi-hepatectomy with Glissonean approach after portal vein embolization (PVE) is difficult because of the obstructing materials located at the right portal branch. The aim of this study was to evaluate the utility of the Glissonean approach with an individual isolation technique (GI technique) in right hemi-hepatectomies after PVE. Patients and Methods: We retrospectively analyzed 21 patients who underwent the GI technique between March 2007 and June 2012. Results: In one of the 21 patients, we could not perform the GI technique because of severe adhesions following previous operation; however, there were no troubles in the remaining 20 cases. In addition, none of the patients that were treated using this method developed massive ascites after right hemi-hepatectomy, despite 8 patients (40%) exhibiting severe fibrosis (F3 or F4). Conclusion: Even in right hemi-hepatectomy following PVE, our GI technique may be a useful procedures for patients.

http://ift.tt/2kahCNA

Mucinous Cystic Neoplasms Lined by Abundant Mucinous Epithelium Frequently Involve KRAS Mutations and Malignant Progression

Background: Pancreatic and hepatic mucinous cyst neoplasms (MCNs) have a malignant potential, but indolent MCNs are not uncommon. Materials and Methods: The pathological and genetic characteristics of resected MCNs (n=15) categorized by the amount of mucin of the lining epithelium were investigated. Results: MCNs were divided into two groups: (i) a rich (r)-MCN group (n=6), in which more than half of the epithelium was lined by abundant mucinous epithelium; and (ii) a poor (p)-MCN group (n=9), which consisted of the remaining cases. Three patients in the r-MCN group showed invasive carcinoma or high-grade dysplasia, whereas all patients in the p-MCN group showed low-grade dysplasia. Mutations of Kirsten rat sarcoma viral oncogene homolog (KRAS) were more frequent in the r-MCN group (83%) (p-MCN; 11%, p<0.05). Conclusion: Mucinous MCNs more frequently have KRAS mutations and higher risk of malignant progression.

http://ift.tt/2By0HJ0

Characterization of Prognostic Factors and the Efficacy of Adjuvant S-1 Chemotherapy in Patients with Post-surgery Extrahepatic Bile Duct Cancer

Background/Aim: There is no clear consensus on the type of adjuvant therapy that should be used for patients with extrahepatic bile duct cancer. Patients and Methods: Two hundred and seventy-one patients that had undergone surgical resection for extrahepatic bile duct cancer composed the study cohort. Demographics, treatments, and relationships between the potential prognostic factors and survival rates were analyzed. Results: The overall 3-year and 5-year survival rates for post-surgery extrahepatic bile duct cancer patients were 49.0% and 35.4%, respectively. Multivariate analysis revealed that regional lymph node metastasis was an independent negative prognostic factor. We observed a significant correlation between node-positive extrahepatic bile duct cancer and postoperative local recurrence, liver metastasis, peritoneal dissemination, and post-surgery lymph node metastasis. Adjuvant S-1 chemotherapy showed a favorable hazard ratio in patients with lymph node metastases or positive vascular invasion. Conclusion: We recommend the use of adjuvant S-1 therapy in patients with lymph node metastases or microvascular invasion.

http://ift.tt/2BxEOtd

BRAF, NRAS and C-KIT Advanced Melanoma: Clinico-pathological Features, Targeted-Therapy Strategies and Survival

Background/Aim: The mutational status of stage III and IV melanomas should be recognized in order to allow for targeted therapies. The aim of our study was the characterization of BRAF, NRAS and C-KIT melanoma patients, in order to define their optimal management. Patients and Methods: Between 1991 and 2015, 63 mutated melanoma patients were treated and monitored during their diagnostic and therapeutic management at a single institution. Results: BRAF-mutated melanoma patients were the most common, representing 70% of the study population, while NRAS- and C-KIT-mutated melanoma represented 19% and 11% respectively. BRAF-mutated melanomas were mostly located at sites of intermittent sun exposure, and were associated with higher Breslow thickness and an increased number of mitosis. NRAS mutated melanoma were mainly observed in chronic sun-damaged areas and had a negative prognostic value, with shorter time to progression and a high incidence of central nervous system involvement. C-KIT mutated melanoma were located at acral and mucosal sites. Overall survival observed in the three groups of patients revealed wide differences. Conclusion: BRAF, NRAS and C-KIT melanomas constitute distinct clinico-pathological entities. BRAF-mutated melanoma benefit from both anti-BRAF and anti-MEK targeted therapies while triple-negative melanomas could benefit from novel anti-CTLA-4 and anti-PD-L1 immunotherapeutic approaches.

http://ift.tt/2k8A7BY

Incidence and Risk Factors of Symptomatic Hiatal Hernia Following Resection for Gastric and Esophageal Cancer

Background/Aim: Symptomatic hiatal hernia (HH) following resection for gastric or esophageal cancer is a potentially life-threatening event that may lead to emergent surgery. However, the incidence and risk factors of this complication remain unclear. Patients and Methods: Data of patients who underwent resection for gastric or esophageal cancer between 2005 and 2012 were assessed and the incidence of symptomatic HH was evaluated. Factors associated with an increased risk for HH were investigated. Results: Resection of gastric or esophageal cancer was performed in 471 patients. The primary tumor was located in the stomach, cardia and esophagus in 36%, 24%, and 40% of patients, respectively. The incidence of symptomatic HH was 2.8% (n=13). All patients underwent surgical hernia repair, 8 patients (61.5%) required emergent procedure, and 3 patients (23%) underwent bowel resection. Morbidity and mortality after HH repair was 38% and 8%, respectively. Factors associated with increased risk for symptomatic HH included Body-Mass-Index (median BMI with HH 27 (23-35) vs. BMI without HH 25 (15-51), p=0.043), diabetes (HH rate: with diabetes, 6.3% vs. without diabetes, 2%, p=0.034), tumor location (HH rate: stomach, 1.2% vs. esophagus, 1.1% vs. cardia, 7.9%, p=0.001), and resection type (HH rate: total/subtotal gastrectomy, 0.7% vs. transthoracic esophagectomy, 2.7% vs. extended gastrectomy, 6.1%, p=0.038). Conclusion: HH is a major adverse event after resection for gastric or esophageal cancer especially among patients undergoing extended gastrectomy for cardia cancer requiring a high rate of repeat surgery. Therefore, intensive follow-up examinations for high-risk patients and early diagnosis of asymptomatic patients are essential for selecting patients for elective surgery to avoid unpredictable emergent events with high morbidity and mortality.

http://ift.tt/2k8A5tQ

A Prospective Study of Intensity-modified Radiation Therapy in Comparison with Conventional 3D-RT for BR Pancreatic Cancer Patients with Arterial Involvement

Background/Aim: Intensity-modulated radiation therapy (IMRT) is a form of radiation therapy that allows accurate irradiation with reduced damage to surrounding tissues. Here, we analyzed borderline-resectable pancreatic cancer (BRPC) with arterial abutment (BR-A) patients with IMRT as neoadjuvant therapy and performed comparisons with patients with conventional RT to clarify the advantages of IMRT as a neoadjuvant therapy. Patients and Methods: Thirty BR-A patients treated at our hospital between January 2012 and December 2015 were divided into two groups: 12 patients underwent conventional 3D-RT before resection (RT group); and 18 patients underwent IMRT before resection (IMRT group). We analyzed safety, tumor resection rate, histological classification of the tumor and overall survival. Results: The R0 rate was 84% for the IMRT group and 83% for the RT group. Local therapeutic effects as assessed by Evans classification showed a higher local control rate in the IMRT group (Grade: 1, 0%; 2a, 25%; 2b, 41.6%; 3, 17%; 4, 8%) than in the RT group (Grade: 1, 17%; 2a, 50%; 2b, 17%; 3, 17%; 4, 0%). The cumulative dose of S1 treatment as adjuvant therapy was much smaller in the RT group (18.3%) compared to that in the IMRT group (57.1%, p=0.047), and with better subsequent overall survival rate (MST 32 months vs. 13.8 months, p=0.0273). Conclusion: The IMRT group showed a better control rate than the RT group. The neoadjuvant IMRT has advantages of higher completion rate of adjuvant chemotherapy with better nutritional status and better subsequent overall survival rate (OS).

http://ift.tt/2BydmLI

Pancreatic Mucinous Cystic Neoplasm Communicating with Main Pancreatic Duct: An Unrecognized Presentation of Pancreatic Mucinous Neoplasm?

Mucinous cystic neoplasms (MCNs) and intraductal papillary mucinous neoplasms (IPMNs) are two well recognized entities of precursor cystic lesions of pancreatic duct adenocarcinoma. The characteristic features of MCNs are the lined mucinous epithelium with underlying ovarian-type stroma, but without communication with the ducts, while that for IPMNs are the communication with the ducts but without the underlying ovarian-type stroma. Here we report a case of MCN communicating with the main pancreatic duct in a 68-year-old woman. The initial radiographic diagnosis was pancreatic IPMN with main pancreatic involvement and this was also confirmed during gross examination. Histologically, the pancreatic cystic neoplasm was lined with mucinous epithelium with underlying ovarian-type of stroma. Immunohistochemical stains confirmed that the stroma cells were positive for ER, PR, alpha-inhibin and focally positive for CD10. The final pathologic diagnosis was pancreatic mucinous cystic neoplasm communicating with the main pancreatic duct. To the best of our knowledge, this is the second pathology confirmed case of MCN communicating with the main pancreatic duct. A careful gross examination and bivalvation of the main duct communicating with the cystic neoplasm helps render the correct diagnosis. If more cases are reported in the future, the MCN communicating with duct could become a new entity of pancreatic mucinous neoplasm.

http://ift.tt/2k8A35c

Predictive Factors and a Survival Score for Patients Irradiated for Metastatic Spinal Cord Compression from Carcinoma of the Salivary Glands

Aim: To our knowledge, this is the first study focusing on metastatic spinal cord compression (MSCC) from carcinoma of the salivary glands. Patients and Methods: Nine patients receiving radiation alone were evaluated for improvement of motor deficits, post-radiation gait function and survival. Results: Of nine characteristics (radiation program, age, sex, additional metastases to bone or to other organs, dynamic of motor deficits, pre-radiation gait function, number of vertebrae affected by MSCC, general condition), strong trends were found for associations between improved motor deficits and their dynamic (p=0.05), post-radiation gait function and pre-treatment ambulatory status (p=0.08) and between survival and additional metastases to other organs (p=0.07), dynamic of motor deficits (p=0.07) and general condition (p=0.07). In addition, a survival score was created. Patients with 2-3 points had a significantly better 6-month survival than those with 0-1 points (100% vs. 0%, p=0.027). Conclusion: Characteristics predicting outcomes identified in this study and the new survival score can guide physicians when making treatment decisions.

http://ift.tt/2BAlvPV

Stereotactic Body Radiation Therapy in Primary and Metastatic Liver Disease

Background/Aim: The aim of this study was to investigate the treatment outcomes and toxicities in patients with liver disease treated by Stereotactic Body Radiation Therapy (SBRT). Patients and Methods: From 2007 to 2016, 43 patients with 58 lesions (6 primary and 37 metastatic liver tumors) were treated with SBRT. Results: Local Control was reached in 47 out of 58 (81%) treated lesions with 12 and 24-month rates of 81% and 74% respectively. The progression-free survival at 12 and 24 months was 42% and 36%, respectively. The disease specific survival at 12 and 24 months was 74% and 46% respectively. Median overall survival (OS) was 20 months and the rates of OS were 74% and 46% at 12 and 24 months respectively. Toxicity was very low consisting mainly of Grade 1 and 2. Conclusion: SBRT provides good local control for both primary and metastatic liver lesions, with minimal toxicity.

http://ift.tt/2ke1UkB

One-pot synthesis of pH-responsive charge-switchable PEGylated nanoscale coordination polymers for improved cancer therapy

Publication date: February 2018
Source:Biomaterials, Volume 156
Author(s): Yu Yang, Ligeng Xu, Wenjun Zhu, Liangzhu Feng, Jingjing Liu, Qian Chen, Ziliang Dong, Jiayue Zhao, Zhuang Liu, Meiwan Chen
Nanoscale coordination polymers (NCPs) are promising nanomedicine platforms featured with biodegradability and versatile functionalities. However, multi-step post-synthesis surface modification is usually required to functionalize as-made NCPs before their biomedical applications. Moreover, efforts are still required to design therapeutic NCPs responsive to the unique tumor microenvironment to achieve more specific and effective therapy. Herein, we uncover a simple yet general strategy to synthesize a series of polyethylene glycol (PEG) modified NCPs via a one-step method by adding poly-histidine-PEG co-polymer into the mixture of metal ions and organic ligands during NCPs formation. With NCPs consisting Ca²⁺/dicarboxylic cisplatin (IV) prodrug as the example, we show that such Ca/Pt(IV)@pHis-PEG NCPs are highly sensitive to pH changes. With slightly negative charges and compact structure under pH 7.4 during blood circulation, those NCPs exhibit efficient passive accumulation in the tumor, in which the reduced pH (c.a. 6.5) would trigger charge conversion and size expansion to enhance their tumor retention and cell internationalization. After cellular uptake, NCPs within cell endo-/lysosomes with further reduced pH would then lead to decomposition of those NCPs and thus drug release. Chemotherapy with Ca/Pt(IV)@pHis-PEG NCPs in our animal tumor model demonstrates great efficacy under low drug doses, and is found to be particularly effective towards solid tumors with reduced pH.

Graphical abstract

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A mitochondrial-targeting near-infrared fluorescent probe for bioimaging and evaluating endogenous superoxide anion changes during ischemia/reperfusion injury

Publication date: February 2018
Source:Biomaterials, Volume 156
Author(s): Xiaoyue Han, Rui Wang, Xinyu Song, Fabiao Yu, Changjun Lv, Lingxin Chen
The outburst of superoxide anion (O2⁻) in mitochondrial during ischemia/reperfusion (I/R) process will cause a series of oxidative damage including polarity loss of mitochondrial membrane potential, overload of secondary cellular calcium, and cascade apoptosis. To monitor the O2⁻ level fluctuations as well as to evaluate the relationship between O2⁻ concentration and the degree of cell apoptosis during I/R process, we propose a ratiometric near-infrared mitochondrial targeting fluorescent probe Mito-Cy-Tfs for the detection of level changes of O2⁻ in cells and in vivo. The probe Mito-Cy-Tfs is composed of three moieties: near-infrared heptamethine cyanine as fluorescence signal transducer, trifluoromethanesulfonamide as fluorescence modulator, and lipophilic triphenylphosphonium cation as mitochondrial guider. The probe can well locate in mitochondria and respond the concentration changes of endogenous O2⁻ selectively and sensitively. The probe has been successfully utilized to image the endogenous O2⁻ fluctuations in four kinds of cell I/R models (glucose deprivation/reperfusion, serum deprivation/reperfusion, oxygen deprivation/reperfusion and glucose-serum-oxygen deprivation/reperfusion). The probe also exhibits deep tissue penetration for real-time imaging of O2⁻concentration in liver of I/R mice model. We confirm that the adoption of ischemic preconditioning (IPC) and postconditioning (IPTC) can protect liver from I/R injury. The probe can be employed to accurately indicate and evaluate the mutual relationship between the levels of O2⁻ and the degrees of organ damage during I/R, IPC and IPTC processes. The above applications make our new probe a potential candidate for the clinical surgery assessment.



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Mechanistic insights into the role of glycosaminoglycans in delivery of polymeric nucleic acid nanoparticles by molecular dynamics simulations

Publication date: February 2018
Source:Biomaterials, Volume 156
Author(s): Deniz Meneksedag-Erol, Tian Tang, Hasan Uludağ
Delivery of polynucleotide-based therapeutics into target cells involves interactions with glycosaminoglycan chains that are located on cell membrane milieu. Mechanisms governing glycosaminoglycan-mediated changes in the nanoparticulate structures of polymer-polynucleotide complexes are unknown, and cannot be fully elucidated without atomistic level details of molecular interactions. We selected a representative nanoparticulate system consisting of a short interfering RNA (siRNA)-polyethylenimine complex, and performed all-atom molecular dynamics simulations with the prototypical glycosaminoglycan heparin. We monitored the binding between the complex constituents and the heparin, and identified key features contributing to the response of the siRNA nanoparticles to heparin. We observed three main metastable states that the siRNA nanoparticles might visit in the presence of heparin, which can be translated into different functional outcomes. By correlating our data with the widely different and seemingly contradictory roles previously assigned to glycosaminoglycans, this study provides unique insights into the discrepancies in the experimental literature concerning the role of glycosaminoglycans in the polymeric nanoparticle delivery.

Graphical abstract

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When stem cells meet graphene: Opportunities and challenges in regenerative medicine

Publication date: February 2018
Source:Biomaterials, Volume 155
Author(s): Kenry, Wong Cheng Lee, Kian Ping Loh, Chwee Teck Lim
Recent advances in stem cell research and nanotechnology have significantly influenced the landscape of tissue engineering and regenerative medicine. Precise and reproducible control of the fate of stem cells and their lineage specification have, therefore, become more crucial than ever for the success of stem cell-based technologies. Extensive research has been geared towards developing materials that are capable of mimicking the physiological microenvironment of stem cells and at the same time, controlling their eventual fate. An interesting example of these materials is two-dimensional graphene and its related derivatives. A high specific surface area coupled with superior chemical stability, biocompatibility, and flexibility in functionalization render graphene-based nanomaterials one of the most exciting platforms for tissue engineering and regenerative medicine applications, especially for stem cell growth, proliferation, and differentiation. In this review, we discuss the love-hate relationship between stem cells and graphene-based nanomaterials in tissue engineering and regenerative medicine. We first discuss the role and importance of stem cells in tissue engineering and regenerative medicine. We then highlight the use of nanomaterials for stem cell control, the interaction between stem cells and graphene nanomaterials as well as their biocompatibility, biodistribution, and biodegradability considerations. We also offer our perspectives on the various challenges and opportunities facing the use of graphene and its derivatives for stem cell growth and differentiation.



http://ift.tt/2i0cWWe

Lingual tonsillectomy in children with Down syndrome: Is it safe?

Evaluate peri-operative course and morbidity in children with Down syndrome (DS) who underwent a lingual tonsillectomy (LT) for residual obstructive sleep apnea (rOSA).

http://ift.tt/2AndJuZ

Making and working of a new electronic resource for patients, carers and professionals: maxfacts.uk

Many maxillofacial patients have serious short, medium, or long-term problems, as well as having to make informed decisions about often life-changing interventions. Validated comprehensive information, at the right time and the right level for a diverse group of users (patients, carers, and professionals), is vital if patients are to make a serious contribution to their treatment. We describe the development of an online resource for this purpose. Maxfacts.uk aims to cover every aspect of oral and maxillofacial surgery and care, from neck dissection and ballistic wounds to physiotherapy and texture-modified foods.

http://ift.tt/2ApINue

Nodular fasciitis of the temporomandibular joint: a case report

Nodular fasciitis is a relatively rare benign lesion of the soft tissue, which often presents in the fascia or deep subcutaneous tissues. It most commonly presents in the upper extremities and trunk and the head and neck region, particularly in younger patients. Its pathogenesis is poorly understood and it is predominantly thought to be a reactive lesion, although some have suggested that it may be a benign neoplasm. Advances in molecular testing and imaging have greatly assisted diagnosis. We discuss the benefits of ubiquitin-specific protease 6 (USP6) gene rearrangement testing and magnetic resonance imaging (MRI) to aid this uncommon diagnosis.

http://ift.tt/2ilnq6b

Prognosis of oral cancer: a comparison of the staging systems given in the 7th and 8th editions of the American Joint Committee on Cancer Staging Manual

The 8th edition of the American Joint Committee on Cancer (AJCC) Staging Manual introduces "depth of invasion" and "extranodal extension" into the head and neck section, and our aim was to find out if these changes have an impact on prognosis. We evaluated 174 patients who had had oral squamous cell carcinomas (SCC) resected between 2003 and 2012. The clinical records were reviewed, the patients' tumours restaged according to the 8th edition of the AJCC, and we analysed five-year survival to verify whether different correlations were made between the T and N stages and disease-specific survival using the 7th and 8th editions.

http://ift.tt/2AnuUwG

Is it better to bend wires occlusally or apically during placement of arch bars for intermaxillary fixation?

We evaluated 78 patients who had intermaxillary fixation (IMF) of fractured mandibular condyles with arch bars and wires. Depending on whether the wires were bent apically or occlusally during placement of the arch bars, we randomly divided the patients into two groups (n=39 in each), then compared pain, satisfaction with oral hygiene, and complications between the groups at five to six weeks postoperatively when the arch bars were removed. Outcomes were significantly better in the occlusal group than in the apical group.

http://ift.tt/2ApxHVS

Retroseptal transconjunctival approach for fractures of the zygomaticomaxillary complex: a retrospective study

We designed a retrospective study to evaluate the efficacy of retroseptal transconjunctival approaches in the management of fractures of the zygomaticomaxillary complex (ZMC). The patients were from a single institution, and had had three-point fixation of fractures of the ZMC between 2008 and 2016. A total of 77 patients (56 men and 21 women with a mean (range) age of 28 (18–54) years), were divided into two groups. Group I (n=51) had had reduction and fixation of the infraorbital rim using a retroseptal transconjunctival approach.

http://ift.tt/2ipDnIy

Tracking the Growth of Tense and Agreement in Children With Specific Language Impairment: Differences Between Measures of Accuracy, Diversity, and Productivity

Purpose

Composite measures of children's use of tense and agreement morphology differ in their emphasis on accuracy, diversity, or productivity, yet little is known about how these different measures change over time. An understanding of these differences is especially important for the study of children with specific language impairment, given these children's extraordinary difficulty with this aspect of grammar.

Method

We computed 3 types of composite scores from spontaneous speech samples obtained from 17 preschoolers with specific language impairment before, during, and after their participation in a language intervention study. These measures were the Finite Verb Morphology Composite (a measure of accuracy), the Tense Marker Total (a measure of diversity), and the Productivity Score (a measure of productivity).

Results

The 3 measures differed in their growth trajectories. Sample size did not alter the linear or quadratic nature of growth of any composite, although it did affect the absolute values found for the Tense Marker Total and Productivity Score.

Conclusion

Even when sample size is controlled, early growth can be seen in tense and agreement accuracy with relatively limited diversity and productivity, whereas later growth in diversity and productivity can occur with very little change in accuracy.

http://article/doi/10.1044/2017_JSLHR-L-16-0427/2665179/Tracking-the-Growth-of-Tense-and-Agreement-in

Evaluation of an Automated Pipeline for Large Scale EEG Spectral Analysis: The National Sleep Research Resource

We present an automated sleep electroencephalogram (EEG) spectral analysis pipeline that includes an automated artifact detection step, and we test the hypothesis that spectral power density estimates computed with this pipeline are comparable to those computed with a commercial method preceded by visual artifact detection by a sleep expert (standard approach).

http://ift.tt/2j4OCU7

Option grids in melanoma - an underused tool

It is not uncommon for patients faced with a new diagnosis of malignant melanoma to experience significant upset and confusion. During this distressing period, NICE guidance (NG14) recommends that patients with AJCC Stage IB-IIC disease should consider whether they wish to undergo sentinel lymph node biopsy (SLNB)1. The decision to undergo SLNB can be difficult and should ideally be reached following informed and considered discussion with patients guided as to the relative merits of SLNB by their plastic surgeon.

http://ift.tt/2jyDJt8

Patient-specific puzzle implant preformed with 3d-printed rapid prototype model for combined orbital floor and medial wall fracture

The management of combined orbital floor and medial wall fractures involving the inferomedial strut is challenging due to absence of stable cornerstone. In this article, we proposed surgical strategies using customized 3D puzzle implant preformed with Rapid Prototype (RP) skull model.

http://ift.tt/2jxQcNt

The extent of surgery for benign parotid pathology and its influence on complications: A prospective cohort analysis

The surgical management of benign parotid tumors is aimed at complete extirpation of the mass with preservation of facial nerve function. There is a relative paucity of literature pertaining to complications after benign parotid surgery and related risk factors. We aim to critically review the outcomes following treatment of benign parotid pathology when surgery entailed either complete superficial parotidectomy (CSP), partial superficial parotidectomy (PSP) or extracapsular dissection (ECD).

http://ift.tt/2AoC2sm

The extent of surgery for benign parotid pathology and its influence on complications: A prospective cohort analysis

The surgical management of benign parotid tumors is aimed at complete extirpation of the mass with preservation of facial nerve function. There is a relative paucity of literature pertaining to complications after benign parotid surgery and related risk factors. We aim to critically review the outcomes following treatment of benign parotid pathology when surgery entailed either complete superficial parotidectomy (CSP), partial superficial parotidectomy (PSP) or extracapsular dissection (ECD).

http://ift.tt/2AoC2sm

Comparing Traditional Service Delivery and Telepractice for Speech Sound Production Using a Functional Outcome Measure

Purpose

Using American Speech-Language-Hearing Association's (ASHA's) National Outcomes Measurement System (NOMS) Functional Communication Measure (FCM) as a common metric, this investigation compared traditional service delivery and telepractice service delivery for children receiving therapy for the NOMS diagnostic category of "speech sound production."

Method

De-identified cases were secured from ASHA's NOMS database and a proprietary database from a private e-learning provider. Cases were included if they met 3 criteria: (a) children received treatment exclusively for speech sound production, (b) they were between 6.0 and 9.5 years old, and (c) they received therapy lasting between 4 and 9 months. A total of 1,331 ASHA NOMS cases and 428 telepractice cases were included. The 2 groups were matched by initial FCM scores. Mann–Whitney U tests were completed to compare differences in the median change scores (the difference between the initial and final FCM scores) between the 2 groups.

Results

There were no significant differences in the median change scores between the traditional group and the telepractice group.

Conclusions

These results suggest comparable treatment outcomes between traditional service delivery and telepractice for treatment of children exhibiting speech sound disorders. The findings provide support for the use of telepractice for school-age children.

http://article/doi/10.1044/2017_AJSLP-16-0070/2665178/Comparing-Traditional-Service-Delivery-and

Uranium(VI) sorption complexes on silica in the presence of calcium and carbonate

Publication date: February 2018
Source:Journal of Environmental Radioactivity, Volume 182
Author(s): Alaaeldine Sh. Saleh, Jun-Yeop Lee, Yongheum Jo, Jong-Il Yun
Uranium sorption on minerals and related solids depends to a large degree on its aqueous speciation. The present work attempts to understand the U(VI) sorption behavior on silica under environmentally relevant conditions, i.e. at neutral to weakly alkaline pH and in the presence of dissolved calcium and carbonate. Under these conditions, Ca(UO2)(CO3)3²⁻ and Ca2(UO2)(CO3)3(aq) complexes emerge as the dominant aqueous U(VI) species. The U(VI) sorption affinity was measured as a function of contact time, solution pH, and humic acid. The U(VI) sorption decreased with increase of pH and was not affected by the addition of 50 mg/L humic acid. On the other hand, nitric acid was more effective than EDTA and carbonate at desorbing U(VI). Generally, the U(VI) sorbed on silica at neutral pH was less readily desorbed than that sorbed at higher pH values. Therefore, the U(VI) complex favorably sorbed on silica at the neutral pH is more strongly bound to the silica surface than that sorbed at higher pH values. Time-resolved laser fluorescence spectroscopy confirmed the results of the batch sorption experiments and revealed the presence of two surface U(VI) complexes with fluorescence lifetimes 251 ± 8 μs and 807 ± 24 μs.

Graphical abstract

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Postmortem MRI and histology demonstrate differential iron accumulation and cortical myelin organization in early- and late-onset Alzheimer's disease

Publication date: February 2018
Source:Neurobiology of Aging, Volume 62
Author(s): Marjolein Bulk, Walid M. Abdelmoula, Rob J.A. Nabuurs, Linda M. van der Graaf, Coen W.H. Mulders, Aat A. Mulder, Carolina R. Jost, Abraham J. Koster, Mark A. van Buchem, Remco Natté, Jouke Dijkstra, Louise van der Weerd
Previous MRI studies reported cortical iron accumulation in early-onset (EOAD) compared to late-onset (LOAD) Alzheimer disease patients. However, the pattern and origin of iron accumulation is poorly understood. This study investigated the histopathological correlates of MRI contrast in both EOAD and LOAD. T2*-weighted MRI was performed on postmortem frontal cortex of controls, EOAD, and LOAD. Images were ordinally scored using predefined criteria followed by histology. Nonlinear histology-MRI registration was used to calculate pixel-wise spatial correlations based on the signal intensity. EOAD and LOAD were distinguishable based on 7T MRI from controls and from each other. Histology-MRI correlation analysis of the pixel intensities showed that the MRI contrast is best explained by increased iron accumulation and changes in cortical myelin, whereas amyloid and tau showed less spatial correspondence with T2*-weighted MRI. Neuropathologically, subtypes of Alzheimer's disease showed different patterns of iron accumulation and cortical myelin changes independent of amyloid and tau that may be detected by high-field susceptibility-based MRI.



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Intertriginous and Seborrheic Dermatitis-Like Lesions in an Endocrine Patient

No abstract available

http://ift.tt/2il24WA

Blistering and Skin Fragility Due to Imatinib Therapy: Loss of Laminin and Collagen IV as a Possible Cause of Cutaneous Basement Membrane Instability

Abstract: Imatinib mesylate (Glivec; Novartis AG, Basel, Switzerland) is a tyrosine kinase inhibitor which is used in the treatment of oncologic diseases like chronic myeloid leukemia and gastrointestinal stroma tumor (GIST). Among cutaneous side effects, bullous reactions are rare. The authors describe the case of a 66-year-old woman developing blistering and skin fragility on her hands, foot, lower legs, and back after intake of imatinib for treatment of GIST. Biopsy showed vacuolar alteration at the dermoepidermal junction (DEJ) associated with a few lymphocytes and a subepidermal blister. The upper papillary dermis below the vacuolar alteration and below the blister showed hyalinization and loss of elastic microfibrils. Direct immunofluorescence was negative for deposits of immunoglobulins. Immunofluorescence on cryosections revealed loss of laminin and collagen IV in vacuoles at the DEJ. Electron microscopy showed dissolution of lamina lucida and lamina densa of the basement membrane below as well as next to the vacuoles and blister. In conclusion, the authors present the first patient with GIST with blistering and skin fragility due to imatinib therapy. As a pathophysiological explanation the authors propose loss of laminin and collagen IV at the DEJ leading to basement membrane instability and blistering. This case also suggests additional features reminiscent of lichen sclerosus induced by imatinib, a drug which is actually known for its antifibrotic effects. Reprints: Sebastian Mühl, MD, Universitätshautklinik Münster, Dermatohistologisches Labor, Von-Esmarch-Strasse 58, D-48149 Münster, Germany (e-mail: Sebastian.Muehl@ukmuenster.de). The authors declare no conflicts of interest. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Relationship Between Pityriasis Lichenoides and Mycosis Fungoides: A Clinicopathological, Immunohistochemical, and Molecular Study

Background: Several cases of pityriasis lichenoides (PL) have been reported to evolve into mycosis fungoides (MF). Objective: To elucidate clues to this progression. Methods: Fifty-eight patients with PL between 2000 and 2013 (follow-up: 3–16 years, average: 8.3). Results: A total of 3 (5.2%) of the 58 patients with PL developed MF after 3–11 years of prolonged clinical course. Papules and small plaques characterized PLs, and patches and larger plaques subsequent MFs. A total of 35 of 41 (85%) followed up non-MF associated patients with PL reported lasting complete remissions. Histopathologically, apoptotic keratinocytes disappeared mostly or completely in subsequent MFs. The presence of epidermotropism, folliculotropism, and epidermal lymphocytic nuclear atypia in PLs was not predictive of MF. CD8+ cells were the dominant intraepidermal lymphocytes in the 3 PLs but remained so in only 1 subsequent MF. CD7+ lymphocytes decreased substantially in 2 MFs, and lymphocytic nuclear atypia increased markedly in 1. T-cell receptor gene rearrangement studies demonstrated clonal populations in 1 of 2 studied PLs and in all 3 subsequent MFs. Conclusions: A few PLs may evolve into MF. Prolonged clinical course, appearance of patches and larger plaques, markedly increased lymphocytic nuclear atypia, marked diminution of apoptotic keratinocytes and CD7+ and CD8+ lymphocytes, and clonal T-cell receptor gene rearrangement may serve as clues. Reprints: Reuven Bergman, MD, Department of Dermatology, Rambam Health Care Campus and the Bruce Rappaport Faculty of Medicine, Technion, Haifa 3109601, Israel (e-mail: r_bergman@rambam.health.gov.il). The authors declare no conflicts of interest. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2imzzaT

Intradermal Proliferative Fasciitis Occurring With Chondrodermatitis Nodularis Helicis

Abstract: Nodular fasciitis is a benign myofibroblastic tumor. Its uncommon variant, proliferative fasciitis (PF), can present in an even less common intradermal form. We report a case of intradermal PF of the ear in a 45-year-old man who presented with recurrent episodes of pain and swelling of the lesion. Histologic examination showed a dermal, nodular proliferation of ganglion-like basophilic fibroblasts with prominent nuclei and nucleoli, admixed with foamy histiocytes and areas of spindle cells arranged in intersecting fascicles in a fibromyxoid background. Lesional cells stained positive for smooth muscle actin and were negative for AE1/AE3, p63, and Melan-A. CD68 highlighted intervening histiocytes. We postulate that the underlying chondrodermatitis nodularis helicis was a triggering etiology, consistent with the current speculation that intradermal PF results from trauma. Reprints: Sasha Getty, MS4, UC Irvine Dermatology, 118 Med Surg 1, Irvine, CA 92697-2400 (e-mail: sgetty@uci.edu@uci.edu). The authors declare no conflicts of interest. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2AmsqhR

Young adult e-cigarette use outcome expectancies: Validity of a revised scale and a short scale

Publication date: March 2018
Source:Addictive Behaviors, Volume 78
Author(s): Pallav Pokhrel, Tony H. Lam, Ian Pagano, Crissy T. Kawamoto, Thaddeus A. Herzog
The revised youth e-cigarette outcome expectancies measure adds new items informed by recent qualitative research with young adult e-cigarette users, especially in the domain of positive "smoking" experience. Positive "smoking" experience represents beliefs that use of e-cigarettes provides outcomes associated with a better "smoking" alternative: for example, an alternative that is more socially approved, more suitable for indoor use, and that provides a safer means of enjoying nicotine. In addition, we tested a short, 8-item version of the measure which may be more easily incorporated into surveys. We tested the validity of the revised measure, both long and short versions, in terms of factor structure and associations of the expectancy factors with current e-cigarette use, e-cigarette use susceptibility, and e-cigarette use dependence. Participants were young adults (N=470; 65% women; mean age=20.9, SD=2.1). Results replicated the findings of the previous study as well as highlighted the importance of the added domain of positive "smoking" experience and the validity of the short scale. Furthermore, results showed that positive outcome expectancies are strongly associated with e-cigarette use dependence. The long and short versions of the revised youth e-cigarette outcome expectancies scale appear to be valid and useful for application not only among cigarette smokers and e-cigarette users but also among never smokers and never e-cigarette users.



http://ift.tt/2zQa7lS