AI learns to write its own code by stealing from other programs

Software called DeepCoder has solved simple programming challenges by piecing together bits of borrowed code

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JCM, Vol. 6, Pages 23: Role of Protein Phosphatase 2A in Osteoblast Differentiation and Function

The reversible phosphorylation of proteins plays hugely important roles in a variety of cellular processes, such as differentiation, proliferation, and apoptosis. These processes are strictly controlled by protein kinases (phosphorylation) and phosphatases (de-phosphorylation). Here we provide a brief history of the study of protein phosphorylation, including a summary of different types of protein kinases and phosphatases. One of the most physiologically important serine/threonine phosphatases is PP2A. This review provides a description of the phenotypes of various PP2A transgenic mice and further focuses on the known functions of PP2A in bone formation, including its role in osteoblast differentiation and function. A reduction in PP2A promotes bone formation and osteoblast differentiation through the regulation of bone-related transcription factors such as Osterix. Interestingly, downregulation of PP2A also stimulates adipocyte differentiation from undifferentiated mesenchymal cells under the appropriate adipogenic differentiation conditions. In osteoblasts, PP2A is also involved in the ability to control osteoclastogenesis as well as in the proliferation and metastasis of osteosarcoma cells. Thus, PP2A is considered to be a comprehensive factor in controlling the differentiation and function of cells derived from mesenchymal cells such as osteoblasts and adipocytes.

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Out-of-pocket costs and burden among rural breast cancer survivors

Abstract

Little is known about out-of-pocket (OOP) costs incurred for medical and health needs by rural breast cancer survivors and what factors may be associated with higher OOP costs and the associated economic burden. Data were examined for 432 survivors participating in the Rural Breast Cancer Survivor Intervention trial. OOP costs were collected using the Work and Finances Inventory survey at baseline and four assessments every 3 months. Mean and median OOP costs and burden (percent of monthly income spent on OOP costs) were reported and factors associated with OOP costs and burden identified with generalized linear models fitted with over-dispersed gamma distributions and logarithmic links (OOP costs) and with beta distributions with logit link (OOP burden). OOP costs per month since the end of treatment were on average $232.7 (median $95.6), declined at the next assessment point to $186.5 (median $89.1), and thereafter remained at that level. Mean OOP burden was 9% at baseline and between 7% and 8% at the next assessments. Factors suggestive of contributing to higher OOP costs and OOP burden were the following: younger age, lower income, time in survivorship from diagnosis, and use of supportive services. OOP costs burden rural breast cancer survivors, particularly those who are younger and low income. Research should investigate the impact of OOP costs and interventions to reduce economic burden.

Among 432 rural breast cancer survivors who had completed treatment, out-of-pocket costs related to cancer were more than $180 per month over a 1-year period, burdening survivors with low income disproportionately. Further research is warranted to understand the consequences of this burden and develop the means to reduce its impact.

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Brain Sciences, Vol. 7, Pages 23: Hyperarousal and Beyond: New Insights to the Pathophysiology of Insomnia Disorder through Functional Neuroimaging Studies

Neuroimaging studies have produced seemingly contradictory findings in regards to the pathophysiology of insomnia. Although most study results are interpreted from the perspective of a “hyperarousal” model, the aggregate findings from neuroimaging studies suggest a more complex model is needed. We provide a review of the major findings from neuroimaging studies, then discuss them in relation to a heuristic model of sleep-wake states that involves three major factors: wake drive, sleep drive, and level of conscious awareness. We propose that insomnia involves dysregulation in these factors, resulting in subtle dysregulation of sleep-wake states throughout the 24 h light/dark cycle.

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Autism

Autism: A spectrum of neuropsychiatric disorders characterized by deficits in social interaction and communication, and unusual and repetitive behavior. Some, but not all, people with autism are non-verbal.

Autism is normally diagnosed before age six and may be diagnosed in infancy in some cases. The degree of autism varies from mild to severe in different children. Severely afflicted patients can appear profoundly retarded.

The cause (or causes) of autism are not yet fully understood. However, it is believed that at least some cases involve an inherited or acquired genetic defect. Researchers have proposed that the immune-system, metabolic, and environmental factors may play an important part as well. It is not caused by emotional trauma, as was once theorized.

Autism or autistic-like behavior may co-occur with many other neurological conditions.

The optimal treatment of autism involves an educational program that is suited to the child's developmental level.

Autism is also called the Kanner syndrome or infantile autism. See also Asperger syndrome, elective mutism, Pervasive Developmental Disorder, Rett syndrome.

MedTerms (TM) is the Medical Dictionary of MedicineNet.com.
We Bring Doctors' Knowledge To You

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Pathogenic ASXL1 somatic variants in reference databases complicate germline variant interpretation for Bohring-Opitz Syndrome

Abstract

The clinical interpretation of genetic variants has come to rely heavily on reference population databases such as the Exome Aggregation Consortium (ExAC) database. Pathogenic variants in genes associated with severe, pediatric-onset, highly penetrant, autosomal dominant conditions are assumed to be absent or rare in these databases. Exome sequencing of a six-year-old female patient with seizures, developmental delay, dysmorphic features and failure to thrive identified an ASXL1 variant previously reported as causative of Bohring-Opitz syndrome (BOS). Surprisingly, the variant was observed seven times in the ExAC database, presumably in individuals without BOS. Although the BOS phenotype fit, the presence of the variant in reference population databases introduced ambiguity in result interpretation. Review of the literature revealed that acquired somatic mosaicism of ASXL1 variants (including pathogenic variants) during hematopoietic clonal expansion can occur with aging in healthy individuals. We examined all ASXL1 truncating variants in the ExAC database and determined most are likely somatic. Failure to consider somatic mosaicism may lead to the inaccurate assumption that conditions like Bohring-Opitz syndrome have reduced penetrance, or the misclassification of potentially pathogenic variants.

This article is protected by copyright. All rights reserved

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Aims and Scope & Editorial Board

Publication date: January 2017
Source:Bioactive Carbohydrates and Dietary Fibre, Volume 9





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Purification and characterization of a novel ubiquitin-like antitumour protein with hemagglutinating and deoxyribonuclease activities from the edible mushroom Ramaria botrytis

A novel ubiquitin-like antitumour protein (RBUP) was isolated from fruiting bodies of the edible mushroom Ramaria botrytis. The protein was isolated with a purification protocol involving ion exchange chromatogra...

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Design and pharmacodynamics of recombinant NZ2114 histidine mutants with improved activity against methicillin-resistant Staphylococcus aureus

NZ2114 is a promising candidate for therapeutic application owing to its potent activity to Staphylococcus aureus. Our objective was to identify NZ2114 derivatives with improved activity through substitution of H...

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The Antagonistically Bifunctional Retinoid Oxidoreductase Complex Is Required for Maintenance of All-trans-retinoic Acid Homeostasis. [Enzymology]

All-trans-retinoic acid (RA), a bioactive derivative of vitamin A, exhibits diverse effects on gene transcription and non-genomic regulatory pathways. The steady-state levels of RA are therefore tightly controlled, but the mechanisms responsible for RA homeostasis are not fully understood. We report a molecular mechanism that allows cells to maintain a stable rate of RA biosynthesis by utilizing a biological circuit generated by a bifunctional retinoid oxidoreductive complex (ROC). We show that ROC is composed of at least two subunits of NAD+-dependent retinol dehydrogenase 10 (RDH10), which catalyzes the oxidation of retinol to retinaldehyde, and two subunits of NADPH-dependent dehydrogenase reductase 3 (DHRS3), which catalyzes the reduction of retinaldehyde back to retinol. RDH10 and DHRS3 also exist as homooligomers. When complexed, RDH10 and DHRS3 mutually activate and stabilize each other. These features of ROC ensure that the rate of RA biosynthesis in whole cells is largely independent of the concentration of the individual ROC components. ROC operates in various subcellular fractions including microsomes, mitochondria, and lipid droplets; however, lipid droplets display weaker mutual activation between RDH10 and DHRS3, suggesting reduced formation of ROC. Importantly, disruption of the ROC-generated circuit by a knockdown of DHRS3 results in an increased flux through the RA biosynthesis pathway and elevated RA levels despite the decrease in RDH10 protein destabilized by the absence of DHRS3, hence demonstrating a loss of control. Thus, the bifunctional nature of ROC provides the RA-based signaling system with robustness by safeguarding appropriate RA concentration despite naturally occurring fluctuations in RDH10 and DHRS3.

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PI3K/mTOR inhibitors may be effective against some uterine sarcomas

The protein P-S6S240 may serve as an indicator of poor prognosis for patients with a hard-to-treat type of uterine sarcoma called leiomyosarcoma, and preclinical data suggest that patients whose tumours have this protein may respond to PI3K/mTOR...

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JACC: Heart Failure

JACC: Heart Failure, published by American College of Cardiology, last updated on 2017-02-22, available at http://ift.tt/2meBc7X

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The multimorbid polysensitized phenotype is associated with the severity of allergic diseases

We read with great interest 3 consecutive articles recently published in the Journal.1-3

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Reply

We appreciate this correspondence from Bousquet et al1 that our study affirms the importance of the allergy multimorbid, polysensitized phenotype in childhood asthma severity. In our Inner-City Asthma Consortium's Asthma Phenotypes in the Inner City study of children with persistent asthma characterized with 1 year of guidelines-based asthma and rhinitis management, 1 phenotype, cluster E, was distinguished by high asthma severity and exacerbation rates, as well as allergic multimorbidity and polysensitization.

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Wogonin, a plant derived small molecule, exerts potent anti-inflammatory and chondroprotective effects through the activation of ROS/ERK/Nrf2 signaling pathways in human Osteoarthritis chondrocytes

Publication date: Available online 22 February 2017
Source:Free Radical Biology and Medicine
Author(s): Nazir M. Khan, Abdul Haseeb, Mohammad Y. Ansari, Pratap Devarapalli, Sara Haynie, Tariq M. Haqqi
Osteoarthritis (OA), characterized by progressive destruction of articular cartilage, is the most common form of human arthritis. Here, we evaluated the potential chondroprotective and anti-inflammatory effects of Wogonin, a naturally occurring flavonoid, in IL-1β-stimulated human OA chondrocytes and cartilage explants. Wogonin completely suppressed the expression and production of inflammatory mediators including IL-6, COX-2, PGE2, iNOS and NO in IL-1β-stimulated OA chondrocytes. Further, Wogonin exhibits potent chondroprotective potential by switching the signaling axis of matrix degradation from catabolic towards anabolic ends and inhibited the expression, production and activities of matrix degrading proteases including MMP-13, MMP-3, MMP-9, and ADAMTS-4 in OA chondrocytes, and blocked the release of s-GAG and COL2A1 in IL-1β-stimulated OA cartilage explants. Wogonin also elevated the expression of cartilage anabolic factors COL2A1 and ACAN in chondrocytes and inhibited the IL-1β-mediated depletion of COL2A1 and proteoglycan content in the matrix of cartilage explants. The suppressive effect of Wogonin was not mediated through the inhibition of MAPKs or NF-κB activation. Instead, Wogonin induced mild oxidative stress through the generation of ROS and depletion of cellular GSH, thereby modulating the cellular redox leading to the induction of Nrf2/ARE pathways through activation of ROS/ERK/Nrf2/HO-1-SOD2-NQO1-GCLC signaling axis in OA chondrocytes. Molecular docking studies revealed that Wogonin can disrupt KEAP-1/Nrf-2 interaction by directly blocking the binding site of Nrf-2 in the KEAP-1 protein. Genetic ablation of Nrf2 using specific siRNA, significantly abrogated the anti-inflammatory and chondroprotective potential of Wogonin in IL-1β-stimulated OA chondrocytes. Our data indicates that Wogonin exerts chondroprotective effects through the suppression of molecular events involved in oxidative stress, inflammation and matrix degradation in OA chondrocytes and cartilage explants. The study provides novel insights into the development of Nrf2 as a promising candidate and Wogonin as a therapeutic agent for the management of OA.



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A SAMHD1 mutation associated with Aicardi-Goutières Syndrome uncouples the ability of SAMHD1 to restrict HIV-1 from its ability to downmodulate type I interferon in humans

Abstract

Mutations in the human SAMHD1 gene are known to correlate with the development of the Aicardi-Goutières Syndrome (AGS), which is an inflammatory encephalopathy that exhibits neurological dysfunction characterized by increased production of type I interferon (IFN); this evidence has lead to the concept that the SAMHD1 protein negatively regulates the type I IFN response. Additionally, the SAMHD1 protein has been shown to prevent efficient HIV-1 infection of macrophages, dendritic cells and resting CD4+ T cells. To gain insights on the SAMHD1 molecular determinants that are responsible for the deregulated production of type I IFN, we explored the biochemical, cellular and antiviral properties of human SAMHD1 mutants known to correlate with the development of Aicardi-Goutières Syndrome. Most of the studied SAMHD1 AGS mutants exhibit defects in the ability to oligomerize, decrease the levels of cellular dNTPs in human cells, localize exclusively to the nucleus, and restrict HIV-1 infection. At least half of the tested variants preserved the ability to be degraded by the lentiviral protein Vpx, and all of them interacted with RNA. Our investigations revealed that the SAMHD1 AGS variant p.G209S preserve all tested biochemical, cellular and antiviral properties, suggesting that this residue is a determinant for the ability of SAMHD1 to negatively regulate the type I interferon response in human patients with AGS. Overall, our work genetically separated the ability of SAMHD1 to negatively regulate the type I IFN response from its ability to restrict HIV-1.

This article is protected by copyright. All rights reserved

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A variant in a Cis-regulatory element enhances claudin-14 expression and is associated with pediatric-onset hypercalciuria and kidney stones

Abstract

The greatest risk factor for kidney stones is hypercalciuria, the etiology of which is largely unknown. A recent genome-wide association study (GWAS) linked hypercalciuria and kidney stones to a claudin-14 (CLDN14) risk haplotype. However, the underlying molecular mechanism was not delineated. Recently, renal CLDN14 expression was found to increase in response to increased plasma calcium, thereby inducing calciuria. We hypothesized therefore that some children with hypercalciuria and kidney stones harbor a CLDN14 variant that inappropriately increases gene expression. To test this hypothesis, we sequenced the CLDN14 risk haplotype in a cohort of children with idiopathic hypercalciuria and kidney stones. An intronic single nucleotide polymorphism (SNP) was more frequent in affected children. Dual luciferase and cell based assays demonstrated increased reporter or CLDN14 expression when this polymorphism was introduced. In silico studies predicted the SNP introduced a novel insulinoma-associated 1 (INSM1) transcription factor binding site. Consistent with this, repeating the dual luciferase assay in the presence of INSM1, further increased reporter expression. Our data suggest that children with the INSM1 binding site within the CLDN14 risk haplotype have a higher likelihood of hypercalciruia and kidney stones. Enhanced CLDN14 expression may play a role in the pathophysiology of their hypercalciuria.

This article is protected by copyright. All rights reserved

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Mutations in Genes Encoding Polycomb Repressive Complex 2 Subunits Cause Weaver Syndrome

Abstract

Weaver syndrome is a rare congenital overgrowth disorder caused by heterozygous mutations in EZH2 (enhancer of zeste homolog 2) or EED (embryonic ectoderm development). EZH2 and EED are core components of the polycomb repressive complex 2 (PRC2), which possesses histone methyltransferase activity and catalyzes trimethylation of histone H3 at lysine 27. Here, we analyzed eight probands with clinically suspected Weaver syndrome by whole exome sequencing and identified three mutations: a 25.4-kb deletion partially involving EZH2 and CUL1 (individual 1), a missense mutation (c.707G>C, p.Arg236Thr) in EED (individual 2), and a missense mutation (c.1829A>T, p.Glu610Val) in SUZ12 (suppressor of zeste 12 homolog) (individual 3) inherited from her father (individual 4) with a mosaic mutation. SUZ12 is another component of PRC2 and germline mutations in SUZ12 have not been previously reported in humans. In vitro functional analyses demonstrated that the identified EED and SUZ12 missense mutations cause decreased trimethylation of lysine 27 of histone H3. These data indicate that loss-of-function mutations of PRC2 components are an important cause of Weaver syndrome.

This article is protected by copyright. All rights reserved

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Changes in ambient temperature elicit divergent control of metabolic and cardiovascular actions by leptin [Research]

Interactions of hypothalamic signaling pathways that control body temperature (BT), blood pressure (BP), and energy balance are poorly understood. We investigated whether the chronic BP and metabolic actions of leptin are differentially modulated by changes in ambient temperature (T_A). Mean arterial pressure (MAP), heart rate (HR), BT, motor activity (MA), and oxygen consumption (Vo₂) were measured 24 h/d at normal laboratory T_A (23°C), at thermoneutral zone (TNZ, 30°C) for mice or during cold exposure (15°C) in male wild-type mice. After control measurements, leptin (4 μg/kg/min) or saline vehicle was infused for 7 d. At TNZ, leptin reduced food intake (–11.0 ± 0.5 g cumulative deficit) and body weight by 6% but caused no changes in MAP or HR. At 15°C, leptin infusion did not alter food intake but increased MAP and HR (8 ± 1 mmHg and 33 ± 7 bpm), while Vo₂ increased by ~10%. Leptin reduced plasma glucose and insulin levels at 15°C but not at 30°C. These results demonstrate that the chronic anorexic effects of leptin are enhanced at TNZ, while its effects on insulin and glucose levels are attenuated and its effects on BP and HR are abolished. Conversely, cold T_A caused resistance to leptin’s anorexic effects but amplified its effects to raise BP and reduce insulin and glucose levels. Thus, the brain circuits by which leptin regulates food intake and cardiovascular function are differentially influenced by changes in T_A.—Do Carmo, J. M., da Silva, A. A., G. Romero, D. G., Hall, J. E. Changes in ambient temperature elicit divergent control of metabolic and cardiovascular actions by leptin.

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Early events in the assembly of E-cadherin adhesions

Publication date: Available online 22 February 2017
Source:Experimental Cell Research
Author(s): Kabir H Biswas, Ronen Zaidel-Bar
E-cadherin is a calcium dependent cell adhesion molecule that is key to the organization of cells in the epithelial tissue. It is a multidomain, trans-membrane protein in which the extracellular domain forms the homotypic, adhesive interaction while the intracellular domain interacts with the actin cytoskeleton through the catenin family of adaptor proteins. A number of recent studies have provided novel insights into the mechanism of adhesion formation by this class of adhesion proteins. Here, we describe an updated view of the process of E-cadherin adhesion formation with an emphasis on the role of molecular mobility, clustering, and active cellular processes.



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SIPA1 promotes invasion and migration in human oral squamous cell carcinoma by ITGB1 and MMP7

Publication date: Available online 22 February 2017
Source:Experimental Cell Research
Author(s): Toshikazu Takahara, Atsushi Kasamatsu, Masanobu Yamatoji, Manabu Iyoda, Hiroki Kasama, Tomoaki Saito, Shin Takeuchi, Yosuke Endo-Sakamoto, Masashi Shiiba, Hideki Tanzawa, Katsuhiro Uzawa
Signal-induced proliferation-associated protein 1 (SIPA1) is known to be a GTPase activating protein. Overexpressed SIPA1 is related to metastatic progression in breast and prostate cancers; however, the relevance of SIPA1 in oral squamous cell carcinoma (OSCC) is still unknown. The aim of this study was to examine SIPA1 expression and its functional mechanisms in OSCC. SIPA1 mRNA and protein expressions were analyzed by quantitative reverse transcriptase-polymerase chain reaction, Western blot analysis, and immunohistochemistry. The expressions of SIPA1 were up-regulated significantly in vitro and in vivo. Moreover, SIPA1 expression was correlated with regional lymph node metastasis. We next assessed the cellular functions associated with tumoral metastasis using SIPA1 knockdown (shSIPA1) cells and analyzed the downstream molecules of SIPA1, i.e., bromodomain containing protein 4(BRD4), integrin beta1 (ITGB1), and matrix metalloproteinase 7 (MMP7). The shSIPA1 cells showed decreased invasiveness and migratory activities, however cellular adhesion ability was maintained at a high level. In addition, ITGB1 expression was greater in shSIPA1 cells, whereas MMP7 expression was lower than in control cells. This research is the first to establish that SIPA1 promotes cancer metastasis by regulating the ITGB1 and MMP7.Therefore, SIPA1 might be a novel therapeutic target for patients with lymph node metastasis of OSCC.



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The formation of quiescent glomerular endothelial cell monolayer in vitro is strongly dependent on the choice of extracellular matrix coating

Publication date: Available online 22 February 2017
Source:Experimental Cell Research
Author(s): Kamilla Pajęcka, Malik Nygaard Nielsen, Troels Krarup Hansen, Julie M Williams
BACKGROUND AND AIMSNephropathy involves pathophysiological changes to the glomerulus. The primary glomerular endothelial cells (GEnCs) have emerged as an important tool for studying glomerulosclerotic mechanisms and in the screening process for drug-candidates. The success of the studies is dependent on the quality of the cell model. Therefore, we set out to establish an easy, reproducible model of the quiescent endothelial monolayer with the use of commercially available extracellular matrices (ECMs).METHODSPrimary hGEnCs were seeded on various ECMs. Cell adhesion was monitored by an impedance sensing system. The localization of junctional proteins was assessed by immunofluorescence and the barrier function by passage of fluorescent dextrans and magnitude of VEGF response.RESULTSAll ECM matrices except recombinant human laminin 111 (rhLN111) supported comparable cell proliferation. Culturing hGEnCs on rhLN521, rhLN511 or fibronectin resulted in a physiologically relevant barrier to 70kDa dextrans which was 82% tighter than that formed on collagen type IV. Furthermore, only hGEnCs cultured on rhLN521 or rhLN511 showed plasma-membrane localized zonula occludens-1 and vascular endothelial cadherin indicative of proper tight and adherens junctions (AJ).CONCLUSIONWe recommend culturing hGEnCs on the mature glomerular basement membrane laminin - rhLN521 – which, as the only commercially available ECM, promotes all of the characteristics of the quiescent hGEnC monolayer: cobblestone morphology, well-defined AJs and physiological perm-selectivity.



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The flashlights on a distinct role of protein kinase C δ: Phosphorylation of regulatory and catalytic domain upon oxidative stress in glioma cells

Publication date: Available online 22 February 2017
Source:Cellular Signalling
Author(s): Matus Misuth, Jaroslava Joniova, Denis Horvath, Lenka Dzurova, Zuzana Nichtova, Marta Novotova, Pavol Miskovsky, Katarina Stroffekova, Veronika Huntosova
Glioblastoma multiforme are considered to be aggressive high-grade tumors with poor prognosis for patient survival. Photodynamic therapy is one of the adjuvant therapies which has been used for glioblastoma multiforme during last decade. Hypericin, a photosensitizer, can be employed in this treatment. We have studied the effect of hypericin on PKCδ phosphorylation in U87 MG cells before and after light application. Hypericin increased PKCδ phosphorylation at tyrosine 155 in the regulatory domain and serine 645 in the catalytic domain. However, use of the light resulted in apoptosis, decreased phosphorylation of tyrosine 155 and enhanced serine 645. The PKCδ localization and phosphorylation of regulatory and catalytic domains were shown to play a distinct role in the anti-apoptotic response of glioma cells. We hypothesized that PKCδ phosphorylated at the regulatory domain is primarily present in the cytoplasm and in mitochondria before irradiation, and it may participate in Bcl-2 phosphorylation. After hypericin and light application, PKCδ phosphorylated at a regulatory domain which is in the nucleus. In contrast, PKCδ phosphorylated at the catalytic domain may be mostly active in the nucleus before irradiation, but active in the cytoplasm after the irradiation. In summary, light-induced oxidative stress significantly regulates PKCδ pro-survival and pro-apoptotic activity in glioma cells by its phosphorylation at serine 645 and tyrosine 155.

Graphical abstract

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Role of Akt/PKB and PFKFB isoenzymes in the control of glycolysis, cell proliferation and protein synthesis in mitogen-stimulated thymocytes

Publication date: Available online 22 February 2017
Source:Cellular Signalling
Author(s): Amina Houddane, Laurent Bultot, Laura Novellasdemunt, Manuel Johanns, Marie-Agnès Gueuning, Didier Vertommen, Pierre G. Coulie, Ramon Bartrons, Louis Hue, Mark H. Rider
Proliferating cells depend on glycolysis mainly to supply precursors for macromolecular synthesis. Fructose-2,6-bisphosphate (Fru-2,6-P2) is the most potent positive allosteric effector of 6-phosphofructo-1-kinase (PFK-1), and hence of glycolysis. Mitogen stimulation of rat thymocytes with concanavalin A (ConA) led to time-dependent increases in lactate accumulation (6-fold), Fru-2,6-P2 content (4-fold), 6-phosphofructo-2-kinase (PFK-2)/fructose-2,6-bisphosphatase isoenzyme 3 and 4 (PFKFB3 and PFKFB4) protein levels (~2-fold and ~15-fold, respectively) and rates of cell proliferation (~40-fold) and protein synthesis (10-fold) after 68h of incubation compared with resting cells. After 54h of ConA stimulation, PFKFB3 mRNA levels were 45-fold higher than those of PFKFB4 mRNA. Although PFKFB3 could be phosphorylated at Ser461 by protein kinase B (PKB) in vitro leading to PFK-2 activation, PFKFB3 Ser461 phosphorylation was barely detectable in resting cells and only increased slightly in ConA-stimulated cells. On the other hand, PFKFB3 and PFKFB4 mRNA levels were decreased (90% and 70%, respectively) by exposure of ConA-stimulated cells to low doses of PKB inhibitor (MK-2206), suggesting control of expression of the two PFKFB isoenzymes by PKB. Incubation of thymocytes with ConA resulted in increased expression and phosphorylation of the translation factors eukaryotic initiation factor-4E-binding protein-1 (4E-BP1) and ribosomal protein S6 (rpS6). Treatment of ConA-stimulated thymocytes with PFK-2 inhibitor (3PO) or MK-2206 led to significant decreases in Fru-2,6-P2 content, medium lactate accumulation and rates of cell proliferation and protein synthesis. These data were confirmed by using siRNA knockdown of PFKFB3, PFKFB4 and PKB α/β in the more easily transfectable Jurkat E6-1 cell line. The findings suggest that increased PFKFB3 and PFKFB4 expression, but not increased PFKFB3 Ser461 phosphorylation, plays a role in increasing glycolysis in mitogen-stimulated thymocytes and implicate PKB in the upregulation of PFKFB3 and PFKFB4. The results also support a role for Fru-2,6-P2 in coupling glycolysis to cell proliferation and protein synthesis in this model.



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Hypertensive Disorders of Pregnancy

Abstract

Purpose of Review

Although pregnancy-related deaths are rare in the USA, they are on the rise and have more than doubled in the last 20 years. A substantial portion of these deaths are related to cardiovascular disease, specifically hypertensive disorders of pregnancy (HDP). In this review, we will discuss the definitions and proposed pathophysiology of HDP as well as its potential role in cardiovascular morbidity and mortality.

Recent Findings

Placental hypoperfusion may lead to an imbalance in proangiogenic and antiangiogenic factors, notably an increase in soluble fms-like tyrosine kinsase-1 (sFlt-1), thereby leading to endothelial dysfunction.

Summary

Progress has been made in terms of determining the factors which lead to preeclampsia. Potential novel biomarkers for predicting preeclampsia risk have been identified through this research. Preeclampsia not only has important implications for the health during pregnancy but also for future cardiovascular risk. However, the exact mechanism by which it increases cardiovascular risk and the degree of risk it portends are yet to be elucidated.

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Adjuvant chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma: Long-term results of a phase 3 multicentre randomised controlled trial

Publication date: April 2017
Source:European Journal of Cancer, Volume 75
Author(s): Lei Chen, Chao-Su Hu, Xiao-Zhong Chen, Guo-Qing Hu, Zhi-Bin Cheng, Yan Sun, Wei-Xiong Li, Yuan-Yuan Chen, Fang-Yun Xie, Shao-Bo Liang, Yong Chen, Ting-Ting Xu, Bin Li, Guo-Xian Long, Si-Yang Wang, Bao-Min Zheng, Ying Guo, Ying Sun, Yan-Ping Mao, Ling-Long Tang, Yu-Ming Chen, Meng-Zhong Liu, Jun Ma
Aim of the studyPrevious results from our trial showed that adjuvant cisplatin and fluorouracil chemotherapy did not significantly improve survival after concurrent chemoradiotherapy (CCRT) in locoregionally advanced nasopharyngeal carcinoma (NPC) at 2 years. Here, we present the data of long-term survival and late toxicities to further assess the ultimate therapeutic index of adjuvant chemotherapy (AC).MethodsPatients with stage III–IVB (except T3-4N0) NPC were randomly assigned to receive CCRT plus AC or CCRT only at seven institutions in China. Patients in both groups received cisplatin 40 mg/m² weekly up to 7 weeks concurrently with radiotherapy. The CCRT plus AC group subsequently received adjuvant cisplatin 80 mg/m² and fluorouracil 800 mg/m²/d for 120 h every 4 weeks for three cycles. The primary end-point was failure-free survival.ResultsTwo hundred and fifty-one patients were randomised to the CCRT plus AC group and 257 to the CCRT only group. After a median follow-up of 68.4 months, estimated 5-year failure-free survival rate was 75% in the CCRT plus AC group and 71% in the CCRT only group (hazard ratio 0.88, 95% confidence interval 0.64–1.22; p = 0.45). 66 (27%) of 249 patients in the CCRT plus AC group and 53 (21%) of 254 patients in the CCRT only group developed one or more late grade 3–4 toxicities (p = 0.14).ConclusionAdjuvant cisplatin and fluorouracil chemotherapy still failed to demonstrate significant survival benefit after CCRT in locoregionally advanced NPC based on the long-term follow-up data, and addition of adjuvant cisplatin and fluorouracil did not significantly increase late toxicities.Registration numberNCT00677118.



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Acceptable regret model in the end-of-life setting: Patients require high level of certainty before forgoing management recommendations

Publication date: April 2017
Source:European Journal of Cancer, Volume 75
Author(s): Athanasios Tsalatsanis, Iztok Hozo, Benjamin Djulbegovic
BackgroundThe acceptable regret model postulates that under some circumstances decision-makers may tolerate wrong decisions. The purpose of this work is to empirically evaluate the acceptable regret model of decision-making in the end-of-life care setting, where terminally ill patients consider seeking curative treatment versus accepting hospice/palliative care.MethodsWe conducted interviews with 48 terminally ill patients to assess their preferences about end-of-life treatment choices. We first elicited the patient's regret of potentially wrong choices with regards to the recommended management and provided information on life expectancy estimated by two prognostication models. We then elicited the patients' level of acceptable regret by assessing their tolerance for potentially wrongly accepting hospice care versus continuing unnecessary treatment. Using the levels of acceptable regret, we computed: (1) the probability of death above which a patient would tolerate wrongly accepting hospice care and (2) the probability of death below which the patient would tolerate unnecessary treatment. We also assessed patients' understanding of the interview questions using a 7-point Likert scale.ResultsWe found that the median probability of death above which a patient would tolerate wrongly accepting hospice care was 96% (95% CI 94–98%), whereas the median probability of death below which a patient would tolerate unnecessary treatment was 2.5% (95% CI 0.3–5%). We also found that the levels of acceptable regret measured for wrong hospice referral (mean = 1.52; SD = 2.26; min = 0; max = 7.72) were similar to the levels of acceptable regret measured for unnecessary treatment (mean = 2.10; SD = 4.33; min = 0; max = 23) (KW test; p = 0.68) indicating that acceptable regret levels for either of the wrong decisions is felt similarly. The results were independent of the estimated probability of death communicated to patients before the acceptable regret interview.ConclusionsWe have elicited empirical data that corroborated the acceptable regret hypothesis. The requirement for high level of certainty before accepting recommended management may explain the difficulties related to decision-making in the end-of-life setting.



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Childhood academic ability in relation to cigarette, alcohol and cannabis use from adolescence into early adulthood: Longitudinal Study of Young People in England (LSYPE)

Objectives

Our aim was to determine the association between childhood academic ability and the onset and persistence of tobacco, alcohol and cannabis use across adolescence in a representative sample of English schools pupils. Previous research has produced conflicting findings.

Design

Data from 7 years of the Longitudinal Study of Young People in England (LSYPE), 2004–2010 (age 13/14–19/20).

Setting

Self-completion questionnaires during home visits, face-to-face interviews and web-based questionnaires.

Participants

Data from 6059 participants (3093 females) with information on academic ability around age 11 and health behaviours from age 13/14 to 16/17 (early adolescence) and from age 18/19 to 19/20 (late adolescence).

Outcome measures

Regularity of cigarette smoking, alcohol drinking and cannabis use from early to late adolescence.

Results

In multinomial logistic regression models adjusting for a range of covariates, the high (vs low) academic ability reduced the risk of persistent cigarette smoking (RR=0.62; CI 95% 0.48 to 0.81) in early adolescence. High (vs low) academic ability increased the risk of occasional (RR=1.25; CI 95% 1.04 to 1.51) and persistent (RR=1.83; CI 95% 1.50 to 2.23) regular alcohol drinking in early adolescence and persistent (RR=2.28; CI 95% 1.84 to 2.82) but not occasional regular alcohol drinking in late adolescence. High academic ability was also positively associated with occasional (RR=1.83; CI 95% 1.50 to 2.23) and persistent (RR=1.83; CI 95% 1.50 to 2.23) cannabis use in late adolescence.

Conclusions

In a sample of over 6000 young people in England, high childhood academic at age 11 is associated with a reduced risk of cigarette smoking but an increased risk of drinking alcohol regularly and cannabis use. These associations persist into early adulthood, providing evidence against the hypothesis that high academic ability is associated with temporary ‘experimentation’ with substance use.

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Patient experience with discharge instructions in postdischarge recovery: a qualitative study

Objectives

We examined the role of discharge instructions in postoperative recovery for patients undergoing colorectal surgery and report themes related to patient perceptions of discharge instructions and postdischarge experience.

Design

Semistructured interviews were conducted as part of a formative evaluation of a Project Re-Engineered Discharge intervention adapted for surgical patients.

Setting

Michael E. DeBakey VA Medical Center, a tertiary referral centre in Houston, Texas.

Participants

Twelve patients undergoing elective colorectal surgery. Interviews were conducted at the two-week postoperative appointment.

Results

Participants demonstrated understanding of the content in the discharge instructions. During the interviews, participants reported several positive roles for discharge instructions in their postdischarge care: a sense of security, a reminder of inhospital education, a living document and a source of empowerment. Despite these positive associations, participants reported that the instructions provided insufficient information to promote access to care that effectively addressed acute issues following discharge. Participants noted difficulty reaching providers after discharge, which resulted in the adoption of workarounds to overcome system barriers.

Conclusions

Despite concerted efforts to provide patient-centred instructions, the discharge instructions did not provide enough context to effectively guide postdischarge interactions with the healthcare system. Insufficient information on how to access and communicate with the most appropriate personnel in the healthcare system is an important barrier to patients receiving high-quality postdischarge care. Tools and strategies from team training programmes, such as team strategies and tools to enhance performance and patient safety, could be adapted to include patients and provide them with structured methods for communicating with healthcare providers post discharge.

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Mortality, greenhouse gas emissions and consumer cost impacts of combined diet and physical activity scenarios: a health impact assessment study

Objective

To quantify changes in mortality, greenhouse gas (GHG) emissions and consumer costs for physical activity and diet scenarios.

Design

For the physical activity scenarios, all car trips from <1 to <8 miles long were progressively replaced with cycling. For the diet scenarios, the study population was assumed to increase fruit and vegetable (F&V) consumption by 1–5 portions of F&V per day, or to eat at least 5 portions per day. Health effects were modelled with the comparative risk assessment method. Consumer costs were based on fuel cost savings and average costs of F&V, and GHG emissions to fuel usage and F&V production.

Setting

Working age population for England.

Participants

Data from the Health Survey for England, National Travel Survey and National Diet and Nutrition Survey.

Primary outcomes measured

Changes in premature deaths, consumer costs and GHG emissions stratified by age, gender and socioeconomic status (SES).

Results

Premature deaths were reduced by between 75 and 7648 cases per year for the physical activity scenarios, and 3255 and 6187 cases per year for the diet scenarios. Mortality reductions were greater among people of medium and high SES in the physical activity scenarios, whereas people with lower SES benefited more in the diet scenarios. Similarly, transport fuel costs fell more for people of high SES, whereas diet costs increased most for the lowest SES group. Net GHG emissions decreased by between 0.2 and 10.6 million tons of carbon dioxide equivalent (MtCO₂e) per year for the physical activity scenarios and increased by between 1.3 and 6.3 MtCO₂e/year for the diet scenarios.

Conclusions

Increasing F&V consumption offers the potential for large health benefits and reduces health inequalities. Replacing short car trips with cycling offers the potential for net benefits for health, GHG emissions and consumer costs.

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Is the effect of person-organisation fit on turnover intention mediated by job satisfaction? A survey of community health workers in China

Objectives

Person-organisation fit (P-O fit) is a predictor of work attitude. However, in the area of human resource for health, the literature of P-O fit is quite limited. It is unclear whether P-O fit directly or indirectly affects turnover intention. This study aims to examine the mediation effect of job satisfaction on the relationship between P-O fit and turnover intention based on data from China.

Design and methods

This is a cross-sectional survey of community health workers (CHWs) in China in 2013. A questionnaire of P-O fit, job satisfaction and turnover intention was developed, and its validity and reliability were assessed. Multiple regression and structural equation modelling were used to examine the relationship among P-O fit, job satisfaction and turnover intention.

Setting and participants

Multistage sampling was applied. In total, 656 valid questionnaire responses were collected from CHWs in four provincial regions in China, namely Shanghai, Shaanxi, Shandong and Anhui.

Results

P-O fit was directly related to job satisfaction (standardised β 0.246) and inversely related to turnover intention (standardised β –0.186). In the mediation model, the total effect of P-O fit on turnover intention was –0.186 (p<0.001); the direct effect of P-O fit on turnover intention was –0.094 (p<0.01); the indirect effect of job satisfaction on the relationship between P-O fit and turnover intention was –0.092 (p<0.001).

Conclusions

The effect of P-O fit on turnover intention was partially mediated through job satisfaction. It is suggested that more work attitude variables and different dimensions of P-O fit be taken into account to examine the complete mechanism of person-organisation interaction. Indirect measures of P-O fit should be encouraged in practice to enhance work attitudes of health workers.

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Healthcare professionals views of the use and administration of two salvage therapy drugs for acute ulcerative colitis: a nested qualitative study within the CONSTRUCT trial

Objectives

Insight into healthcare professionals’ views and experiences of the use of ciclosporin and infliximab as salvage therapies for acute ulcerative colitis (UC) and how this may affect participation in a comparison trial is lacking. The study aimed to capture views and opinions of healthcare professionals about the two drugs within the CONSTRUCT trial.

Design

An interview-based qualitative study using Framework Analysis embedded within an open-label, pragmatic randomised trial.

Setting

National Health Service Health Boards and Trusts, including large teaching and district hospitals in England, Scotland and Wales.

Participants

Principal Investigators (PIs) for trial sites (who were all consultant gastroenterologists) and nurses responsible for administering and monitoring the salvage therapy drugs across trial sites. 15 PIs and 8 nurses recruited from a range of sites stratified by site recruitment rates were interviewed.

Results

Interviews revealed that professionals made judgements regarding the salvage therapies largely based on experience of giving the two drugs and perceptions of effectiveness and adverse side effects. A clear preference for infliximab among nurses was revealed, largely based on experiences of administration and drug handling, with some doctors strongly favouring infliximab based on experience of prescribing the drug as well as patient views and the existing evidence base. Most doctors were more equivocal, and all were prepared to suspend preferences and wait for evidence of effectiveness and safety from the CONSTRUCT trial. PIs also questioned guidelines around drug use and restrictions placed on personal autonomy in delivering best patient care.

Conclusions

Findings highlight healthcare professionals’ preference for the salvage treatment, infliximab in treating steroid-resistant UC, largely based on resource intensive nursing requirements of intravenous administration of ciclosporin. Not all doctors expressed this preference, being more equivocal, and all professionals were content to suspend preferences within the CONSTRUCT trial and recognised the importance of establishing relative effectiveness and safety.

Trial registration number

ISRCTN 22663589.

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Correction

Deighton J, Edbrooke-Childs J, Stapley E, et al. Realistic evaluation of Situation Awareness for Everyone (SAFE) on paediatric wards: study protocol. BMJ Open 2016;6:e014014. doi: 10.1136/bmjopen-2016-014014

Peter Lachman should also be affiliated with ‘National Clinical Lead SAFE, Royal College of Paediatrics and Child Health’.

 The last sentence of the ‘Contributors’ section should read: "PL is the clinical lead on the implementation team for the project at the Royal College of Paediatrics and Child Health (the lead organisation in the delivery of the programme) and he provided input to the drafting of the introduction and discussion sections."

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Study protocol for a natural experiment in a lower socioeconomic area to examine the health-related effects of refurbishment to parks including built-shade (ShadePlus)

Introduction

Parks in disadvantaged suburbs often have low quality and few amenities, which is likely to result in them being underutilised for recreation and physical activity. Refurbishment of parks, including shade, walking paths and other amenities, may have broad health-related benefits.

Methods and analysis

The study design, methods and planned analyses for a natural experiment examining the effects of refurbishments including built-shade added to parks in disadvantaged outer suburbs of Melbourne are described. Three intervention parks and three comparison parks matched for equivalence of park and neighbourhood characteristics were selected. Using mixed methods, the outcomes will be assessed during three consecutive spring–summer periods (T1: 2013–2014; T2: 2014–2015: T3: 2015–2016). Primary outcomes included: observed park use, physical activity and shade use. Self-reported social connectedness, community engagement and psychological well-being were assessed as secondary outcomes.

Ethics and dissemination

This study was approved by Cancer Council Victoria's Human Research Ethics Committee. Studies such as ShadePlus can improve understanding of the broader effects of park refurbishments (including physical activity levels and sun protection behaviours, as well as social connectedness and psychological well-being). The study findings will be disseminated through established urban planning and parks and recreation networks, peer review publications and conference presentations.

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Correction

Lee SMK, Leem J, Park JH, et al. Close look at the experiences of patients enrolled in a clinical trial of acupuncture treatment for atrial fibrillation in Korea: a qualitative study nested within a randomised controlled trial. BMJ Open 2017;7:e013180. doi: 10.1136/bmjopen-2016-013180

There should be two Corresponding authors. Both Sanghoon Lee and Weon Kim should be considered the Corresponding authors for this paper. The Correspondence section should read:

Correspondence to

Dr Sanghoon Lee; shlee777@gmail.com

and

Weon Kim; mylovekw@hanmail.net

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Nurses' decision-making in ethically relevant clinical situations using the example of breathlessness: study protocol of a reflexive grounded theory integrating Goffman's framework analysis

Introduction

Decision-making (DM) in healthcare can be understood as an interactive process addressing decision makers' reasoning as well as their visible behaviour after the decision is made. Other key elements of DM are ethical aspects and the role as well as the treatment options of the examined professions. Nurses' DM to choose interventions in situations of severe breathlessness is such interactions. They are also ethically relevant regarding the vulnerability of affected patients and possible restrictions or treatment options. The study aims to explore which factors influence nurses' DM to use nursing interventions in situations where patients suffer from severe breathlessness.

Methods and analysis

Qualitative study including nurses in German hospital wards and hospices. A triangulation of different methods of data collection—participant observation and qualitative expert interviews—and analysis merge in a reflexive grounded theory approach which integrates Goffman's framework analysis. It allows an analysis of nurses' self-statements about DM, their behaviour in relevant clinical situations and its influences. Data collection and analysis will be examined simultaneously.

Ethics and dissemination

Informed consent will be gained from all participants and the institutional stakeholders. Ongoing consent has to be ensured since observations will take place in healthcare institutions and many patients will be highly vulnerable. The study has been evaluated and approved by the Witten/Herdecke University Ethics Committee, Witten, Germany. Results of the study will be published at congresses and in journal papers.

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Assessing dose-response effects of national essential medicine policy in China: comparison of two methods for handling data with a stepped wedge-like design and hierarchical structure

Objectives

To introduce multilevel repeated measures (RM) models and compare them with multilevel difference-in-differences (DID) models in assessing the linear relationship between the length of the policy intervention period and healthcare outcomes (dose–response effect) for data from a stepped-wedge design with a hierarchical structure.

Design

The implementation of national essential medicine policy (NEMP) in China was a stepped-wedge-like design of five time points with a hierarchical structure. Using one key healthcare outcome from the national NEMP surveillance data as an example, we illustrate how a series of multilevel DID models and one multilevel RM model can be fitted to answer some research questions on policy effects.

Setting

Routinely and annually collected national data on China from 2008 to 2012.

Participants

34 506 primary healthcare facilities in 2675 counties of 31 provinces.

Outcome measures

Agreement and differences in estimates of dose–response effect and variation in such effect between the two methods on the logarithm-transformed total number of outpatient visits per facility per year (LG-OPV).

Results

The estimated dose–response effect was approximately 0.015 according to four multilevel DID models and precisely 0.012 from one multilevel RM model. Both types of model estimated an increase in LG-OPV by 2.55 times from 2009 to 2012, but 2–4.3 times larger SEs of those estimates were found by the multilevel DID models. Similar estimates of mean effects of covariates and random effects of the average LG-OPV among all levels in the example dataset were obtained by both types of model. Significant variances in the dose–response among provinces, counties and facilities were estimated, and the ‘lowest’ or ‘highest’ units by their dose–response effects were pinpointed only by the multilevel RM model.

Conclusions

For examining dose–response effect based on data from multiple time points with hierarchical structure and the stepped wedge-like designs, multilevel RM models are more efficient, convenient and informative than the multilevel DID models.

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Protocol for a scoping review of existing policies on the prevention and control of obesity across countries in Africa

Introduction

The obesity epidemic is a public health challenge for all, including low-income countries. The behavioural patterns known to contribute to the rise in obesity prevalence occur in an environmental context which is not conducive for healthy choices. A policy approach to obesity prevention constitutes a form of public intervention in that it extends beyond individuals to influence entire populations and is a mechanism for creating healthier environments. Little is known about obesity prevention policies in Africa. This scoping review seeks to examine the nature, extent and range of policies covering obesity prevention in Africa in order to assess how they align with international efforts in creating less obesogenic environments. This will help identify gaps in the approaches that are adopted in Africa.

Methods and analysis

Using the Arksey and O'Malley's scoping methodological framework as a guide, a comprehensive search of MEDLINE (PubMed), MEDLINE (EbscoHost) CINAHL (EbscoHost), Academic Search Complete (EbscoHost) and ISI Web of Science (Science Citation Index) databases will be carried out for peer reviewed journal articles related to obesity prevention policies using the African search filter. A grey literature search for policy documents and reports will also be conducted. There will be no language and date restrictions. Eligible policy documents and reports will be obtained and screened using the inclusion criteria. Data will be extracted and results analysed using descriptive numerical summary analysis and qualitative thematic analysis.

Ethics and dissemination

No primary data will be collected since all data that will be presented in this review are based on published articles and publicly available documents, and therefore ethics committee approval is not a requirement. The findings of this systematic review will be presented at workshops and conferences; and will be submitted for publication in peer-reviewed journal. This will also form a chapter of a PhD thesis.

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Intimate partner violence among pregnant women in Rwanda, its associated risk factors and relationship to ANC services attendance: a population-based study

Objectives

To investigate the prevalence of four forms of intimate partner violence during pregnancy in Rwandan women, associated sociodemographic and psychosocial factors and relationship to antenatal care service usage.

Design

This was a cross-sectional population-based study conducted in the Northern province of Rwanda and in Kigali city.

Participants and settings

A total of 921 women who gave birth within the past 13 months were included. Villages in the study area were selected using a multistage random sampling technique and community health workers helped in identifying eligible participants. Clinical psychologists, nurses or midwives carried out face-to-face interviews using a structured questionnaire. Bivariable and multivariable logistic regression were used to assess associations.

Results

The prevalence rates of physical, sexual, psychological violence and controlling behaviour during pregnancy were 10.2% (95% CI 8.3 to 12.2), 9.7% (95% CI 7.8 to 11.6), 17.0% (95% CI 14.6 to 19.4) and 20.0% (95% CI 17.4 to 22.6), respectively. Usage of antenatal care services was less common among women who reported controlling behaviour (OR) 1.93 (95% CI 1.34 to 2.79). No statistically significant associations between physical, psychological and sexual violence and antenatal care usage were found. Low socioeconomic status was associated with physical violence exposure (OR) 2.27 (95% CI 1.29 to 3.98). Also, young age, living in urban areas and poor social support were statistically significant in their associations with violence exposure during pregnancy.

Conclusions

Intimate partner violence inquiry should be included in the standard antenatal care services package and professionals should be trained in giving support, advice and care to those exposed. Gender-based violence is criminalised behaviour in Rwanda; existing policies and laws must be followed and awareness raised in society for preventive purposes.

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Open and Arthroscopic with Mini-Open Surgical Hip Approaches for Treatment of Pigmented Villonodular Synovitis and Concomitant Hip Pathology

Background. Pigmented villonodular synovitis (PVNS) is a rare benign tumor affecting large joints and prompts excision to prevent local destruction of the joint. The purpose of this case report is to describe two differing surgical approaches for management of PVNS of the hip in patients requiring concomitant treatment for additional hip pathology. Methods. This report discusses the presentation, clinical and radiographic findings, and operative management of two contrasting cases of PVNS of the hip. Case describes a 31-year-old female with localized PVNS in addition to a labral tear treated with arthroscopic labral repair followed by tumor excision via a mini-open incision. Case describes a 29-year-old male with more diffuse PVNS in addition to a cam deformity managed with open surgical dislocation of the hip, tumor excision, and restoration of the femoral head/neck junction. Results. This report demonstrates two cases of successful excision of PVNS of the hip in addition to addressing concomitant hip pathology in both cases. Conclusions. Open surgical dislocation of the hip or arthroscopic surgery with a mini-open incision may be used in appropriately selected patients to successfully excise PVNS lesions in addition to addressing concomitant hip pathology.

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Shigella sonnei Bacteremia Presenting with Profound Hepatic Dysfunction

Worldwide, Shigellosis is a significant public health issue, associated with nearly one million deaths annually. About half a million cases of Shigella infection are reported annually in the United States. Shigella bacteremia is uncommon and generally seen in children and immunocompromised adults. We present a case of a Shigella sonnei bacteremia with marked hepatic derangement in a 27-year-old previously healthy homosexual male with history of Roux-en-Y gastric bypass, who presented to the emergency room with a 4-day history of loose watery stool, abdominal cramps, nausea and vomiting, and yellow skin of 2-day duration. He reports similar diarrhea illness in two close contacts in preceding days. On examination, he was fully oriented but dehydrated, icteric, and febrile. Laboratory data revealed WBC of 2200/μL, elevated AST and ALT (201 IU/L, 73 IU/L resp.), normal alkaline phosphatase, elevated total and direct bilirubin of 8.2 mg/dL and 4.4 mg/dL, albumin of 3.2 g/dL, INR of 2.9, prothrombin time of 31.7, and platelet of 96,000/μL. Workup for infectious, autoimmune and medication-induced hepatitis, Wilson’s disease, and hemochromatosis was negative. Abdominal ultrasound and computed tomography of the abdomen showed hepatic steatosis and right-sided colitis. Stool and blood cultures were positive for Shigella sonnei. He was treated with ciprofloxacin with improvement in liver function. Follow-up blood test 4 months later was within normal limits.

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Extensive Renal Arteriovenous Malformations Treated by Transcatheter Arterial Embolization

An 84-year-old woman was referred to our department due to gross hematuria. Enhanced computed tomography revealed early enhancement of the right renal vein and multiple tortuous vessels around the right renal hilus, part of which had invaded into the renal parenchyma and renal calix. We diagnosed her with arteriovenous malformations (AVMs) and performed transcatheter arterial embolization (TAE). Angiography showed extensive and complex AVMs located in the central and peripheral areas of her kidney. After TAE, the hematuria resolved and she became hemodynamically stable.

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Effects of a Supraseasonal Drought on the Ecological Attributes of Plagioscion squamosissimus (Heckel, 1840) (Pisces, Sciaenidae) in a Brazilian Reservoir

The aim of this study was to evaluate the effect of a supraseasonal drought on the ecological attributes of Plagioscion squamosissimus. The fish were caught quarterly from February 2010 to November 2014 using gill nets in the reservoir of Santa Cruz, Rio Grande do Norte, Brazil. The abundance of the species was evaluated with the catch per unit effort (CPUE) metric and then correlated with the accumulated rainfall and water volume of the reservoir. The diet of the fish was evaluated using the feeding index (IAi). The proportional similarity index (PSi) was used to evaluate the variation in the niches of the fish. The body condition was inferred through the relative condition factor, and its variation was assessed with ANOVA. A reduction in the abundance of the species that were positively correlated with the reservoir water volume was observed. The diet of the fish comprised shrimp, gastropods, fish, insects, shrimp larvae, and vegetable matter, with shrimp being the major component. PSi showed the occurrence of individual specialization during November 2013 and November 2014. The relative condition factor was not correlated with a reduction in the water volume of the reservoir. The supraseasonal drought did not affect the relative condition factor, diet, and the trophic niche, but it did affect the species abundance.

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Esthetic Rehabilitation of Anterior Teeth with Copy-Milled Restorations: A Report of Two Cases

Digitalization has become part and parcel of contemporary prosthodontics with the probability of most of the procedures being based on the digital techniques in the near future. This digital revolution started in the latter half of the 20th century by converting analog objects/signals into digital bits and bytes. Recent developments in all-ceramic materials and systems of computer-aided designing and computer-aided manufacturing (CAD/CAM), copy milling, and so forth offer excellent esthetics and superb biocompatibility. Copy milling system for ceramics enables milling of the zirconia cores of all-ceramic restorations precisely and also if this system is properly used the procedure for fabricating all-ceramic restorations can be substantially simplified. This case report presents fabrication of all-ceramic Maryland Bridge and post-core with a copy milling system for esthetics and preservation of integrity of tooth. For both of the patients, the use of biologic, all-ceramic, copy-milled restorations resulted in clinical success and recovered function and esthetics.

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Utilizing Fullerenols as Surfactant for Carbon Nanotubes Dispersions Preparation

Dispersions of individual carbon nanotubes (CNTs) are crucial for nanodevices and polymer/CNTs nanocomposites. In this paper, stable and homogenous dispersions of individual multiwalled carbon nanotubes (MWCNTs) have been synthesized. The factors influencing the dispersibility mechanism, including the surfactant concentration and the pH value, have been investigated. SEM images display the impurities sticking on MWCNTs which have been removed. The oxygen-containing groups on the surface of MWCNTs sample have been detected through FT-IR and Raman spectra. All experimental results illustrate that using fullerenols as surfactant can greatly improve the dispersibility of MWCNTs. Moreover, the prepared dispersions exhibit good stability that the sediment percentage of fullerenols-MWCNTs is only 5.2% after 5 days.

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Relationship between serum anti-heat shock protein 27 antibody levels and obesity

Publication date: Available online 22 February 2017
Source:Clinical Biochemistry
Author(s): Mehrdad Kargari, Samira Tavassoli, Amir Avan, Mahmoud Ebrahimi, Mahmoud Reza Azarpazhooh, Rasool Asoodeh, Mohsen Nematy, Seyed Mahdi Hassanian, Farzad Rahmani, Elham Mohammadzade, Habibollah Esmaeili, Mohsen Moohebati, Gordon A. Ferns, Majid Ghayour-Mobarhan, Seyed Mohammad Reza Parizadeh
BackgroundHeat shock protein 27 (HSP27) is an intracellular molecular chaperone that is expressed at high levels following the exposure of cells to environmental stressors such as heat, toxins, and free radicals. High levels of HSP antigens and antibody titers have been reported in several conditions including cardiovascular disease and cancers. We measured serum anti-HSP27 antibody levels in 993 subjects and assessed the associations between serum anti-HSP27 antibody levels and demographic characteristics including coronary risk factors.MethodsA total of 993 subjects were recruited as part of the Mashhad Stroke and Heart Atherosclerotic Disorders (MASHAD) cohort study. Demographic, clinical, and biochemical parameters and serum anti-HSP27 antibody titers were determined in all the subjects.ResultsSerum anti-HSP27 antibody levels increased with increasing age in men. No significant differences in levels were detected between men and women. Serum anti-HSP27 antibody levels were significantly higher in obese subjects than in nonobese subjects (P=0.046); however, no significant influence of smoking status was observed. Moreover, serum anti-HSP27 antibody titers were positively associated with age, body mass index, waist/hip ratio, the presence of diabetes mellitus, nonsmoking habit, serum triglycerides, cholesterol, and high-sensitivity c-reactive protein.ConclusionWe have found that serum anti-HSP27 antibody titers are related to several cardiovascular risk factors, necessitating further studies on the value of this emerging marker for risk stratification.



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Systematic analysis of early phase clinical studies for patients with breast cancer: Inclusion of patients with brain metastasis

Publication date: Available online 22 February 2017
Source:Cancer Treatment Reviews
Author(s): R. Costa, N. Gill, A.W. Rademaker, B.A. Carneiro, Y.K. Chae, P. Kumthekar, W.J. Gradishar, R. Kurzrock, F.J. Giles
PurposeThis systematic review aims to better define the limitations and patterns with which patients with MBC and CNS metastasis are enrolled into early phase developmental therapeutics trials.MethodsIn June 2016, PubMed search was conducted using the following keywords: “Breast cancer”. Drug-development phase 1, phase 2 or phase 1/2 trials for patients with MBC were included. Multiple-histology trials and trials without an efficacy endpoint were excluded.ResultsIn total, 1,474 studies were included; Inclusion criteria for 423 (29%) allowed for CNS metastasis, 770 (52%) either excluded or did not document eligibility of patients with CNS disease. Trials accruing patients with HER2-positive MBC and including targeted therapies had higher odds of allowing for patients with CNS disease (adjusted OR 1.56, 95% CI 1.08-2.2.6;p = 0.019 and 1.49, 95% 1.08-2.06; p = 0.014, respectively). There were also higher odds of accrual of patients with CNS involvement into clinical trials over time (odds ratio = 1.10, 95% CI 1.07-1.12; p < 0.0001).ConclusionMost published early phase clinical trials either did not clearly document or did not allow for accrual of patients with CNS disease. Early phase trials with targeted agents or enrolling HER2+ MBC had higher odds of permitting CNS metastases.



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Ovarian Ablation for Premenopausal Breast Cancer: A Review of Treatment Considerations and the Impact of Premature Menopause

Publication date: Available online 22 February 2017
Source:Cancer Treatment Reviews
Author(s): Melica Nourmoussavi, Gary Pansegrau, Jason Popesku, Geoffrey L. Hammond, Janice S. Kwon, Mark S. Carey
Historically, ovarian ablation (OA) was used as therapy for women with recurrent hormone-receptor-positive (HRP) premenopausal breast cancer. With the publication of the SOFT (Suppression of Ovarian Function Trial) and TEXT (Tamoxifen and Exemestane Trial) randomized trials, there is considerable interest in OA as an adjuvant treatment, either in combination with tamoxifen or an aromatase inhibitor (AI). Thus, we have reviewed current guidelines and key studies on this important topic and have highlighted the relevant biological and pharmacological aspects of the various endocrine therapies. The results of two key randomized trials addressing the use and controversies of OA in premenopausal breast cancer are discussed and recent research emphasizing the detrimental consequences of premature menopause and the cost-effectiveness of OA is presented. In low-risk patients with HRP premenopausal breast cancer, OA is not beneficial and tamoxifen remains the anti-hormone treatment of choice. In high-risk women (previous chemotherapy or women younger than 35), OA in combination with AI is more effective but is arguably not cost-effective, particularly when OA is achieved medically using a GnRH agonist/antagonist. Compared to tamoxifen alone, the SOFT trial showed a 4.5-7.7% reduction in breast cancer relapse using OA (in combination with either tamoxifen or AI) in high-risk women, though the 5-year overall survival benefit was limited (1.4-3.6%). Premature menopause is associated with long-term mortality risks and women often experience significant menopausal symptoms that impact on quality of life. These considerations should play a role in the treatment selection of those patients who may benefit from adjuvant OA.



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Cutaneous Lymphadenoma: A Trichoblastoma with Regressive Inflammatory Changes

Facial plast Surg 2017; 33: 109-111
DOI: 10.1055/s-0036-1597951

The authors address the entity of cutaneous lymphadenoma. Although considered benign, cutaneous lymphadenoma can be easily misdiagnosed as basal cell carcinoma because of its close clinical and histological resemblance. This entity is rare and controversial both in terms of its histogenesis and the various diagnostic terms assigned to it throughout the literature. While rare, cutaneous lymphadenoma should be considered in the differential of any facial nodule or papule in addition to the more common basal cell carcinoma, nevi, cysts, and appendiceal tumors.
[...]

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Nasal Anatomy and Function

Facial plast Surg 2017; 33: 003-008
DOI: 10.1055/s-0036-1597950

The nose is a complex structure important in facial aesthetics and in respiratory physiology. Nasal defects can pose a challenge to reconstructive surgeons who must re-create nasal symmetry while maintaining nasal function. A basic understanding of the underlying nasal anatomy is thus necessary for successful nasal reconstruction.
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Trends in Nasal Subunit Reconstruction by Facial Plastic and Reconstructive Surgeons

Facial plast Surg 2017; 33: 017-019
DOI: 10.1055/s-0036-1597683

To determine if facial plastic and reconstructive surgeons still adhere to the classic nasal subunit principle as described by Burget and Menick. Observational survey. A Weill Cornell Medicine institutional review board approved electronic survey that was sent via e-mail to active members of the American Academy of Facial Plastic and Reconstructive Surgery (AAFPRS). The survey consisted of 32 multiple-choice questions pertaining to the operative management of small (22–30%), medium (50–58%), and large (75–81%) defects of each subunit of the nose, as well as demographic, provider, and practice characteristics. There were 111 responses to the survey (10.1% response rate). Ninety-eight percent of respondents reported familiarity with the subunit principle, and 59.6% considered the subunit principle in greater than 90% of cases. Almost three-quarters (70.4%) of respondents felt the subunit principle should be applied but could be modified based on the particular nasal defect, whereas 28.7% felt it was only sometimes helpful and was not mandatory for successful nasal reconstruction. Large defects of the tip and ala are generally treated by excision of the remaining subunit (79.4 and 80.6%, respectively). Fewer surgeons would excise the remaining subunit for large defects of the dorsum (39.8%), sidewall (38.8%), and soft tissue facet (18.4%). Simple repair without additional excision was the treatment of choice for small defects of the tip (58.2%), ala (59.2%), sidewall (65%), dorsum (68%), and soft tissue facet (71.8%). However, in many small- (up to 32%) and medium- (up to 51%) sized defects of the tip, ala, sidewall, and dorsum, respondents reported partial subunit excision. The majority of AAFPRS members abide to the classical subunit principle by completely excising the remaining subunit for large defects of the tip and ala. Many surgeons modify the subunit principle in small and medium defects.
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Principles of Nasal Reconstruction

Facial plast Surg 2017; 33: 009-016
DOI: 10.1055/s-0036-1597949

The rise in cutaneous malignancies over the past 20 years has led to significant advances in reconstructing the nose from an aesthetic and functional standpoint. The principles of nasal reconstruction center on application of the nasal subunit principle, three-layered reconstruction, nasal skin characteristics, and patient factors. Reconstructive planning starts with proper defect analysis, followed by application of the reconstructive ladder for soft-tissue repair, adequate structural support, and repair of nasal lining deficits. Optimal reconstructive methods depend on the location and size of the defect. Finally, refinement of the reconstruction is achieved through dermabrasion, scar revision, and flap thinning techniques.
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Delayed Facial Nerve Paralysis following Blast Trauma

Facial plast Surg 2017; 33: 116-118
DOI: 10.1055/s-0036-1597983

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Using Grafts and Granulation to Improve Nasal Repair

Facial plast Surg 2017; 33: 020-026
DOI: 10.1055/s-0036-1597948

Skin grafts offer a dynamic repair option for nasal defects of appropriate size, depth, and location. Granulation and grafting can successfully be used as stand-alone reconstructive options or in conjunction with flap repair. This article reviews suitable indications for graft and granulation use in nasal repair to achieve optimum functional and esthetic outcomes.
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Applying a Visual Assessment Tool to Facial Linear Scars

Facial plast Surg 2017; 33: 097-101
DOI: 10.1055/s-0036-1597684

Previous scar scales have focused on verbal descriptions. A nonverbal visual assessment tool would provide a simple way for patients and physicians to quantify scar appearance. The authors sought to use a validated visual assessment tool for linear surgical scars to assess linear scars on the face and to determine whether patients and surgeons rate scars similarly. A total of 143 patients with linear facial scars resulting from repair of Mohs micrographic surgery defects used the visual assessment tool to rate their surgical scar. Six physicians used the tool to rate a subset of the patients' scar photographs. The scar ratings for patients and physicians were compared. Among the scars rated by both the patients and physicians (n = 79), patients had a significantly lower mean (i.e., more favorable) rating compared with the physicians. This was a single-center study including only Caucasian patients. The visual assessment tool to rate linear surgical scars provided a simple method for both patients and physicians to assess the overall appearance of postsurgical scars. Difference in the scar ranking between patients and physicians indicate the importance of incorporating both patient and physician point of view when assessing scars.
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Local Cutaneous Flaps in Nasal Reconstruction

Facial plast Surg 2017; 33: 027-033
DOI: 10.1055/s-0036-1597982

Facial plastic surgeons use a variety of reconstruction techniques to overcome challenges in restoring the function, structural integrity, and intricate nasal contour in nasal reconstruction. Local cutaneous flaps provide excellent skin texture, thickness, and color match in nasal reconstruction. They offer an excellent cosmetic appearance for small- to medium-sized defects and are preferentially utilized when feasible. This article aims to provide an updated review of local cutaneous flaps for nasal defect repair and describe the major principles related to flap selection.
[...]

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Nasal Reconstruction

Facial plast Surg 2017; 33: 001-002
DOI: 10.1055/s-0037-1598090

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Interpolated Flaps

Facial plast Surg 2017; 33: 034-042
DOI: 10.1055/s-0037-1598170

Nasal reconstruction has been articulated in the literature since 700 B.C. when the earliest iteration of the forehead flap was described in the Indian medical treatise, the Sushruta Samhita. Since then it has evolved into the interpolated flap which has served as a powerful tool for facial reconstruction. The interpolated flap is constructed from nonadjacent donor tissue that has an inherent blood supply. It requires a multistaged approach and is best suited for reconstruction of large or deep defects of the nose. There are three types of interpolated flaps used for nasal reconstruction: the forehead, melolabial, and nasofacial interpolation flaps. The nose is the central feature of the human face and its placement is both aesthetic and functional. Any defects owing to accidental or iatrogenic trauma can cause physiologic and psychological injury to patients. This article aims to review the aforementioned flaps and give indications, contraindications, procedure details, and future directions of these flaps.
[...]

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Adjuncts to Improve Nasal Reconstruction Results

Facial plast Surg 2017; 33: 082-086
DOI: 10.1055/s-0036-1597899

The final cosmetic appearance of nasal reconstruction scars is of paramount importance to both the patient and surgeon. Ideal postreconstruction nasal scars are flat and indistinguishable from surrounding skin. Unfortunately, even with meticulous surgical execution, nasal scars can occasionally be suboptimal. Abnormal fibroblast response can lead to hypertrophic nasal scars, and excessive angiogenesis may lead to telangiectasias or an erythematous scar. Imperfect surgical closure or poor postoperative management can lead to surgical outcomes with step-offs, depressions, suture marks, or dyspigmentation. Aesthetically unacceptable nasal scars can cause pruritus, tenderness, pain, sleep disturbance, and anxiety and depression in postsurgical patients. Fortunately, there are several minimally invasive or noninvasive techniques that allow for enhancement and improvement of cosmetic results with minimal risk and associated downtime. This article provides an overview of adjuncts to improve nasal reconstruction with a focus on techniques to be used in the postoperative period. Armed with an understanding of relevant available therapies, skillful surgeons may drastically improve the final cosmesis and outcome of nasal reconstruction scars.
[...]

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Osseous and Cartilaginous Nasal Reconstruction

Facial plast Surg 2017; 33: 043-051
DOI: 10.1055/s-0036-1597897

The nose is a complex, three-dimensional structure that is supported by a framework of osseous and cartilaginous structures. Disruption of this framework can result in nasal deformity and functional deficits. Nasal reconstruction requires restoration of the osseous and cartilaginous framework. This requires careful preoperative assessment of the nasal defect and understanding the nasal and facial aesthetics that are supported by the osseous and cartilaginous support structures. Structural grafts can be classified as restorative, supportive, or contouring. Surgeons must understand the requirements for each type of grafting and which materials to use to provide the necessary structural reconstruction. Autogenous, homologous, and allogenic materials can be used for reconstruction of the structural deficits. Autogenous grafts from the septum, ear, rib, and calvarium are preferred for structural reconstruction, but surgeons should be well versed with alternative structural grafting materials. Smaller defects can be corrected through cartilaginous grafts, while larger defects require more rigid bony support to withstand the contractive forces of wound healing. Titanium mesh can serve as a viable alternative for rigid structural reconstruction. The ultimate goal of nasal reconstruction is to restore nasal form and function, and successful reconstruction starts with establishing a stable, functional, and anatomically sound osseocartilaginous framework.
[...]

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Hyaluronic Acid Fillers in Soft Tissue Regeneration

Facial plast Surg 2017; 33: 087-096
DOI: 10.1055/s-0036-1597685

Over the last years, hyaluronic acid (HA) injectable dermal fillers (DFs) have become the most popular agents for soft tissue contouring and volumizing. HA fillers are characterized by most of the properties that an ideal DF should have, due to HA unique chemical-physical properties, biocompatibility, biodegradability, and versatility. Therefore, HA DFs have revolutionized the filler market with a high number of products, which differ in terms of HA source, cross-linkage (agent and degree), HA concentration, hardness, cohesivity, consistency, inclusion or lack of anesthetic, indication, and longevity of correction. The article first provides a general introduction to DF world, and an overview of the different materials is available for fillers. Second, it describes the characteristics and the peculiarities of HA fillers, their differences from the other available materials, and therefore the reasons at the base of their success. Moreover, an update regarding the main Food and Drug Administration (FDA) approved fillers is presented.
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Nasal Reconstruction Involving Multiple Subunit Defects

Facial plast Surg 2017; 33: 058-066
DOI: 10.1055/s-0036-1597898

The challenges of nasal reconstruction are readily apparent to any surgeon who has undertaken this task. Defects involving multiple subunits of the nose usually require adjacent tissue transferred to the wound typically in the form of a forehead flap or other local flaps. Herein, we describe current thought on the subunit principle and the application of local flaps and grafts in reconstructing larger superficial defects of the nose. Primary attention is paid to analysis and patient counseling.
[...]

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Mandibular Rim Trilogy with Botulinum Toxin Injection: Reduction, Projection, and Lift

Facial plast Surg 2017; 33: 102-108
DOI: 10.1055/s-0037-1600525

“Onabotulinum toxin A (Botox) revolution” has brought the fundamental change in the facial rejuvenation as well as the concept of microinjection. The aesthetic standard tends to be the “globalization”; however, Asians have different aesthetic cultures and unique facial features compared with Caucasians. A new rejuvenation concept is proposed during our practice; the Asian face should preserve the original facial identity during Botox treatments. The lower face is treated with botulinum toxin to achieve a harmonious facial profile. Twenty young females ranging in age from 30 to 45 years consented and received the three-pronged procedure from March 2014 to April 2015; photography at baseline and follow-up visit were taken and analyzed. After posttreatment for 2 months, significant improvement was observed compared with the baseline. And the reduced masseter prominence and prominent chin were obtained, showing a favorable facial contour and harmonious appearance during the follow-up. The novel three-pronged approach to lower facial rejuvenation was aimed at the Asian characteristic of hypertrophic masseter, chin retrusion, and the facial sagging during the aging process. Botox treatment was a quite effective and safe strategy to improve the appearance and contour of the lower face in Asian patients.
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Reconstruction of the Intranasal Lining

Facial plast Surg 2017; 33: 067-073
DOI: 10.1055/s-0036-1597988

Reconstruction of full-thickness nasal defects has been the subject of surgical inquiry and innovation for over 2,000 years. The replacement of the internal nasal lining is a critical feature of complex nasal reconstruction. Successful reconstruction can prevent cicatricial contraction, external distortion, and internal stenosis. An array of reconstructive possibilities has been described, including cutaneous, mucosal, and fascial options. The challenge to the reconstructive surgeon is to select the repair that maximizes internal stability, while maintaining a patent nasal airway, minimizing morbidity, and meeting patient expectations. This article reviews the options available for the reconstruction of the intranasal lining.
[...]

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Titanium Mesh Nasal Repair without Nasal Lining

Facial plast Surg 2017; 33: 052-057
DOI: 10.1055/s-0036-1593747

The objective of this study was to describe outcomes for patients who underwent titanium mesh reconstruction of full-thickness nasal defects without internal lining repair. This is a retrospective cohort study. Patients with through-and-through nasal defects were identified at a single academic institution between 2008 and 2016. Nasal reconstruction was performed with either titanium mesh and external skin reconstruction without repair of the intranasal lining or traditional three-layer closure. Five patients underwent titanium mesh reconstruction and 11 underwent traditional three-layer repair. Median follow-up was 11 months (range, 2–66 months). The only significant difference between groups was older age in patients undergoing titanium reconstruction (mean, 81 vs. 63 years; difference of 18; 95% confidence interval [CI], 4–32 years). Defect extent including overall size and structures removed was similar between groups (p > 0.05). Paramedian forehead flap was the most common external reconstruction in both groups (100% for titanium mesh and 73% for three-layer closure). Time under anesthesia was significantly shorter for titanium mesh reconstruction (median, 119 vs. 314 minutes; difference of 195; 95% CI, 45–237). Estimated blood loss and length of hospital stay were similar between groups (p > 0.05). Complication rates were substantial although not significantly different, 40 and 36% in titanium and three-layer reconstruction, respectively (p > 0.05). All patients with complications after titanium reconstruction had prior or postoperative radiotherapy. Titanium mesh reconstruction of through-and-through nasal defects can successfully be performed without reconstruction of the intranasal lining, significantly decreasing operative times. This reconstructive technique may not be suitable for patients who undergo radiotherapy.
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