The aim of this study was to investigate the convergent and divergent validity between the Body Coordination Test for Children (KTK) and the Motor Proficiency Test for 4- to 6-Year-Old Children (MOT 4-6). A total of 638 children (5–6 yr old) took part in the study. The results showed a moderately positive association between the total scores of both tests (r = .63). Moreover, the KTK total score correlated more highly with the MOT 4-6 gross motor score than with the MOT 4-6 fine motor score (r = .62 vs. .32). Levels of agreement were moderate when identifying children with moderate or severe motor problems and low at best when detecting children with higher motor-competence levels. This study provides evidence of convergent and divergent validity between the KTK and MOT 4-6. However, given the moderate to low levels of agreement, either measurement may lead to possible categorization errors. Therefore, it is recommended that children's motor competence not be judged based on the result of a single test.
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Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Παρασκευή 29 Ιανουαρίου 2016
Convergent and divergent validity between the KTK and MOT 4-6 motor tests in early childhood
How to return to subjectivity? Natorp, Husserl, and Lacan on the limits of reflection
This article discusses the recent call within contemporary phenomenology to return to subjectivity in response to certain limitations of naturalistic explanations of the mind. The meaning and feasibility of this call is elaborated by connecting it to a classical issue within the phenomenological tradition concerning the possibility of investigating the first-person perspective through reflection. We will discuss how this methodological question is respectively treated and reconfigured in the works of Natorp, Husserl, and Lacan. Finally, we will lay out some possible consequences of such a cross-reading for the conception of subjectivity and the concomitant effort to account for this dimension of first-person experience in response and in addition to its omission within the standard third-person perspective of psychological research.
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How to implement quality indicators successfully in palliative care services: perceptions of team members about facilitators of and barriers to implementation
There is an increasing demand for the use of quality indicators in palliative care. With previous research about implementation in this field lacking, we aimed to evaluate the barriers to and facilitators of implementation. Three focus group interviews were organized with 21 caregivers from 18 different specialized palliative care services in Belgium. Four had already worked with the indicators during a pilot study. The focus group discussions were transcribed verbatim and analyzed using the thematic framework approach. The caregivers anticipated that a positive attitude by the team towards quality improvement, the presence of a good leader, and the possible link between quality indicators and reimbursement might facilitate the implementation of quality indicators in specialized palliative care services. Other facilitators concerned the presence of a need to demonstrate quality of care, to perform improvement actions, and to learn from other caregivers and services in the field. A negative attitude by caregivers towards quality measurement and a lack of skills, time, and staff were mentioned as barriers to successful implementation. Palliative caregivers anticipate a number of opportunities and problems when implementing quality indicators. These relate to the attitudes of the team regarding quality measurement; the attitudes, knowledge, and skills of the individual caregivers within the team; and the organizational context and the economic and political context. Training in the advantages of quality indicators and how to use them is indispensable, as are structural changes in the policy concerning palliative care, in order to progress towards systematic quality monitoring.
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Belgian social law and its journals: a reflected history
Through the analysis of the emergence of contemporary social law, Bruno Debaenst stresses the multiple links resulting from the creation of a new field in law and its specialized journals. These milestones underline how actors interact to define and manage an autonomous space in the legal culture in the making. Progressively, the two founding pillars of social law, labour law and social security law emancipated. Thus, journals follow a similar path to become distinct and specialized. Since the end of the nineteenth century, as the author lists the multiple titles, legal practitioners, lawyers and magistrates animate the journals until the Second World War. With the integration of social law in the legal curriculum, these journals received attention of Liège, Louvain and Brussels universities professors. In a way, this analysis documents how legal journals contribute to the definition of legal culture, beyond reflecting it.
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Fibromyalgie, een klinische beschouwing: 'Hoe een lichaam lijdt aan een waarheid die het miskent'
In de kliniek worden we steeds vaker geconfronteerd met de diagnose van fibromyalgie. Het valt hierbij op dat deze patiënten nogal vaak doorverwezen worden met de boodschap dat ze bij een therapeut dienen te gaan om hun fibromyalgie te aanvaarden. Dit roept meteen de vraag op of dit dan de enige richting is die we kunnen uitgaan me de behandeling. De hypothese dat het zou gaan om een psychosomatisch fenomeen werd tijdens de conferentie te Kopenhagen in 1992, waar de diagnose voor het eerst werd besproken, niet weerhouden. Is dit wel terecht en verliezen we op die manier niet enkele interessante behandelingsmogelijkheden? Al stelt Lacan, in zijn conferentie te Genève over het symptoom, dat we ons op het gebied van psychosomatiek vaak op een ongekend gebied bevinden, kunnen we vanuit een Freudiaans-Lacaniaans denken wel verschillende richtingen voor behandeling naar voor schuiven...
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Chromosomal aberrations and prognosis in patients with concomitant chemoradiotherapy for resected head and neck cancer.
| Related Articles |
Chromosomal aberrations and prognosis in patients with concomitant chemoradiotherapy for resected head and neck cancer.
Oncol Rep. 2016 Jan 26;
Authors: Park SW, Joo YH, Jung SH, Yim SH, Nam IC, Cho KJ, Kim MS, Chung YJ
Abstract
Although concomitant chemoradiotherapy (CCRT) has recently become a mainstay of a primary treatment modality in advanced head and neck squamous cell carcinoma (HNSCC), some of the patients experience CCRT failure. If we can predict the CCRT outcomes, we can reduce unnecessary CCRT avoiding risk of CCRT‑related complication. We aimed to identify genetic alteration markers related to treatment failure in HNSCC patients who underwent radical surgery and CCRT. Genome‑wide copy number alterations (CNAs) were analyzed in 18 HNSCC patients with (n=9) or without (n=9) recurrence using oligoarray‑comparative genomic hybridization and candidate CNAs were validated by quantitative RT‑PCR. A total of 15 recurrently altered regions (RARs) were identified in the 18 HNSCC cases. Among them, two RARs were significantly associated with CCRT‑failure: copy number gained RARs of 7p11.2 harboring EGFR (P=0.029) and 18p11.32 harboring TYMS gene (P=0.029). Three RARs (7p11.2, 9p21.3 and 18p11.32) were significantly associated with poor disease‑specific survival in univariate analysis, and 7p11.2 was consistently significant in the multivariate analysis (HR 40.68, P=0.003). In conclusion, we defined novel genomic alterations associated with CCRT‑failure: 7p11.2 (EGFR) and 18p11.32 (TYMS). Our results provide useful clues for the elucidation of the molecular pathogenesis of HNSCC and to predict CCRT‑failure.
PMID: 26821349 [PubMed - as supplied by publisher]
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Seven major genomic deletions of vaccinia virus Tiantan strain are sufficient to decrease pathogenicity.
| Related Articles |
Seven major genomic deletions of vaccinia virus Tiantan strain are sufficient to decrease pathogenicity.
Antiviral Res. 2016 Jan 25;
Authors: Li Y, Sheng Y, Chu Y, Ji H, Jiang S, Lan T, Li M, Chen S, Fan Y, Li W, Li X, Sun L, Jin N
Abstract
Attenuated strain TTVAC7, as a multi-gene-deleted vaccinia virus Tiantan strain (VTT), was constructed by knocking out parts of non-essential genes related to virulence, host range and immunomodulation of VTT, and by combining double marker screening with exogenous selectable marker knockout techniques. In this study, shuttle vector plasmids pTC-EGFP, pTA35-EGFP, pTA66-EGFP, pTE-EGFP, pTB-EGFP, pTI-EGFP and pTJ-EGFP were constructed, which contained seven pairs of recombinant arms linked to the early and late strong promoter pE/L, as well as to enhanced green fluorescent protein (EGFP) as an exogenous selectable marker. BHK cells were co-transfected/infected successively with the above plasmids and VTT or gene-deleted VTT, and homologous recombination and fluorescence plaque screening methods were used to knock out the gene fragments (TC: TC7L ∼ TK2L; TA35: TA35L; TA66: TA66R; TE: TE3L ∼ TE4L; TB: TB13R; TI: TI4L; TJ: TJ2R). The Cre/LoxP system was then applied to knock out the exogenous selectable marker, and ultimately the gene-deleted attenuated strain TTVAC7 was obtained. A series of in vivo and in vitro experiments demonstrated that not only the host range of TTVAC7 could be narrowed and its toxicity weakened significantly, but its high immunogenicity was maintained at the same time. These results support the potential of TTVAC7 to be developed as a safe viral vector or vaccine.
PMID: 26821204 [PubMed - as supplied by publisher]
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Is Brain Activity during Action Observation Modulated by the Perceived Fairness of the Actor?
| Related Articles |
Is Brain Activity during Action Observation Modulated by the Perceived Fairness of the Actor?
PLoS One. 2016;11(1):e0145350
Authors: Etzel JA, Valchev N, Gazzola V, Keysers C
Abstract
Perceiving other people's actions triggers activity in premotor and parietal areas, brain areas also involved in executing and sensing our own actions. Paralleling this phenomenon, observing emotional states (including pain) in others is associated with activity in the same brain areas as activated when experiencing similar emotions directly. This emotion perception associated activity has been shown to be affected by the perceived fairness of the actor, and in-group membership more generally. Here, we examine whether action observation associated brain activity is also affected by the perceived social fairness of the actors. Perceived fairness was manipulated using an alternating iterated Prisoner's Dilemma game between the participant and two confederates, one of whom played fairly and the other unfairly. During fMRI scanning the participants watched movies of the confederates performing object-directed hand actions, and then performed hand actions themselves. Mass-univariate analysis showed that observing the actions triggered robust activation in regions associated with action execution, but failed to identify a strong modulation of this activation based on perceived fairness. Multivariate pattern analysis, however, identified clusters potentially carrying information about the perceived fairness of the actor in the middle temporal gyrus, left postcentral gyrus, right inferior parietal lobule, right middle cingulate cortex, right angular gyrus, and right superioroccipital gyrus. Despite being identified by a whole-brain searchlight analysis (and so without anatomical restriction), these clusters fall into areas frequently associated with action observation. We conclude that brain activity during action observation may be modulated by perceived fairness, but such modulation is subtle; robust activity is associated with observing the actions of both fair and unfair individuals.
PMID: 26820995 [PubMed - as supplied by publisher]
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Differential Protein Expression Profiles in Glaucomatous Trabecular Meshwork: An Evaluation Study on a Small Primary Open Angle Glaucoma Population.
| Related Articles |
Differential Protein Expression Profiles in Glaucomatous Trabecular Meshwork: An Evaluation Study on a Small Primary Open Angle Glaucoma Population.
Adv Ther. 2016 Jan 28;
Authors: Micera A, Quaranta L, Esposito G, Floriani I, Pocobelli A, Saccà SC, Riva I, Manni G, Oddone F
Abstract
INTRODUCTION: Primary open angle glaucoma (POAG) is a progressive optic neuropathy characterized by impaired aqueous outflow and extensive remodeling in the trabecular meshwork (TM). The aim of this study was to characterize and compare the expression patterns of selected proteins belonging to the tissue remodeling, inflammation and growth factor pathways in ex vivo glaucomatous and post-mortem TMs using protein-array analysis.
METHODS: TM specimens were collected from 63 white subjects, including 40 patients with glaucoma and 23 controls. Forty POAG TMs were collected at the time of surgery and 23 post-mortem specimens were from non-glaucomatous donor sclerocorneal tissues. Protein profiles were evaluated using a chip-based array consisting of 60 literature-selected antibodies.
RESULTS: A different expression of some factors was observed in POAG TMs with respect to post-mortem specimens, either in abundance (interleukin [IL]10, IL6, IL5, IL7, IL12, IL3, macrophage inflammatory protein [MIP]1δ/α, vascular endothelial growth factor [VEGF], transforming growth factor beta 1 [TGFβ1], soluble tumor necrosis factor receptor I [sTNFRI]) or in scarcity (IL16, IL18, intercellular adhesion molecule 3 [ICAM3], matrix metalloproteinase-7 [MMP7], tissue inhibitor of metalloproteinase 1 [TIMP1]). MMP2, MMP7, TGFβ1, and VEGF expressions were confirmed by Western blot, zymography, and polymerase chain reaction. No difference in protein profile expression was detected between glaucomatous subtypes.
CONCLUSION: The analysis of this small TM population highlighted some proteins linked to POAG, some previously reported and others of new detection (IL7, MIPs, sTNFαRI). A larger POAG population is required to select promising disease-associated biomarker candidates.
FUNDING: This study was partially supported by the Fondazione Roma, the Italian Ministry of Health and the "National 5xMille 2010 tax donation to IRCCS-G.B. Bietti Foundation".
PMID: 26820987 [PubMed - as supplied by publisher]
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Prosthetic Rehabilitation of Patients After Surgical Treatment of Maxillary Tumors with Respect to Upper Airway Protection.
| Related Articles |
Prosthetic Rehabilitation of Patients After Surgical Treatment of Maxillary Tumors with Respect to Upper Airway Protection.
Adv Exp Med Biol. 2016 Jan 29;
Authors: Rolski D, Kostrzewa-Janicka J, Nieborak R, Przybyłowska D, Stopa Z, Mierzwińska-Nastalska E
Abstract
As a consequence of surgical treatment of maxillary tumors, a connection between oral and nasal cavities is formed, which leads to serious functional disorders, manifested by inability to normally ingest food, proper speech articulation, and to respiratory route disorders and upper airway inflammation. These morphological and functional disorders are intensified by adjunctive radio- or chemotherapy. The aim of this paper is to present different possible methods of rehabilitation, including application of interim obturators and individually planned prosthetic restorations to improve respiratory efficiency in patients after extensive maxillary resections. In the course of prosthetic treatment, cooperation with the laryngologist to consider every aspect of chronic paranasal sinusitis, accompanied by concurrent inflammation of oral, nasal, or laryngeal mucous membranes, was of paramount importance. Based on the quality of life questionnaire, used in this study, evident improvement in the masticatory efficiency, speech articulation, and respiration was observed. Particularly good effects were obtained in edentulous patients, in whom implant-prosthetic treatment was possible to apply. Comprehensive and multidisciplinary care of postoperative patients greatly contributes to their better quality of life and facilitates their return to prior living conditions, as well as to occupational and family lives.
PMID: 26820729 [PubMed - as supplied by publisher]
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Successful endoscopic ablation of a pyriform sinus fistula in a child: case report and literature review.
| Related Articles |
Successful endoscopic ablation of a pyriform sinus fistula in a child: case report and literature review.
Pediatr Surg Int. 2016 Jan 28;
Authors: Abbas PI, Roehm CE, Friedman EM, Athanassaki I, Kim ES, Brandt ML, Wesson DE, Lopez ME
Abstract
Recurrent thyroid infections are rare in children. When present, patients should be evaluated for anatomic anomalies such as pyriform sinus fistulae. We describe a 12-year-old girl with history of recurrent thyroid abscesses secondary to a pyriform sinus fistula and managed with concurrent endoscopic ablation and incision and drainage.
PMID: 26820515 [PubMed - as supplied by publisher]
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MMP2-sensing up-conversion nanoparticle for fluorescence biosensing in head and neck cancer cells.
| Related Articles |
MMP2-sensing up-conversion nanoparticle for fluorescence biosensing in head and neck cancer cells.
Biosens Bioelectron. 2016 Jan 19;80:131-139
Authors: Chan YC, Chen CW, Chan MH, Chang YC, Chang WM, Chi LH, Yu HM, Lin YF, Tsai DP, Liu RS, Hsiao M
Abstract
Upconversion nanoparticles (UCNPs) have extensive biological-applications because of their bio-compatibility, tunable optical properties and their ability to be excited by infrared radiation. Matrix metalloproteinases (MMPs) play important roles in extracellular matrix remodelling; they are usually found to significantly increase during cancer progression, and these increases may lead to poor patient survival. In this study, we produced a biosensor that can be recognized by MMP2 and then be unravelled by the attached quencher to emit visible light. We used 3.5-nm gold nanoparticles as a quencher that absorbed emission from UCNPs at a wavelength of 540nm. The biosensor consists of an upconversion nanoparticle, MMP2-recognized polypeptides and quenchers. Here, UCNPs consisting of NaYF4:Yb(3+)/Er(3+) were prepared via a high temperature co-precipitation method while protecting the oleic acid ligand. To improve the biocompatibility and modify the UCNPs with a polypeptide, they were coated with a silica shell and further conjugated with MMP-recognizing polypeptides. The polypeptide has two ends of featuring carboxylic and thiol groups that react with UCNPs and AuNPs, and the resulting nanoparticles were referred to as UCNP@p-Au. According to the in vitro cell viability analysis, UCNP@p-Au exhibited little toxicity and biocompatibility in head and neck cancer cells. Cellular uptake studies showed that the MMP-based biosensor was activated by 980-nm irradiation to emit green light. This MMP-based biosensor may serve as sensitive and specific molecular fluorescent probe in biological-applications.
PMID: 26820361 [PubMed - as supplied by publisher]
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Head and Neck Pathology.
| Related Articles |
Head and Neck Pathology.
Mod Pathol. 2016 Feb;29(S2):316-333
Authors:
PMID: 26820335 [PubMed - as supplied by publisher]
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Effects of HSP27 downregulation on PDT resistance through PDT-induced autophagy in head and neck cancer cells.
| Related Articles |
Effects of HSP27 downregulation on PDT resistance through PDT-induced autophagy in head and neck cancer cells.
Oncol Rep. 2016 Jan 26;
Authors: Kim J, Lim H, Kim S, Cho H, Kim Y, Li X, Choi H, Kim O
Abstract
We previously reported that photodynamic therapy (PDT) induces cell death in head and neck cancer through both autophagy and apoptosis. Regulation of cell death by autophagy and apoptosis is important to enhance the effects of PDT. Autophagy maintains a balance between cell death and PDT resistance. Downregulation of heat shock protein 27 (HSP27) induces PDT resistance in head and neck cancer cells. Furthermore, HSP70 regulates apoptosis during oxidative stress. However, the role of HSPs in PDT-induced cell death through autophagy and apoptosis is unclear. Therefore, in the present study, we investigated the effects of HSP27 and HSP70 on PDT-induced cell death of oral cancer cells through autophagy and apoptosis. Cancer cells were treated with hematoporphyrin at varying doses, followed by irradiation at 635 nm with an energy density of 5 mW/cm2. We determined the changes in HSP expression by determining the levels of PARP-1 and LC3II in PDT-resistant cells. Furthermore, we assessed cell death signaling after downregulating HSPs by transfecting specific siRNAs. We observed that PDT decreased HSP27 expression but increased HSP70 expression in the head and neck cancer cells. Treatment of cells with LC3II and PARP-1 inhibitors resulted in upregulation of HSP70 and HSP27 expression, respectively. Downregulation of HSP27 and HSP70 induced cell death and PDT resistance through autophagy and apoptosis. Moreover, downregulation of HSP27 in PDT-resistant cells resulted in enhanced survival. These results indicate that the regulation of HSP27 and HSP70 plays a principal role in increasing the effects of PDT by inducing autophagic and apoptotic cell death.
PMID: 26820233 [PubMed - as supplied by publisher]
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Traumatic dysgeusia, an unusual complication of facial trauma: A case report.
Publication date: Available online 28 January 2016
Source:Journal of Oral and Maxillofacial Surgery
Author(s): João Paulo Bonardi, Fernanda Herrera da Costa, Glaykon Alex Vitti Stabile, Cecilia Luiz Pereira- Stabile
The chemical senses of taste and smell are important to human life, as they play an important role in detecting potential environmental hazards. Humans are able to identify countless different flavors by means of the simultaneous perception of taste and smell. Reports of sensory loss after craniocerebral trauma began to appear in the medical literature in the middle 1800s. Dysgeusia associated with head injuries is rare and its reported incidence is of 0.4-0.5%. This paper presents the clinical case of a 32-year-old male patient with Le Fort I and III fractures, treated with surgical reduction and fixation. The patient presented dysgeusia after a slight improvement of his preoperative anosmia. The prognosis is favorable and the treatment is prospective.
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The Use of BOTOX®(onabotulinumtoxin A) for the treatment of parotid sialocele and fistula post extirpation of buccal squamous cell carcinoma with immediate reconstruction utilizing microvascular free flap. A Report of Three Cases
Publication date: Available online 29 January 2016
Source:Journal of Oral and Maxillofacial Surgery
Author(s): James Melville, Daniel Stackowicz, Jonathon S. Jundt, Jonathan W. Shum
Buccal squamous cell carcinoma is an aggressive form of oral carcinoma with a high recurrence rate.1 Injury to the parotid duct is often unavoidable when surgically treating buccal squamous cell carcinoma due to the intimate anatomic relationship between the buccal mucosa, Stensen's duct and the parotid gland. It is often difficult to achieve negative margins and preserve the integrity of the parotid duct.2 Sialocele formation is a frequent and untoward complication due to extravasation of saliva into the surgical defect which delays healing, creates fistulas and produces painful facial swelling. Currently, no consensus exists regarding the management of a parotid sialocele.3 Multiple authors have described varying modalities of treatment such as repeated percutaneous needle aspiration, pressure dressings, anti-sialagogue therapy, radiotherapy, botulinum toxin and surgical techniques including duct repair, diversion, ligation, drain placement, and parotidectomy.4,5 With the approval of the University of Texas Health Sciences Center at Houston (UTHealth) IRB, we present three cases of parotid siaolcele and non-healing fistulas successfully treated with Botox (onabotulinumtoxin A) after tumor extirpation, neck dissection and reconstruction with a microvascular free flap. At our institution the radiation oncologist would prefer not to start adjunctive radiation treatment with a non-healing wound or a drain in the field of radiation. Ideally, a standard timing of adjuvant radiotherapy is 6-8 weeks post surgery and 60cGy should be completed before 7 month. With the use of Botox we were able resolve the non-healing wound and remove the drain at least 2 weeks before the initiation of adjunctive radiotherapy and minimize the delay in adjuvant treatment.
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Periarticular Cysts Of The Temporomandibular Joint Are More Frequently Synovial Than Ganglion
Publication date: Available online 28 January 2016
Source:Journal of Oral and Maxillofacial Surgery
Author(s): J. Partridge, N. Cipriani, W.C. Faquin, S.K. Chuang, D.A. Keith, E. Lahey
PurposeDifferentiating between ganglion and synovial cysts by standard histology is difficult, leading to inaccurate statements on frequency for each of these periarticular lesions. The purpose of this study is to use immunohistochemical (IHC) analysis to 1) calculate the accuracy of the histological diagnoses, 2) determine the frequency of ganglion and synovial cysts of the temporomandibular joint (TMJ) and 3) compare the frequency of these lesions in the TMJ compared to the extracranial skeleton in patients treated at Massachusetts General Hospital (MGH).Materials and MethodsThis is a retrospective cohort study of all patients undergoing treatment of TMJ cysts at MGH between 2001 and 2013. IHC analysis of tissue samples for each patient was completed and compared to original histological diagnoses. Categorical variables including age, gender and sidedness were recorded. A natural language search of the Department of Pathology database determined the frequency of extracranial periarticular cysts during the same timeframe.ResultsThirteen patients met the inclusion criteria. Eleven cysts were synovial and two were ganglion based on histology. IHC analysis identified two false positive synovial cyst diagnoses resulting in 100% sensitivity and 50% specificity for the original histological assessment and a percent error of 22%. Of the periarticular TMJ lesions, 69% were synovial cysts while 31% were ganglion. The frequency of TMJ versus extracranial ganglion cysts is 0.24%, and the frequency of TMJ versus extracranial synovial cysts is 0.60% based on a total of 3,176 extracranial cysts (1506 synovial; 1670 ganglion).ConclusionThis study represents the largest single-institution experience with periarticular cysts of the TMJ and contrary to previous reports, TMJ cysts appear to be more frequently synovial than ganglion. IHC can be used to overcome the relatively poor specificity of histological diagnosis of synovial cysts.
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Hepatitis B prevalence and treatment needs among Tibetan refugees residing in India
Abstract
Background
Untreated chronic hepatitis B can lead to liver failure and/or liver cancer. These complications can be avoided through prevention with vaccination or treatment of disease. To inform health policy for the Tibetan community in India, we conducted study of hepatitis B prevalence and treatment needs.
Methods
We conducted a cross-sectional study over three months of 2013. Households were randomly selected for participation via a satellite map; one boarding school and one residential monastery were also included. Participants were asked questions and a whole blood sample was collected for HBsAg assay. Participants with a positive HBsAg result were tested for hepatitis B e antigen, ALT, and AST. Participants with a negative HBsAg result were tested for anti-hepatitis B core antibodies.
Results
We recruited 2,769 participants; of which 247 (8.9%) were positive for HBsAg. Participants more likely to have a positive HBsAg result were those born in Tibet (12.4%) and aged 30 to 59 years old. Of those with a positive HBsAg result, 60.7% were positive for hepatitis B e antigen 7% of whom fit into a likely treatment-needed category; the others fit into management categories requiring repeat ALT testing with or without liver fibrosis assessment. Among participants negative for HBsAg, 52.9% from household sampling had anti-HBc antibodies.
Summary
We identified a high endemicity of chronic hepatitis B in a Tibetan community in India. Resource appropriate approaches are needed for managing chronic hepatitis B in settings such as this one. This article is protected by copyright. All rights reserved
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Sequencing Ebola and Marburg viruses genomes using microarrays
Abstract
Periodic outbreaks of Ebola and Marburg hemorrhagic fevers have occurred in Africa over the past four decades with case fatality rates reaching as high as 90%. The latest Ebola outbreak in West Africa in 2014 raised concerns that these infections can spread across continents and pose serious health risks. Early and accurate identification of the causative agents is necessary to contain outbreaks. In this report, we describe sequencing-by-hybridization (SBH) technique using high density microarrays to identify Ebola and Marburg viruses. The microarrays were designed to interrogate the sequences of entire viral genomes, and were evaluated with three species of Ebolavirus (Reston, Sudan and Zaire), and three strains of Marburgvirus (Angola, Musoke and Ravn). The results showed that the consensus sequences generated with four or more hybridizations had 92.1% to 98.9% accuracy over 95% to 99% of the genomes. Additionally, with SBH microarrays it was possible to distinguish between different strains of the Lake Victoria Marburgvirus. This article is protected by copyright. All rights reserved
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"Drug-Induced Liver Injury Clinical Consortia: a global research response for a worldwide health challenge".
| Related Articles |
"Drug-Induced Liver Injury Clinical Consortia: a global research response for a worldwide health challenge".
Expert Opin Drug Metab Toxicol. 2016 Jan 28;
Authors: Andrade RJ, Ortega-Alonso A, Lucena MI
PMID: 26820043 [PubMed - as supplied by publisher]
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Quantitative clinical pharmacology practice for optimal use of antibiotics during the neonatal period.
| Related Articles |
Quantitative clinical pharmacology practice for optimal use of antibiotics during the neonatal period.
Expert Opin Drug Metab Toxicol. 2016 Jan 27;
Authors: Samardzic J, Allegaert K, Wilbaux M, Pfister M, van den Anker JN
Abstract
INTRODUCTION: For safe and effective neonatal antibiotic therapy, knowledge of the pharmacokinetic parameters of antibacterial agents in neonates is a prerequisite. Fast maturational changes during the neonatal period influence pharmacokinetic and pharmacodynamic parameters and their variability. Consequently, the need for applying quantitative clinical pharmacology and determining optimal drug dosing regimens in neonates has become increasingly recognized. Areas covered: Modern quantitative approaches, such as pharmacometrics, are increasingly utilized to characterize, understand and predict the pharmacokinetics of a drug and its effect, and to quantify the variability in the neonatal population. Individual factors, called covariates in modeling, are integrated in such approaches to explain inter-individual pharmacokinetic variability. Pharmacometrics has been shown to be a relevant tool to evaluate, optimize and individualize drug dosing regimens. Expert opinion: Challenges for optimal use of antibiotics in neonates can largely be overcome with quantitative clinical pharmacology practice. Clinicians should be aware that there is a next step to support the clinical decision-making based on clinical characteristics and therapeutic drug monitoring, through Bayesian-based modeling and simulation methods. Pharmacometric modeling and simulation approaches permit us to characterize population average, inter-subject and intra-subject variability of pharmacokinetic parameters such as clearance and volume of distribution, and to identify and quantify key factors that influence the pharmacokinetic behavior of antibiotics during the neonatal period.
PMID: 26817821 [PubMed - as supplied by publisher]
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"J Korean Neurosurg Soc"[jour]; +17 new citations
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[Lymphatic malformations in the head and neck area].
[Lymphatic malformations in the head and neck area].
HNO. 2016 Jan 28;
Authors: Wiegand S, Werner JA
Abstract
Lymphatic malformations are congenital malformations of the lymphatic system. They are mainly located in the head and neck area, and grow proportional to the patients' body growth. Depending on the morphology, it can be distinguished between macrocystic, microcystic and mixed lymphatic malformations. Due to their infiltrative growth, microcystic lymphatic malformations are particularly difficult to treat. Therapeutic approaches include conventional surgical resection, laser therapy, sclerotherapy and systemic drug therapies.
PMID: 26820157 [PubMed - as supplied by publisher]
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Comparison of Cisplatin/Etoposide versus Carboplatin/Etoposide concurrent chemoradiotherapy for limited-stage small cell lung cancer (LS-SCLC) in the elderly population (age >65) using national SEER-Medicare data
Publication date: Available online 28 January 2016
Source:Practical Radiation Oncology
Author(s): Ellen Kim, Tithi Biswas, Paul Bakaki, Afshin Dowlati, Neelesh Sharma, Mitchell Machtay
PurposeStandard therapy for limited stage small cell lung cancer (SCLC) (AJCC stages I-III) is concurrent chemoradiation (CRT) with cisplatin/etoposide (EP) but carboplatin/etoposide (EC) is often used in clinical practice. Though a growing proportion of this disease is diagnosed in older patients, there are limited studies of older patients comparing cisplatin to carboplatin. This study compared survival outcomes of elderly patients with limited stage SCLC treated with concurrent EC or EP and radiation.Methods and MaterialsLimited stage SCLC diagnosed at ages 66–80 during 1992–2007 were selected from the (Surveillance Epidemiology and End Results) SEER-Medicare database to compare EP with EC. Concurrent CRT was defined as starting radiation and cisplatin or carboplatin within 14 days. Study endpoints were overall survival (OS, time from diagnosis until death) and cause specific survival (CSS, time from diagnosis until death from lung cancer).ResultsFinal analysis included 565 cases: 219 EP (39%) and 346 EC (61%), with median age 72 and gender ratio 1.0. A majority of the cases were stage III (85%). Median and 5-year OS were 13.8 months [95% confidence interval 11.4-15.0 months] and 10.2% [95% CI 6.2-15.3%] for EP, versus 13.7 months [95% CI 12.0-15.6 months] and 10.9% [95% CI 7.6-14.8%] for EC (p-value 0.51). CSS were also similar (p-value 0.91). OS and CSS were not statistically different in single- or multi-variable survival analysis.ConclusionsEC and EP had similar survival outcomes, suggesting EC could be used with (or instead of) EP as the standard of care, at least in the elderly population.
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Radiotherapy Quality-of-Care Indicators for Locally Advanced Cervical Cancer: A Consensus Guideline
Publication date: Available online 28 January 2016
Source:Practical Radiation Oncology
Author(s): J. Croke, A. Fyles, L. Barbera, D. D'Souza, R. Pearcey, T. Stuckless, B. Bass, M. Brundage, M. Milosevic
PurposeRadiotherapy plays an important curative role for patients with locally advanced cervical cancer (LACC). There are no standards to define best practice. The purpose of this study was to develop a suite of radiotherapy key quality of care indicators (KQIs) for the curative management of LACC based on expert consensus.MethodsA modified Delphi method was used after identifying candidate KQIs. Round 1 involved surveying all Canadian GYN radiation oncologists. The current and anticipated future (5 years) importance and current achievability of each KQI was ranked. Round 2 consisted of a facilitated face-to-face meeting with a smaller expert panel to discuss, revise and develop consensus on the KQIs.ResultsThe literature review identified 83 candidate KQIs. Survey response was 71%. Round 2 yielded a final suite of 40 KQIs in the following categories: Pre-treatment assessment, External beam radiotherapy, Brachytherapy, Follow-up and Expertise/Workload. A prominent theme was the importance of having KQIs to measure the current state, evolution and future uptake of MR-guided brachytherapy.ConclusionsTo our knowledge this is the first study establishing radiotherapy KQIs in LACC based on expert consensus. These KQIs should be used to guide programmatic direction and resource allocation to assure consistent and optimal patient care.
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French comment on article: Repeat peroral endoscopic myotomy: a salvage option for persistent/recurrent symptoms.
French comment on article: Repeat peroral endoscopic myotomy: a salvage option for persistent/recurrent symptoms.
Endoscopy. 2016 Feb;48(2):206
Authors:
PMID: 26820089 [PubMed - as supplied by publisher]
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(-)-β-hydrastine suppresses the proliferation and invasion of human lung adenocarcinoma cells by inhibiting PAK4 kinase activity.
(-)-β-hydrastine suppresses the proliferation and invasion of human lung adenocarcinoma cells by inhibiting PAK4 kinase activity.
Oncol Rep. 2016 Jan 25;
Authors: Guo B, Li X, Song S, Chen M, Cheng M, Zhao D, Li F
Abstract
(-)-β-hydrastine is one of the main active components of the medicinal plant, Hydrastis canadensis, which is used in many dietary supplements intended to enhance the immune system. However, whether (-)-β-hydrastine affects the tumor signaling pathway remains unexplored. In the present study, we found that (-)-β-hydrastine inhibited the kinase activity of p21-activated kinase 4 (PAK4), which is involved in the regulation of cytoskeletal reorganization, cell proliferation, gene transcription, oncogenic transformation and cell invasion. In the present study, (-)-β-hydrastine suppressed lung adenocarcinoma cell proliferation by inhibiting expression of cyclin D1/D3 and CDK2/4/6, leading to cell cycle arrest at the G1 phase, in a PAK4 kinase-dependent manner. Moreover, inhibition of PAK4 kinase activity by (-)-β-hydrastine also promoted the early apoptosis of lung adenocarcinoma cells through the mitochondrial apoptosis pathway. In addition, (-)-β-hydrastine significantly suppressed the migration and invasion of human lung adenocarcinoma cells in conjunction with concomitant blockage of the PAK4/LIMK1/cofilin, PAK4/SCG10 and PAK4/MMP2 pathways. All of these data indicate that (-)-β-hydrastine, as a novel PAK4 inhibitor, suppresses the proliferation and invasion of lung adenocarcinoma cells. Taken together, these results provide novel insight into the development of a PAK4 kinase inhibitor and a potential therapeutic strategy for lung cancer.
PMID: 26821251 [PubMed - as supplied by publisher]
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Association between probiotic and yogurt consumption and kidney disease: insights from NHANES.
Association between probiotic and yogurt consumption and kidney disease: insights from NHANES.
Nutr J. 2016;15(1):10
Authors: Yacoub R, Kaji D, Patel SN, Simoes PK, Busayavalasa D, Nadkarni GN, He JC, Coca SG, Uribarri J
Abstract
BACKGROUND: Data from experimental animals suggest that probiotic supplements may retard CKD progression. However, the relationship between probiotic use, frequent yogurt consumption (as a natural probiotic source), and kidney parameters have not been evaluated in humans.
FINDINGS: We utilized NHANES data, and analyzed the association of probiotic alone (1999-2012) and yogurt/probiotic (2003-2006) use with albuminuria and eGFR after adjustment for demographic and clinical parameters. Frequent yogurt consumption was defined as thrice or more weekly over the year prior to the interview. Frequent yogurt/probiotic consumers had lower adjusted odds of developing combined outcome (albuminuria and/or eGFR < 60 ml/min/1.73 m(2)) compared to infrequent consumers (OR = 0.76; 95 % CI = 0.61-0.94). When evaluated separately, frequent consumers had lower odds of albuminuria and nonsignificant trend towards decreased odds of low eGFR compared to infrequent consumers. In the probiotic cohort, probiotic consumers were found to have a lower adjusted odds of albuminuria compared to nonusers (OR = 0.59; 95 % CI = 0.37-0.94).
CONCLUSION: Frequent yogurt and/or probiotics use is associated with decreased odds of proteinuric kidney disease. These hypothesis-generating results warrant further translational studies to further delineate the relationship between yogurt/probiotics with kidney dysfunction, as well as microbiome and dysbiosis as potential mediators.
PMID: 26818246 [PubMed - in process]
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Table of Contents.
| Related Articles |
Table of Contents.
Chem Senses. 2016 Feb;41(2):NP
Authors:
PMID: 26819343 [PubMed - in process]
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Subscriptions.
| Related Articles |
Subscriptions.
Chem Senses. 2016 Feb;41(2):NP
Authors:
PMID: 26819342 [PubMed - in process]
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Editorial Board.
| Related Articles |
Editorial Board.
Chem Senses. 2016 Feb;41(2):NP
Authors:
PMID: 26819341 [PubMed - in process]
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Cover.
| Related Articles |
Cover.
Chem Senses. 2016 Feb;41(2):NP
Authors:
PMID: 26819340 [PubMed - in process]
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An accelerated hypofractionated schedule with a daily concomitant boost after breast conservation surgery: the feasibility and toxicity
Publication date: Available online 28 January 2016
Source:Journal of the Egyptian National Cancer Institute
Author(s): Amr Abd El-Aziz Ghannam, Rasha Abd El-Ghany Khedr
Aims and backgroundReduction of overall treatment time of postoperative irradiation and evaluation of the feasibility and preliminary toxicity of an accelerated hypofractionated whole breast irradiation with an addition of a concomitant daily boost in patients with early breast cancer submitted to conservation surgery.MaterialsBetween June 2010 and September 2011, 122 patients underwent accelerated hypofractionated adjuvant radiation after conservation surgery (pT1 or pT2, pN0-N1). Radiotherapy consisted of 45Gy, to the whole breast in 20 fractions with 2.25Gy/fraction; an additional daily boost dose of 0.25Gy was concomitantly delivered to the lumpectomy cavity, total dose 5Gy. Toxicity was assessed at the end of radiation therapy and at 3, 6, and 12months using the RTOG/EORTC toxicity scale. Cosmetic results were assessed in agreement with the Harvard criteria.ResultsMedian follow-up was 31months, 74% showed grade 0–1 skin toxicity, 20% grade 2, and 6% grade 3. At 3months of follow-up, grade 0 skin toxicity was observed in 51% of cases; grade 1 in 36%, and grade 2 in 13%. At 6months, late skin and subcutaneous tissue toxicities were scored as grade 0 in 71%, grade 1 in 18%, and grade 2 in 11% of patients.At 1year almost all the patients showed grade 0–1 skin toxicity. 97% of patients showed excellent or good cosmetic results.ConclusionsAccelerated hypofractionated radiotherapy for early breast cancer with concomitant electron boost seems to be feasible providing consistent clinical results with acceptable toxicity profile.
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Infection Prevention in Transplantation
Abstract
The number of patients undergoing hematopoietic cell and solid organ transplantation are increasing every year, as are the number of centers both transplanting and caring for these patients. Improvements in transplant procedures, immunosuppressive regimens, and prevention of transplant-associated complications have led to marked improvements in survival in both populations. Infections remain one of the most important sources of excess morbidity and mortality in transplant, and therefore, infection prevention strategies are a critical element for avoiding these complications in centers caring for high-risk patients. This manuscript aims to provide an update of recent data on prevention of major healthcare-associated infections unique to transplantation, reviews the emergence of antimicrobial resistant infections, and discusses updated strategies to both identify and prevent transmission of these pathogens in transplant recipients.
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Pair exposure with conspecific during fear conditioning induces the link between freezing and passive avoidance behaviors in rats
Source:Neuroscience Research
Author(s): Hyunchan Lee, Jihyun Noh
Social factor plays an important role in dealing with posttraumatic stress disorder related to excessive physiological fear response and insufficient fear memory extinction of the brain. However, although social circumstances are occurred not only during contextual retrieval but also during fear conditioning, most previous studies focused on the advantageous aspects of social buffering in fear retrieval period. To demonstrate the association between fear responses and fear memory from social stimuli during fear conditioning, pair exposed rats with conspecific as social buffering were subjected to a fear conditioning of passive avoidance test to evaluate memory function and freezing behavior. Whereas single exposed rats showed the significant increase of freezing behaviors and passive avoidance behaviors compared to control rats, pair exposed rats showed significant alleviation of the freezing behaviors and passive avoidance behaviors compared to single exposed rats. Furthermore, we determined a significant correlation between freezing and passive avoidance behavioral alteration in pair exposed rats. Taken together, we suggest that pair exposure with conspecific during fear conditioning helps to cope with both freezing response and fear memory systems and their reciprocal interaction has a crucial potential as a resource for the relief of unreasonable stress responses in posttraumatic stress disorder.
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Neural mechanism of the nucleus accumbens circuit in reward and aversive learning
Source:Neuroscience Research
Author(s): Takatoshi Hikida, Makiko Morita, Tom Macpherson
The basal ganglia are key neural substrates not only for motor function, but also cognitive functions including reward and aversive learning. Critical for these processes are the functional role played by two projection neurons within nucleus accumbens (NAc); the D1- and D2-expressing neurons. Recently, we have developed a novel reversible neurotransmission blocking technique that specifically blocks neurotransmission from NAc D1- and D2-expressing neurons, allowing for in vivo analysis. In this review, we outline the functional dissociation of NAc D1- and D2-expressing neurons of the basal ganglia in reward and aversive learning, as well as drug addiction. These studies have revealed the importance of activation of NAc D1 receptors for reward learning and drug addiction, and inactivation of NAc D2 receptors for aversive learning and flexibility. Based on these findings, we propose a neural mechanism, in which dopamine neurons in the ventral tegmental area that send inputs to the NAc work as a switch between D1- and D2-expressing neurons. These basal ganglia neural mechanisms will give us new insights into the pathophysiology of neuropsychiatric diseases.
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Femoral facial syndrome associated with a de novo complex chromosome 2q37 rearrangement
The femoral facial syndrome (FFS) is a rare congenital anomaly syndrome characterized by bilateral femoral hypoplasia and facial dysmorphism. The etiology of FFS is currently unknown but maternal/gestational diabetes has been proposed as a strong risk factor for syndromic femoral hypoplasia. In affected children born to non-diabetic mothers, a genetic contribution to FFS is suspected; however, no chromosomal anomalies or gene mutations have been identified so far. Here, we report on a girl with FFS and a de novo complex chromosome rearrangement of terminal chromosome 2q37.2. Radiographs of the pelvis and lower limbs showed bilateral shortening and bowing of the femur and radiographs of hands and feet revealed a brachydactyly type E (BDE). Using high resolution array-CGH, qPCR, and FISH, we detected a ∼1.9 Mb duplication in the chromosomal region 2q37.2 and a ∼5.4 Mb deletion on chromosome 2q37.3 that were absent in the parents. The duplication contains six genes and the deletion encompasses 68 genes; the latter has previously been shown to cause BDE (through haploinsufficiency for HDAC4) but not femoral hypoplasia. Therefore, we propose that the duplication 2q37.2 could be causative for the femur phenotype. To the best of our knowledge, our report is the first to propose a genetic cause in a case of FFS. © 2016 Wiley Periodicals, Inc.
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Upper gastrointestinal tumours in Japanese familial adenomatous polyposis patients.
Upper gastrointestinal tumours in Japanese familial adenomatous polyposis patients.
Jpn J Clin Oncol. 2016 Jan 26;
Authors: Yamaguchi T, Ishida H, Ueno H, Kobayashi H, Hinoi T, Inoue Y, Ishida F, Kanemitsu Y, Konishi T, Tomita N, Matsubara N, Watanabe T, Sugihara K
Abstract
OBJECTIVE: The upper gastrointestinal characteristics in Japanese familial adenomatous polyposis patients have not yet been clarified. The aim of the present study was to elucidate these characteristics in Japanese familial adenomatous polyposis patients.
METHODS: This study was conducted by the study group for familial adenomatous polyposis in the Japanese Society for Cancer of the Colon and Rectum. Familial adenomatous polyposis patients who underwent surgical resection from 2000 to 2012 were included in the study.
RESULTS: In total, 303 familial adenomatous polyposis patients were enrolled, with 265 cases of classical familial adenomatous polyposis (≥100 adenomas) and 38 cases of attenuated familial adenomatous polyposis (<100 adenomas). Fundic gland polyps were significantly more common in classical familial adenomatous polyposis than in attenuated familial adenomatous polyposis; however, gastric cancer was significantly less common in classical familial adenomatous polyposis than in attenuated familial adenomatous polyposis. Gastric cancer and duodenal adenoma were significantly more common in familial adenomatous polyposis patients with gastric adenoma than in those without gastric adenoma. Duodenal cancer was detected in 7 of 72 familial adenomatous polyposis patients with duodenal adenoma. The median tumour risk in 50-year-old familial adenomatous polyposis patients was 55.3, 21.8, 3.8, 39.2 and 7.7% for fundic gland polyp, gastric adenoma, gastric cancer, duodenal adenoma and duodenal cancer, respectively.
CONCLUSIONS: Upper gastrointestinal tumours/polyps were frequently found in familial adenomatous polyposis patients, and their incidences were correlated; however, the frequency of gastric cancer in Japanese familial adenomatous polyposis patients was similar to that in the general population.
PMID: 26819281 [PubMed - as supplied by publisher]
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ATAD2 overexpression is associated with progression and prognosis in colorectal cancer.
ATAD2 overexpression is associated with progression and prognosis in colorectal cancer.
Jpn J Clin Oncol. 2016 Jan 26;
Authors: Hou M, Huang R, Song Y, Feng D, Jiang Y, Liu M
Abstract
OBJECTIVES: ATPase family AAA domain-containing 2 plays an important role in tumor progression including cell cycle, proliferation, apoptosis and chemoresistance. However, the expression of ATPase family AAA domain-containing 2 in colorectal cancer and its significance are still unclear. The aim of this study was to examine the expression of ATPase family AAA domain-containing 2 in colorectal cancer.
METHODS: Immunohistochemistry was used to determine the expression of ATPase family AAA domain-containing 2 in 155 colorectal cancer and 30 matched adjacent noncancerous tissues. The correlation of ATPase family AAA domain-containing 2 expression with clinicopathological variables was assessed using chi-square test. Patient survival was analyzed using the Kaplan-Meier and log-rank tests. Cox regression was performed for the multivariate analysis of prognostic factors.
RESULTS: High expression of ATPase family AAA domain-containing 2 was detected in 58.1% of the colorectal cancers and was significantly associated with advanced tumor-node-metastasis stage (P = 0.044), poor differentiation (P = 0.028), deep infiltration (P < 0.001), lymphovascular invasion (P = 0.006), lymph node metastasis (P = 0.024) and recurrence (P = 0.022). Patients with high ATPase family AAA domain-containing 2 expression had significantly poorer overall survival and disease-free survival (both P < 0.001) when compared with patients with low expression of ATPase family AAA domain-containing 2. The multivariate analysis showed that ATPase family AAA domain-containing 2 was an independent factor for both overall survival (P = 0.003; hazard ratio (HR): 2.356; 95% confidence interval (CI): 1.335-4.158) and disease-free survival (P = 0.001; HR: 2.643; 95% CI: 1.489-4.693).
CONCLUSIONS: These results showed that ATPase family AAA domain-containing 2 overexpression was associated with progression and prognosis of colorectal cancer.
PMID: 26819280 [PubMed - as supplied by publisher]
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Laparoscopic gastrointestinal anastomoses using knotless barbed absorbable sutures are safe and reproducible: a single-center experience with 242 patients.
Laparoscopic gastrointestinal anastomoses using knotless barbed absorbable sutures are safe and reproducible: a single-center experience with 242 patients.
Jpn J Clin Oncol. 2016 Jan 26;
Authors: Lee SW, Kawai M, Tashiro K, Nomura E, Tokuhara T, Kawashima S, Tanaka R, Uchiyama K
Abstract
OBJECTIVE: Intracorporeal reconstruction of the digestive tract is technically challenging. The V-Loc 180 wound closure device (Covidien) is a self-anchoring unidirectional barbed suture that obviates the need for knot tying. The aim of this prospective cohort study was to investigate the use of the novel suture in gastrointestinal enterotomy closure.
METHODS: The subjects comprised patients with malignant disease who were scheduled to undergo laparoscopic gastrectomy with curative intent. The barbed suture was used to close the entry hole for the linear stapler during intracorporeal reconstruction following laparoscopic gastric resection. The primary endpoint was the proportion of patients who developed anastomotic leakage at the site where the barbed suture was applied.
RESULTS: Between July 2012 and March 2015, 242 patients were enrolled. Of 362 anastomoses, the enterotomy hole at 256 sites was closed using the barbed suture. These 256 sites consisted of 95 gastroduodenostomies, 25 gastrogastrostomies, 13 gastrojejunostomies, 90 jejunojejunostomies, 17 esophagojejunostomies and 16 primary closures of the stomach following local gastric resection. There were no anastomosis-related complications, conversion to usual sutures, mechanical closure of the entry hole and reoperation due to adhesive obstructions or mortality over a median follow-up period of 17.8 months.
CONCLUSIONS: The use of the unidirectional barbed absorbable suture for gastrointestinal closure is safe and effective in laparoscopic gastrectomy.
PMID: 26819279 [PubMed - as supplied by publisher]
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Prognostic nomogram for previously untreated patients with esophageal squamous cell carcinoma after esophagectomy followed by adjuvant chemotherapy.
Prognostic nomogram for previously untreated patients with esophageal squamous cell carcinoma after esophagectomy followed by adjuvant chemotherapy.
Jpn J Clin Oncol. 2016 Jan 26;
Authors: Duan J, Deng T, Ying G, Huang D, Zhang H, Zhou L, Bai M, Li H, Yang H, Qu Y, Wang X, Ba Y
Abstract
OBJECTIVE: The aim of the study was to establish an effective prognostic nomogram for esophageal squamous cell carcinoma after radical esophagectomy followed by adjuvant chemotherapy in those previously untreated patients.
METHODS: The clinicopathological data from 328 patients who underwent radical esophagectomy followed by adjuvant chemotherapy or not at the Tianjin Medical University Cancer Institute and Hospital between 2006 and 2010 were retrospectively studied. Nomograms which predicted survival of esophageal squamous cell carcinoma were established based on the Cox proportional hazards regression model. To determine its predictive accuracy and discriminatory capacity, the concordance index and calibration curve were calculated after bootstrapping in the internal validation. An external validation of 76 patients in 2011 was prospectively studied at the same institution. To verify the performance of the nomogram, the comparison between the nomogram and Tumor-Node-Metastasis staging system was conducted.
RESULTS: The 5-year overall survival was 43.1% in the primary cohort. Based on multivariate analyses, five independent prognostic variables including gender, tumor length, T stage, N stage and chemotherapy cycles were selected to build the nomograms to predict disease-free survival and overall survival. The concordance index of the nomogram to predict overall survival was 0.71 (95% confidence interval, 0.63-0.79), which was superior to the predictive power of Tumor-Node-Metastasis staging system (0.64) in the primary cohort. Meanwhile, the calibration curve showed good accuracy between predictive and actual overall survival. In the validation cohort, the concordance index (0.77) and calibration plot displayed favorable performances. The other nomogram to predict disease-free survival also performed well.
CONCLUSIONS: The prognostic nomogram provided individualized risk estimate of survival in patients after esophagectomy followed by adjuvant chemotherapy.
PMID: 26819278 [PubMed - as supplied by publisher]
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Current status of immunotherapy.
Current status of immunotherapy.
Jpn J Clin Oncol. 2016 Jan 26;
Authors: Suzuki S, Ishida T, Yoshikawa K, Ueda R
Abstract
The successful use of immune checkpoint inhibitors has been big breakthrough in the development of cancer immunotherapy. Anti-CTLA-4 monoclonal antibody, ipilimumab, is the first-approved immune checkpoint inhibitor and has shown durable objective responses for advanced melanoma beyond the effect of dacarbazine. Anti-PD-1 monoclonal antibodies, nivolumab and pembrolizumab, are other immune checkpoint inhibitors that have demonstrated more effective results than conventional drugs in clinical trials for a variety of advanced solid tumors including melanoma, non-small cell lung carcinoma and renal carcinoma. These studies have indicated that the enhancement of anti-cancer immunity by controlling the immune suppressive environment in cancer tissues is an important issue for the development of cancer immune-therapy. Accordingly, in recent years, the enthusiasm for research of cancer immunology has shifted to studies regarding the formation of the immune suppressive environment, immune suppression mechanisms in cancer tissues and the molecules and cells involved in these pathways. Novel findings from these studies might lead to the development of cancer immunotherapy based on control of the immune suppressive environment.
PMID: 26819277 [PubMed - as supplied by publisher]
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Ten years of optimizing outcomes for women with type 1 and type 2 diabetes in pregnancy - the Atlantic DIP experience.
Ten years of optimizing outcomes for women with type 1 and type 2 diabetes in pregnancy - the Atlantic DIP experience.
J Clin Endocrinol Metab. 2016 Jan 28;:jc20153817
Authors: Owens LA, Egan AM, Carmody L, Dunne F
Abstract
CONTEXT: Pregnancy for women with type 1 or type 2 diabetes is a time of increased risk for both mother and baby. The Atlantic Diabetes in pregnancy program provides coordinated, evidence-based care for women with diabetes in Ireland. Founded in 2005 we now share outcomes over our first decade in caring for pregnant women with diabetes.
OBJECTIVE: The objective was to assess improvements in clinical outcomes after introduction of interventions.
DESIGN, SETTING, PARTICIPANTS: We retrospectively examined 445 pregnancies in women with Type 1 and Type 2 diabetes and compared them over two time points, 2005-2009,2010-2014.
INTERVENTIONS: Interventions introduced over that time include; provision of combined antenatal/diabetes clinics, pre-pregnancy care, electronic data management, local clinical care guidelines, professional and patient education materials, an app and website.
MAIN OUTCOMES MEASURED: Pregnancy outcomes Results: The introduction of the Atlantic DIP program has been associated with a reduction in adverse neonatal outcomes. There has been a reduction in congenital malformations (5% to 1.8%,p=0.04), stillbirths (2.3 v 0.4%,P=0.09), despite an upward trend in maternal age (mean age 31.7 v 33), obesity (29% v 43% BMI>30kg/m(2)) and excessive gestational weight gain (24% v 38%,p=0.002). These improvements in outcomes occur alongside an increase in attendance at pre-pregnancy care (23% to 49%,p<0.001), use of folic acid (45 v 71%,p<0.001) and sustained improvement in glycemic control.
CONCLUSIONS: Changing the process of clinical care delivery and utilizing evidence-based interventions in a pragmatic clinical setting improves pregnancy outcomes for women with pre-gestational diabetes. We now need to target optimization of maternal body mass index prior to pregnancy and put a greater focus on gestational weight gain through education and monitoring.
PMID: 26820715 [PubMed - as supplied by publisher]
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Vitamin D3 Inhibits Wnt/β-Catenin and mTOR Signaling Pathways in Human Uterine Fibroid Cells.
Vitamin D3 Inhibits Wnt/β-Catenin and mTOR Signaling Pathways in Human Uterine Fibroid Cells.
J Clin Endocrinol Metab. 2016 Jan 28;:jc20153555
Authors: Al-Hendy A, Diamond MP, Boyer TG, Halder SK
Abstract
CONTEXT: Somatic mutations in the Med12 gene are known to activate Wnt/β-catenin signaling in human uterine fibroids (UFs).
OBJECTIVE: To examine the role of vitamin D3 in modulation of Wnt/β-catenin and mTOR signaling in human UF cells.
DESIGN: Immortalized human UF cells (HuLM) and human primary UF (PUF) cells were treated with increasing concentrations of vitamin D3 and thereafter analyzed using western blots and immunocytochemistry.
MAIN OUTCOME MEASURES: Wnt/β-catenin, and mTOR signaling proteins in cultured HuLM and PUF cells.
RESULTS: UF tumors with Med12 somatic mutations showed upregulation of Wnt4 and β-catenin as compared with adjacent myometrium. Vitamin D3 administration reduced the levels of Wnt4 and β-catenin in both HuLM and PUF cells. Vitamin D3 also reduced the expression/activation of mTOR signaling in both cell types. In contrast, vitamin D3 induced the expression of DDIT4 (an inhibitor of mTOR) and tuberous sclerosis genes (TSC1/2) in a concentration-dependent manner in HuLM cells. Furthermore, we observed a concentration-dependent reduction of Wisp1 (Wnt induced signaling protein 1) and FEN 1 proteins in HuLM cells. Additionally, abrogation of vitamin D receptor (VDR) expression (by silencing) in normal myometrial cells induces Wnt4/β-catenin as well as prompts a fibrotic process including an increase in cell proliferation and increased ECM production. Together, these results suggest that vitamin D3 functions as an inhibitor of Wnt4/β-catenin and mTOR signaling pathways, which may play major roles in fibroid pathogenesis.
CONCLUSION: Vitamin D3 may have utility as a novel long-term therapeutic and/or preventive option for uterine fibroids.
PMID: 26820714 [PubMed - as supplied by publisher]
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