Τετάρτη, 3 Μαΐου 2017

Synthesis, characterization, and photocatalytic properties of Ni 12 P 5 hollow microspheres

Abstract

Ni12P5 hollow microspheres were prepared by a simple mixed cetyltrimethyl ammonium bromide/sodium dodecyl sulfate surfactant-assisted hydrothermal route. The as-prepared Ni12P5 microstructures were characterized by X-ray powder diffraction (XRD), field emission scanning electron microscopy (FE-SEM), and transmission electron microscopy (TEM). It was interesting to find that cetyltrimethyl ammonium bromide/sodium dodecyl sulfate could form a micro-reactor by the mixed micelles in the aqueous solution, which served as a soft template for Ni12P5 hollow microspheres with a diameter of 2~6 μm. Moreover, the as-prepared Ni12P5 hollow microspheres exhibited a good photocatalytic degradation activity for some organic dyes (such as Rhodamine B, Methylene Blue, Pyronine B, and Safranine T), and the degradation ratio could achieve more than 80%.



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Selective perception of novel science: how definitions affect information processing about nanotechnology

Abstract

This study examines how familiarity with an issue—nanotechnology—moderates the effect of exposure to science information on how people process mediated messages about a complex issue. In an online experiment, we provide a nationally representative sample three definitions of nanotechnology (technical, technical applications, and technical risk/benefit definitions). We then ask them to read an article about the topic. We find significant interactions between perceived nano-familiarity and the definition received in terms of how respondents perceive favorable information conveyed in the stimulus. People less familiar with nanotechnology were more significantly affected by the type of definition they received.



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A novel physical colonoscopy simulator based on analysis of data from computed tomography colonography

Abstract

Purpose

Laparoscopic surgery is now practiced widely because of its lower postoperative morbidity. As flexible endoscopy during laparoscopic surgery minimizes surgical trauma further, training in endoscopy will become more important for surgeons. Thus, we designed a physical simulator, the Noda–Kitada–Suzuki (NKS) model, which could provide the more realistic insertion of a colonoscope.

Methods

We designed a colonoscopy simulator, based on information from computed tomography colonography scans of the anatomy and kinetic properties of the colon and rectum.

Results

The transparent skeleton body of the NKS model provides instant visual feedback to the operator and the trainer. Our novel colonoscopy simulator replicates the realistic and reproducible insertion of a colonoscope from the rectum to cecum, providing authentic views of the Houston's valves, the flexures, and mucosal folds. This was verified through an objective questionnaire, with 14 of 16 colonoscopists preferring the NKS model over the previous CM15 model for training purposes. Moreover, the Modified Colonoscopy Simulator Realism Questionnaire analysis confirmed that the NKS model was significantly more realistic than the CM15 for 7 (21.2%) of the 33 items when assessed by 12 colonoscopists.

Conclusion

The NKS model provides a realistic training platform and may improve the quality of training in colonoscopy.



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Erratum to: Osteosarcoma follow-up: chest X-ray or computed tomography?



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Noisy knees may be early sign of knee osteoarthritis

Patients who report that they hear grating, cracking, or popping sounds in or around the knee joint may be at increased risk of developing knee osteoarthritis, a study published in Arthritis Care &...
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Heterologous Gene Expression in E.coli



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FTIR microscopy contribution for comprehension of degradation mechanisms in PLA-based implantable medical devices

Abstract

The integration and evolution of implantable medical devices made of bioresorbable polymers and used for temporary biomedical applications are crucial criteria in the success of a therapy and means of follow-up after implantation are needed. The objective of this work is to develop and evaluate a method based on microscopic Fourier Transform InfraRed spectroscopy (FTIR) mappings to monitor the degradation of such polymers on tissue explant sections, after implantation. This technique provided information on their location and on both their composition and crystallinity, which is directly linked to their state of degradation induced predominantly by chain scissions. An in vitro study was first performed on poly(L-lactic acid) (PLLA) meshes to validate the procedure and the assumption that changes observed on FTIR spectra are indeed a consequence of degradation. Then, mappings of in vivo degraded PLLA meshes were realized to follow up their degradation and to better visualize their degradation mechanisms. This work further warrants its translation to medical implants made of copolymers of lactic acid and to other polyesters.

Graphical Abstract



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Drug loaded microbeads entrapped electrospun mat for wound dressing application

Abstract

A new design of antibiotic loaded wound dressing and its initial in vitro evaluation is described. Chitosan microbeads loaded with ampicillin were sandwiched within polycaprolactone electrospun mat (MbAPPCL). The morphology was analyzed by scanning electron microscopy and surface chemistry was characterized by Fourier Transform Infrared Spectroscopy. In vitro cytotoxicity using L-929 fibroblast cells by direct contact test and elution assay revealed non-cytotoxic nature of MbAPPCL. The cell adhesion and viability analysis further confirmed the cytocompatibility of MbAPPCL as a wound dressing material. Percentage hemolysis and platelet adhesion on the mat exposed to blood substantiated the hemocompatibility. The antibiotic susceptibility test analyzed on Staphylococcus aureus by agar plate method confirmed the drug release and antimicrobial property. The proposed wound dressing model explained with ampicillin as a candidate drug has the potential to include microbeads with different antibiotics for multi drug treatment.

Graphical Abstract



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In-vivo evaluation of subcutaneously implanted cell-loaded apatite microcarriers for osteogenic potency

Abstract

Cell-loaded apatite microcarriers present as potential scaffolds for direct in-vivo delivery of cells post-expansion to promote bone regeneration. The objective of this study was to evaluate the osteogenic potency of human foetal mesenchymal stem cells (hfMSC)-loaded apatite microcarriers when implanted subcutaneously in a mouse model. This was done by examining for ectopic bone formation at 2 weeks, 1 month and 2 months, which were intended to coincide with the inflammation, healing and remodelling phases, respectively. Three histological examinations including haematoxylin and eosin staining to examine general tissue morphology, Masson's trichrome staining to identify tissue type, and Von Kossa staining to examine extent of tissue mineralisation were performed. In addition, immunohistochemistry assay of osteopontin was conducted to confirm active bone formation by the seeded hfMSCs. Results showed a high level of tissue organisation and new bone formation, with active bone remodelling being observed at the end of 2 months, and an increase in tissue density, organisation, and mineralisation could also be observed for hfMSC-loaded apatite microcarriers. Various cell morphology resembling that of osteoblasts and osteoclasts could be seen on the surfaces of the hfMSC-loaded apatite microcarriers, with presence of woven bone tissue formation being observed at the intergranular space. These observations were consistent with evidence of ectopic bone formation, which were absent in group containing apatite microcarriers only. Overall, results suggested that hfMSC-loaded apatite microcarriers retained their osteogenic potency after implantation, and provided an effective platform for bone tissue regeneration.

Graphical Abstract



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Cyclosporine is a potential curative treatment option for advanced thymoma

Abstract

Background

Thymectomy can effectively cure most thymoma patients; however, patients with advanced thymoma typically require chemotherapy, which is associated with limited efficacy in this context. Here we provide the first report of a patient with recurrent thymoma who achieved complete remission (CR) using cyclosporine therapy.

Case presentation

A 63-year-old woman who had undergone resection surgery for recurrent type B1 thymoma developed pure red cell aplasia (PRCA), and CT findings revealed thymoma recurrence. After the initiation of orally-administered cyclosporine, PRCA quickly resolved, and the thymoma disappeared without the administration of any anti-thymoma therapy. The patient has remained in CR for over 3 years using only cyclosporine.

Conclusions

This is the first report describing the curative potential of cyclosporine for the treatment of advanced thymoma. Although the mechanism underlying this effect remains unclear, cyclosporine can become a less toxic and more cost-effective treatment option for thymoma compared with conventional therapy. Clinical trials are needed to confirm the therapeutic potential of cyclosporine as a new treatment option for thymoma.



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Synergistic activity of synthetic N-terminal peptide of human lactoferrin in combination with various antibiotics against carbapenem-resistant Klebsiella pneumoniae strains

Abstract

The spread of multi-drug resistant (MDR) Klebsiella pneumoniae strains producing carbapenemases points to a pressing need for new antibacterial agents. To this end, the in-vitro antibacterial activity of a synthetic N-terminal peptide of human lactoferrin, further referred to as hLF1–11, was evaluated against K. pneumoniae strains harboring different carbapenemase genes (i.e. OXA-48, KPC-2, KPC-3, VIM-1), with different susceptibility to colistin and other antibiotics, alone or in combination with conventional antibiotics (gentamicin, tigecycline, rifampicin, clindamycin, and clarithromycin). An antimicrobial peptide susceptibility assay was used to assess the bactericidal activity of hLF1–11 against the different K. pneumoniae strains tested. The synergistic activity was evaluated by a checkerboard titration method, and the fractional inhibitory concentration (FIC) index was calculated for the various combinations. hLF1–11 was more efficient in killing a K. pneumoniae strain susceptible to most antimicrobials (including colistin) than a colistin-susceptible strain and a colistin-resistant MDR K. pneumoniae strain. In addition, hLF1–11 exhibited a synergistic effect with the tested antibiotics against MDR K. pneumoniae strains. The results of this study indicate that resistance to hLF1–11 and colistin are not strictly associated, and suggest an hLF1–11-induced sensitizing effect of K. pneumoniae to antibiotics, especially to hydrophobic antibiotics, which are normally not effective on Gram-negative bacteria. Altogether, these data indicate that hLF1–11 in combination with antibiotics is a promising candidate to treat infections caused by MDR-K. pneumoniae strains.



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Screening for mismatch repair deficiency in colorectal cancer: data from three academic medical centers

Abstract

Reflex immunohistochemistry (rIHC) for mismatch repair (MMR) protein expression can be used as a screening tool to detect Lynch Syndrome (LS). Increasingly the mismatch repair-deficient (dMMR) phenotype has therapeutic implications. We investigated the pattern and consequence of testing for dMMR in three Irish Cancer Centres (CCs). CRC databases were analyzed from January 2005–December 2013. CC1 performs IHC upon physician request, CC2 implemented rIHC in November 2008, and CC3 has been performing rIHC since 2004. The number of eligible patients referred to clinical genetic services (CGS), and the number of LS patients per center was determined. 3906 patients were included over a 9-year period. dMMR CRCs were found in 32/153 (21%) of patients at CC1 and 55/536 (10%) at CC2, accounting for 3% and 5% of the CRC population, respectively. At CC3, 182/1737 patients (10%) had dMMR CRCs (P < 0.001). Additional testing for the BRAF V600E mutation, was performed in 49 patients at CC3 prior to CGS referral, of which 29 were positive and considered sporadic CRC. Referrals to CGS were made in 66%, 33%, and 30% of eligible patients at CC1, CC2, and CC3, respectively. LS accounted for CRC in eight patients (0.8%) at CC1, eight patients (0.7%) at CC2, and 20 patients (1.2%) at CC3. Cascade testing of patients with dMMR CRC was not completed in 56%. Universal screening increases the detection of dMMR tumors and LS kindreds. Successful implementation of this approach requires adequate resources for appropriate downstream management of these patients.

Thumbnail image of graphical abstract

Universal screening for MMR deficiency using IHC has been recommended as a screening tool for Lynch Syndrome and is increasingly performed as a molecular predictor of response to immune checkpoint inhibition. Over half of patients in our study with dMMR colorectal cancer did not have downstream investigations for Lynch Syndrome. Successful implementation requires appropriate resourcing to ensure complete cascade testing.



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More from #ELCC2017 finds pretreatment of #NSCLC with checkpoint inhibition boots salvage chemo responsehttps://t.co/pS4g789rJw

More from #ELCC2017 finds pretreatment of #NSCLC with checkpoint inhibition boots salvage chemo response https://t.co/pS4g789rJw

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IJMS, Vol. 18, Pages 927: Identification and Expression Profiling of the Auxin Response Factors in Dendrobium officinale under Abiotic Stresses

Auxin response factor (ARF) proteins play roles in plant responses to diverse environmental stresses by binding specifically to the auxin response element in the promoters of target genes. Using our latest public Dendrobium transcriptomes, a comprehensive characterization and analysis of 14 DnARF genes were performed. Three selected DnARFs, including DnARF1, DnARF4, and DnARF6, were confirmed to be nuclear proteins according to their transient expression in epidermal cells of Nicotiana benthamiana leaves. Furthermore, the transcription activation abilities of DnARF1, DnARF4, and DnARF6 were tested in a yeast system. Our data showed that DnARF6 is a transcriptional activator in Dendrobium officinale. To uncover the basic information of DnARF gene responses to abiotic stresses, we analyzed their expression patterns under various hormones and abiotic treatments. Based on our data, several hormones and significant stress responsive DnARF genes have been identified. Since auxin and ARF genes have been identified in many plant species, our data is imperative to reveal the function of ARF mediated auxin signaling in the adaptation to the challenging Dendrobium environment.

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D-cleft: An innovative method for feeding neonates born with cleft palate

Anubhav Jannu, Abhishek Nagaraj, Ruchi Gupta

Journal of Cleft Lip Palate and Craniofacial Anomalies 2017 4(1):34-36

Introduction: Babies born with cleft palate suffer from feeding problems which interfere with their nutrition and development; thereby, hampering the criteria for subsequent corrective surgery. The palatal cleft interferes with nursing and causes insufficient suckling or nasal regurgitation of food. Because of altered anatomy and presence of oro-nasal fistula, baby tends to present suction difficulties due to lack of negative intraoral pressure. Upper respiratory tract infection and chronic catarrh are not frequent. Materials and Methods: Here is a patented device for attaching on commercially-available feeding bottles to facilitate effective nutrition method. The device's journey from concept to clinical use has been presented with a case series. Results: The device was tried and tested successfully in many babies born with Cleft palate. It has been successfully used to feeding neonates by their mothers/care-takers with almost no training required. Conclusion: The device is extremely easy to use, easy to maintain and economical. In cases where modifying the feeding position alone cannot make much difference, these attachments can be advocated.

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Cleft palate associated with Turner's syndrome and anterior cervical hypertrichosis

Anil Kumar Desai, Niranjan Kumar, Sameer Pandey, Sandhya S Pavate

Journal of Cleft Lip Palate and Craniofacial Anomalies 2017 4(1):73-76

Turner's syndrome is a rare genetic disorder that affects development in female. It is associated with multiple medical issues such as impaired growth, ovarian insufficiency, cardiovascular abnormalities, and endocrine and skeletal abnormalities. Hypertrichosis is the growth of an increased quantity of thick hair on any part of the skin surface; it is mostly seen as an isolated finding but rarely associated with other abnormalities. Cleft lip and palate are uncommon anomalies in Turner's syndrome and anterior cervical hypertrichosis. We report a case of cleft palate associated with Turner syndrome and anterior cervical hypertrichosis. The clinical features, diagnosis, and its management are discussed.

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The relationship between orofacial clefts and consanguineous marriages: A hospital register-based study in Dharwad, South India

BR Rajeev, K. V. V Prasad, Preetha J Shetty, Raman Preet

Journal of Cleft Lip Palate and Craniofacial Anomalies 2017 4(1):3-8

Context: Orofacial cleft (OFC) is one of the common craniofacial malformations. The etiology of these OFCs is multifactorial. One of the etiological factors is consanguinity (marriage between blood relatives). There is a lack of literature reporting the number of people affected with OFCs due to consanguinity. Aims: The aim of this study is to report the occurrence of OFC and associated factors in relation to consanguinity from a craniofacial hospital specializing in OFCs, head and neck cancer, and trauma management in South India. Setting and Design: This was a hospital-based study, retrospective case record analysis. Methodology: One thousand two hundred and forty-seven consecutive patients' secondary data records with cleft lip (CL), cleft palate (CP) and cleft lip and palate (CL/P) were collected from January 2007 to July 2009. Statistics: Frequency of consanguinity in relation to OFC was analyzed using Chi-square test according to the nature of clefts and selected demographic features such as sex, region, and religion. Results: A total of 47.2% patients' parents had consanguineous marriage. Consanguinity was seen in 60.2% of male and 39.7% of female patients. CL/P was noticed in 40.9%, followed by CL (36.7%) and CP (22.2%). Males predominated in all types of clefts proportionally with the study population as compared to females. Statistically, significant association (P = 0.04) was seen with consanguinity and CP. Conclusion: Nearly half of the study population had a positive history of consanguinity. Statistically, a significant association was seen between CP and consanguinity. CL/P cases were the most common type identified, followed by CL and CP. Males predominated in all types of clefts. The prevalence of OFC is high, and there is a potential of congenital disabilities from consanguinity. These findings indicate a clear and urgent need for setting up a National Registry of Congenital Anomalies along with craniofacial defects, to monitor these trends and the corresponding need for supportive services.

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Congenital sudoriferous cyst of the orbit: A case report and review of literature

Parit S Ladani, Hermann Sailer, Sandeep M Thadani, Mita Shah

Journal of Cleft Lip Palate and Craniofacial Anomalies 2017 4(1):65-68

Apocrine gland cyst (sudoriferous cyst and apocrine hidrocystoma) is fairly uncommon in the eyelid, where it derives from the apocrine glands of Moll. In rare instances, an apocrine gland cyst can occur in the anterior portion of the orbit. If an orbital cyst affects the globe or extraocular muscles, it should be excised as soon as possible to prevent strabismus and amblyopia. Herewith, we are presenting the case of sudoriferous cyst in a 9-year-old child managed with surgical excision.

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Linkage evidence and methylation at 2q region in nonsyndromic cleft lip and/or palate of Malay population

Nurul Syazana Mohamad Shah, Sarina Sulong, Wan Azman Wan Sulaiman, Ahmad Sukari Halim

Journal of Cleft Lip Palate and Craniofacial Anomalies 2017 4(1):9-14

Introduction: Nonsyndromic cleft lip and/or palate (NSCLP) occurs as a result of multifactorial determinants, involving both genetic and environmental factors. Several candidate genes associated with NSCLP have been discovered through genetic approach, but there is paucity of studies focusing on epigenetic determinants in NSCLP. We are interested to reveal linkage evidence of SATB2 at 2q region in large-extended NSCLP families of Malay population and its methylation activity in causing cleft formation. Materials and Methods: Eight large-extended families were included in this study. Microarray analysis was carried out and genome-wide linkage was determined using GeneHunter Multipoint Linkage Analysis v2.1r5. SATB2 methylation was tested on 100 NSCLP patients by DNA sequencing. Results: Genome-wide linkage analysis has revealed significant nonparametric linkage score and suggestive logarithm of the odds (LOD) score at 2q region in family 50 and family 100. Genome-wide heterogeneity LOD score of 2.63 and α =0.122 were found in total families at 2q33.1-q35 region. Significant copy number loss (P < 0.05) in NSCLP family compared with the normal control supports the linkage evidence of SATB2 in those families with positive linkage. Epigenetic testing found SATB2 unmethylation at DNA promoter region. Discussion: Linkage evidence and significant low copy number of SATB2 in NSCLP family of Malay population confirmed that genetic factors play a major role in causing cleft defects. SATB2 unmethylation could not support the epigenetic occurrence in causing craniofacial deformities. Conclusions: Linkage evidence and significant low copy number of SATB2 in NSCLP family of Malay population confirmed that genetic factors play a major role in causing cleft defects. SATB2 unmethylation could not support the epigenetic occurrence in causing craniofacial deformities.

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Cleft Congress 2017: An opportunity to showcase

Divya Narain Upadhyaya, Karoon Agrawal

Journal of Cleft Lip Palate and Craniofacial Anomalies 2017 4(1):1-2



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Mandibular symmetry in participants with a unilateral cleft lip and palate

Ozge Uslu-Akcam, Ufuk Toygar Memikoglu, Mehmet Okan Akcam, Mehmet Birol Ozel

Journal of Cleft Lip Palate and Craniofacial Anomalies 2017 4(1):15-21

Context: Facial asymmetry has been reported to be a typical morphological characteristic of unilateral cleft lip and palate (UCLP). Posteroanterior cephalometric radiographs have shown that in addition to an asymmetrically developed nasomaxillary complex, children with UCLP may also have distorted mandibles. Aims: The aim of this retrospective study was to evaluate mandibular symmetry in participants with a complete unilateral left cleft lip and palate (ULCLP) using panoramic radiographs. Subjects and Methods: Pretreatment records of 163 participants (84 ULCLP, 79 Angle Class I without a cleft; mean age: 12.9 ± 3.5 years) were retrieved from the orthodontic department archives. A total of ten anatomic landmarks were marked on panoramic radiographs, and measurements were performed using the PORDIOS software. Statistical Analysis Used: Intra- and inter-group differences were analyzed using Student's t-test. Results: Mandibular right and left ramus, total ramus, condylar, and mandibular molar alveolar heights were significantly shorter in the ULCLP group when compared to controls (P < 0.05 to P< 0.001). In the ULCLP group, mandibular and corpus lengths were shorter on the left side (P < 0.05), whereas in the control group, mandibular and corpus lengths and ramal, condylar, and molar alveolar heights were shorter on the right side when compared to the left side. In addition, ramus/corpus angles were significantly larger in the ULCLP group when compared to the control group (P < 0.001). Conclusions: Mandibular asymmetry exists to varying extents in ULCLP patients and is characterized mainly by smaller cleft-side dimensions. Discrepancies in left-right mandibular dimensions also occur in normal participants.

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Pathologic anatomy of the soft palate, part 1: Embryology, the hard tissue platform, and evolution

Michael H Carstens

Journal of Cleft Lip Palate and Craniofacial Anomalies 2017 4(1):37-64

The purpose of this communication is to explore in detail the developmental anatomy of the soft palate, its pathologies, and strategies for management. Despite the voluminous literature regarding complete cleft palate in its usual presentation, little attention has been paid to the biology of the isolated soft palate cleft. It exists as a spectrum, ranging in severity from the submucous variant, with nothing notable save a groove and a palpable defect of the posterior spine, all the way to a complete disruption of the soft tissue envelope and the horizontal palatine shelves. All these presentations are but variations of common pathology. Much can be gained from a disciplined examination of these. Our discussion includes two parts. The first part is on the embryologic events that generate the mesenchymal building blocks from which the posterior palate is constructed: palatine bone, oral and nasal mucosa, palatine aponeurosis, and muscle slings. Palate structures develop from neural crest and mesoderm; these tissues originate at specific sites along the axis of the embryo and they can be mapped according to the developmental units of the central nervous system (CNS) from which they are innervated. These units, called neuromeres, are specific zones within the neural tube, the boundaries of which are established by the expression pattern of homeotic genes. The forebrain (prosencephalon) has telencephalon and 3 prosomeres, the midbrain (mesencephalon) has 1-2 mesomeres, and the hindbrain (rhombencephalon) has 12 rhombomeres. Each neuromere has a specific neuroanatomic content and is hardwired to specific tissues outside the brain. We next consider a model of the palate which is analogous to a pinball machine that consists of a platform (bone) and mobile “flippers” or lever arms (the velum). In this study, the osseous platform is discussed in detail with neural crest bones being coded by the sensory innervation of their surrounding soft-tissue envelope. Maxilla, palatine bone, and vomers are all derivatives of hindbrain neural crest arising from rhombomere 2 but distributed according to various neurovascular pedicles of the V2 stapedial system, the anatomy of which will be explained in detail. Next, the evolution of palate will be presented as a series of innovations favoring increased metabolic capacity. A final appendix presents a functional classification of cranial nerves which I have endeavored to make straightforward. This will prove useful when reading the second part of this manuscript having to do with the neuromuscular apparatus of the soft palate.

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Comparative efficacy of autologous alveolar bone grafting with autologous platelet-rich plasma and without platelet-rich plasma in cleft alveolus patients

Rohan Suhas Deshpande, Abhilasha Omprakash Yadav, Rajiv Mukund Borle, Atul Vijay Kala, SN Jajoo, Deep Thakkar

Journal of Cleft Lip Palate and Craniofacial Anomalies 2017 4(1):22-25

Aim: The aim of this longitudinal study was to evaluate the efficacy of alveolar bone grafting with autologous platelet-rich plasma (PRP) over cancellous bone grafting alone in cleft alveolus patients. Materials and Methods: A total of 30 patients were evaluated, out of which 15 patients were subjected to alveolar bone grafting with cancellous bone and 15 patients underwent alveolar bone grafting with autologous PRP along with cancellous bone graft. Autologous PRP was extracted using a plasma centrifuge machine. Chi-square test was used for statistical analysis, which revealed statistically significant (P < 0.05) in the study group and control group. Results: Radiographic evaluation was done on the amount of graft resorption at the end of 6 months postoperatively. Success of the graft was assessed with the help of Bergland scoring criteria. Conclusion: Results obtained from our study suggested that resorption of bone graft was comparatively less in the study group as compared to control group.

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Treacher collins syndrome - Report of a classical case

Shweta Gangotri Sumbh, Jaishree Pagare, Bharat Sumbh

Journal of Cleft Lip Palate and Craniofacial Anomalies 2017 4(1):69-72

Treacher Collins syndrome (TCS) or Franceschetti syndrome is an autosomal dominant disorder of craniofacial development with variable expressivity. Incidence of this syndrome is approximately 1 in 50,000 live births and it affects both genders equally. This article describes clinical features of TCS in a 12-year-old female who had reported to the Department of Oral Medicine and Radiology. TCS affects structures which are derivatives of the first and second brachial arches which was also observed in this patient presenting with antimongoloid slanting of the palpebral fissures, colobomas of the lower eyelid, hypoplasia of zygoma and mandible, and an ear abnormality.

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Esthetic outcomes of unilateral cleft lip repaired by Millard technique through a proposed scoring system

Shivani Atri, Brijesh Mishra, Divya Narain Upadhayaya, Arun Kumar Singh, Vijay Kumar, Veerendra Prasad

Journal of Cleft Lip Palate and Craniofacial Anomalies 2017 4(1):26-33

Introduction: Measurement of treatment outcome is vital in estimating the success of cleft management and for quality improvement, especially in the present age. Scoring systems for the measurement of cleft lip treatment outcome can be broadly divided into qualitative and quantitative methods. Millard's rotation-advancement technique is a commonly used technique for cleft lip repair. Aims and Objectives: The aim and objective of this study was to assess the esthetic outcome of unilateral cleft lip repaired by Millard technique through a scoring system. Materials and Methods: The study comprised fifty patients with unilateral cleft lip who presented to our department for lip repair. Specific preoperative assessment of the extent of deformity was done by photographic evaluation and scoring. The preoperative assessment was done using an initial scoring system (ISS). Different scores were allotted to each of the nose and lip components, so as to grade the deformity from nil to severe. On the basis of ISS scoring, the cleft lip patients' preoperative deformity was graded into three grades: Mild, moderate, and severe. All patients were operated by a single surgeon, with extensive experience in cleft care. Postoperative evaluation was performed on the same lines, using postsurgical score as proposed by Asher-McDade et al., and further graded into excellent, good, fair, poor, and very poor. Nasolabial areas were evaluated independently by a panel of five investigators preoperatively and postoperatively at 1 week, 1 month, 3 months, and 1 year, the mean value and standard deviation were calculated in each group. Statistical analysis was done in all patients using appropriate statistical tools, with a confidence interval of 95%. Results: Incomplete cleft lip has better esthetic outcome than complete cleft lip repair using Millard's technique. Conclusions: Esthetic outcome depends on the extent of preoperative deformity, and the Millard method of lip repair shows excellent outcome in incomplete lip repair.

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Commentary on cleft palate associated with Turner's syndrome and anterior cervical hypertrichosis

Richie Gupta, Seema Thakur

Journal of Cleft Lip Palate and Craniofacial Anomalies 2017 4(1):77-79



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Punica granatum peel extracts: HPLC fractionation and LC MS analysis to quest compounds having activity against multidrug resistant bacteria

Medicinal plants are rich source of traditional herbal medicine around the globe. Most of the plant’s therapeutic properties are due to the presence of secondary bioactive compounds.

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(−)-Epicatechin 3-O-β-d-allopyranoside prevent ovariectomy-induced bone loss in mice by suppressing RANKL-induced NF-κB and NFATc-1 signaling pathways

Davallia formosana Hayata is a herb that has been used in Chinese medicine to treat bone diseases, including arthritis, bone fractures and osteoporosis. The rhizome of D. formosana H. ...

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Change in the P300 index – a pilot randomized controlled trial of low-frequency electrical stimulation of acupuncture points in middle-aged men and women

The P300 is a major index used to evaluate improvements in brain function. Although a few studies have reported evaluating the effectiveness of manual acupuncture or electro-acupuncture by monitoring the P300,...

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Confident failures: Lapses of working memory reveal a metacognitive blind spot

Abstract

Working memory performance fluctuates dramatically from trial to trial. On many trials, performance is no better than chance. Here, we assessed participants' awareness of working memory failures. We used a whole-report visual working memory task to quantify both trial-by-trial performance and trial-by-trial subjective ratings of inattention to the task. In Experiment 1 (N = 41), participants were probed for task-unrelated thoughts immediately following 20% of trials. In Experiment 2 (N = 30), participants gave a rating of their attentional state following 25% of trials. Finally, in Experiments 3a (N = 44) and 3b (N = 34), participants reported confidence of every response using a simple mouse-click judgment. Attention-state ratings and off-task thoughts predicted the number of items correctly identified on each trial, replicating previous findings that subjective measures of attention state predict working memory performance. However, participants correctly identified failures on only around 28% of failure trials. Across experiments, participants' metacognitive judgments reliably predicted variation in working memory performance but consistently and severely underestimated the extent of failures. Further, individual differences in metacognitive accuracy correlated with overall working memory performance, suggesting that metacognitive monitoring may be key to working memory success.



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Sildenafil suppresses Inflammation-driven Colorectal Cancer in mice

Intestinal cyclic guanosine monophosphate (cGMP) signaling regulates epithelial homeostasis and has been implicated in the suppression of colitis and colon cancer. In this study, we investigated the cGMP-elevating ability of the phosphodiesterase-5 (PDE5) inhibitor sildenafil to prevent disease in the azoxymethane/dextran sulfate sodium (AOM/DSS) inflammation-driven colorectal cancer model. Treatment of mice with sildenafil activated cGMP signaling in the colon mucosa and protected against DSS-induced barrier dysfunction. In mice treated with AOM/DSS, oral administration of sildenafil throughout the disease course reduced polyp multiplicity by 50% compared to untreated controls. Polyps that did form in sildenafil treated mice were less proliferative and more differentiated compared to polyps from untreated mice, but apoptosis was unaffected. Polyps in sildenafil treated mice were also less inflamed; they exhibited reduced myeloid-cell infiltration, and reduced expression of iNOS, IFN, and IL-6 compared to untreated controls. Most of the protection conferred by sildenafil was during the initiation stage of carcinogenesis (38% reduction in multiplicity). Administration of sildenafil during the later promotion stages did not affect multiplicity but had a similar effect on the polyp phenotype, including increased mucus production, and reduced proliferation and inflammation. In summary, the results demonstrate that oral administration of sildenafil suppresses polyp formation and inflammation in mice treated with AOM/DSS. This validation of PDE5 as a target highlights the potential therapeutic value of PDE5 inhibitors for the prevention of colitis-driven colon cancer in humans.



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Interaction Effects between HIV and Aging on Selective Neurocognitive Impairment

Abstract

HIV infection and aging are each associated with neurocognitive impairment (NCI). This study examined the combined effects of HIV infection and aging on NCI. We performed a cross-sectional survey among 345 HIV-infected and 345 HIV-uninfected participants aged at least 40 years. The International HIV Dementia Scale (IHDS) and Chinese version of Mini-mental State Examination (MMSE) were administered to screen for NCI. HIV-infected individuals had higher prevalence of NCI than uninfected individuals (46.7% vs 15.1% for IHDS using cut-off of ≤ 10; 17.1% vs 2.6% for MMSE). Significant main effects of HIV and age were observed on IHDS and MMSE composite scores and all domains except for HIV on attention and calculation. Significant interaction effects between HIV and age were observed on motor speed, orientation, registration and recall, and mainly attributed to the inferior performance of HIV-infected patients aged over 60 years. Among HIV-infected individuals, in multivariable logistic models, older age, depressive symptoms and history of nevirapine treatment were associated with NCI using both IHDS and MMSE, whereas lower education current smoker and current CD4 ≥ 800 cells/μL were associated only with NCI using IHDS, and hypertension was associated only with NCI using MMSE. Findings suggest that HIV and older age may confer interactive effects on cognitive function in several domains with older HIV-infected adults experiencing greater NCI, which requires further longitudinal investigation. Furthermore, HIV early diagnosis and treatment may prevent or reverse NCI, but extra attention should be given to adverse effects including metabolic changes associated with long-term treatment.



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Critical roles of mucin-1 in sensitivity of lung cancer cells to tumor necrosis factor-alpha and dexamethasone

Abstract

Lung cancer is the leading cause of death from cancer. Mucins are glycoproteins with high molecular weight, responsible for cell growth, differentiation, and signaling, and were proposed to be correlated with gene heterogeneity of lung cancer. Here, we report aberrant expression of mucin genes and tumor necrosis factor receptors in lung adenocarcinoma tissues compared with normal tissues in GEO datasets. Mucin-1 (MUC1) gene was selected and considered as the target gene; furthermore, the expression pattern of adenocarcinomic cells (A549, H1650, or H1299 cells) was validated under the stimulation with tumor necrosis factor-alpha (TNFα) or dexamethasone (DEX), separately. MUC1 gene interference was done to A549 cells to show its role in sensitivity of lung cancer cells to TNFα and DEX. Results of our experiments indicate that MUC1 may regulate the influence of inflammatory mediators in effects of glucocorticoids (GCs), as a regulatory target to improve therapeutics. It shows the potential effect of MUC1 and GCs in lung adenocarcinoma (LADC), which may help in LADC treatment in the future.



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Contact allergy in children with atopic dermatitis: a systematic review

Abstract

The importance of contact allergy in children with atopic dermatitis is frequently debated. Previously, patients with atopic dermatitis were believed to have a reduced ability to produce a type IV immunologic response. However, this belief has been challenged and authors have highlighted the risk of underestimating and overlooking allergic contact dermatitis in children with atopic dermatitis. Several studies have been published aiming to shed light on this important question but results are contradictory. To provide an overview of the existing knowledge, we systematically reviewed studies that report frequencies of positive patch test reactions in children with atopic dermatitis. We identified 436 manuscripts of which 31 met the inclusion criteria. Although the literature is conflicting, it is evident that contact allergy is a common problem in children with atopic dermatitis.

This article is protected by copyright. All rights reserved.



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Airway microbiome and responses to corticosteroids in corticosteroid-resistant asthma patients treated with acid suppression medications

Patients with refractory, difficult to treat asthma often have gastroesophageal reflux disease (GERD).1 Studies to date emphasize the complexity of interactions between the respiratory and gastrointestinal system. This makes it challenging to discern the mechanisms that link reflux and lung disease.1 Acid suppression medications—proton pump inhibitors (PPIs) and histamine receptor 2 antagonists (H2 blockers)—are widely prescribed in patients with asthma and chronic cough. Studies also report that esophageal microbiota are subject to change in health and disease, including in patients with esophagitis and GERD.

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Thrombin Activation of Protein C Requires Prior Processing by a Liver Proprotein Convertase [Metabolism]

Protein C, a secretory vitamin K-dependent anticoagulant serine protease, inactivates factors Va/VIIIa. It is exclusively synthesized in liver hepatocytes as an inactive zymogen (proProtein C). In human, thrombin cleavage of the propeptide at PR221↓ results in activated Protein C (APC; residues 222-461). However, the propeptide is also cleaved by a furin-like proprotein convertase(s) at KKRSHLKR199↓, but the order of cleavage is unknown. Herein, we present evidence that at the cell surface of Cos-1 cells, mouse proProtein C is first cleaved by the convertases furin, PC5/6A and PACE4. In mouse, this cleavage occurs at the equivalent site KKRKILKR198↓, and requires the presence of Arg198 at P1, and a combination of two other basic residues at either P2 (Lys197), P6 (Arg193) or P8 (Lys191) positions. Notably, the thrombin-resistant R221A mutant is still cleaved by these convertases, revealing that convertase cleavage can precede thrombin activation. This conclusion was supported by the fact that the APC-specific activity in the medium of Cos-1 cells is exclusively dependent on prior cleavage by the convertases, as both R198A and R221A lack Protein C activity. Primary cultures of hepatocytes derived from wild type, or hepatocyte-specific furin, PC5/6 or complete PACE4 knockout mice suggested that the cleavage of overexpressed proProtein C is predominantly performed by furin intracellularly, and by all three PCs at the cell surface. Indeed, plasma analyses of single PC-knockout mice showed that loss of the convertases furin or PC5/6 in hepatocytes results in a ~30% decrease in APC levels, with no significant contribution from PACE4. We conclude that prior convertase-cleavage of Protein C in hepatocytes is critical for its thrombin-activation.

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The DEAD-box Protein DDX43 (HAGE) Is a Dual RNA-DNA Helicase and Has a K-homology Domain Required for Full Nucleic Acid Unwinding Activity [Enzymology]

The K-homology (KH) domain is a nucleic acid-binding domain present in many proteins, but has not been reported in helicases. DDX43, also known as HAGE (helicase antigen gene), is a member of the DEAD-box protein family. It contains a helicase core domain in its C-terminus and a potential KH domain in its N-terminus. DDX43 is highly expressed in many tumors, and is therefore considered a potential target for immunotherapy. Despite its potential as a therapeutic target, little is known about its activities. Here, we purified recombinant DDX43 protein to near homogeneity and found that it exists as a monomer in solution. Biochemical assays demonstrated that it is an ATP-dependent RNA and DNA helicase. Although DDX43 was active on duplex RNA regardless of the orientation of the single-stranded RNA tail, it preferred a 5′ to 3′ polarity on RNA, and a 3′ to 5′ direction on DNA. Truncation mutations and site-directed mutagenesis confirmed that the KH domain in DDX43 is responsible for nucleic acid binding. Compared with the activity of the full-length protein, the C-terminal helicase domain had no unwinding activity on RNA substrates and had significantly reduced unwinding activity on DNA. Moreover, the full length DDX43 protein, with single amino acid change in the KH domain, had reduced unwinding and binding activates on RNA and DNA substrates. Our results demonstrate that DDX43 is a dual helicase and the KH domain is required for its full unwinding activity.

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Neuropilin-1 mediates Neutrophil Elastase uptake and cross-presentation in breast cancer cells [Immunology]

Neutrophil elastase (NE) can be rapidly taken up by tumor cells that lack endogenous NE expression, including breast cancer, which results in cross-presentation of PR1, an NE-derived HLA-A2-restricted peptide that is an immunotherapy target in hematological and solid tumor malignancies. The mechanism of NE uptake, however, remains unknown. Using the mass spectometry-based approach, we identify neuropilin-1 (NRP1) as a NE receptor that mediates uptake and PR1 cross-presentation in breast cancer cells. We demonstrated that soluble NE is a specific, high-affinity ligand for NRP1 with a calculated Kd=38.7nM. Furthermore, we showed that NRP1 binds to RRXR motif in NE. Notably, NRP1 knockdown with interfering RNA or CRISPR-cas9 system and blocking using anti-NRP1antibody decreased NE uptake, and subsequently, susceptibility to lysis by PR1-specific cytotoxic T cells. Expression of NRP1 in NRP1-deficient cells was sufficient to induce NE uptake. All together, because NRP1 is broadly expressed on tumors, our findings suggest a role for this receptor in immunotherapy strategies that target cross-presented antigens.

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HMG-CoA synthase 1 is a synthetic lethal partner of BRAFV600E in human cancers [Molecular Bases of Disease]

Contributions of metabolic changes to cancer development and maintenance have received increasing attention in recent years. Although many human cancers share similar metabolic alterations, it remains unclear whether oncogene-specific metabolic alterations are required for tumor development. Using RNAi-based screen targeting the majority of the known metabolic proteins, we recently found that oncogenic BRAFV600E upregulates HMG-CoA lyase (HMGCL), which converts HMG-CoA to acetyl-CoA and a ketone body, acetoacetate, that selectively enhances BRAFV600E-dependent MEK1 activation in human cancer. Here, we identified HMG-CoA synthase 1 (HMGCS1), the upstream ketogenic enzyme of HMGCL, as an additional synthetic lethal partner of BRAFV600E. Although HMGCS1 expression did not correlate with BRAFV600E mutation in human melanoma cells, HMGCS1 was selectively important for proliferation of BRAFV600E-positive melanoma and colon cancer cells but not control cells harboring active N/KRAS mutants, and stable knockdown of HMGCS1 only attenuated colony formation and tumor growth potential of BRAFV600E melanoma cells. Moreover, cytosolic HMGCS1 that co-localized with HMGCL and BRAFV600E was more important than the mitochondrial HMGCS2 isoform in BRAFV600E-expressing cancer cells in terms of acetoacetate production. Interestingly, HMGCL knockdown did not affect HMGCS1 expression levels, whereas HMGCS1 knockdown caused a compensating increase in HMGCL protein level due to attenuated protein degradation. However, this increase did not reverse the reduced ketogenesis in HMGCS1 knockdown cells. Mechanistically, HMGCS1 inhibition decreased intracellular acetoacetate levels, leading to reduced BRAFV600E -MEK1 binding and consequent MEK1 activation. We conclude that the ketogenic HMGCS1-HMGCL-acetoacetate axis may represent a promising therapeutic target for managing BRAFV600E-positive human cancers.

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Small Molecule-mediated Inhibition of {beta}-2-Microglobulin Amyloid Fibril Formation [Protein Structure and Folding]

In dialysis patients, β-2 microglobulin (β2m) can aggregate and eventually form amyloid fibrils in a condition known as dialysis-related amyloidosis, which deleteriously affects joint and bone function. Recently, several small molecules have been identified as potential inhibitors of β2m amyloid formation in vitro. Here, we investigate if these molecules are more broadly applicable inhibitors of β2m amyloid formation by studying their effect on Cu(II)-induced β2m amyloid formation. Using a variety of biophysical techniques, we also examine their inhibitory mechanisms. We found that two molecules, doxycycline and rifamycin SV, can inhibit β2m amyloid formation in vitro by causing the formation of amorphous, re-dissolvable aggregates. Rather than interfering with β2m amyloid formation at the monomer stage, we found that doxycycline and rifamycin SV exert their effect by binding to oligomeric species both in solution and in gas phase. Their binding results in a diversion of the expected Cu(II)-induced progression of oligomers toward a heterogeneous collection of oligomers, including trimers and pentamers, that ultimately matures into amorphous aggregates. Using ion mobility mass spectrometry, we show both inhibitors promote the compaction of the initially formed β2m dimer, which causes the formation of other off-pathway and amyloid-incompetent oligomers that are isomeric with amyloid-competent oligomers in some cases. Overall, our results suggest that doxycycline and rifamycin are general inhibitors of Cu(II)-induced β2m amyloid formation. Interestingly, the putative mechanism of their activity is different depending on how amyloid formation is initiated with β2m, which underscores the complexity of how these structures assemble in vitro.

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Fluorescence and NMR spectroscopy together with molecular simulations reveal amphiphilic characteristics of a Burkholderia biofilm exopolysaccharide [Microbiology]

Biofilms are a collective mode of bacterial life in which a self-produced matrix confines cells in close proximity to each other. Biofilms confer many advantages including: protection form chemicals including antibiotics, entrapment of useful extracellular enzymes and nutrients, as well as opportunities for efficient recycling of molecules from dead cells. Biofilm matrices are aqueous gel-like structures composed of polysaccharides, proteins and DNA stabilized by intermolecular interactions which may include non-polar connections. Recently, polysaccharides extracted from biofilms produced by species of the Burkholderia cepacia complex were shown to possess clusters of rhamnose, a 6-deoxy-sugar with non-polar characteristics. Molecular dynamics simulations are well suited to characterizing the structure and dynamics of polysaccharides, but only relatively few such studies exist on their interaction with non-polar molecules. Here, we report an investigation into the hydrophobic properties of the exopolysaccharide produced by Burkholderia multivorans strain C1576. Fluorescence experiments with two hydrophobic fluorescent probes established that this polysaccharide complexes hydrophobic species, and NMR experiments confirmed these interactions. Molecular simulations to model the hydrodynamics of the polysaccharide and the interaction with guest species revealed a very flexible, amphiphilic carbohydrate chain that has frequent dynamic interactions with apolar molecules: both hexane and a long chain fatty acid belonging to the quorum sensing system of B. multivorans were tested. A possible role of the non-polar domains of the exopolysaccharide in facilitating the diffusion of aliphatic species towards specific targets within the biofilm aqueous matrix is proposed.

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The Impact of Different Lactic Acid Bacteria Sourdoughs on the Quality Characteristics of Toast Bread

The effect of sourdough inoculated with three novel single strains of lactic acid bacteria (LAB) (Lactobacillus casei jQ412732, Lactobacillus plantarum jQ301799, and Lactobacillus brevis IBRC-M10790) as well as mixed strains was evaluated on the quality characteristics of Toast bread. Antifungal properties of sourdoughs due to organic acid production were measured by HPLC, and storability was evaluated by thermal and textural analysis in days 1, 3, and 6. Despite the impact of sourdough concentration on microbial preservation, no significant effect was observed in the case of enthalpy reduction. Mixed LAB strains showed the best results in reducing the enthalpy and hardness of bread as well as better microbial preservation by producing the highest amount of organic acids, justified by sensory panelists. Among single strains, L. casei gave better results in reducing hardness and staling rate of bread. Scanning Electron Microscopy micrographs of bread also showed the differences.

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Antimicrobial Activity of a Cationic Guanidine Compound against Two Pathogenic Oral Bacteria

This study evaluated the potential antimicrobial properties of a polyguanidine (CatDex) on two oral bacteria. Chlorhexidine gluconate 1340 μmoL L−1 (CHX 0.12%) was used as control. Streptococcus mutans (S. mutans) and Porphyromonas gingivalis (P. gingivalis) were grown in BHI media. Bacterial sensitivity and antimicrobial activity were determined by the minimum inhibitory concentration (MIC) and Kirby-Bauer methods. To study side effects, that is, toxicity, dental pulp stem cells (DPSCs) were used. Fluorometric cytotoxicity and confocal microscopy assays were used in order to test cell viability. CatDex inhibited growth of S. mutans at all concentrations and growth of P. gingivalis at all concentrations except 25 μmoL L−1. The MIC of CatDex was 50 μmoL L−1 for both S. mutans and P. gingivalis. The inhibition of bacteria exposed for 8 h at 50 μmoL L−1 of CatDex exhibited increased antimicrobial activity over time, with 91% inhibition in both bacteria. The antimicrobial activities of CatDex and CHX were similar when tested on two common bacteria. CatDex was significantly less toxic to DPSCs. CatDex toxicity depended on time and not on concentration. With regard to clinical relevance, CatDex may have potential as a novel antimicrobial agent. Further studies are in progress.

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The Adaptive-Clustering and Error-Correction Method for Forecasting Cyanobacteria Blooms in Lakes and Reservoirs

Globally, cyanobacteria blooms frequently occur, and effective prediction of cyanobacteria blooms in lakes and reservoirs could constitute an essential proactive strategy for water-resource protection. However, cyanobacteria blooms are very complicated because of the internal stochastic nature of the system evolution and the external uncertainty of the observation data. In this study, an adaptive-clustering algorithm is introduced to obtain some typical operating intervals. In addition, the number of nearest neighbors used for modeling was optimized by particle swarm optimization. Finally, a fuzzy linear regression method based on error-correction was used to revise the model dynamically near the operating point. We found that the combined method can characterize the evolutionary track of cyanobacteria blooms in lakes and reservoirs. The model constructed in this paper is compared to other cyanobacteria-bloom forecasting methods (e.g., phase space reconstruction and traditional-clustering linear regression), and, then, the average relative error and average absolute error are used to compare the accuracies of these models. The results suggest that the proposed model is superior. As such, the newly developed approach achieves more precise predictions, which can be used to prevent the further deterioration of the water environment.

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Recent Advances of Curcumin in the Prevention and Treatment of Renal Fibrosis

Curcumin, a polyphenol derived from the turmeric, has received attention as a potential treatment for renal fibrosis primarily because it is a relatively safe and inexpensive compound that contributes to kidney health. Here, we review the literatures on the applications of curcumin in resolving renal fibrosis in animal models and summarize the mechanisms of curcumin and its analogs (C66 and (1E,4E)-1,5-bis(2-bromophenyl) penta-1,4-dien-3-one(B06)) in preventing inflammatory molecules release and reducing the deposition of extracellular matrix at the priming and activation stage of renal fibrosis in animal models by consulting PubMed and Cnki databases over the past 15 years. Curcumin exerts antifibrotic effect through reducing inflammation related factors (MCP-1, NF-κB, TNF-α, IL-1β, COX-2, and cav-1) and inducing the expression of anti-inflammation factors (HO-1, M6PRBP1, and NEDD4) as well as targeting TGF-β/Smads, MAPK/ERK, and PPAR-γ pathways in animal models. As a food derived compound, curcumin is becoming a promising drug candidate for improving renal health.

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Improving Classification Performance through an Advanced Ensemble Based Heterogeneous Extreme Learning Machines

Extreme Learning Machine (ELM) is a fast-learning algorithm for a single-hidden layer feedforward neural network (SLFN). It often has good generalization performance. However, there are chances that it might overfit the training data due to having more hidden nodes than needed. To address the generalization performance, we use a heterogeneous ensemble approach. We propose an Advanced ELM Ensemble (AELME) for classification, which includes Regularized-ELM, -norm-optimized ELM (ELML2), and Kernel-ELM. The ensemble is constructed by training a randomly chosen ELM classifier on a subset of training data selected through random resampling. The proposed AELM-Ensemble is evolved by employing an objective function of increasing diversity and accuracy among the final ensemble. Finally, the class label of unseen data is predicted using majority vote approach. Splitting the training data into subsets and incorporation of heterogeneous ELM classifiers result in higher prediction accuracy, better generalization, and a lower number of base classifiers, as compared to other models (Adaboost, Bagging, Dynamic ELM ensemble, data splitting ELM ensemble, and ELM ensemble). The validity of AELME is confirmed through classification on several real-world benchmark datasets.

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Ribonuclease from Bacillus Acts as an Antiviral Agent against Negative- and Positive-Sense Single Stranded Human Respiratory RNA Viruses

Bacillus pumilus ribonuclease (binase) was shown to be a promising antiviral agent in animal models and cell cultures. However, the mode of its antiviral action remains unknown. To assess the binase effect on intracellular viral RNA we have selected single stranded negative- and positive-sense RNA viruses, influenza virus, and rhinovirus, respectively, which annually cause respiratory illnesses and are characterized by high contagious nature, mutation rate, and antigen variability. We have shown that binase exerts an antiviral effect on both viruses at the same concentration, which does not alter the spectrum of A549 cellular proteins and expression of housekeeping genes. The titers of influenza A (H1N1pdm) virus and human rhinovirus serotype 1A were reduced by 40% and 65%, respectively. A preincubation of influenza virus with binase before infection significantly reduced viral titer after single-cycle replication of the virus. Using influenza A virus mini genome system we showed that binase reduced GFP reporter signaling indicating a binase action on the expression of viral mRNA. Binase reduced the level of H1N1pdm viral NP mRNA accumulation in A549 cells by 20%. Since the viral mRNA is a possible target for binase this agent could be potentially applied in the antiviral therapy against both negative- and positive-sense RNA viruses.

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Ensemble Learning for Short-Term Traffic Prediction Based on Gradient Boosting Machine

Short-term traffic prediction is vital for intelligent traffic systems and influenced by neighboring traffic condition. Gradient boosting decision trees (GBDT), an ensemble learning method, is proposed to make short-term traffic prediction based on the traffic volume data collected by loop detectors on the freeway. Each new simple decision tree is sequentially added and trained with the error of the previous whole ensemble model at each iteration. The relative importance of variables can be quantified in the training process of GBDT, indicating the interaction between input variables and response. The influence of neighboring traffic condition on prediction performance is identified through combining the traffic volume data collected by different upstream and downstream detectors as the input, which can also improve prediction performance. The relative importance of input variables for 15 GBDT models is different, and the impact of upstream traffic condition is not balanced with that of downstream. The prediction accuracy of GBDT is generally higher than SVM and BPNN for different steps ahead, and the accuracy of multi-step-ahead models is lower than 1-step-ahead models. For 1-step-ahead models, the prediction errors of GBDT are smaller than SVM and BPNN for both peak and nonpeak hours.

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Myocyte enhancer factor 2D promotes colorectal cancer angiogenesis downstream of hypoxia-inducible factor 1α

Myocyte enhancer factor 2D (MEF2D) is involved in many aspects of cancer progression, including cell proliferation, invasion, and migration. However, little is known about the role of MEF2D in tumor angiogenesis. Using clinical specimens, colorectal cancer (CRC) cell lines and a mouse model in the present study, we found that MEF2D expression was positively correlated with CD31-positive microvascular density in CRC tissues. MEF2D promoted tumor angiogenesis in vitro and in vivo and induced the expression of proangiogenic cytokines in CRC cells.

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Determining the Number of Test Fires Needed to Represent the Variability Present within 9 mm Luger Firearms

Firearm examiners are often asked to determine whether or not a cartridge case recovered at a crime scene had been fired by a firearm found in possession of a suspect. Comparisons are performed by comparing the impressions left on the cartridge cases by use of a comparison microscope, allowing for the similarities and differences to be noted. Finally, conclusions are made based on the opinion of the examiner, taking into account observations and automated database results if performed. For the purposes of this study, only the breech face and firing pin impressions will be compared.

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IL-33 in clinical practice: size matters?



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New blood test predicts who will benefit from targeted prostate cancer treatments

A new blood test could predict which men with advanced prostate cancer will respond to new targeted treatments for the disease. Researchers were able to detect tumour DNA in men’s blood and pick out cancers with multiple copies of the androgen receptor...

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African T. rex was one of last dinosaurs alive before extinction

15230013-1.jpg

An African version of a tyrannosaur-like predator has been discovered by chance in a mine in Morocco

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African T. rex was one of last dinosaurs alive before extinction

An African version of a tyrannosaur-like predator has been discovered by chance in a mine in Morocco

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A multidisciplinary approach to reducing alarm fatigue and cost through appropriate use of cardiac telemetry

Background

Alarm fatigue (AF) is a distressing factor for staff and patients in the hospital. Using cardiac telemetry (CT) without clinical indications can create unnecessary alarms, and increase AF and cost of healthcare. We sought to reduce AF and cost associated with CT monitoring.

Methods

After implementing a new protocol for CT placement, data were collected on telemetry orders, alarms and bed cost for 13 weeks from 1 January 2015 through 31 March 2015. We also retrospectively collected data on the same variables for the 13 weeks prior to the intervention. A survey was administered to nurses to assess past and present perceptions of AF. Interventions included protocol creation and education for participants.

Results

At baseline, 77% of patients were monitored with CT. A total of 145 (31%) order discrepancies were discovered during data collection, of which 72% had no indication for CT, so CT was discontinued. The other 28% had indications, so orders were placed. A total of 8336 alarms were recorded during 4 weeks of data collection, of which 333 (4%) were classified as true actionable alarms. Postintervention data showed 67% CT assignment with 10% reduction in CT usage, with no increase in mortality (p<0.001 and >0.05, respectively). A 42% cost reduction was achieved after adjusting the patient status. Nurses reported 27% perceived reduction in AF. One-year follow-up revealed that 69% of patients were being monitored by CT, and the rate of order discrepancies due to lack of indication was 9%.

Conclusion

All hospital units may benefit from the protocols created during this study. If applied appropriately, these protocols can lead to reduced AF and cost per episode of care.



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Association of HLA-DQB1 polymorphisms with rheumatoid arthritis: a meta-analysis

Aim

Studies investigating the association between HLA-DQB1 alleles and rheumatoid arthritis (RA) have reported conflicting results. The purpose of this study was to evaluate whether DQB1 alleles confer susceptibility to RA.

Design

A comprehensive literature search up to May 2016 was conducted to identify case-control studies on the association of HLA-DQB1 alleles with RA. Pooled ORs with 95% CIs were used to assess the strength of association.

Setting

The literature indicates that HLA-DQB1 is associated with susceptibility to RA.

Main outcome measures

Frequencies of HLA-DQB1 alleles and phenotype in RA patients and healthy controls.

Results

Fifteen studies with 1250 cases and 1621 controls were included in this meta-analysis. DQB1 alleles were associated with RA susceptibility. The frequencies of DQB1*06 were lower in RA (p-value for comparability=0.007, OR 0.726,95% CI 0.576 to 0.916; p=0.004, OR 0.611,95% CI 0.438 to 0.852). The frequencies of DQB1*02 were lower in RA (p=0.044, OR 0.731,95% CI 0.597 to 0.895). A higher frequency of DQB1*04 was observed in RA (p=0.023, OR 1.604,95% CI 1.067 to 2.410).

Conclusions

This meta-analysis demonstrates that DQB1*02 and DQB1*06 may be negatively associated with RA. Conversely, DQB1*04 may confer susceptibility to RA.



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Barriers to timely discharge from the general medicine service at an academic teaching hospital

Background

Reducing delays for patients who are safe to be discharged is important for minimising complications, managing costs and improving quality. Barriers to discharge include placement, multispecialty coordination of care and ineffective communication. There are a few recent studies that describe barriers from the perspective of all members of the multidisciplinary team.

Study objective

To identify the barriers to discharge for patients from our medicine service who had a discharge delay of over 24 hours.

Methodology

We developed and implemented a biweekly survey that was reviewed with attending physicians on each of the five medicine services to identify patients with an unnecessary delay. Separately, we conducted interviews with staff members involved in the discharge process to identify common barriers they observed on the wards.

Results

Over the study period from 28 October to 22 November 2013, out of 259 total discharges, 87 patients had a delay of over 24 hours (33.6%) and experienced a total of 181 barriers. The top barriers from the survey included patient readiness, prolonged wait times for procedures or results, consult recommendations and facility placement. A total of 20 interviews were conducted, from which the top barriers included communication both between staff members and with the patient, timely notification of discharge and lack of discharge standardisation.

Conclusions

There are a number of frequent barriers to discharge encountered in our hospital that may be avoidable with planning, effective communication methods, more timely preparation and tools to standardise the discharge process.



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The implementation of cardiac arrest treatment recommendations in English acute NHS trusts: a national survey

Purpose of the study

There are approximately 35 000 in-hospital cardiac arrests in the UK each year. Successful resuscitation requires integration of the medical science, training and education of clinicians and implementation of best practice in the clinical setting. In 2015, the International Liaison Committee on Resuscitation (ILCOR) published its latest resuscitation treatment recommendations. It is currently unknown the extent to which these treatment recommendations have been successfully implemented in practice in English NHS acute hospital trusts.

Methods

We conducted an electronic survey of English acute NHS trusts to assess the implementation of key ILCOR resuscitation treatment recommendations in relation to in-hospital cardiac arrest practice at English NHS acute hospital trusts.

Results

Of 137 eligible trusts, 73 responded to the survey (response rate 53.3%). The survey identified significant variation in the implementation of ILCOR recommendations. In particular, the use of waveform capnography (n=33, 45.2%) and ultrasound (n=29, 39.7%) was often reported to be available only in specialist areas. Post-resuscitation debriefing occurs following every in-hospital cardiac arrest in few trusts (5.5%, n=4), despite a strong ILCOR recommendation. In contrast, participation in a range of quality improvement strategies such as the National Cardiac Arrest Audit (90.4%, n=66) and resuscitation equipment provision/audit (91.8%, n=67) were high. Financial restrictions were identified by 65.8% (n=48) as the main barrier to guideline implementation.

Conclusion

Our survey found that ILCOR treatment recommendations had not been fully implemented in most English NHS acute hospital trusts. Further work is required to better understand barriers to implementation.



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Initial size of unilateral pleural effusion determines impact of thoracocentesis on oxygenation

Background

There have been contradicting reports in the literature regarding the impact of pleural fluid aspiration on patients’ oxygenation. The aim of this study was to assess the role of the initial size of effusion on post-drainage oxygenation.

Methods

We studied 122 patients, aged (mean±SD) 61.2±16.8 years, with unilateral pleural effusion and no remarkable parenchymal lesion, by determining PaO2, PaCO2 and [A–a] PaO2 just before thoracocentesis (T1), 30 min after its completion (T2) and 48 hours after the procedure (T3). Patients were divided into group A (75 patients) with small and moderate sized effusions and group B (47 patients) with large and massive effusions. The position of the meniscus line on the posteroanterior film, being arbitrarily set at just above the upper costal margin of the sixth anterior rib, was used to divide the two groups. Patients were studied at rest, breathing room air in the sitting position. Repeated measures ANOVA (related samples) and the Friedman test when the normality assumption was violated were used.

Results

In group A, at T3, PaO2(mm Hg) showed a statistically significant increase versus T1 (p<0.001) and T2 (p=0.002), while [A-a] PaO2 displayed a statistically significant decrease compared with T1 (p<0.001) and T2 (p=0.001). In group B, at T2, PaO2 presented significant decrease versus T1 (p<0.001) and T3 (p<0.001), while [A-a] PO2 was found to be significantly increased compared with both T1 and T3 (p<0.001).

Conclusion

Patients with smaller effusions showed a small improvement in their oxygenation 48 hours post-thoracocentesis (T3). Patients with larger effusions exhibited a transient reduction in their oxygenation immediately after fluid removal (T2).



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Absolute benefits of empagliflozin in type 2 diabetes: a game changer?

The modes of action and clinical implications of several of the newest classes of antidiabetic drugs used as monotherapy and as add-on therapy have been extensively reviewed in recent publications.1 2 Sodium-glucose cotransporter 2 (SGLT-2) inhibitors (eg, empagliflozin) belong to one such novel class and act via interference with proximal renal tubular reabsorption of glucose; about 90% of such reabsorption depends on this cotransporter. They therefore reduce blood glucose concentrations, promote weight reduction and lower blood pressure through glycosuria and osmotic diuresis. Moreover, since their activity is independent of insulin, they are efficacious even in the presence of pancreatic beta cell failure, which is in marked contrast to many other antidiabetic drugs. Furthermore, polyuria and polydipsia are uncommon. Gliptins (eg, saxagliptin) form another new class of oral antidiabetic agents that reduce glucagon secretion but promote insulin release by interfering with the degradation of incretins (intestinal hormones...



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Tumor cell expression of immune inhibitory molecules and tumor-infiltrating lymphocyte count predict cancer-specific survival in pancreatic and ampullary cancer

Abstract

Understanding the mechanisms of immune resistance in pancreatic and ampullary cancers is crucial for the development of suitable biomarkers and effective immunotherapeutics. Our aim was to examine the expression of the immune inhibiting molecules PD-L1, Galectin-9, HVEM, IDO and HLA-G, as well as CD8+ and FoxP3+ tumor infiltrating lymphocytes (TIL), in pancreatic and ampullary cancers, and to relate their individual, as well as their combined expression, to cancer survival. Tumor tissue from 224 patients with resected pancreatic (n=148) and ampullary (n=76) cancer was used to construct tissue-microarrays. Expression of immune inhibitory molecules and TIL was examined by immunohistochemistry. We show that immune inhibitory molecules are prevalently expressed. Moreover, high tumor expression of PD-L1 (p=.002), Gal-9 (p=.003), HVEM (p=.001), IDO (p=.049), HLA-G (p=.004) and high CD8/FoxP3 TIL ratio (p=.006) were associated with improved cancer-specific survival. All immune biomarkers, with the exception of IDO, were individually predictive of cancer-specific survival when adjusted for clinicopathologic characteristics. For every additional immune biomarker present survival was almost two-fold prolonged (HR 0.57 95%CI 0.47-0.69, p<.0001). When patients with pancreatic and ampullary cancer were analyzed separately the results were similar. We conclude that pancreas and ampullary cancers are rich in expression of immune-inhibitory molecules. These molecules can be targets for future immunotherapeutics, as well as form powerful immunological biomarkers. We propose that such immune biomarker panels be included in future prospective immunotherapy trials. This article is protected by copyright. All rights reserved.



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Long-distance interaction of the integrated HPV fragment with MYC gene and 8q24.22 region up-regulating the allele-specific MYC expression in HeLa cells

Abstract

Human papillomavirus (HPV) infection is the most important risk factor for cervical cancer development. In HeLa cell line, the HPV viral genome is integrated at 8q24 in one allele of chromosome 8. It has been reported that the HPV fragment integrated in HeLa genome can cis-activate the expression of proto-oncogene MYC, which is located at 500 kb downstream of the integrated site. However, the underlying molecular mechanism of this regulation is unknown. A recent study reported that MYC was highly expressed exclusively from the HPV-integrated haplotype, and a long-range chromatin interaction between the integrated HPV fragment and MYC gene has been hypothesized. In this study, we provided the experimental evidences supporting this long-range chromatin interaction in HeLa cells by using Chromosome Conformation Capture (3C) method. We found that the integrated HPV fragment, MYC and 8q24.22 was close to each other and might form a trimer in spatial location. When knocking out the integrated HPV fragment or 8q24.22 region from chromosome 8 by CRISPR/Cas9 system, the expression of MYC reduced dramatically in HeLa cells. Interestingly, decreased expression was only observed in three from eight cell clones, when only one 8q24.22 allele was knocked out. Functionally, HPV knockout caused senescence-associated acidic β-gal activity in HeLa cells. These data indicate a long-distance interaction of the integrated HPV fragment with MYC gene and 8q24.22 region, providing an alternative mechanism relevant to the carcinogenicity of HPV integration. This article is protected by copyright. All rights reserved.



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Genetic polymorphisms associated with pancreatic cancer survival: A genome-wide association study

Abstract

Previous findings on the association of genetic factors and pancreatic cancer survival are limited and inconsistent. In a two-stage study, we analyzed the existing genome-wide association study dataset of 868 pancreatic cancer patients from MD Anderson Cancer Center in relation to overall survival using Cox regression. Top hits were selected for replication in another 820 patients from the same institution using the Taqman genotyping method. Functional annotation, pathway analysis, and gene expression analysis were conducted using existing software and databases. We discovered genome-wide significant associations of patient survival with three imputed SNPs which, in complete LD (r2=1), were intronic SNPs of the PAIP2B (rs113988120) and DYSF genes (rs112493246 and rs138529893) located on chromosome 2. The variant alleles were associated with a 3.06-fold higher risk of death (95% confidence interval [CI]=2.10-4.47, P = 6.4 × 10-9) after adjusting for clinical factors. Eleven SNPs were tested in the replication study and the association of rs113988120 with survival was confirmed (HR: 1.57, 95% CI: 1.13-2.20,P = 0.008). In silico analysis found rs1139988120 might lead to altered motif. This locus is in LD (D'=0.77) with 3 eQTL SNPs near or belong to the NAGK and MCEE genes. According to The Cancer Genome Atlas data and our previous RNA-sequencing data, the mRNA expression level of PAIP2B but not NAGK, MCEE or DYSF was significantly lower in pancreatic tumors than in normal adjacent tissues. Additional validation efforts and functional studies are warranted to demonstrate whether PAIP2B is a novel tumor suppressor gene and a potential therapeutic target for pancreatic cancer. This article is protected by copyright. All rights reserved.



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Human papillomavirus E7 protein detection as a method of triage to colposcopy of HPV positive women, in comparison to genotyping and cytology. Final results of the PIPAVIR study



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Patient monitoring through liquid biopsies using circulating tumor DNA

Abstract

Tumors release components such as circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and tumor-derived extracellular vesicles into the circulation. Multiple studies have demonstrated that molecular information about tumors and metastases can be extracted from these factors, which are therefore frequently referred to as "liquid biopsies". Liquid biopsies allow the longitudinal monitoring of tumor genomes non-invasively and may hence ensure that patients receive appropriate treatments that target the molecular features of their disease. Accordingly, the number of studies employing liquid biopsy based assays has been skyrocketing in the last few years. Here, we focus on three important issues, which are of high relevance for monitoring tumor genomes. First, we analyze the relation between the allele frequency of somatic tumor-specific mutations and the tumor fraction within plasma DNA. Second, we ask how well current tumor evolution models correlate with findings in longitudinal liquid biopsy studies. And, finally, as sensitivity is one of the key challenges of mutation detection, we address the challenge of detecting mutations occurring at very low allele frequencies in plasma DNA. This article is protected by copyright. All rights reserved.



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Benefit-to-harm ratio of the Danish breast cancer screening programme

ABSTRACT

The primary aim of breast cancer screening is to reduce breast cancer mortality, but screening also has negative side-effects as overdiagnosis. To evaluate a screening programme, both benefits and harms should be considered. Published estimates of the benefit-to-harm ratio, the number of breast cancer deaths prevented divided by the number of overdiagnosed breast cancer cases, varied considerably. The objective of the study was to estimate the benefit-to-harm ratio of breast cancer screening in Denmark. The numbers of breast cancer deaths prevented and overdiagnosed cases (invasive and ductal carcinoma in situ (DCIS)) were estimated per 1,000 women aged 50-79, using national published estimates for breast cancer mortality and overdiagnosis, and national incidence and mortality rates. Estimations were made for both invited and screened women. Among 1,000 women invited to screening from age 50 to age 69 and followed until age 79, we estimated that 5.4 breast cancer deaths would be prevented and 2.1 cases overdiagnosed, under the observed scenario in Denmark of a breast cancer mortality reduction of 23.4% and 2.3% of the breast cancer cases being overdiagnosed. The estimated benefit-to-harm ratio was 2.6 for invited women and 2.5 for screened women. Hence, 2-3 women would be prevented from dying from breast cancer for every woman overdiagnosed with invasive breast cancer or DCIS. The difference between the previous published ratios and 2.6 for Denmark is probably more a reflection of the accuracy of the underlying estimates than of the actual screening programmes. Therefore, benefit-to-harm ratios should be used cautiously. This article is protected by copyright. All rights reserved.



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An integrative Chinese-Western diagnostic approach to predict a positive response to acupuncture

Background

Our recent paper published in Acupuncture in Medicine showed that the response to acupuncture was difficult to predict; the only significant predictor of a positive response to 3 weeks of thrice-weekly traditional needle acupuncture for insomnia was educational level.1 In view of this challenging situation, we explored whether an integrative Chinese-Western diagnostic approach could be useful for predicting treatment response.

Traditional Chinese Medicine theory

Over the years, different theories of Traditional Chinese Medicine (TCM) have been developed to understand illnesses and bodily disharmony and are sometimes used to guide TCM therapies, including acupuncture. The most accepted categorisation is a description in terms of Yin and Yang, external and internal, hot and cold, and excess and deficiency, in addition to Qi, Blood, body-fluid and zang-fu differentiation. We have earlier examined the response to acupuncture in different TCM patterns. Although response rates varied, being highest for Liver-qi stagnation transforming into fire...



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What is lost in the acupuncture trial when using a sham intervention?

Controversy still surrounds the evaluation of acupuncture’s effectiveness as a therapeutic intervention in the era of evidence-based medicine, and this is exemplified by published clinical research on acupuncture for menopausal hot flushes among climacteric women. Ee et al1 conducted a randomised control trial (RCT) in patients experiencing hot flushes who were mainly acupuncture-naïve Caucasian women in Australia. Patients were randomised to receive 10 treatment sessions of either verum acupuncture, which involved needle insertion at six classical acupuncture points, or sham acupuncture, which involved stimulation at six non-acupuncture sham points with sham devices, over the course of 8 weeks. It was demonstrated that both interventions improved the hot flush score (the primary outcome of this study) by approximately 40% relative to baseline, and that the improvement continued up to 6 months following the end of treatment in both groups with no statistically significant difference between the two arms. Soon...



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Acupuncture upregulates G protein coupled activity in SAMP8 mice

Background

Transmembrane and intracellular signal transduction of G protein is closely related to the pathophysiology of Alzheimer's disease (AD).

Objective

To explore the effects of Sanjiao acupuncture on G protein signal transduction pathways in the pathogenesis of AD.

Methods

36 senescence-accelerated (SAM) prone 8 mice were divided into three groups that remained untreated (SAMP8, n=12) or received Sanjiao acupuncture (SAMP8+SA, n=12) or control acupuncture (SAMP8+CA, n=12). An additional control group of SAM resistant 1 mice was included (SAMR1 group, n=12). Morris water maze tests were used to investigate learning and memory abilities. Immunoprecipitation and Western blotting were used to study expression of G protein subunits and their activities in the cortex/hippocampus.

Results

Behavioural analysis showed that acupuncture attenuated the severe cognitive deficits observed in untreated/CA-treated SAMP8 mice. The findings of the G protein activation assays via immunoprecipitation and Western blots were that the physiologically coupled activation rate (PCAR) and maximal coupled activation rate (MCAR) of Gαs and Gαi were decreased in the cortex of SAMP8 vs SAMR1 mice. Sanjiao acupuncture induced an upregulation in the PCAR of Gαs and Gαi. In the hippocampus of untreated SAMP8 mice, the PCAR of Gαs and MCAR of both Gαs and Gαi declined, and Sanjiao acupuncture was associated with an upregulation in the MCAR of Gαs and Gαi. There were no significant differences in Gαs and Gαi expression between the groups.

Conclusions

Sanjiao acupuncture attenuates cognitive deficits in a mouse model of AD via upregulation of G protein activity and stabilisation of the cellular signal.



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Patients and physiotherapists belief in and use of acupuncture for cancer-related symptoms

Background

It is important to investigate attitudes to acupuncture, because therapists’ and patients’ expectations may affect the treatment outcome.

Aim

To explore the use of and belief in acupuncture among oncological physiotherapists and to explore patients’ interest in receiving acupuncture during cancer therapy and their belief in its effectiveness.

Methods

522 patients (80% female, mean age 67 years) reported on their interest in receiving acupuncture for nausea during radiotherapy treatment; a subgroup (n=198) additionally disclosed their belief in the effectiveness of acupuncture. 117 Swedish oncological physiotherapists (96% female, mean age 48 years) answered a questionnaire regarding their use of and belief in acupuncture.

Results

Of the patients initiating cancer therapy, 359 (69%) were interested in receiving acupuncture. The patients believed acupuncture to be effective for pain (79%), nausea (79%) and vasomotor symptoms (48%). Of the 117 physiotherapists, 66 (56%) practised acupuncture. Physiotherapists generally believed in the effectiveness of acupuncture. For pain, 89% believed that acupuncture was effective and 42% of them practised it. Similar responses were noted for chemotherapy-induced nausea (86% and 38%, respectively) and vasomotor symptoms (80% and 28%, respectively). Younger physiotherapists and patients were more likely to believe in the effectiveness of acupuncture compared with older ones.

Conclusions

More than two thirds of patients with cancer were interested in receiving acupuncture during therapy. Patients and oncological physiotherapists believed that acupuncture was effective for cancer pain, nausea and vasomotor symptoms. Further studies of acupuncture for cancer-related symptoms and of the effect of patients’ and clinicians’ therapeutic relationships, including treatment expectations, would be welcome.



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Neurofunctional Correlates of Behavioral Inhibition System Sensitivity during Attentional Control are Modulated by Perceptual Load

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Publication date: Available online 3 May 2017
Source:Biological Psychology
Author(s): Nora Bunford, Julia Roberts, Amy E. Kennedy, Heide Klumpp
Although the Behavioral Inhibition System (BIS) is associated with threat-sensitivity, little is known about its neurofunctional correlates during cognitive control over task-irrelevant threat distractors. Thirty non-clinical participants, who ranged in BIS sensitivity, completed an attentional control paradigm during fMRI. The paradigm varied in cognitive demand with low perceptual load comprising identical target letters and high perceptual load comprising a target letter in a mixed letter string; each superimposed on threatening and neutral face distractors. Whole-brain results indicated that individuals with higher, relative to lower BIS sensitivity, exhibited enhanced dorsolateral prefrontal cortex activation to angry (vs. neutral) and enhanced dorsal anterior cingulate cortex activation to fearful (vs. neutral) face distractors under low load whereas no differences in activation were observed under high load. These findings are consistent with literature indicating that the BIS is involved in conflict processing, including between cognitive and emotional or motivational goals.



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Salutary effects of an attention bias modification mobile application on biobehavioral measures of stress and anxiety during pregnancy

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Publication date: Available online 3 May 2017
Source:Biological Psychology
Author(s): Tracy A. Dennis-Tiwary, Samantha Denefrio, Shari Gelber
Stress and anxiety during pregnancy are associated with a range of adverse health outcomes, thus there is an unmet need for low-barrier treatments that target stress and anxiety. One such treatment approach, attention bias modification training (ABMT), reduces the anxiety-related attentional threat bias, which is also associated with disrupted neural processing of threat. It remains unclear, however, whether reducing treatment barriers via mobile delivery of ABMT is effective and whether ABMT efficacy varies depending on individual differences in neural processing of threat. The present study tested whether mobile, gamified ABMT reduced prenatal threat bias, anxiety and stress, and whether ABMT efficacy varied with individual differences in neural responses to threat. Participants were 29 women in their 19th–29th week of pregnancy, randomized to four weeks of ABMT versus placebo training (PT) versions of the mobile app using a double-blind design. Self-report of anxiety, depression, and stress were obtained, and salivary cortisol was collected at home and in lab in response to stressors to index biological stress reactivity. Threat bias was measured using a computerized attention assay during which EEG was recorded to generate event-related potentials (ERPs) to threat cues. Results showed lower levels of threat bias (1-tailed) and lab cortisol following ABMT versus PT. Although the main effect of ABMT on subjective anxiety was not significant, the magnitude of cortisol reduction was correlated with lower levels of subjective anxiety and threat bias. Those receiving ABMT also reported less anxiety when showing smaller ERPs to threat (P1, P2) prior to training, but, conversely reported more anxiety when showing larger ERPs to threat. Use of gamified, mobile ABMT reduced biobehavioral indices of prenatal stress and anxiety, but effects on anxiety varied with individual differences in cortisol response and neurocognitive indices of early attention to threat.



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Making your Skin Crawl: The Role of Tactile Sensitivity in Disease Avoidance

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Publication date: Available online 3 May 2017
Source:Biological Psychology
Author(s): David Francis Hunt, Grace Cannell, Nicholas A. Davenhill, Stephanie A. Horsford, Diana S. Fleischman, Justin H. Park
Mounting evidence indicates that animals, including humans, have evolved a behavioral disease-avoidance system designed to facilitate the detection and avoidance of sources of pathogens, and that this system interacts with physiological defenses. The skin acts as an important anatomical barrier, yet little research has investigated the role of tactile sensitivity in disease avoidance. Increased tactile sensitivity in the presence of potential sources of pathogens may facilitate prophylactic behaviors such as self-grooming. Across three studies, we tested the hypothesis that the induction of disgust—the key emotion underlying disease avoidance—may lead to greater tactile sensitivity compared to control conditions. A nonsignificant trend was found in Study 1, which was replicated (and found to be significant) in Studies 2 and 3. To our knowledge, these results are the first to demonstrate disgust-induced changes in tactile sensitivity, and they contribute to the growing literature on the integrated evolved defenses against infectious disease.



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First 60 fetal in-utero myelomeningocele repairs at Saint Louis Fetal Care Institute in the post-MOMS trial era: hydrocephalus treatment outcomes (endoscopic third ventriculostomy versus ventriculo-peritoneal shunt)

Abstract

Introduction

The published results of the Management of Myelomeningocele Study (MOMS) trial in 2011 showed improved outcomes (reduced need for shunting, decreased incidence of Chiari II malformation, and improved scores of mental development and motor function) in the fetal prenatal repair group compared to the postnatal group. Historically, endoscopic third ventriculostomy (ETV) remains as a controversial hydrocephalus treatment option with high failure rates in pediatric patients with a history of myelomeningocele (MMC). We report hydrocephalus treatment outcomes in the fetal in-utero myelomeningocele repair patients who underwent repair at our Saint Louis Fetal Care Institute following the MOMS trial. We looked carefully at ETV outcomes in this patient population and we identified risk factors for failure.

Methods

At our Saint Louis Fetal Care Institute, we followed the maternal and fetal inclusion and exclusion criteria used by the MOMS trial. The records of our first 60 fetal MMC repairs performed at our institute between 2011 and 2017 were examined. We retrospectively reviewed the charts, prenatal fetal magnetic resonance imaging (MRI) and ultrasound (US) imaging findings, postnatal brain MRI, and Bayley neurodevelopment testing results for infants and children who underwent surgical treatment of symptomatic hydrocephalus (VP shunt versus ETV). Multiple variables possibly related to ETV failure were considered for identifying risk factors for ETV failure.

Results

Between May 2011 and March 2017, 60 pregnant female patients underwent the prenatal MMC repair for their fetuses between 20 and 26 weeks' gestational age (GA) utilizing the standard hysterotomy for exposure of the fetus, and microsurgical repair of the MMC defect. All MMC defects underwent successful in-utero repair, with subsequent progression of the pregnancy. At the time of this study, 58 babies have been born, 56 are alive since there were 2 mortalities in the neonatal period due to prematurity. One patient was excluded given lack of consent for research purposes. From the remaining 55 patient included in this study, a total of 30 infants and toddlers underwent treatment of hydrocephalus (ETV and VPS groups). Twenty-five patients underwent ETV (24 primary ETV and 1 after shunt failure). Nineteen patients underwent shunt placements (6 primary/13 after ETV failure). Mean GA at time of MMC repair for the ETV group was 24 + 6/7 weeks (range 22 + 4/7 to 25 + 6/7). Mean follow up for patients who had a successful ETV was 17.25 months (range 4–57 months). Bayley neurodevelopmental testing results were examined pre- and post-ETV. Overall ETV success rate was 11/24 (45.8%) at the time of this study. The total number of patients who underwent shunt placement was 19/55 (34.5%), while shunting rate was 40% in the MOMS trial. Using a simple logistic regression analysis to identify predictors of ETV failure, ETV age ≤6 months and gestational age ≥23 weeks at repair of myelomeningocele were significant predictors for ETV failure while in-utero ventricular stability ≤4 mm and in-utero ventricular size post-repair ≤15.5 mm were significant predictors for ETV success. None of the listed variables independently predicted classification into ETV success versus ETV failure groups when entered into multiple logistic regression analysis.

Conclusions

ETV, as an alternative to initial shunting, may continue to show promising results for treating fetal MMC repair patient population who present with symptomatic hydrocephalus during infancy and early childhood. Although our overall CSF diversion rate (ETV and VPS groups) in our fetal MMC group is higher than the MOMS trial, our shunting rate is lower given our higher incidence of patients with successful ETV. To our knowledge, this is the largest reported ETV series in patients who underwent fetal MMC repair. ETV deserves a closer look in the setting of improved hindbrain herniation in fetal in-utero MMC repair patients. In our series, young age (less than 6 months) and late GA at time of fetal MMC repair (after 23 weeks GA) were predictors for ETV failure, while in-utero stability of ventricular size (less than 4 mm) and in-utero ventricular size post-repair ≤15.5 mm were predictors for ETV success. Larger series and potential prospective randomized studies are required for further evaluation of risk factors for ETV failure in the fetal MMC patient population.



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