Inhibition of Rad51 sensitizes breast cancer cells with wild-type PTEN to olaparib

Publication date: October 2017
Source:Biomedicine & Pharmacotherapy, Volume 94
Author(s): Qian Zhao, Jiawei Guan, Zhiwei Zhang, Jian Lv, Yulu Wang, Likun Liu, Qi Zhou, Weifeng Mao
PTEN is a tumor suppressor gene well characterized as a phosphatase. However, more evidences demonstrate PTEN functions in DNA repair independent of its phosphatase activity, which affects the efficacy of DNA damage anti-tumoral drugs in treating cancer cells with PTEN variations. Using BT549 breast cancer cells, we studied the roles of PTEN in DNA repair and in sensitization of breast cancer cells to olaparib, a poly(ADP-ribose) polymerase (PARP) inhibitor. Comet assay showed PTEN promoted DNA repair. PTEN-deficient BT549 cells are sensitive to olaparib, which shows the synthetic lethality between PTEN and PARP1. We expressed PTEN in BT549 cells and found PTEN-proficient BT549 cells resist to olaparib. Western blot showed that PTEN up-regulated Rad51 expression, suggesting PTEN promotes DNA repair through Rad51-dependnent homologous recombination. We used 5μM olaparib or 5μM RI-1, a Rad51 inhibitor, to treat PTEN-proficient BT549 cells respectively. The immunofluorescent analysis showed the combination of olaparib and RI-1 induced more than 4-fold of γH2AX foci than either of them. MTT assay showed 5μM RI-1 did not change the survival of PTEN-proficient BT549 cells, however, this dose of RI-1 sensitized PTEN-proficient BT549 cells to olaparib. Consequently, these results demonstrate that inhibition of Rad51 can sensitize BT549 cells with wild type PTEN to olaparib, which would contribute to using PARP inhibitors in individual treatment of breast cancer patients with PTEN variations.

Graphical abstract

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Navel orange peel hydroethanolic extract, naringin and naringenin have anti-diabetic potentials in type 2 diabetic rats

Publication date: October 2017
Source:Biomedicine & Pharmacotherapy, Volume 94
Author(s): Osama M. Ahmed, Mohamed A. Hassan, Sanaa M. Abdel-Twab, Manal N. Abdel Azeem
The therapy of Type 2 Diabetes Mellitus (T2DM) stays a challenging issue. During the last decade, there has been an interest in the expansion of anti-diabetic drugs especially those of natural sources. Thus, the aim of this study was to assess the anti-hyperglycemic and the anti-hyperlipidemic effects as well as the anti-oxidant activities of navel orange hydroethanolic extract and its constituting flavonoids naringin and naringenin on nicotineamide (NA)/streptozotocin (STZ)-induced type 2 diabetic rats. To induce T2DM, 16h-fasted rats were intraperitoneally injected with STZ at dose of 50mg/kg body weight (b. w.), 15min after the intraperitoneal administration of NA (120mg/kg b. w.). The NA/STZ-induced type 2 diabetic rats were orally treated with navel orange peel hydroethanolic extract, naringin and narengenin at dose level of 100mg/kg b. w./day for 4 weeks. The treatments with navel orange peel hydroethanolic extract, naringin and narengenin potentially alleviated the lowered serum insulin and C-peptide levels, the depleted liver glycogen content, the elevated liver glucose-6-phosphatase and glycogen phosphorylase activities, the deteriorated serum lipid profile, and the suppressed liver antioxidant defense system of NA/STZ-induced type 2 diabetic rats. The treatments also enhanced the mRNA expression of insulin receptor β-subunit, GLUT4 and adiponectin in adipose tissue of STZ/NA-induced type 2 diabetic rats. In conclusion, the navel orange peel hydroethanolic extract, naringin and naringenin have potent anti-diabetic effects in NA/STZ-induced type 2 diabetic rats via their insulinotropic effects and insulin improving action which in turn may be mediated through enhancing insulin receptor, GLUT4 and adiponectin expression in adipose tissue.



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Kiwi fruit (Actinidia deliciosa) ameliorates gentamicin-induced nephrotoxicity in albino mice via the activation of Nrf2 and the inhibition of NF-κB (Kiwi & gentamicin-induced nephrotoxicity)

Publication date: October 2017
Source:Biomedicine & Pharmacotherapy, Volume 94
Author(s): Yomna I. Mahmoud
Gentamicin is a potent aminoglycoside antibiotic, but the risk of nephrotoxicity limits its prolonged use. The toxicity of gentamicin is believed to result from oxidative stress, a condition that could be counteracted by dietary antioxidants. This study determines the possible renoprotective effects of kiwifruit against the pathophysiological and ultrastructural alterations induced by gentamicin. Mice were intraperitoneally injected with gentamicin (100mg/kg body weight) for eight consecutive days, and kiwi juice was administered for 8days, either concomitant to or after gentamicin injection. Gentamicin caused nephrotoxicity evidenced by the significant elevation of serum creatinine and blood urea nitrogen levels, along with significant reduction of serum sodium and potassium ions, compared to normal controls. This was associated with proximal tubular necrosis, lysosomal accumulation and mitochondrial alterations, together with glomerular atrophy, mesangial hypercellularity, and inflammatory cell infiltration. Moreover, immunohistochemical results pointed to the relevant role of Nrf2 and NF-κB in gentamicin-induced nephrotoxicity. Kiwi administration, especially when given after gentamicin injection, significantly ameliorated gentamicin-induced pathophysiological alterations, increased the nuclear immunoreactivity of Nrf2 and decreased that of NF-κB. In short, kiwi fruit shows a promising role as a nephroprotective agent against gentamicin-induced nephrotoxicity via attenuating oxidative stress, inflammation and cell death.



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Rhein ameliorates adenomyosis by inhibiting NF-κB and β-Catenin signaling pathway

Publication date: October 2017
Source:Biomedicine & Pharmacotherapy, Volume 94
Author(s): Tingting Feng, Shaobin Wei, Yan Wang, Xianyun Fu, Ling Shi, Liyuan Qu, Xiaoxue Fan
In the present study, we examined the effects of rhein on pituitary gland implantation-induced adenomyosis, an animal model which mimics human adenomyosis. Oral administration of rhein dose-dependently attenuated hyperplastic and hypertrophic myometrium and improved adenomyosis. The activation of NF-κB and β-catenin signaling pathway was observed in the ectopic endometria. While, rhein dose dependently inhibited the expressions of p-p65, p-AKT and actived Rac1. As Rac1 activation controlled nuclear localization of β-catenin during canonical Wnt signaling, we found that the degradation complex of β-catenin was improved by rhein. In addition, β-catenin nuclear translocation and its downstream genes were markedly suppressed by different doses of rhein. At the same time, decreased activation of epithelial–mesenchymal transition (EMT)-associated proteins including Snail and ZEB1 was detected in rhein-treated mice, indicating that the activation of Wnt signaling pathway was suppressed by rhein. The in vitro study verified a negative regulation of rhein on β-catenin in stromal cells. Stimulation of IL-1β significantly increased the nuclear translocation of β-catenin and improved its target genes expressions. While, rhein remarkably abolished the enhancement in a dose dependent manner. Taken together, our results demonstrated the ability of rhein to inhibit Wnt/β-catenin activation and its potential use in the treatment of adenomyosis and other abnormal activation of β-catenin −associated diseases.



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Raising Awareness of Graves’ Orbitopathy with Early Warning Cards

Abstract

Background

Clinically significant Graves' orbitopathy (GO) develops in about 25% of those with Graves' disease (GD); most cases of GD in the UK are managed by endocrinologists. Despite this, patients report significant delays before a diagnosis of GO is made. Measures to increase awareness of the early signs of GO and establishing a fast-track referral pathway to specialist care should overcome these delays and potentially improve outcomes.

Aims

We aimed to determine whether issuing a "GO early warning card" to all GD patients raises awareness of GO and facilitates early diagnosis, what percentage of cards result in a telephone contact, the number of "false reports" from card carriers and patient perceptions of the cards.

Methods

We designed cards, detailing common GO symptoms and a telephone number for patients developing symptoms. Cards were distributed to 160 GD patients, without known GO, attending four endocrine clinics in the UK (December 2015 - March 2016). We recorded telephone contacts over twelve months from when the last card was distributed and gathered patient feedback.

Results

The early warning cards were well received by patients in general. Over twelve months, ten telephone contacts from nine patients, all related to ocular symptoms, were received (6% of cards issued). Nine calls resulted in an additional clinic review (for eight patients) and four diagnoses of GO were made.

Conclusions

This pilot study demonstrates that it is feasible to distribute GO early warning cards in clinic and that they can be used to facilitate an early diagnosis of GO.

This article is protected by copyright. All rights reserved.

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A distinct serum metabolic signature of distant metastatic papillary thyroid carcinoma

Summary

Background

Although the incidence rate for thyroid cancer seems to have begun stabilizing in recent years, an increased rate of advanced stage of this disease has been reported. Additionally, distant metastasis is one of the most important prognostic factors of patients with papillary thyroid carcinoma (PTC). Unfortunately, the underlying mechanisms of distant metastasis as well as cell status like metabolism changes in distant metastatic tumors have not been clearly elucidated.

Objective

To identify serum metabolic signature of distant metastatic PTC.

Design, patients and measurementsIn

this study, gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) was used to analyze the serum from 77 patients diagnosed with PTC (37 in distant metastasis group and 40 in ablation group). Principal component analysis (PCA) and orthogonal partial least-squares-discriminant analysis (OPLS-DA)scores plots were used to analyze the data.

Results

PCA and OPLS-DA analyses demonstrated an evident trend of separation between 40 serum samples from the ablation group and 37 samples from distant metastasis group. A total of 31 metabolites were identified which are related to amino acid, lipid, glucose, vitamin metabolism and diet/gut microbiota interaction. Pathway analysis showed 'alanine, aspartate and glutamate metabolism' and 'inositol phosphate metabolism' were the most relevant pathways.

Conclusion

Serum metabolomics profiling could significantly discriminate papillary thyroid cancer patients according to distant metastasis. Potential metabolic aberration in distant metastatic PTC could be involved in different biologic behaviors of tumor cells including proliferation, invasion/migration, and immune escape. Diet/gut microbiota produced metabolites could play an important role in these effects. This work may provide new clues to find the underlying mechanisms regarding to the distant metastasis of PTC as well as potential adjuvant therapy targets.

This article is protected by copyright. All rights reserved.

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Sarcoid-like granulomas in renal cell carcinoma: The Houston Methodist Hospital experience

Publication date: Available online 29 July 2017
Source:Annals of Diagnostic Pathology
Author(s): Komal Arora, Mukul K. Divatia, Luan Truong, Steven S. Shen, Alberto G. Ayala, Jae Y. Ro
Sarcoid-like (SL) granulomas have been previously described in association with malignant tumors. These granulomas appear to be tumor-related but are not indicative of systemic sarcoidosis, and hence are referred to as SL reactions. These SL reactions can be seen within the primary tumor, its vicinity, or in uninvolved sites such as the spleen, bone marrow, skin, and/or regional lymph nodes draining the tumor. It is a widely held view that SL granulomas are caused by soluble antigenic factors, shed by tumor cells or released due to tumor necrosis. SL reactions reported in Hodgkin lymphoma have been associated with a better prognosis. SL granulomas are thought to play an important role in the host's defenses against metastatic extension. SL granulomas have been reported in approximately 4.4% of carcinomas. Isolated cases of renal cell carcinoma (RCC) with SL granulomas have been reported with questionable prognostic significance. We identified 11 cases of RCCs with SL granulomas. Interestingly, all cases had abundant clear cell cytoplasm (10 clear cell RCC cases and 1 clear cell papillary RCC). We propose that this clear, abundant cytoplasm of the tumor cells with high content of glycogen and lipids may trigger granuloma formation akin to that seen in seminomas with SL granulomas. To date, this is the largest case series of RCCs with SL granulomas.



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Editorial Board

Publication date: October 2017
Source:Medical Image Analysis, Volume 41





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Editorial Board

Publication date: August 2017
Source:Medical Image Analysis, Volume 40





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New methods for the geometrical analysis of tubular organs

Publication date: Available online 29 July 2017
Source:Medical Image Analysis
Author(s): Florent Grélard, Fabien Baldacci, Anne Vialard, Jean-Philippe Domenger
This paper presents new methods to study the shape of tubular organs. Determining precise cross-sections is of major importance to perform geometrical measurements, such as diameter, wall-thickness estimation or area measurement. Our first contribution is a robust method to estimate orthogonal planes based on the Voronoi Covariance Measure. Our method is not relying on a curve-skeleton computation beforehand. This means our orthogonal plane estimator can be used either on the skeleton or on the volume. Another important step towards tubular organ characterization is achieved through curve-skeletonization, as skeletons allow to compare two tubular organs, and to perform virtual endoscopy. Our second contribution is dedicated to correcting common defects of the skeleton by new pruning and recentering methods. Finally, we propose a new method for curve-skeleton extraction. Various results are shown on different types of segmented tubular organs, such as neurons, airway-tree and blood vessels.

Graphical abstract

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d-Tyrosyl-tRNA Deacylase: A New Function

Publication date: Available online 29 July 2017
Source:Trends in Biochemical Sciences
Author(s): Richard Calendar
d-Aminoacyl-tRNA deacylase (DTD) hydrolyzes d-amino acids mistakenly attached to tRNAs and, thus, has been implicated in perpetuating protein homochirality. Fifty years after the discovery of DTD, it has now been shown that its function extends beyond 'chiral proofreading' because it also eliminates glycine that has been erroneously coupled to tRNA^Ala.



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The potential of proton therapy to reduce acute haematological toxicity in concurrent chemoradiotherapy for oesophageal cancer

Publication date: Available online 29 July 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Samantha Warren, Christopher N. Hurt, Thomas Crosby, Mike Partridge, Maria A. Hawkins
Radiotherapy dose escalation using a simultaneous integrated boost (SIB) is predicted to improve local tumour control in oesophageal cancer, yet any increase in acute haematological toxicity (HT) could limit the predicted improvement in patient outcome. Proton therapy has been shown to significantly reduce HT in lung cancer patients receiving concurrent chemotherapy, we therefore investigated the potential of bone marrow sparing with protons for oesophageal tumours.21 mid-oesophageal cancer patients treated with conformal radiotherapy (3D50) were selected. Two surrogates for bone marrow were created by outlining thoracic bones (bone) and only the body of the thoracic vertebrae (TV) in Eclipse (Varian). The % overlap of TV with the PTV was recorded for each patient. Additional plans were created retrospectively: a volumetric modulated arctherapy plan (VMAT50) with the same dose as 3D50; a VMAT SIB plan with a dose prescription of 62.5 Gy to the high risk sub-region within the planning treatment volume (VMAT62.5); a re-optimised TV sparing VMAT plan (VMAT62.5bm) and a proton therapy plan (SFO62.5) with the same SIB dose prescription. Bone and TV dose-metrics were recorded and compared across all plans and variation with respect to PTV size and % overlap for each patient was studied.3D50 plans show the highest bone mean dose and TV V30Gy values for each patient. VMAT plans irradiate a larger bone V10Gy volume than 3D50 plans. Re-optimised VMAT62.5bm plans showed improved sparing of the TV volume, but only proton plans showed significant sparing for bone V10Gy and bone mean dose, especially for patients with larger PTV size.

Teaser

Radiotherapy dose escalation is predicted to improve local tumour control in oesophageal cancer, yet any increase in acute haematological toxicity (HT) could limit the predicted improvement in patient outcome. We investigated the bone marrow dose of VMAT, proton plans, and marrow-sparing VMAT plans for oesophageal tumours. Improved marrow sparing was possible with VMAT, but only protons showed significant sparing for bone V10Gy and bone mean dose, especially for patients with larger PTV size.


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Reirradiation for Recurrent Pediatric CNS Malignancies: A Multi-Institutional Review

Publication date: Available online 29 July 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Avani D. Rao, Arif Rashid, Qinyu Chen, Rosangela C. Villar, Daria Kobyzeva, Kristina Nilsson, Karin Dieckmann, Alexey Nechesnyuk, Ralph Ermoian, Sara Alcorn, Shannon M. MacDonald, Matthew M. Ladra, Eric C. Ford, Brian A. Winey, Maria Luisa S. Figueiredo, Michael J. Chen, Stephanie A. Terezakis
PurposeReirradiation has been proposed as an effective modality for recurrent CNS malignancies for adults. We evaluated toxicity and outcomes of CNS reirradiation in pediatric patients.Methods and MaterialsPediatric patients age <21 years at time of initial diagnosis who developed a recurrent CNS malignancy treated with repeat radiation therapy (RT) across 5 facilities in an international pediatric research consortium were retrospectively reviewed.ResultsSixty-seven pediatric patients were treated with CNS reirradiation. Primary diagnoses included medulloblastoma/primitive neuroendocrine tumor (n=20, 30%), ependymoma (n=19, 28%), germ cell tumor (n=8, 12%), high grade glioma (n=9, 13%), low grade glioma (n=5, 7%), and other (n=6, 9%). Median age at first course of RT was 8.5 years (range:0.5-19.5 years) and 12.3 years (range:3.3-30.2 years) at time of reirradiation. The median time interval between RT courses was 2.0 years (range: 0.3-16.5). Median dose and fractionation of RT in equivalent 2 Gy fractions (EQD2) was 63.7 Gy (range 27.6-74.8 Gy) for initial RT and 53.1 Gy (range 18.6-70.1 Gy) for repeat RT. Location of relapse was infield in 52 patients (78%) and surrounding initial RT field in 15 patients (22%). Thirty-seven patients (58%) underwent gross- or sub-total resection at time of recurrence. Techniques for reirradiation were IMRT (n=46), 3D-CRT (n=9), SRS (n=4, 12-13Gyx1 or 5 Gyx5), protons (n=4), combined modality (n=3), 2D-RT (n=1), and brachytherapy (n=1). Radiation necrosis was detected in 2 cases after first course of RT and 1 additional patient after reirradiation. Six patients (9%) experienced secondary neoplasms following initial RT (1 hematologic, 5 intracranial neoplasms). One patient developed a secondary neoplasm identified shortly after repeat RT. Median overall survival following end of reirradiation was 12.8 months in the entire cohort and 20.5 and 8.4 months for patients with recurrent ependymoma and medulloblastoma following reirradiation.ConclusionsCNS reirradiation in pediatric patients may be a reasonable treatment option with moderate survival noted following repeat RT; although, prospective data characterizing rates of local control and toxicity are needed.

Teaser

This is a unique study evaluating the treatment parameters, toxicity, and outcomes of pediatric CNS reirradiation through a multi-national, multi-institutional pediatric research consortium. Low rates of radiation necrosis were observed and patients experienced reasonable survival rates following repeat radiation therapy to recurrent CNS tumors that may justify the risks of reirradiation.


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Hamartome conjonctif étendu de l’enfant

Publication date: Available online 29 July 2017
Source:Annales de Dermatologie et de Vénéréologie
Author(s): O. Lafargue, S. Fraitag, O. Boccara, F. Comoz, J. Rod, C. Turgis Mezerette, A. Dompmartin
IntroductionL'hamartome conjonctif (HC) est une anomalie rare des composants de la matrice extracellulaire qui se présente habituellement sous la forme de papules couleur de peau normale. Cette atteinte peut être syndromique ou sporadique.ObservationsNous rapportons deux cas d'HC isolés de l'enfant, très étendus et infiltrants, qui entraînaient un risque d'enraidissement articulaire. Il s'agissait d'un hamartome mixte et d'un collagénome.DiscussionIl est difficile de dater l'apparition de ces lésions qui passent souvent inaperçues au début. Devant un HC étendu, les principaux diagnostics différentiels à éliminer grâce à la biopsie cutanée sont la fasciite à éosinophiles et la morphée. L'HC peut être associé à des lésions d'osteopœcilie dans le syndrome de Buschke-Ollendorf, à rechercher par un bilan radiologique itératif. La prise en charge est symptomatique.BackgroundConnective tissue nevus (CTN) is a rare condition of the extracellular matrix components that generally presents as papulae of normal skin colour. This condition may be syndromic or sporadic.Patients and methodsWe report herein two isolated cases of extensive and infiltrative CTN in children at risk for subsequent joint stiffening. The pathology samples displayed respectively mixed hamartoma and a collagenoma.DiscussionThe onset of these lesions is often difficult to establish, since they are usually unnoticeable at first. When confronted with extensive CTN, the main differential diagnoses are eosinophilic fasciitis and morphea, and these must be ruled out by skin biopsy. CTN is associated with osteopoikilosis in Buschke-Ollendorf syndrome. Skeletal lesions are asymptomatic and are detected by means of iterative X-ray. Their management comprises symptomatic care.



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Hypersensibilité aux sels de platine et aux taxanes : intérêt des tests cutanés et des inductions de tolérance

Publication date: Available online 29 July 2017
Source:Annales de Dermatologie et de Vénéréologie
Author(s): F. Brault, J. Waton, C. Poreaux, J.-L. Schmutz, A. Barbaud
ButLes réactions d'hypersensibilité (HS) aux sels de platine (SP) et aux taxanes (TX) sont fréquentes. L'objectif de notre étude était d'évaluer l'intérêt des tests cutanés et des inductions de tolérance aux SP et TX.MéthodesIl s'agit d'une étude rétrospective réalisée entre janvier 2007 et février 2016, incluant les patients adressés pour suspicion d'HS immédiate ou retardée. Les tests cutanés, prick tests (pT) et intradermoréaction (IDR), étaient réalisés selon les recommandations de l'ENDA/EAACI et les inductions de tolérance (IT) selon un protocole en 12 paliers.RésultatsChez les 99 patients inclus (30 hommes, 69 femmes, âge moyen 60,4 ans), les SP étaient suspectés chez 86 et les TX chez 13. Les tests cutanés étaient positifs chez 25 patients (7 pT et 18 IDR), 23 avec les SP et 2 avec les TX. Une IT était proposée chez 50 patients, réalisée chez 33 (30 avec SP et 3 avec TX), bien supportée chez 29, nécessitant une adaptation chez 7 mais échouait chez 4 patients. Chez ces 4 derniers, les tests cutanés étaient positifs. Parmi les patients ayant des tests positifs à l'oxaliplatine, 75 % avaient une réaction d'HS lors de l'IT, soit une proportion deux fois plus grande que parmi les patients ayant des tests cutanés négatifs. Des réactions croisées survenaient dans 2 % des cas avec les SP et 7 % avec les TX.ConclusionCette expérience française confirme l'intérêt des IT en 12 étapes, permettant dans la plupart des cas de poursuivre une chimiothérapie chez un patient avec HS. Les tests cutanés sont utiles pour l'étude des réactions croisées, cependant leur réalisation doit être considérée au cas par cas.AimThe rate of hypersensitivity reactions to platinum salts (PS) and taxanes (TX) is on the increase. The aim of our study was to show the value of skin testing and efficacy of rapid drug desensitization.Patients and methodsThis was a retrospective study conducted between January 2007 and February 2016 in patients consulting for immediate or delayed hypersensitivity to PS and TX. Skin prick tests (pT) and intradermal reaction tests (IDR) were performed according to the ENDA/EAACI recommendations. We used a 12-step desensitization protocol for rapid drug desensitization.ResultsAmong the 99 patients included (30 men, 69 women, age 60.4) PS were suspected in 86 cases and taxanes in 13 cases. Skin tests were positive in 25 patients (7 pT, 18 IDR), 23 for platinum salts and 2 for taxanes. Rapid drug desensitization was proposed in 50 patients and performed in 33 (30 PS and 3 TX), proved effective in 29 patients, with protocol adaptation being necessary in 7 cases, and was ineffective in 4 patients. The skin tests for the latter 4 patients were positive. Seventy-five percent of patients with positive skin tests to oxaliplatin presented hypersensitivity reactions during desensitization, i.e. twice as many as patients having negative skin tests. Two percent of patient for PS and 7% for TX had cross reactivity.ConclusionThis French study confirms the efficacy of the 12-step protocol that allows patients to receive chemotherapy after hypersensitivity reaction. Skin test permits the detection of cross-reactions but their practice must be considered based on the patient's history.



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Strategies for Decreasing Screening Mammography Recall Rates While Maintaining Performance Metrics

Publication date: Available online 29 July 2017
Source:Academic Radiology
Author(s): Lisa A. Mullen, Babita Panigrahi, Jacqueline Hollada, Benita Panigrahi, Eniola T. Falomo, Susan C. Harvey
Rationale and ObjectiveThis study aimed to determine the impact of interventions designed to reduce screening mammography recall rates on screening performance metrics.Materials and MethodsWe assessed baseline performance for full-field digital mammography (FFDM) and digital breast tomosynthesis mammography (DBT) for a 3-year period before intervention. The first intervention sought to increase awareness of recalls from screening mammography. Breast imagers discussed their perceptions regarding screening recalls and were required to review their own recalled cases, including outcomes of diagnostic evaluation and biopsy. The second intervention implemented consensus double reading of all recalls, requiring two radiologists to agree if recall was necessary. Recall rates, cancer detection rates, and positive predictive value 1 (PPV1) were compared before and after each intervention.ResultsThe baseline recall rate, cancer detection rate, and PPV1 were 11.1%, 3.8/1000, and 3.4%, respectively, for FFDM, and 7.6%, 4.8/1000, and 6.0%, respectively, for DBT. Recall rates decreased significantly to 9.2% for FFDM and to 6.6% for DBT after the first intervention promoting awareness, as well as to 9.9% for FFDM after the second intervention implementing group consensus. PPV1 increased significantly to 5.7% for FFDM and to 9.0% for DBT after the second intervention. Cancer detection rate did not significantly change with the implementation of these interventions. An average of 2.3 minutes was spent consulting for each recall.ConclusionReduction in recall rates is desirable, provided performance metrics remain favorable. Our interventions improved performance and could be implemented in other breast imaging settings.



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Does the Oral “Mock Board” Examination Still Have a Role as a Training Tool?

Publication date: Available online 29 July 2017
Source:Academic Radiology
Author(s): Colin Strickland, Alexandria Jensen, Tatum McArthur
Rationale and ObjectivesThe American Board of Radiology has adopted a new standardized board examination and the traditional oral examination has been abandoned. Although many programs have changed their educational efforts to reflect the new test format, some faculty members and residents have expressed a desire to keep an oral examination as a component of education and evaluation in radiology residency programs.Materials and MethodsAn oral comprehensive examination including all the appropriate subspecialties was administered to each second year and third year resident in our training program by faculty members. Both the resident examinees and faculty examiners were surveyed after the examination to gauge the perceived value of the experience.ResultsResidents were divided in their perceptions of the fairness and utility of an oral examination as a tool to aid in board preparation and as an assessment of their knowledge and communication skill. Faculty members were universal in their endorsement of the oral examination and suggested continued use of the technique.ConclusionsResidents and faculty members have differing perceptions of an oral examination delivered during training to assess knowledge and communication skill. The value of an oral examination in providing actionable feedback to trainees and the possibility of detecting struggling residents made it useful in our training program, and it thus it has been implemented for future years. Whether resident performance measured by this technique is predictive of success on American Board of Radiology examinations remains unclear.



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The Addition of Automated Breast Ultrasound to Mammography in Breast Cancer Screening Decreases Stage at Diagnosis

Publication date: Available online 29 July 2017
Source:Academic Radiology
Author(s): Ian Grady, Nailya Chanisheva, Tony Vasquez
Rationale and ObjectivesThis study aimed to determine the best screening strategy using automated whole-breast ultrasound and mammography in women with increased breast density or an elevated risk of breast cancer.Materials and MethodsAfter an institutional review board waiver was obtained, a retrospective review of 122 cancer cases diagnosed in 3435 women with increased breast density or an elevated risk of breast cancer, screened with mammography and supplemental automated whole-breast ultrasound, was performed. The imaging modality on which each cancer was seen was noted. Screening strategies were postulated.For each screening strategy, rates of advanced cancer diagnosis, with 95% confidence limits, are calculated using the Clopper-Pearson method. Differences in outcomes were calculated using Cochrane Q test and McNemar test for paired observations. Results were expressed for all stages of cancer and for invasive cancers only.ResultsWhen all cancer stages are considered, mammographic screening reduces advanced cancers by 31% over no screening. Ultrasound-only screening results in a 32% reduction. The combination of mammographic and ultrasound screening reduces advanced cancers by 40% (P < .05).Compared to mammographic screening, mammographic plus ultrasound screening reduces advanced-stage cancers by 5.7% (P = 0.03) for all stages and 10.8% (P = 0.02) for invasive cancers.ConclusionsFor women with increased breast density or who are at high risk of developing breast cancer, a combination of screening mammography and whole-breast automated ultrasound is superior to mammographic screening. Screening ultrasound alone is also an effective screening strategy.



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Auditory Dysfunction in Patients with Huntington’s Disease

Publication date: Available online 29 July 2017
Source:Clinical Neurophysiology
Author(s): Oliver Profant, Jan Roth, Zbyněk Bureš, Zuzana Balogová, Irena Lišková, Jan Betka, Josef Syka
ObjectiveHuntingtońs disease (HD) is an autosomal, dominantly inherited, neurodegenerative disease. The main clinical features are motor impairment, progressive cognitive deterioration and behavioral changes. The aim of our study was to find out whether patients with HD suffer from disorders of the auditory system.MethodsA group of 17 genetically verified patients (11 males, 6 females) with various stages of HD (examined by UHDRS – motor part and total functional capacity, MMSE for cognitive functions) underwent an audiological examination (high frequency pure tone audiometry, otoacoustic emissions, speech audiometry, speech audiometry in babble noise, auditory brainstem responses). Additionally, 5 patients underwent a more extensive audiological examination, focused on central auditory processing. The results were compared with a group of age-matched healthy volunteers.ResultsOur results show that HD patients have physiologic hearing thresholds, otoacoustic emissions and auditory brainstem responses; however, they display a significant decrease in speech understanding, especially under demanding conditions (speech in noise) compared to age-matched controls. Additional auditory tests also show deficits in sound source localization, based on temporal and intensity cues. We also observed a statistically significant correlation between the perception of speech in noise, and motoric and cognitive functions. However, a correlation between genetic predisposition (number of triplets) and function of inner ear was not found.ConclusionsWe conclude that HD negatively influences the function of the central part of the auditory system at cortical and subcortical levels, altering predominantly speech processing and sound source lateralization.SignificanceWe have thoroughly characterized auditory pathology in patients with HD that suggests involvement of central auditory and cognitive areas.



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Benevolent personification of the MoH increases compliance with an emergency polio vaccination

Publication date: Available online 29 July 2017
Source:Vaccine
Author(s): Golan Shahar, Gal Noyman-Veksler, Shai Itamar, David Greenberg, Itamar Grotto
ObjectiveParental compliance is crucial to the success of mass vaccination campaigns targeting children. Relying on psychological/neuroscientific research concerning the role of personification (i.e., viewing the inanimate as human) in behavior, the authors examined the effect of parents' personification of the Israeli Ministry of Health (MoH) on compliance with a publicly controversial mass vaccination campaign, which was aimed at stopping the spread of a wild poliovirus.MethodsParticipants were 555 parents of children aged 9 or younger, residing in the center/north of Israel, an area covered by Phase 2 of the campaign. T1 assessment, employed two days prior to Phase 2, tapped into demographics, attitudes towards vaccination, intent to comply, and a benevolent personification of the MoH (i.e., "The MoH is caring") vs. a malevolent personification of the MoH ("The MoH is hysteric"). T2 assessment, transpiring four months after the end of the campaign, addressed presence and reasons for (non-)compliance.ResultsThe study's overall compliance rate was 61.8%. The principal reason for compliance was "adherence to the recommendations of the MoH" (68.49%). In a multivariate logistic regression analysis, prospective predictors of compliance were: an early intent to comply (O.R.=2.56, p=0.000), being male (O. R.=1.51, p=0.023), and a benevolent personification of the MoH (O.R.=1.21, p=0.019).ConclusionParents who experienced the Israeli MoH as a benevolent protagonist were more likely to comply with the mass vaccination campaign. Findings highlight the role of leadership in public health campaigns during emergencies.



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Macrophage-derived insulin-like growth factor-1 affects influenza vaccine efficacy through the regulation of immune cell homeostasis

Publication date: Available online 29 July 2017
Source:Vaccine
Author(s): Il-Sub Yoon, Hyelim Park, Hye-Won Kwak, Yong Woo Jung, Jae-Hwan Nam
The level of antibody production induced by a vaccine involves a variety of host factors. One of these, insulin-like growth factor-1 (IGF-1), plays an important role in lymphocyte maturation and antibody expression. Here, we investigated the role of macrophage-derived IGF-1 in the induction of influenza vaccine-specific antibodies using macrophage-derived IGF-1 gene knockout (MIKO) mice. The titers of vaccine-specific total immunoglobulin G (IgG) and IgG1 after immunization were about two- to fourfold lower in MIKO mice than in WT mice. Moreover, MIKO mice showed a relatively weak booster effect of repeated immunization. In contrast, antigen-nonspecific total IgG was about threefold higher in MIKO mice than in WT mice. After viral challenge, the viral titer and the pathological damage in lungs of MIKO mice were higher than those in WT mice despite vaccination. Interestingly, the proportions of proinflammatory immune cells including M1 macrophages, Th1 and Th17 cells was higher in unvaccinated MIKO mice than in unvaccinated WT mice. This suggests that nonspecific activation of immune cells may paradoxically impair the response to the vaccine. In addition, although the proportions of T follicular helper (Tfh) cells and GL-7⁺ germinal center (GC) B cells were higher in MIKO mice than in WT mice, the population of CD138⁺B220⁺ antibody-secreting plasmablasts was lower in MIKO mice, which may be a cause of the low influenza-specific antibody titer in MIKO mice. Taken together, these results suggest that macrophage-derived IGF-1 might play an important role in the vaccine-triggered immune response by regulating immune cell homeostasis.



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Influenza vaccination rates in children decline when the live attenuated influenza vaccine is not recommended

Publication date: Available online 29 July 2017
Source:Vaccine
Author(s): Benjamin Fogel, Steven Hicks
BackgroundIn 2016 the Centers for Disease Control and Prevention (CDC) recommended against using the live attenuated influenza vaccine (LAIV) for the 2016–2017 influenza season. This recommendation is potentially important for vaccination rates because perceived effectiveness and ease of administration are among the primary determinants of families decisions to vaccinate their children. This investigation sought to determine whether rates of pediatric influenza vaccination changed in a season when the LAIV was not recommended.MethodsThis study used cohort and cross sectional data from an academic primary care pediatric center in central Pennsylvania that serves approximately 12,500 patients. Early season (prior to November 1) and end-of-season (prior to March 1) vaccination rates in the 2015–16 and 2016–17 influenza seasons were recorded for individuals 2–17years old. Repeat vaccination rates (percentage of children receiving influenza vaccination in one season who were also vaccinated in the next season) were recorded for the 2015–16 into 2016–17 seasons. A logistic regression model adjusting for race, ethnicity, age, insurance type and type of vaccination received was employed to identify predictors of repeat vaccination.ResultsIn the absence of LAIV (2016–17) early vaccination rates were significantly higher (24.7% vs 22.8%, p=0.004), but end-of-season rates were lower (50.4% vs 52.0%, p=0.03) than when LAIV was offered (2015–16). After adjusting for covariates, those who had received IIV in the 2015–16 season had higher odds (OR 1.32, 95% CI, 1.15–1.52) of getting a repeat vaccination in the 2016–17 season, compared with those who had received LAIV in the 2015–16 season.ConclusionsEnd-of-season vaccination rates were lower in 2016–17 when LAIV was not recommended, particularly among children who received LAIV in the preceding year. Unavailability of LAIV in the 2016–17 season may have impacted influenza vaccination convenience and perceived effectiveness, two factors which could influence vaccine uptake in pediatric populations.

Graphical abstract

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Summary of workshop “global burden of diarrheal diseases among children in developing countries: Incidence, etiology, and insights from new molecular diagnostic techniques”

Publication date: Available online 29 July 2017
Source:Vaccine
Author(s): Karen L. Kotloff, James A. Platts-Mills, Dilruba Nasrin, Anna Roose, William C. Blackwelder, Myron M. Levine
The Global Enteric Multicenter Study (GEMS) demonstrated that Shigella and enterotoxigenic Escherichia coli (ETEC) producing heat stable toxin (ST) (either alone or in combination with heat labile toxin) are among the most important pathogens associated with moderate-to-severe diarrhea (MSD) in children younger than 5years of age living in developing countries. To inform the design of vaccines and other interventions, we reviewed published data and new results from GEMS characterizing the burden of Shigella and ST-ETEC infections. Clinical parameters were assessed to examine the value of various case definitions as indicators of MSD associated with Shigella and ST-ETEC for use in clinical trials. We discussed advantages and disadvantages of culture-based and culture-independent molecular diagnostics for detecting clinically and epidemiologically relevant disease. Shigella serotyping data from GEMS were examined to identify desirable components of Shigella and ETEC vaccines likely to confer broad protection. These findings can inform the development and implementation of vaccines to prevent these important infections among infants and children in developing countries.



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WHO position paper, Meningococcal A conjugate vaccine: Updated guidance, February 2015

Publication date: Available online 29 July 2017
Source:Vaccine
Author(s): World Health Organization
This article presents the World Health Organization's (WHO) updated recommendations on the use of meningococcal vaccines excerpted from the WHO position paper on Meningococcal A conjugate vaccine: updated guidance, February 2015, published in the Weekly Epidemiological Record [1].A position paper on meningococcal vaccines was published in 2011 and its recommendations remain valid [2]. This update adds to the previous recommendations specifically concerning routine immunization of infants and young children in the African meningitis belt with meningococcal A conjugate vaccine.Footnotes to this paper provide a number of core references including references to grading tables that assess the quality of the scientific evidence. In accordance with its mandate to provide guidance to Member States on health policy matters, WHO issues a series of regularly updated position papers on vaccines and combinations of vaccines against diseases that have an international public health impact. These papers are concerned primarily with the use of vaccines in large-scale immunization programmes; they summarize essential background information on diseases and vaccines, and conclude with WHO's current position on the use of vaccines in the global context. Recommendations on the use of the Meningococcal A conjugate vaccine were discussed by SAGE in October 2014; evidence presented at these meetings can be accessed at: http://ift.tt/2u7r0k0.



http://ift.tt/2tRM03k

Chronically ill adolescents are also incompletely vaccinated: A cross-sectional study in France

Publication date: Available online 29 July 2017
Source:Vaccine
Author(s): Christèle Gras-Le Guen, Arnaud Legrand, Marylène Caquard, Xavier Micaelli, Georges Picherot, Sylvie Lacroix, Christelle Volteau, Elise Launay
BackgroundAdolescent vaccination coverage tends to be suboptimal, leading to resurgent infectious pathologies and vulnerability to various pathogens. The low frequency of medical consultations and missed opportunities for vaccination are often used to explain the low rate of vaccination. The aim of this study was to assess if the vaccination coverage rate is higher in chronically ill adolescents (CIA) who require a close pediatric specialized follow-up versus the rate in healthy adolescents (HA).MethodsA monocentric cross-sectional study was conducted in the Nantes University Hospital. We included 114 CIA and 266 HA. The vaccination coverage rate and the up-to-date immunization status were compared between ill versus healthy adolescents for each of the following vaccines: diphtheria, tetanus, acellular pertussis, inactivated poliovirus (DTaP/IPV), measles-mumps-rubella (MMR), hepatitis B (HepB), meningococcal C conjugate (MnC), human papillomavirus (HPV) and composite combinations (e.g. DTaP/IPV-MMR-HepB-MnC).ResultsThe overall immunization rate for DTaP/IPV-MMR-HepB-MnC was very low, with no significant difference between CIA and HA (9.6% versus 13.5%; p=0.28). Most of the investigated vaccines exhibited similar immunization patterns for the two groups: DTaP/IPV (77.2vs. 76.7%; p=0.97), MMR (92.1vs. 95.9%; p=0.14), HepB (51.8vs. 48.5%; p=0.51) with the exception of the MnC (18.4vs. 27.8%; p=0.05) and HPV (28.6vs. 16.1%; p=0.04).ConclusionDespite undergoing specialized and close medical follow-up, we found that the vaccination coverage rate for the CIA remained suboptimal. This indicates that pediatricians need to check the vaccination status and, when required, ensure that the vaccination schedules for these fragile patients are up-to-date.



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Measles vaccines: WHO position paper, April 2017 – Recommendations

Publication date: Available online 29 July 2017
Source:Vaccine
Author(s): World Health Organization
This article presents the World Health Organization's (WHO) recommendations on the use of measles vaccines excerpted from the WHO position paper on Measles vaccines: WHO position paper – April 2017, published in the Weekly Epidemiological Record [1]. This position paper replaces the 2009 WHO position paper on measles vaccines [2]. The position paper summarizes the most recent developments in the field of measles and includes removal of introduction criteria for the routine second dose of measles-containing vaccine (MCV2), guidance on when to vaccinate infants from 6months of age, and guidance on re-vaccination of HIV-infected children receiving highly active anti-retroviral therapy (HAART).Footnotes to this paper provide a number of core references including references to grading tables that assess the quality of the scientific evidence, and to the evidence-to-recommendation table. In accordance with its mandate to provide guidance to Member States on health policy matters, WHO issues a series of regularly updated position papers on vaccines and combinations of vaccines against diseases that have an international public health impact. These papers are concerned primarily with the use of vaccines in large-scale immunization programmes; they summarize essential background information on diseases and vaccines, and conclude with WHO's current position on the use of vaccines in the global context. Recommendations on the use of measles vaccines were discussed by SAGE in November 2013, October 2015 and October 2016; evidence presented at these meetings can be accessed at: http://ift.tt/2tSkItk, http://ift.tt/2u7wCuL and http://ift.tt/2owj3Da.



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Socioeconomic risk factors for cholera in different transmission settings: An analysis of the data of a cluster randomized trial in Bangladesh

Publication date: Available online 29 July 2017
Source:Vaccine
Author(s): Amit Saha, Andrew Hayen, Mohammad Ali, Alexander Rosewell, John D. Clemens, C. Raina MacIntyre, Firdausi Qadri
BackgroundCholera remains a threat globally, and socioeconomic factors play an important role in transmission of the disease. We assessed socioeconomic risk factors for cholera in vaccinated and non-vaccinated communities to understand whether the socioeconomic risk factors differ by transmission patterns for cholera.MethodsWe used data from a cluster randomized control trial conducted in Dhaka, Bangladesh. There were 90 geographic clusters; 30 in each of the three arms of the study: vaccine (VAC), vaccine plus behavioural change (VBC), and non-intervention. The data were analysed for the three populations: (1) vaccinees in the vaccinated communities (VAC and VBC arms), (2) non-vaccinated individuals in the vaccinated communities and (3) all individuals in the non-vaccinated communities (non-intervention arm). A generalized estimating equation with logit link function was used to evaluate the risk factors for cholera among these different populations adjusting for household level correlation in the data.ResultsA total of 528 cholera and 226 cholera with severe dehydration (CSD) in 268,896 persons were observed during the two-year follow-up. For population 1, the cholera risk was not associated with any socioeconomic factors; however CSD was less likely to occur among individuals living in a household having ≤4 members (aOR=0.55, 95% CI=0.32–0.96). Among population 2, younger participants and individuals reporting diarrhoea during registration were more likely to have cholera. Females and individuals reporting diarrhoea during registration were at increased risk of CSD. Among population 3, individuals living in a household without a concrete floor, in an area with high population density, closer to the study hospital, or not treating drinking water were at significantly higher risk for both cholera and CSD.ConclusionThe profile of socioeconomic factors associated with cholera varies by individuals' vaccination status as well as the transmission setting. In a vaccinated community where transmission would be expected to be lower, socioeconomic factors may not increase the risk of the disease.



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The benefit of the doubt or doubts over benefits? A systematic literature review of perceived risks of vaccines in European populations

Publication date: Available online 29 July 2017
Source:Vaccine
Author(s): Emilie Karafillakis, Heidi J. Larson
ObjectivesThe success of vaccination strategies depends in part on population perceptions of benefits and risks of vaccines and related confidence in vaccination. Better knowledge of public concerns about vaccines and what is driving them is needed to inform vaccination strategies and communications. This literature reviewer examined studies on vaccine and vaccination risk perceptions and concerns across European populations.MethodsA systematic literature review was conducted to identify studies published between 2004 and 2014 in Europe. A descriptive analysis was performed.FindingsA total of 145 articles were selected, most of which were conducted in the UK, the Netherlands and France and studied seasonal influenza, HPV and pandemic influenza vaccination. Across all countries and vaccines, the primary area of concern was vaccine safety, followed by perceptions of low likelihood of contracting vaccine-preventable diseases (VPDs), perceived low severity of VPDs, beliefs that vaccines do not work, and overall lack of information. Concerns were found to be vaccine-, country- and population-specific.ConclusionIn addition to identifying concerns about vaccination in Europe, this study confirmed the notion that individuals have many safety concerns about vaccination and often believe that the risks of vaccination outweigh their benefits. More research needs to be conducted to explore the impact of different types of communication strategies, which would frame the benefits of vaccination as well as risks of not vaccinating. Strategies to better inform public perceptions of vaccines should include the provision of unbiased, comprehensive information tailored to population information needs, and delivered using multiple and new communication technologies such as social media.



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Regulatory considerations in development of vaccines to prevent disease caused by Chikungunya virus

Publication date: Available online 29 July 2017
Source:Vaccine
Author(s): Sixun Yang, Doran Fink, Andrea Hulse, R. Douglas Pratt
Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus. Chikungunya disease (CHIK) in humans is characterized by sudden onset of high fever, cutaneous rash, myalgia and debilitating polyarthralgia. Until recently the virus was considered endemic to only Africa and Asia, but since 2004 CHIK has spread to previously non-endemic regions, including Europe and the Americas, thereby emerging as a global health threat. Although a variety of CHIKV vaccine candidates have been tested in animals, and a few have advanced to human clinical trials, no licensed vaccine is currently available for prevention of disease. In this article, we review recent efforts in CHIKV vaccine development and discuss regulatory considerations for CHIKV vaccine licensure under U.S. FDA regulations. Several licensure pathways are available, and the most appropriate licensure pathway for a CHIK vaccine will depend on the type of evidence that can be generated to demonstrate the vaccine's effectiveness. If "traditional approval" following demonstration of direct benefit in adequate and well-controlled clinical disease endpoint studies is not possible, the Accelerated Approval and Animal Rule pathways are potential alternatives. In terms of vaccine safety, the potential for vaccine associated arthralgia and antibody-dependent enhancement of infectivity and disease severity are important issues that should be addressed in both pre-clinical and clinical studies. CHIK vaccine developers are encouraged to communicate with the FDA during all stages of vaccine development.



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Improving the prediction of overall survival for head and neck cancer patients using image biomarkers in combination with clinical parameters

Publication date: Available online 29 July 2017
Source:Radiotherapy and Oncology
Author(s): Tian-Tian Zhai, Lisanne V. van Dijk, Bao-Tian Huang, Zhi-Xiong Lin, Cássia O. Ribeiro, Charlotte L. Brouwer, Sjoukje F. Oosting, Gyorgy B. Halmos, Max J.H. Witjes, Johannes A. Langendijk, Roel J.H.M. Steenbakkers, Nanna M. Sijtsema
PurposeTo develop and validate prediction models of overall survival (OS) for head and neck cancer (HNC) patients based on image biomarkers (IBMs) of the primary tumor and positive lymph nodes (Ln) in combination with clinical parameters.Material and methodsThe study cohort was composed of 289 nasopharyngeal cancer (NPC) patients from China and 298 HNC patients from the Netherlands. Multivariable Cox-regression analysis was performed to select clinical parameters from the NPC and HNC datasets, and IBMs from the NPC dataset. Final prediction models were based on both IBMs and clinical parameters.ResultsMultivariable Cox-regression analysis identified three independent IBMs (tumor Volume-density, Run Length Non-uniformity and Ln Major-axis-length). This IBM model showed a concordance(c)-index of 0.72 (95%CI: 0.65–0.79) for the NPC dataset, which performed reasonably with a c-index of 0.67 (95%CI: 0.62–0.72) in the external validation HNC dataset. When IBMs were added in clinical models, the c-index of the NPC and HNC datasets improved to 0.75 (95%CI: 0.68–0.82; p=0.019) and 0.75 (95%CI: 0.70–0.81; p<0.001), respectively.ConclusionThe addition of IBMs from the primary tumor and Ln improved the prognostic performance of the models containing clinical factors only. These combined models may improve pre-treatment individualized prediction of OS for HNC patients.



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Profile of European proton and carbon ion therapy centers assessed by the EORTC facility questionnaire

Publication date: Available online 29 July 2017
Source:Radiotherapy and Oncology
Author(s): Damien C. Weber, André Abrunhosa-Branquinho, Alessandra Bolsi, Andrzej Kacperek, Rémi Dendale, Dirk Geismar, Barbara Bachtiary, Annika Hall, Jens Heufelder, Klaus Herfarth, Jürgen Debus, Maurizio Amichetti, Mechthild Krause, Roberto Orecchia, Vladimir Vondracek, Juliette Thariat, Tomasz Kajdrowicz, Kristina Nilsson, Cai Grau
BackgroundWe performed a survey using the modified EORTC Facility questionnaire (pFQ) to evaluate the human, technical and organizational resources of particle centers in Europe.Material and methodsThe modified pFQ consisted of 235 questions distributed in 11 sections accessible on line on an EORTC server. Fifteen centers from 8 countries completed the pFQ between May 2015 and December 2015.ResultsThe average number of patients treated per year and per particle center was 221 (range, 40–557). The majority (66.7%) of centers had pencil beam or raster scanning capability. Four (27%) centers were dedicated to eye treatment only. An increase in the patients-health professional FTE ratio was observed for eye tumor only centers when compared to other centers. All centers treated routinely chordomas/chondrosarcomas, brain tumors and sarcomas but rarely breast cancer. The majority of centers treated pediatric cases with particles. Only a minority of the queried institutions treated non-static targets.ConclusionsAs the number of particle centers coming online will increase, the experience with this treatment modality will rise in Europe. Children can currently be treated in these facilities in a majority of cases. The majority of these centers provide state of the art particle beam therapy.



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Pulsed-dose rate brachytherapy for pediatric bladder prostate rhabdomyosarcoma: Compliance and early clinical results

Publication date: Available online 28 July 2017
Source:Radiotherapy and Oncology
Author(s): Cyrus Chargari, Hélène Martelli, Florent Guérin, Warren Bacorro, Guénolée de Lambert, Alexandre Escande, Véronique Minard-Colin, Isabelle Dumas, Eric Deutsch, Christine Haie-Meder
ObjectiveNo data are available on the feasibility of pulsed dose rate (PDR) brachytherapy in very young children. Our experience of PDR brachytherapy for bladder prostate (BP) rhabdomyosarcoma (RMS) is reported, with focus on compliance and dosimetric parameters.Materials and methodsTreatment parameters and outcome of consecutive BP RMS patients treated in our center were examined. Treatment was carried out as part of a multimodal conservative radio-surgical treatment. Four single leader plastic tubes were implanted under perioperative guidance, encompassing the prostate/bladder neck. Tubes were systematically sutured to the bladder wall. Treatment planning was based on a computed tomography and followed Paris system rules. Continuous hourly pulses of 0.42Gy were delivered, to a total dose of 60Gy.Results32 patients were treated, median age 2.6years (10months–12years). Median duration of each pulse was 8.5min (3.8–17.4min). The minimal dose in the most irradiated 1cm³ of rectum was 44.7Gyα/β=3 (range: 4.1–77.3Gyα/β=3). Brachytherapy was conducted without significant compliance concern in all but two patients, 24 and 25months-old, who pulled out plastic tubes before treatment completion. Another child needed re-planning because of slight tube displacement. With median follow-up of 14.4months (15days–75months), all patients were free from any relapse after local treatment. Four grade 3 acute urinary complications were encountered. All long-term side effects were grade 2 or less.ConclusionPDR brachytherapy is feasible in very young patients, and associated with acceptable acute toxicity rates. Longer follow-up is required to ensure that local control and long-term side effects profile are comparable to the results of low dose rate brachytherapy.



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Partial breast irradiation with interstitial multi-catheter high-dose-rate brachytherapy. Long-term results of a phase II prospective study

Publication date: Available online 29 July 2017
Source:Radiotherapy and Oncology
Author(s): Cynthia Aristei, Ernesto Maranzano, Valentina Lancellotta, Luigia Chirico, Claudio Zucchetti, Marco Italiani, Paola Anselmo, Cristina Mariucci, Elisabetta Perrucci, Fabio Arcidiacono, Fabio Trippa, György Kovacs, Vittorio Bini, Isabella Palumbo
PurposeWe report the long-term results of phase II prospective study with accelerated partial breast irradiation (APBI) using interstitial multi-catheter high-dose-rate brachytherapy.Methods240 patients received APBI (4Gy, twice daily; total dose 32Gy).ResultsMedian follow-up was 96months. Recurrences in the treated breast developed in 8 patients (3.3%) at a median of 73months after APBI. The 5- and 10-year cumulative incidences were respectively, 1.8% (95%CI: 0.6–4.3) and 6.6% (95%CI: 2.7–12.9). Regional recurrences developed in 5 patients (2%) at a median of 28months and distant metastases in 8 (3.3%) at a median of 32.5months. Breast cancer specific mortality occurred in 6 patients (2.5%) at a median of 60months. Acute toxicity developed in 71 (29.6%) patients (G1 in 60 and G2 in 11). Almost all were skin toxicity and hematomas. Late toxicity was observed in 90 patients (37.5%), G1 in 97 cases and G2 in 11. Some patients presented with more than one type of toxicity. Teleangectasia and fibrosis were the most common (48 and 44 cases respectively), followed by fat necrosis (in 18 patients) Tamoxifen emerged as the only risk factor for breast fibrosis (p=0.007). Cosmetic results were judged by the physicians as excellent in 174 (83.7%) patients, good in 25 (12%) fair in 8 (3.8%) and poor in 1 (0.5%); 174 patients (83.7%) judged outcomes as excellent, 26 (12.4%) as good, 7 (3.4%) as fair and 1 (0.5%) as poor. Physician/patient agreement was good (weighted k-value 0.72).ConclusionsAPBI with interstitial multi-catheter brachytherapy was associated with good outcomes, low relapse and toxicity rates. Few events during this long-term follow-up preclude identifying specific features of patients at risk of relapse and illustrate the need for a large data-base.



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Anandamide-ceramide interactions in a membrane environment: Molecular dynamic simulations data

Publication date: October 2017
Source:Data in Brief, Volume 14
Author(s): Coralie Di Scala, Morgane Mazzarino, Nouara Yahi, Karine Varini, Nicolas Garmy, Jacques Fantini, Henri Chahinian
Anandamide is a lipid neurotransmitter that interacts with various plasma membrane lipids. The data here consists of molecular dynamics simulations of anandamide, C18-ceramide and cholesterol performed in vacuo and within a hydrated palmitoyl-oleoyl-phosphatidylcholine (POPC)/cholesterol membrane. Several models of anandamide/cholesterol and anandamide/ceramide complexes are presented. The energy of interaction and the nature of the intermolecular forces involved in each of these complexes are detailed. The impact of water molecules hydrating the POPC/cholesterol membrane for the stability of the anandamide/cholesterol and anandamide/ceramide complexes is also analyzed. From a total number of 1920 water molecules stochatiscally merged with the lipid matrix, 48 were eventually redistributed around the polar head groups of the anandamide/ceramide complex, whereas only 15 reached with the anandamide/cholesterol complex. The interpretation of this dataset is presented in the accompanying article "Ceramide binding to anandamide increases its half-life and potentiates its cytotoxicity in human neuroblastoma cells" [1].



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Data and analyses of woody restoration planting survival and growth as a function of wild ungulate herbivory

Publication date: October 2017
Source:Data in Brief, Volume 14
Author(s): Joshua P. Averett, Michael J. Wisdom, Bridgett J. Naylor, Mary M. Rowland, Bryan A. Endress
These data and analyses support the research article "Wild ungulate herbivory suppresses deciduous woody plant establishment following salmonid stream restoration" Averett et al. (2017) [1]. The data and analyses presented here include: (1) planting density, survival and growth (two years post restoration) of riparian plantings along an ~11km stream reach in northeastern Oregon as a function of herbivory treatment (protected/not protected from wild ungulate herbivory), habitat type, and planting species; and (2) abundance and height distributions of naturally occurring deciduous woody species along the restored stream reach two years post restoration. Survival and growth analyses are provided as output from multiple logistic and mixed effect regression models respectively.



http://ift.tt/2vSGtXz

Application of Cu/Mg/Al-chitosan-O3 system for landfill leachate treatment: Experimental and economic evaluation data

Publication date: October 2017
Source:Data in Brief, Volume 14
Author(s): Dariush Ranjbar Vakilabadi, Bahman Ramavandi, Amir Hessam Hassani, Ghasemali Omrani
Landfill leachate contains heavy organic pollutants, which pollute ground and surface waters. This dataset applied a newly-introduced catalyst, Cu/Mg/Al-chitosan, for a landfill leachate treatment during a catalytic oxidation. The data of chemical oxygen demand (COD) and colour removal from the leachate was reported as a function of reaction time (20–460min). Economic evaluation data of the Cu/Mg/Al-chitosan-O3 system showed that the current cost of the system for treating each m³ leachate is US$ 18 and for catalyst synthesis is US$ 54.5. Data could be useful from environmental and economic perspectives to those concerned about landfill leachate threats.



http://ift.tt/2uHZu0d

Dataset on energy efficiency assessment and measurement method for child-friendly space in cold residential area

Publication date: October 2017
Source:Data in Brief, Volume 14
Author(s): Kai Ren, Leiqing Xu
The data related in this paper are related to "Environmental-behavior studies of sustainable construction of the third place – based on outdoor environment-behavior cross-feed symbiotic analysis and verification of selective activities" (Ren, 2017) [1]. The dataset was from a field sub-time extended investigation to children of Hohhot West Inner Mongolia Electric Power Community Residential Area in Inner Mongolia of China that belongs to cold region of ID area according to Chinese design code for buildings. This filed data provided descriptive statistics about outdoor time, behavior scale specificity, age exclusivity and self-centeredness for children in different ages (babies, preschool children, school age children). This data provided five measurement elements of child-friendly space and their weight ratio. The field data set is made publicly available to enable critical or extended analyzes.



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Exploration of UK Lotto results classified into two periods

Publication date: October 2017
Source:Data in Brief, Volume 14
Author(s): Hilary I. Okagbue, Muminu O. Adamu, Pelumi E. Oguntunde, Abiodun A. Opanuga, Manoj K. Rastogi
United Kingdom Lotto results are obtained from urn containing some numbers of which six winning numbers and one bonus are drawn at each draw event. There is always a need from prospective players for analysis that can aid them in increasing their chances of winning. In this paper, historical data of the United Kingdom Lotto results were grouped into two periods (19/11/1994–7/10/2015 and 10/10/2015–10/5/2017). The classification was as a result of increase of the lotto numbers from 49 to 59. Exploratory statistical and mathematical tools were used to obtain new patterns of winning numbers. The data can provide insights on the random nature and distribution of the winning numbers and help prospective players in increasing their chances of winning the lotto.



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Quantitative exploration of factors influencing psychotic disorder ailments in Nigeria

Publication date: October 2017
Source:Data in Brief, Volume 14
Author(s): Adebowale O. Adejumo, Nehemiah A. Ikoba, Esivue A. Suleiman, Hilary I. Okagbue, Pelumi E. Oguntunde, Oluwole A. Odetunmibi, Obalowu Job
In this data article, records on demographic data, family problem issues, as well as results of medical tests from five major classes of psychotic disorder namely: bipolar; vascular dementia, minimal brain dysfunction; insomnia; and schizophrenia, were collected on 500 psychotic patients carefully selected from the pool of medical records of Yaba Psychiatric Hospital, Lagos, Nigeria, for the period of 5 years, between January 2010 and December 2014, were examined. X-squared Statistic was used to examine each of psychotic disorders to identify demographic (age, gender, religion, marital status, and occupation) and family issues (loss of parent, history of such ailment in the family (family status), divorce, head injury, and heredity of such ailment (genetic) factors that influence them. A clear description on each of these psychotic disorders (bipolar; vascular dementia, minimal brain dysfunction (MBD), insomnia and Schizophrenia) was considered separately using tables and bar diagrams. Data analysis results are as follows: firstly, 40.2%, of the 500 psychotic patients tested positive to bipolar, 40.6% to insomnia, 75.0% to schizophrenia, 43.6% to MBD and 69.2% to vascular dementia. Secondly, female patients were more prone to all the psychotic indicators than their male counterpart except in MBD. Thirdly, the oldest age group (> 60 years) is more prone to bipolar and insomnia ailments, while the mid age group (30 – 60 years) is prone to schizophrenia and vascular dementia, and the youngest group (< 30 years) is prone to MBD. Lastly, the factors that influence the ailments are listed: bipolar (age, occupation, marital status, divorce, and spiritual consultation); insomnia (age, occupation, marital status, divorce, and spiritual consultation); schizophrenia (age, occupation, religion, marital status, hereditary, and divorce); MBD (gender, age, occupation, and marital status); and vascular dementia (history of the ailment and spiritual consultation). Bipolar and insomnia are influenced by the same set of factors, which implies that any patient having one is most likely to be at risk of having the other.



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Data on administration of cyclosporine, nicorandil, metoprolol on reperfusion related outcomes in ST-segment Elevation Myocardial Infarction treated with percutaneous coronary intervention

Publication date: October 2017
Source:Data in Brief, Volume 14
Author(s): Gianluca Campo, Rita Pavasini, Giampaolo Morciano, Michael A. Lincoff, Michael C. Gibson, Masafumi Kitakaze, Jacob Lonborg, Amrita Ahluwalia, Hideki Ishii, Michael Frenneaux, Michel Ovize, Marcello Galvani, Dan Atar, Borja Ibanez, Giampaolo Cerisano, Simone Biscaglia, Brandon J. Neil, Masanori Asakura, Thomas Engstrom, Daniel A. Jones, Dana Dawson, Roberto Ferrari, Paolo Pinton, Filippo Ottani
Mortality and morbidity in patients with ST elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) are still high [1]. A huge amount of the myocardial damage is related to the mitochondrial events happening during reperfusion [2]. Several drugs directly and indirectly targeting mitochondria have been administered at the time of the PCI and their effect on fatal (all-cause mortality, cardiovascular (CV) death) and non fatal (hospital readmission for heart failure (HF)) outcomes have been tested showing conflicting results [3–16]. Data from 15 trials have been pooled with the aim to analyze the effect of drug administration versus placebo on outcome [17]. Subgroup analysis are here analyzed: considering only randomized clinical trial (RCT) on cyclosporine or nicorandil [3–5,9–11], excluding a trial on metoprolol [12] and comparing trial with follow-up length <12 months versus those with longer follow-up [3–16]. This article describes data related article titled "Clinical Benefit of Drugs Targeting Mitochondrial Function as an Adjunct to Reperfusion in ST-segment Elevation Myocardial Infarction: a Meta-Analysis of Randomized Clinical Trials" [17].



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Physical, chemical, and optical data of SnS layers and light switching frequency dependent photoresponses

Publication date: October 2017
Source:Data in Brief, Volume 14
Author(s): Malkeshkumar Patel, Hong-Sik Kim, Joondong Kim
In this data article, vertically grown SnS layers were investigated. The growth processes of vertical SnS layers were discussed in our article [1]. This data article provides the chemical analysis using the XPS measurements for the SnS sample grown on a Si wafer. Deposition time varying SnS morphology changes were observed by FESEM. The cross-sectional images were achieved to monitor the SnS layer thickness. Refractive index of the grown SnS film was calculated using the reflectance data. A self-operating photoelectric was realized with structuring of SnS layers on the n-type Si wafer. Transient photoresponses were achieved by tuning the switching frequencies.



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Dataset of anomalies and malicious acts in a cyber-physical subsystem

Publication date: October 2017
Source:Data in Brief, Volume 14
Author(s): Pedro Merino Laso, David Brosset, John Puentes
This article presents a dataset produced to investigate how data and information quality estimations enable to detect aNomalies and malicious acts in cyber-physical systems. Data were acquired making use of a cyber-physical subsystem consisting of liquid containers for fuel or water, along with its automated control and data acquisition infrastructure. Described data consist of temporal series representing five operational scenarios – Normal, aNomalies, breakdown, sabotages, and cyber-attacks – corresponding to 15 different real situations. The dataset is publicly available in the .zip file published with the article, to investigate and compare faulty operation detection and characterization methods for cyber-physical systems.



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“Data characterizing microfabricated human blood vessels created via hydrodynamic focusing”

Publication date: October 2017
Source:Data in Brief, Volume 14
Author(s): Kyle A. DiVito, Michael A. Daniele, Steven A. Roberts, Frances S. Ligler, André A. Adams
This data article provides further detailed information related to our research article titled "Microfabricated Blood Vessels Undergo Neovascularization" (DiVito et al., 2017) [1], in which we report fabrication of human blood vessels using hydrodynamic focusing (HDF). Hydrodynamic focusing with advection inducing chevrons were used in concert to encase one fluid stream within another, shaping the inner core fluid into 'bullseye-like" cross-sections that were preserved through click photochemistry producing streams of cellularized hollow 3-dimensional assemblies, such as human blood vessels (Daniele et al., 2015a, 2015b, 2014, 2016; Roberts et al., 2016) [2–6]. Applications for fabricated blood vessels span general tissue engineering to organ-on-chip technologies, with specific utility in in vitro drug delivery and pharmacodynamics studies. Here, we report data regarding the construction of blood vessels including cellular composition and cell positioning within the engineered vascular construct as well as functional aspects of the tissues.



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64 MS-CTU: Review of techniques and spectrum of the ureteric diseases

Publication date: Available online 27 July 2017
Source:Alexandria Journal of Medicine
Author(s): Mahmoud Agha, Ahmed Fathi Eid
ObjectiveThe study aims to clarify the sensitivity of the CTU, and if is it coast effective and time effective to be used as first and the one-stop shop imaging modality for the diagnosis of the different ureteric diseases.Patients and methods400 patients with different urinary tract complaints (hematuria and/or renal colic) did triphasic CTU examinations, for diagnosis of suspected obstructive or traumatic ureteric uropathy from January 2014 to October 2016. These patients were filtered from a larger number of patients – who were presented with urinary tract complaints by plain KUB X ray and US, which showed no explaining kidneys or urinary bladder pathology.ResultsUreteric duplication was detected in 5 (1.25%) patients, ectopic ureter in one patient (0.25%), UPJ stricture in 4 patients (1%), PUJ vascular impression in 2 patients (0.5%), ureteric calculus in 103 patients (25.75%), pyogenic ureteritis in 8 patients (2%), ureteritis cystica in one patient (0.25%) TCC in 3 patients (0.75%), PRPF in one patient (0.025%) and Trauma in one patient (0.025%).ConclusionCTU is very sensitive tool of imaging and could be confidently considered the one-stop shop imaging tool for accurate diagnosis of the different ureteric lesions.



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An overview about mitochondrial DNA mutations in ovarian cancer

Publication date: Available online 16 June 2017
Source:Alexandria Journal of Medicine
Author(s): Iyer Mahalaxmi, K.S. Santhy
BackgroundOvarian tumour is the second most common form of cancer affecting female reproductive system and the most lethal of the gynaecological malignancies. Since past decades, tremendous efforts have been made to illuminate the molecular basis for initiation and progression of ovarian carcinoma. A low quantity of dysfunction in mitochondrial DNA (mtDNA) is considered to be a risk factor for variety of cancer types. Mitochondrial dysfunctions have been allied with varied metabolic diseases and for occurrence of cancer. Researches say that mtDNA have pivotal role in development of cancer but future work has to be carried out to know the exact significance of specific mitochondrial mutations linked with cancer and disease progression. Most of mtDNA mutations in gynecological cancers are observed in the D-loop region.ObjectiveThis review article provides a detailed summary about the ovarian cancer and mutations observed in mtDNA.ResultFurthermore, this review offers some perspective as to the mtDNA origin of these mutations in ovarian cancer, their functional consequences in ovarian cancer development, to check for incidence rate for transmission of the disease through maternal lineages and possible diagnostic marker implication.



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Prevalence of Toxocara spp. eggs in soil of public areas in Iran: A systematic review and meta-analysis

Publication date: Available online 16 June 2017
Source:Alexandria Journal of Medicine
Author(s): Bahman Maleki, Ali Khorshidi, Mohammad Gorgipour, Aliyar Mirzapour, Hamidreza Majidiani, Masoud Foroutan
Toxocariasis is a zoonotic and widespread infection which manifest as a spectrum of syndromes in humans such as visceral, neural, ocular, covert and asymptomatic. Herein we aimed to design a systematic review and meta-analysis to determine the prevalence of Toxocara spp. eggs in soil depositories in Iran. English (PubMed, Scopus, Google Scholar, Web of Science, Science Direct, EBSCO, and Ovid) and Persian (Scientific Information Database and Magiran) databases were explored. This review resulted in a total of 14 publications meeting the inclusion criteria during January 2000–November 2016. Altogether, 3031 soil samples were examined among which 470 were positive in terms of Toxocara spp. The weighted overall prevalence of Toxocara spp. in soil samples was 16% (95% CI=11–21%), and Tehran and Qazvin provinces had the highest and lowest prevalence rates, respectively. Meta-regression analysis showed that the correlation between prevalence of Toxocara eggs in soil with sample size (P=0.45) and year of study (P=0.42) were not statistically significant. Further studies are highly recommended to enlighten different aspects of toxocariasis in Iran.



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Physiological variables and molecular study of KLK2 and KLK3 among patient with benign prostatic hyperplasia

Publication date: Available online 16 June 2017
Source:Alexandria Journal of Medicine
Author(s): Mustafa F. Dawood, Sameer M. Khalaf, Ahmed A. Suleiman
Prostatic hyperplasia is benign tumor occur in prostate. Benign prostatic hyperplasia is common disease in old men. The incidence of disease arises with increase in age. The patient with benign prostatic hyperplasia are estimated 20% of men in 40s old, and 90% in of men in 80s old, and main causes of prostatic hyperplasia are unknown but there is evidence referring to genetic and hormonal disorders that may cause the disease. This study includes 60 patients with prostatic hyperplasia with an average age of 64years old and 30 samples as a control with same age group. The study obtained that there was significant association (P≤0.05) between PSA (KLK3) and prostatic hyperplasia. Result also mentions that there was significant decrease in testosterone level and significant increase in dihydrotestosterone level. The present study for KLK2 and KLK3 genes showed molecular variation in both genes, varied between polymorphism and allele polymorphism. PCR amplification of specific primers of KLK2 gene showed polymorphisms ranged between 14%, 8%, 10%, and 6% in each KLK2a, KLK2b, KLK2c, and KLK2d primers respectively, while the allele polymorphism in KLK2c amplification with primer reaches 18% of patient. PCR amplification of specific primers of KLK3 gene showed polymorphisms ranged between 10%, 6%, 2%, and 4% in each KLK3a, KLK3b, KLK3c, and KLK3d primer respectively, and allele variation was not detected in amplification product of KLK3.



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Inhibition of chondroitin sulfate glycosaminoglycans incorporation affected odontoblast differentiation in cultured embryonic mouse molars

Abstract

Chondroitin sulfate proteoglycan (CSPG) is an important component of extracellular matrix (ECM), it is composed of a core protein and one or more chondroitin sulfate glycosaminoglycan side chains (CS-GAGs). To investigate the roles of its CS-GAGs in dentinogenesis, the mouse mandibular first molar tooth germs at early bell stage were cultivated with or without β-xyloside. As expected, the CS-GAGs were inhibited on their incorporation to CSPGs by β-xyloside, accompanied by the change of morphology of the cultured tooth germs. The histological results and the transmission electron microscopy (TEM) investigation indicated that β-xyloside exhibited obvious inhibiting effects on odontoblasts differentiation compared with the control group. Meanwhile the results of immunohistochemistry, in situ hybridization and quantitative RT-PCR for type I collagen, dentin matrix acidic phosphoprotein 1 and dentin sialophosphoprotein, the products of differentiated odontoblasts, further proved that odontoblasts differentiation was inhibited. Collagen fibers detected in TEM decreased and arranged in disorder as well. Thus we conclude that the inhibition of CS-GAGs incorporation to CSPGs can affect odontoblast differentiation in cultured embryonic mouse molars.

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Evaluation of Transporters in Drug Development: Current Status and Contemporary Issues

Publication date: Available online 29 July 2017
Source:Advanced Drug Delivery Reviews
Author(s): Sue-Chih Lee, Vikram Arya, Xinning Yang, Donna A. Volpe, Lei Zhang
Transporters govern the access of molecules to cells or their exit from cells, thereby controlling the overall distribution of drugs to their intracellular site of action. Clinically relevant drug-drug interactions mediated by transporters are of increasing interest in drug development. Drug transporters, acting alone or in concert with drug metabolizing enzymes, can play an important role in modulating drug absorption, distribution, metabolism and excretion, thus affecting the pharmacokinetics and/or pharmacodynamics of a drug. The drug interaction guidance documents from regulatory agencies include various decision criteria that may be used to predict the need for in vivo assessment of transporter-mediated drug-drug interactions. Regulatory science research continues to assess the prediction performances of various criteria as well as to examine the strength and limitations of each prediction criterion to foster discussions related to harmonized decision criteria that may be used to facilitate global drug development. This review discusses the role of transporters in drug development with a focus on methodologies in assessing transporter-mediated drug-drug interactions, challenges in both in vitro and in vivo assessments of transporters, and emerging transporter research areas including biomarkers, assessment of tissue concentrations, and effect of diseases on transporters.

Graphical abstract

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Differences of first-pass effect in the liver and intestine contribute to the stereoselective pharmacokinetics of rhynchophylline and isorhynchophylline epimers in rats

Publication date: 14 September 2017
Source:Journal of Ethnopharmacology, Volume 209
Author(s): Xin Wang, Mei Zheng, Jia Liu, Zhifeng Huang, Yidan Bai, Zhuoying Ren, Ziwen Wang, Yangli Tian, Zhou Qiao, Wenyuan Liu, Feng Feng
Ethnopharmacological relevanceUncaria rhynchophylla (Miq.) Miq. ex Havil., is a plant species used in traditional Chinese medicine to treat cardiovascular and central nervous system diseases. Rhynchophylline (RIN) and isorhynchophylline (IRN), a pair of epimers, are major alkaloids isolated from U. rhynchophylla and exhibit diverse pharmacological effects. Our previous study demonstrated that the pharmacokinetics of these epimers existed stereoselectivity after oral administration; however, the specific mechanism remains unknown and merits investigation.Aim of the studyIn the present study, the aim was to elucidate the mechanism underlying stereoselective pharmacokinetic characteristics of RIN and IRN in rats.Materials and methodsThe total (F), hepatic (Fh) and intestinal (Fa·Fg) bioavailabilities of each epimer were measured using portal vein cannulated rats following different dosing routes (intravenous, intraportal and intraduodenal) to assess individual contributions of the liver and intestine in stereoselective pharmacokinetics. Then the differences of first-pass metabolism in the liver and intestine between two epimers were evaluated by in vitro incubation with rat liver microsomes, intestinal S9 and gastrointestinal (GI) content solutions, respectively. Meanwhile, the membrane permeability and efflux by P-glycoprotein (P-gp) were examined by in situ single-pass intestinal perfusion with and without P-gp inhibitor verapamil. The configurational interconversion at different pH values and the excretions via feces and urine were also examined.ResultsPharmacokinetic data showed that the total bioavailability of RIN was 5.9 folds higher than that of IRN (23.4% vs. 4.0%). The hepatic availability of RIN was 4.6 folds higher than that of IRN (46.9% vs. 10.3%), whereas the intestinal availability of RIN (48.1%) was comparable to that of IRN (42.7%). In addition, intestinal perfusion showed that IRN possessed higher intestinal permeability than RIN and co-perfusion with verapamil could affect absorption process of RIN but not IRN. Conversely, the metabolism rate of IRN in rat liver microsomes was significantly faster than that of RIN, resulting in a lower systemic exposure of IRN after oral administration. The degradation in GI lumen and epimerization between two epimers also existed but had small contributions. Additionally, the excretions of both epimers via feces and urine were negligible.ConclusionsTaken together, different first-pass metabolism in the liver was the major factor responsible for the stereoselective pharmacokinetics of RIN and IRN.

Graphical abstract

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Editorial Board

Publication date: August 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 152, Issue 2





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Information for readers

Publication date: August 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 152, Issue 2





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Caught but released

Publication date: August 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 152, Issue 2
Author(s): Laurance Jerrold




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Common errors observed at the American Board of Orthodontics clinical examination

Publication date: August 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 152, Issue 2
Author(s): Chun-Hsi Chung, Larry P. Tadlock, Nicholas Barone, Valmy Pangrazio-Kulbersh, David G. Sabott, Patrick F. Foley, Timothy S. Trulove, Jae Hyun Park, Steven A. Dugoni
The American Board of Orthodontics has developed tools to help examinees select patients to be used for the Board examination. The Case Management Form can be used to evaluate aspects of a patient's treatment that cannot be measured by other tools. The Case Management Form is a structured treatment-neutral assessment of orthodontic objectives and outcomes associated with a patient's treatment. Despite the availability of this form, examiners continue to see problems, including lack of attention to finishing details, inappropriate treatment objectives, excessive proclination of mandibular incisors due to treatment mechanics, excessive expansion of mandibular intercanine width, closing skeletal open bite with extrusion of anterior teeth leading to excessive gingival display, and failure to recognize the importance of controlling the eruption or extrusion of molars during treatment. In addition, some examinees exhibit a lack of understanding of proper cephalometric tracing and superimposition techniques, which lead to improper interpretation of cephalometric data and treatment outcomes.



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Comparison of survival time and comfort between 2 clear overlay retainers with different thicknesses

Publication date: August 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 152, Issue 2
Author(s): Santosh Kumar Goje, Rashmi Bhavasar




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Authors' response

Publication date: August 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 152, Issue 2
Author(s): Yafen Zhu, Jianchang Lin, Hu Long, Niansong Ye, Renhuan Huang, Xin Yang, Fan Jian, Wenli Lai




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Table of Contents

Publication date: August 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 152, Issue 2





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Transport distraction osteogenesis combined with orthodontic treatment

Publication date: August 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 152, Issue 2
Author(s): Sanjeev Verma, Sombir Singh, S.P. Singh




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August 2017:152(2)

Publication date: August 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 152, Issue 2
Author(s): Allen H. Moffitt




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Authors' response

Publication date: August 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 152, Issue 2
Author(s): Seo Yeon Jung, Hyoung Seon Baik




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Bisphenol A in orthodontic adhesives

Publication date: August 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 152, Issue 2
Author(s): S. Divya, Arun S. Urala




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Authors' response

Publication date: August 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 152, Issue 2
Author(s): Mírian A.N. Matsumoto, Paulo Nelson-Filho, Marília R. Moreira




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CBCT imaging vs conventional radiography

Publication date: August 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 152, Issue 2
Author(s): Katja Kritzler




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Residents' journal review

Publication date: August 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 152, Issue 2
Author(s): Dan Grauer




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Courtesy counts

Publication date: August 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 152, Issue 2
Author(s): Peter M. Greco




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Orthodontic-surgical retreatment of facial asymmetry with occlusal cant and severe root resorption: A 3-year follow-up

Publication date: August 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 152, Issue 2
Author(s): Cinthia de Oliveira Lisboa, Marlon Sampaio Borges, Paulo José D'Albuquerque Medeiros, Alexandre Trindade Motta, José Nelson Mucha
Our objective was to report the orthodontic and surgical retreatment of a patient who had undergone a prolonged orthodontic treatment with extractions, but who had unsatisfactory results and persistent side effects. The man, aged 25 years 3 months, sought treatment with major complaints of facial and smile asymmetries. The clinical examination showed a mandibular deviation to the right and a maxillary occlusal cant. A Class II Division 1 subdivision right was observed. Radiographic examination showed extensive root resorptions in the maxillary second premolars and absence of the 4 first premolars. The maxillary midline was deflected 2 mm to the left, and the mandibular midline was shifted 5 mm to the right. Aligning and leveling were performed with orthodontic fixed appliances, with a standard edgewise system (0.022 × 0.028 in), followed by LeFort I maxillary impaction and bilateral sagittal split osteotomy with asymmetrical advancement. Retreatment showed outstanding results that remained stable after 3 years of follow-up. Root resorption in the second premolars did not seem to increase. Orthodontic-surgical intervention is the main choice for correcting esthetic and functional problems in facial asymmetry, particularly in cases of retreatment.



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Randomized controlled trial of a patient decision-making aid for orthodontics

Publication date: August 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 152, Issue 2
Author(s): Kate Parker, Susan J. Cunningham, Aviva Petrie, Fiona S. Ryan
IntroductionPatient decision-making aids (PDAs) are instruments that facilitate shared decision making and enable patients to reach informed, individual decisions regarding health care. The objective of this study was to assess the efficacy of a PDA compared with traditional information provision for adolescent patients considering fixed appliance orthodontic treatment.MethodsBefore treatment, orthodontic patients were randomly allocated into 2 groups: the intervention group received the PDA and standard information regarding fixed appliances, and the control group received the standard information only. Decisional conflict was measured using the Decisional Conflict Scale, and the levels of decisional conflict were compared between the 2 groups.ResultsSeventy-two patients were recruited and randomized in a ratio of 1:1 to the PDA and control groups. Seventy-one patients completed the trial (control group, 36; PDA group, 35); this satisfied the sample size calculation. The median total Decisional Conflict Scale score in the PDA group was lower than in the control group (15.63 and 19.53, respectively). However, this difference was not statistically significant (difference between groups, 3.90; 95% confidence interval of the difference, −4.30 to 12.11). Sex, ethnicity, age, and the time point at which patients were recruited did not have significant effects on Decisional Conflict Scale scores. No harm was observed or reported for any participant in the study.ConclusionsThe results of this study showed that the provision of a PDA to adolescents before they consented for fixed appliances did not significantly reduce decisional conflict. There may be a benefit in providing a PDA for some patients, but it is not yet possible to say how these patients could be identified.RegistrationThis trial was registered with the Harrow National Research Ethics Committee (reference 12/LO/0279).ProtocolThe protocol was not published before trial commencement.



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Poisson regression

Publication date: August 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 152, Issue 2
Author(s): Despina Koletsi, Nikolaos Pandis




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Individualized intervention to reduce anxiety in adult orthodontic patients based on Q methodology

Publication date: August 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 152, Issue 2
Author(s): Feiou Lin, Yan He, Zhenyu Ni, Richard Olive, Manman Ren, Linjie Yao, Qingsong Ye
IntroductionIn this study, we used Q methodology to assess the concerns of adults seeking orthodontic treatment and to determine individualized interventions to reduce their anxiety.MethodsStatements of concern were derived by in-depth interviews with 70 adult patients. Q sorting methodology was then used to identify the main factors associated with anxiety in a cohort of 40 adults who had not been involved in the first part of the study. The final stage involved a randomized study in which 160 new adult patients were recruited and randomized into intervention and control groups. Participants in the intervention group sorted the statements, after which individualized interventions were implemented. Participants in the control group received routine treatment. The State-Trait Anxiety Inventory was used to measure changes in participants' anxiety levels before and during treatment.ResultsIn total, 41 statements were identified, and participants were classified according to 5 factors. Factor 1 participants were concerned about the lack of treatment information; factor 2 represented concerns about cost and other people's opinions; factor 3 represented concerns about impact on work related to wearing braces; factor 4 encompassed concerns about treatment effects, pain, and dental fears; and factor 5 reflected concerns about side effects and finding a partner. The mean state anxiety inventory scores for both the intervention and control groups were highest 24 hours after bonding (intervention group, 44.63 ± 4.49; control group, 49.43 ± 5.42). The intragroup state anxiety inventory scores differed significantly across the 6 time points (P <0.01), with the state anxiety inventory scores of the intervention group significantly lower than those of the control group (P <0.01) at all time points except baseline. No significant intergroup or intragroup differences were found in relation to trait anxiety.ConclusionsAdult orthodontic patients expressed diverse concerns. Individualized interventions based on Q methodology may reduce anxiety in this patient population.



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Directory: AAO Officers and Organizations

Publication date: August 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 152, Issue 2





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Combining Two Methods of Global Sensitivity Analysis to Investigate MRSA Nasal Carriage Model.

Related Articles

Combining Two Methods of Global Sensitivity Analysis to Investigate MRSA Nasal Carriage Model.

Bull Math Biol. 2017 Jul 27;:

Authors: Jarrett AM, Cogan NG, Hussaini MY

Abstract
We apply two different sensitivity techniques to a model of bacterial colonization of the anterior nares to better understand the dynamics of Staphylococcus aureus nasal carriage. Specifically, we use partial rank correlation coefficients to investigate sensitivity as a function of time and identify a reduced model with fewer than half of the parameters of the full model. The reduced model is used for the calculation of Sobol' indices to identify interacting parameters by their additional effects indices. Additionally, we found that the model captures an interesting characteristic of the biological phenomenon related to the initial population size of the infection; only two parameters had any significant additional effects, and these parameters have biological evidence suggesting they are connected but not yet completely understood. Sensitivity is often applied to elucidate model robustness, but we show that combining sensitivity measures can lead to synergistic insight into both model and biological structures.

PMID: 28752384 [PubMed - as supplied by publisher]

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