Use of long implants with distal anchorage in the skull base for treatment of extreme maxillary atrophy: the remote bone anchorage concept

The objectives of this study are to present a new concept of the bone anchorage using long implants in remote bone sites and to discuss four cases treated with this method. Our patients were treated with long implants with a distant anchorage in the skull bone. The planning procedure, the construction of the drill guide, and the surgical protocol are described. In the clinical cases described, all four patients were rehabilitated with the remote bone anchorage concept using long implants anchored in the skull base. Patients were followed for 5 - 12 years and the implants remained present and stable in these time periods. The skull base implant is a new concept of bone anchorage using long implants. It can be a solution for complicated clinical situations (often failed bone reconstructions and implant placements) or an alternative for bone grafting and maxillary augmentation procedures. There is effective implant retention in the skull base, an anatomical area that is often overlooked for implant placement.

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Polymorphisms of the DNA Methyltransferase 1 Gene Predict Survival of Gastric Cancer Patients Receiving Tumorectomy

DNA methyltransferase 1 (DNMT1) plays a pivotal role in maintaining DNA methylation status. Polymorphisms of DNMT1 may modify the role of DNMT1 in prognosis of gastric cancer (GC). Our aim was to test whether polymorphisms of DNMT1 gene were associated with overall survival of GC. Four hundred and forty-seven GC patients who underwent radical tumorectomy were enrolled in the study. Five tagging SNPs (rs10420321, rs16999593, rs2228612, rs2228611, and rs2288349) of the DNMT1 gene were genotyped by TaqMan assays. Kaplan-Meier survival plots and Cox proportional hazard regression were used to analyze the associations between SNPs of DNMT1 and survival of GC. Patients carrying rs2228611 GA/AA genotype tended to live longer than those bearing the GG genotype (HR 0.68, 95% CI: 0.51–0.91, ). Further multivariate Cox regression analysis showed that rs2228611 was an independent prognostic factor (GA/AA versus GG: OR 0.67, 95% CI 0.49–0.91, ). Nevertheless, other SNPs did not show any significant associations with survival of GC. Polymorphisms of the DNMT1 gene may affect overall survival of GC. The SNP rs2228611 has the potentiality to serve as an independent prognostic marker for GC patients.

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Personalized therapy for hepatocellular carcinoma: Where are we now?

Personalized therapy for hepatocellular carcinoma: Where are we now?

Cancer Treat Rev. 2016 Mar 2;45:77-86

Authors: Chan SL, Wong AM, Lee K, Wong N, Chan AK

Abstract
Following the approval of sorafenib, a large number of molecular targeted agents have been tested clinically for advanced hepatocellular carcinoma (HCC), but all have failed to demonstrate significant efficacy in clinical trials. Multiple reasons for this phenomenon have been discussed in the literature, with one reason being the lack of patient selection on the basis of molecular profile in clinical trials. The concept of drug testing in selected populations has been recently suggested by retrospective analyses of HCC clinical trials in which a particular subgroup of patients, either enriched by clinical factors or by tissue biomarkers, derived more benefits from the novel drug. In addition, recent advances in genomic medicine have enhanced the understanding of genetic and epigenetic events occurring in HCC, raising the possibility of personalizing targeted agents in accordance with the genetic make-up of the tumors. The development of 'personalized' treatment for HCC is, however, hindered by the lack of fresh biopsy of advanced HCC, the low incidence of genetic driver mutations in HCC and the tumor heterogeneity. These limitations may be overcome by sequencing cell-free DNA in plasma, frequently known as liquid biopsy, and revolution in the concept of the design of clinical trials. In this review article, we aim to: (1) give a summary of the recent sequencing results of HCC and the related implications for drug development; (2) highlight potential individual targeted agents and existing research on biomarker selection in clinical trials; and (3) discuss future directions, including the potential of liquid biopsy and umbrella clinical trials, to enhance personalized drug testing for HCC.

PMID: 26995632 [PubMed - as supplied by publisher]

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Modified irinotecan and infusional 5-fluorouracil (mFOLFIRI) in patients with refractory advanced pancreas cancer (APC): a single-institution experience.

Modified irinotecan and infusional 5-fluorouracil (mFOLFIRI) in patients with refractory advanced pancreas cancer (APC): a single-institution experience.

Med Oncol. 2016 Apr;33(4):37

Authors: Bupathi M, Ahn DH, Wu C, Ciombor KK, Stephens JA, Reardon J, Goldstein DA, Bekaii-Saab T

Abstract
Pancreatic adenocarcinoma is the fourth leading cause of cancer death. Recently, MM-398 (nanoliposomal irinotecan) was shown to be associated with significant improvement in outcome measures with acceptable toxicities when combined with 5-fluorouracil (5-FU)/leucovorin (LV) compared to 5-FU/LV alone in patients failing one line of gemcitabine-based therapy. There is a paucity of data evaluating the role of irinotecan in combination with 5FU in advanced pancreas cancer (APC). We performed a retrospective analysis of all patients who received mFOLFIRI (minus bolus 5FU and LV). All patients with metastatic disease who had failed at least one line of gemcitabine-based therapy prior to receiving mFOLFIRI were included in this study. Descriptive statistics were used to assess the continuous variables and adverse events (AEs), and Kaplan-Meier methods were used to calculate the median progression-free survival (PFS) and overall survival (OS). Forty patients were included in this analysis. Patients received 1-5 lines of prior therapy (25 % with more than 3 lines of prior therapy). The mean age at diagnosis was 60, and 98 % had ECOG of 1. The mean CA 19-9 at the start of therapy was 33,169 U/ml. The median PFS was 2.59 months [95 % confidence interval (CI) (1.90, 3.54)], and OS was 4.75 months [95 % CI (3.14, 8.98)]. The most common AEs included fatigue (98 %), neuropathy (83 %), anorexia (68 %), nausea (60 %) and constipation (55 %). Grade 3 toxicities included fatigue (13 %) and rash (3 %). There were no observed grade 4 toxicities. In this single-institution retrospective analysis, mFOLFIRI was found to be both tolerable and relatively effective in a heavily pretreated patient population with APC. Future prospective studies should consider evaluating the role of mFOLFIRI in refractory APC.

PMID: 26995224 [PubMed - as supplied by publisher]

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Tracking metastatic breast cancer: the future of biology in biosensors.

Tracking metastatic breast cancer: the future of biology in biosensors.

Med Oncol. 2016 Apr;33(4):36

Authors: Lim YC, Wiegmans AP

Abstract
Circulating tumour cells associated with breast cancer (brCTCs) represent cells that have the capability to establish aggressive secondary metastatic tumours. The isolation and characterization of CTCs from blood in a single device is the future of oncology diagnosis and treatment. The methods of enrichment of CTCs have primarily utilized simple biological interactions with bimodal reporting with biased high purity and low numbers or low purity and high background. In this review, we will discuss the advances in microfluidics that has allowed the use of more complex selection criteria and biological methods to identify CTC populations. We will also discuss a potential new method of selection based on the response of the oncogenic DNA repair pathways within brCTCs. This method would allow insight into not only the oncogenic signalling at play but the chemoresistance mechanisms that could guide future therapeutic intervention at any stage of disease progression.

PMID: 26995223 [PubMed - as supplied by publisher]

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Impact of dermatologic adverse events induced by targeted therapies on quality of life.

Impact of dermatologic adverse events induced by targeted therapies on quality of life.

Crit Rev Oncol Hematol. 2016 Mar 5;

Authors: Charles C, Bungener C, Razavi D, Mateus C, Routier E, Lanoy E, Verschoore M, Robert C, Dauchy S

Abstract
BACKGROUND: Investigations about the impact of dermatologic adverse events on quality of life in the context of targeted therapies are quite recent and results vary in some dimensions. This article aims to summarize the existing data and to clarify needs in terms of clinical management and future research.
METHODS: A literature review was done with Pubmed, Medline, Scopus and PsycInfo databases and it combined the empirical studies published in English and in French over the past ten years.
RESULTS AND CONCLUSIONS: Dermatologic adverse events globally have a low to moderate impact on quality of life, mainly in the physical and emotional domains. Reasons for inter-individual variations in adjustment and long-term impact are still not well known. Making quality of life assessments systematic, making early referrals of patients to dermatology consultations and giving more attention to individual experience were identified as measures that could help prevent deterioration in quality of life.

PMID: 26995080 [PubMed - as supplied by publisher]

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Analysis of nodal coverage utilizing image guided radiation therapy for primary gynecologic tumor volumes.

Analysis of nodal coverage utilizing image guided radiation therapy for primary gynecologic tumor volumes.

Med Dosim. 2016 Mar 16;

Authors: Ahmed F, Sarkar V, Gaffney DK, Salter B, Poppe MM

Abstract
PURPOSE: To evaluate radiation dose delivered to pelvic lymph nodes, if daily Image Guided Radiation Therapy (IGRT) was implemented with treatment shifts based on the primary site (primary clinical target volume [CTV]). Our secondary goal was to compare dosimetric coverage with patient outcomes.
MATERIALS AND METHODS: A total of 10 female patients with gynecologic malignancies were evaluated retrospectively after completion of definitive intensity-modulated radiation therapy (IMRT) to their pelvic lymph nodes and primary tumor site. IGRT consisted of daily kilovoltage computed tomography (CT)-on-rails imaging fused with initial planning scans for position verification. The initial plan was created using Varian׳s Eclipse treatment planning software. Patients were treated with a median radiation dose of 45Gy (range: 37.5 to 50Gy) to the primary volume and 45Gy (range: 45 to 64.8Gy) to nodal structures. One IGRT scan per week was randomly selected from each patient׳s treatment course and re-planned on the Eclipse treatment planning station. CTVs were recreated by fusion on the IGRT image series, and the patient׳s treatment plan was applied to the new image set to calculate delivered dose. We evaluated the minimum, maximum, and 95% dose coverage for primary and nodal structures. Reconstructed primary tumor volumes were recreated within 4.7% of initial planning volume (0.9% to 8.6%), and reconstructed nodal volumes were recreated to within 2.9% of initial planning volume (0.01% to 5.5%).
RESULTS: Dosimetric parameters averaged less than 10% (range: 1% to 9%) of the original planned dose (45Gy) for primary and nodal volumes on all patients (n = 10). For all patients, ≥99.3% of the primary tumor volume received ≥ 95% the prescribed dose (V95%) and the average minimum dose was 96.1% of the prescribed dose. In evaluating nodal CTV coverage, ≥ 99.8% of the volume received ≥ 95% the prescribed dose and the average minimum dose was 93%. In evaluating individual IGRT sessions, we found that 6 patients had an estimated minimal nodal CTV dose less than 90% (range: 78 to 99%) of that planned. With a median follow-up of 42.5 months, 2 patients experienced systemic disease progression at an average of 19.6 months. One patient was found to have a local or regional failure with an average follow-up of 42 months.
CONCLUSION: Using only 3 dimensional IGRT corrections in gynecological radiation allows excellent coverage of the primary target volume and good average nodal CTV coverage. If IGRT corrections are based on alignment to the primary tumor volume, and is only able to be corrected in 3 degrees, this can create situations in which nodal volumes may be under dosed. Utilizing multiple IGRT sessions appears to average out dose discrepancies over the course of treatment. The implication of underdosing in a single IGRT session needs further evaluation in future studies. Based on the concern of minimum dose to a nodal target volume, these findings may signal caution when using IGRT and IMRT in gynecological radiation patients. Possible techniques to overcome this situation may include averaging shifts between tumor and nodal volume, use of a treatment couch with 6° of freedom, deformable registration, or adaptive planning.

PMID: 26994828 [PubMed - as supplied by publisher]

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Simple shielding reduces dose to the contralateral breast during prone breast cancer radiotherapy.

Simple shielding reduces dose to the contralateral breast during prone breast cancer radiotherapy.

Med Dosim. 2016 Mar 16;

Authors: Goyal U, Locke A, Smith-Raymond L, Georgiev GN

Abstract
Our goal was to design a prone breast shield for the contralateral breast and study its efficacy in decreasing scatter radiation to the contralateral breast in a prone breast phantom setup receiving radiation therapy designed for breast cancer. We constructed a prone breast phantom setup consisting of (1) A thermoplastic mask with a left-sided depression created by a water balloon for a breast shape; (2) 2 plastic bags to hold water in the thermoplastic mask depression; (3) 2000mL of water to fill the thermoplastic mask depression to create a water-based false breast; (4) 1-cm thick bolus placed in the contralateral breast holder; (5) 2 lead (Pb) sheets, each 0.1-cm thick for blocking scatter radiation in the contralateral bolus-based false breast; (6) a prone breast board to hold the thermoplastic mask, water, bolus, and lead; (7) 9cm solid water on top of the breast board to simulate body; (8) a diode was used to verify dose for each treatment field of the treated water-based breast; (9) metal-oxide-semiconductor-field effect transistor (MOSFET) dosimeters to measure dose to the contralateral bolus-based breast. The phantom prone breast setup was CT simulated and treatment was designed with 95% isodose line covering the treated breast. The maximum dose was 107.1%. Megavoltage (MV) port images ensured accurate setup. Measurements were done using diodes on the treated water-based breast and MOSFET dosimeters at the medial and lateral sides of the contralateral bolus-based breast without and with the Pb shield. Five treatments were done for each of the 3 data sets and recorded individually for statistical purposes. All treatments were completed with 6MV photons at 200cGy per treatment. The dose contributions from each of the 3 data sets including 15 treatments total without and with the prone lead shield to the medial and lateral portions of contralateral bolus-based breast were averaged individually. Unshielded dose means were 37.11 and 2.94cGy, and shielded dose means were 12.68 and 1.54cGy, respectively. When comparing medial and lateral portions of the contralateral bolus-based doses without and with Pb, the shield significantly reduced dose to both sides of the contralateral breast (medial p = 2.64 × 10(-14), lateral p = 4.91 × 10(-6)). The prone 0.2-cm Pb shield significantly reduced scatter dose to the contralateral breast on the order of 2 to 3 times. Reductions may be clinically relevant for women younger than 45 years by decreasing the risk of contralateral radiation-induced breast cancer in patients receiving radiation therapy for breast cancer. This shield is simple as it would be a part of the prone breast board during treatments, but future studies are warranted for safety and efficacy clinically.

PMID: 26994826 [PubMed - as supplied by publisher]

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Clinical Challenge: An Orbital Hickam's Dictum.

Clinical Challenge: An Orbital Hickam's Dictum.

Surv Ophthalmol. 2016 Mar 16;

Authors: Wilson ME, Thornton S, Murchison AP, Bilyk JR

Abstract
A 53-year old man with hyperthyroidism presented with asymmetric proptosis and diplopia. Thyroid stimulating immunoglobulin was elevated, suggesting active thyroid eye disease (TED). Imaging of the orbits revealed enlargement of the extraocular muscles including irregular enlargement of the left lateral rectus muscle. Biopsy of the lateral rectus muscle demonstrated infiltration of the muscle with Bcl-2 positive B lymphocytes, consistent with chronic lymphocytic leukemia (CLL). Evaluation for systemic lymphoproliferative disease was negative. The patient was treated with orbital radiotherapy at specific dosages for both TED and CLL. He responded well to therapy with a reduction in proptosis and diplopia, and no evidence of recurrent CLL.

PMID: 26994869 [PubMed - as supplied by publisher]

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Validation of a reading assessment for persons with homonymous hemianopia and quadrantanopia

Archives of Physical Medicine and Rehabilitation

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Impact of the US Food and Drug Administration's Safety-Related Announcements on the Use of Bisphosphonates after Hip Fracture

Journal of Bone and Mineral Research

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Outcomes following external iliac and femoral vascular injuries

Annals of Vascular Surgery

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End-tidal carbon dioxide monitoring and load band device for mechanical cardio-pulmonary resuscitation: Never trust the numbers, believe at the curves

Resuscitation

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Prevention and control of carbapenemase-producing organisms at a regional burns centre

Journal of Hospital Infection

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Aspects of posttraumatic stress disorder in long-term testicular cancer survivors: cross-sectional and longitudinal findings

Journal of Cancer Survivorship

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Greater fall risk in elderly women than in men is associated with increased gait variability during multitasking

Journal of the American Medical Directors Association

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The association between neighborhood effects and out-of-hospital cardiac arrest outcomes

Resuscitation

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Visual acuity measured with a smartphone app is more accurate than snellen testing by emergency department providers

Graefe's Archive for Clinical and Experimental Ophthalmology

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The optic nerve sheath diameter as a useful tool for early prediction of outcome after cardiac arrest: A prospective pilot study

Resuscitation

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Targeting frequent users of emergency departments: Prominent risk factors and policy implications

Health Policy

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Epidemiology of meniscal injuries in US high school athletes between 2007 and 2013

Knee Surgery, Sports Traumatology, Arthroscopy

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Decreased Apoptosis Repressor with Caspase Recruitment Domain Confers Resistance to Sunitinib in Renal Cell Carcinoma through Alternate Angiogenesis Pathways.

Decreased Apoptosis Repressor with Caspase Recruitment Domain Confers Resistance to Sunitinib in Renal Cell Carcinoma through Alternate Angiogenesis Pathways.

Biochem Biophys Res Commun. 2016 Mar 16;

Authors: Gobe GC, Ng KL, Small DM, Vesey DA, Johnson DW, Samaratunga H, Kimberley O, Wood S, Barclay JL, Rajandram R, Li L, Morais C

Abstract
Apoptosis repressor with caspase recruitment domain (ARC), an endogenous inhibitor of apoptosis, is upregulated in a number of human cancers, thereby confering drug resistance and giving a rationale for the inhibition of ARC to overcome drug resistance. Our hypothesis was that ARC would be similarly upregulated and targetable for therapy in renal cell carcinoma (RCC). Expression of ARC was assessed in 85 human RCC samples and paired non-neoplastic kidney by qPCR and immunohistochemistry, as well as in four RCC cell lines by qPCR, Western immunoblot and confocal microscopy. Contrary to expectations, ARC was significantly decreased in the majority of clear cell RCC and in three (ACHN, Caki-1 and 786-0) of the four RCC cell lines compared with the HK-2 non-cancerous human proximal tubular epithelial cell line. Inhibition of ARC with shRNA in the RCC cell line (SN12K1) that had shown increased ARC expression conferred resistance to Sunitinib, and upregulated interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF). We therefore propose that decreased ARC, particularly in clear cell RCC, confers resistance to targeted therapy through restoration of tyrosine kinase-independent alternate angiogenesis pathways. Although the results are contrary to expectations from other cancer studies, they were confirmed here with multiple analytical methods. We believe the highly heterogeneous nature of cancers like RCC predicate that expression patterns of molecules must be interpreted in relation to respective matched non-neoplastic regions. In the current study, this procedure indicated that ARC is decreased in RCC.

PMID: 26995091 [PubMed - as supplied by publisher]

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Expanded phenotypic spectrum of the m.8344A>G "MERRF" mutation: data from the German mitoNET registry.

Expanded phenotypic spectrum of the m.8344A>G "MERRF" mutation: data from the German mitoNET registry.

J Neurol. 2016 Mar 19;

Authors: Altmann J, Büchner B, Nadaj-Pakleza A, Schäfer J, Jackson S, Lehmann D, Deschauer M, Kopajtich R, Lautenschläger R, Kuhn KA, Karle K, Schöls L, Schulz JB, Weis J, Prokisch H, Kornblum C, Claeys KG, Klopstock T

Abstract
The m.8344A>G mutation in the MTTK gene, which encodes the mitochondrial transfer RNA for lysine, is traditionally associated with myoclonic epilepsy and ragged-red fibres (MERRF), a multisystemic mitochondrial disease that is characterised by myoclonus, seizures, cerebellar ataxia, and mitochondrial myopathy with ragged-red fibres. We studied the clinical and paraclinical phenotype of 34 patients with the m.8344A>G mutation, mainly derived from the nationwide mitoREGISTER, the multicentric registry of the German network for mitochondrial disorders (mitoNET). Mean age at symptom onset was 24.5 years ±10.9 (6-48 years) with adult onset in 75 % of the patients. In our cohort, the canonical features seizures, myoclonus, cerebellar ataxia and ragged-red fibres that are traditionally associated with MERRF, occurred in only 61, 59, 70, and 63 % of the patients, respectively. In contrast, other features such as hearing impairment were even more frequently present (72 %). Other common features in our cohort were migraine (52 %), psychiatric disorders (54 %), respiratory dysfunction (45 %), gastrointestinal symptoms (38 %), dysarthria (36 %), and dysphagia (35 %). Brain MRI revealed cerebral and/or cerebellar atrophy in 43 % of our patients. There was no correlation between the heteroplasmy level in blood and age at onset or clinical phenotype. Our findings further broaden the clinical spectrum of the m.8344A>G mutation, document the large clinical variability between carriers of the same mutation, even within families and indicate an overlap of the phenotype with other mitochondrial DNA-associated syndromes.

PMID: 26995359 [PubMed - as supplied by publisher]

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Surgical treatment of substernal goiter: An analysis of 44 cases.

Surgical treatment of substernal goiter: An analysis of 44 cases.

Auris Nasus Larynx. 2016 Mar 16;

Authors: Nakaya M, Ito A, Mori A, Oka M, Omura S, Kida W, Inayoshi Y, Inoue A, Fuchigami T

Abstract
OBJECTIVE: Substernal goiters are classified as primary or secondary intrathoracic goiters. Here, we report the diagnosis, symptoms, treatment, and postoperative complications of 44 substernal goiters (2 primary mediastinal goiter and 42 secondary mediastinal goiters).
METHODS: A retrospective chart review of 351 patients undergoing thyroidectomy at the Department of Otolaryngology-Head and Neck Surgery of the Tokyo Metropolitan Tama Medical Center. Between 2009 and 2015, 44 patients underwent surgery for substernal goiter.
RESULTS: The frequency of primary and secondary mediastinal goiters was 0.5% and 11.9%, respectively. The preoperative symptoms were neck mass, dyspnea, and dysphagia. Eight patients were asymptomatic. Thirty-nine patients had benign masses and 5 patients had malignant masses. Most patients were operated on for adenomatous goiters (52.2%). In ten cases beyond the aortic arch, the tumors were benign and there were eight cases of adenomatous goiter. All patients underwent a successful transcervical incision without sternotomy. Even the primary intrathoracic goiters were extracted after total thyroidectomy via the cervical approach without complications. Although one case showed unilateral recurrent nerve paralysis as a postoperative complication, phonetic function improved in 6 postoperative months. No instances of postoperative bleeding or definitive hypoparathyroidism occurred, and tracheostomy was not performed in any of the cases.
CONCLUSION: The cervical approach was safely performed in almost all substernal goiters without an extracervical procedure. Selected cases of primary mediastinal goiter may be excised via the cervical approach.

PMID: 26995097 [PubMed - as supplied by publisher]

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Serum high expression of miR-214 and miR-135b as novel predictor for myeloma bone disease development and prognosis.

Serum high expression of miR-214 and miR-135b as novel predictor for myeloma bone disease development and prognosis.

Oncotarget. 2016 Feb 11;

Authors: Hao M, Zang M, Zhao L, Deng S, Xu Y, Qi F, An G, Qin Y, Sui W, Li F, Yang W, Li Z, Yi S, Zou D, Zhan F, Qiu L

Abstract
Multiple myeloma (MM) originates from malignant plasma cells, leading to multiple destructive lytic bone lesions that occur in more than 80% of MM patients. MicroRNAs have been reported to be involved in development of bone lesions in MM. However, the circulating microRNA as diagnostic and prognostic biomarkers for bone lesions has not been elucidated yet. In this study, we identified differentially expressed miRNAs that are potentially involved in myeloma-related bone disease in serum of MM patients. MiR-214 and miR-135b was shown to be increased in serum of MM patients with bone lesions. Serum level of miR-214 and miR-135b was highly correlated with the severity of lytic bone lesions and demonstrated as a diagnostic tool for identifying bone diseases based on results of a receiver operating characteristic analysis (ROC). In addition, patients with high levels of serum miR-214 had a dismal survival with significantly shortened progression free survival (PFS) and overall survival (OS). Interestingly, bisphosphonates treatment significantly extended PFS and OS in patients with higher level of miR-214 comparing to patients without bisphosphonates treatment. Taken together, our findings revealed the significance of circulating miR-214 and miR-135b levels in detection of bone disease and in prediction of prognosis of patients with multiple myeloma, suggesting its potential clinical applications. The result of this study also set the foundation for searching more circulating miRNA as biomarker for tumor bone lesions.

PMID: 26995755 [PubMed - as supplied by publisher]

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Tuning band alignment by CdS layers using SILAR method to enhance TiO2/CdS/CdSe quantum-dot solar-cell performance

Chem. Commun., 2016, Accepted Manuscript
DOI: 10.1039/C6CC01664B, Communication

Feng Pan, Bingkai Zhang, Jiaxin Zheng, Xiaoning Li, yanyan fang, Lin-Wang Wang, yuan lin
We report tuning band alignment by optimized CdS layers using SILAR method to achieve the recorded best performance with about 6% PCE in TiO2/CdS/CdSe QDSSCs. Combined experimental and theoretical study,...
The content of this RSS Feed (c) The Royal Society of Chemistry

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Monitoring[space]Early[space]Zeolite[space]Formation[space]via[space]in[space]situ[space]Electrochemical[space]Impedance[space]Spectroscopy

Chem. Commun., 2016, Accepted Manuscript
DOI: 10.1039/C6CC01106C, Communication

Gert Brabants, Sara Lieben, Eric Breynaert, Erwin Konrad Reichel, Francis Taulelle, Johan Martens, Bernhard Jakoby, Christine E. A. Kirschhock
Hitherto[space] zeolite[space] formation[space] is[space] not[space] fully[space] understood.[space] Although[space] electrochemical[space] impedance[space] spectroscopy[space] has[space] proven[space] to[space] be[space] a[space] versatile[space]tool[space]for[space]characterizing[space]ionic[space]solutions,[space]it[space]was[space]never[space]used[space] for[space] monitoring[space] zeolite[space] growth.[space] We[space] show[space] here[space] that[space] EIS[space] can[space] quantitatively[space]monitor[space]zeolite[space]formation,[space]especially[space]during[space]crucial[space] early[space]steps[space]where[space]other[space]methods[space]fall[space]short.
The content of this RSS Feed (c) The Royal Society of Chemistry

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Involvement of the Helicobacter heilmannii locus encoding the HOF outer membrane proteins in binding to the gastric mucosa

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Detection, isolation and characterization of a highly prevalent new Fusobacterium species colonizing the stomach of pigs

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A rapid high-performance thin-layer chromatographic screening method for sulfonamides residues in animal muscle tissues

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Adaptation prevents the extinction of Chlamydomonas reinhardtii under toxic beryllium

The current biodiversity crisis represents a historic challenge for natural communities: the environmental rate of change exceeds the population's adaptation capability. Integrating both ecological and evolutionary responses is necessary to make reliable predictions regarding the loss of biodiversity. The race against extinction from an eco-evolutionary perspective is gaining importance in ecological risk assessment. Here, we performed a classical study of population dynamics—a fluctuation analysis—and evaluated the results from an adaption perspective. Fluctuation analysis, widely used with microorganisms, is an effective empirical procedure to study adaptation under strong selective pressure because it incorporates the factors that influence demographic, genetic and environmental changes. The adaptation of phytoplankton to beryllium (Be) is of interest because human activities are increasing the concentration of Be in freshwater reserves; therefore, predicting the effects of human-induced pollutants is necessary for proper risk assessment. The fluctuation analysis was performed with phytoplankton, specifically, the freshwater microalgae Chlamydomonas reinhardtii, under acute Be exposure. High doses of Be led to massive microalgae death; however, by conducting a fluctuation analysis experiment, we found that C. reinhardtii was able to adapt to 33 mg/l of Be due to pre-existing genetic variability. The rescuing adapting genotype presented a mutation rate of 9.61 × 10−6 and a frequency of 10.42 resistant cells per million wild-type cells. The genetic adaptation pathway that was experimentally obtained agreed with the theoretical models of evolutionary rescue (ER). Furthermore, the rescuing genotype presented phenotypic and physiologic differences from the wild-type genotype, was 25% smaller than the Be-resistant genotype and presented a lower fitness and quantum yield performance. The abrupt distinctions between the wild-type and the Be-resistant genotype suggest a pleiotropic effect mediated by an advantageous mutation; however, no sequencing confirmation was performed.

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Evaluation of putative reference genes for quantitative real-time PCR normalization in Lilium regale during development and under stress

Normalization to reference genes is the most common method to avoid bias in real-time quantitative PCR (qPCR), which has been widely used for quantification of gene expression. Despite several studies on gene expression, Lilium, and particularly L. regale, has not been fully investigated regarding the evaluation of reference genes suitable for normalization. In this study, nine putative reference genes, namely 18S rRNA, ACT, BHLH, CLA, CYP, EF1, GAPDH, SAND and TIP41, were analyzed for accurate quantitative PCR normalization at different developmental stages and under different stress conditions, including biotic (Botrytis elliptica), drought, salinity, cold and heat stress. All these genes showed a wide variation in their Cq (quantification Cycle) values, and their stabilities were calculated by geNorm, NormFinder and BestKeeper. In a combination of the results from the three algorithms, BHLH was superior to the other candidates when all the experimental treatments were analyzed together; CLA and EF1 were also recommended by two of the three algorithms. As for specific conditions, EF1 under various developmental stages, SAND under biotic stress, CYP/GAPDH under drought stress, and TIP41 under salinity stress were generally considered suitable. All the algorithms agreed on the stability of SAND and GAPDH under cold stress, while only CYP was selected under heat stress by all of them. Additionally, the selection of optimal reference genes under biotic stress was further verified by analyzing the expression level of LrLOX in leaves inoculated with B. elliptica. Our study would be beneficial for future studies on gene expression and molecular breeding of Lilium.

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GPR18 undergoes a high degree of constitutive trafficking but is unresponsive to N-Arachidonoyl Glycine

The orphan receptor GPR18 has become a research target following the discovery of a putative endogenous agonist, N-arachidonoyl glycine (NAGly). Chemical similarity between NAGly and the endocannabinoid anandamide suggested the hypothesis that GPR18 is a third cannabinoid receptor. GPR18-mediated cellular signalling through inhibition of cyclic adenosine monophosphate (cAMP) and phosphorylation of extracellular signal-regulated kinase (ERK), in addition to physiological consequences such as regulation of cellular migration and proliferation/apoptosis have been described in response to both NAGly and anandamide. However, discordant findings have also been reported. Here we sought to describe the functional consequences of GPR18 activation in heterologously-expressing HEK cells. GPR18 expression was predominantly intracellular in stably transfected cell lines, but moderate cell surface expression could be achieved in transiently transfected cells which also had higher overall expression. Assays were employed to characterise the ability of NAGly or anandamide to inhibit cAMP or induce ERK phosphorylation through GPR18, or induce receptor trafficking. Positive control experiments, which utilised cells expressing hCB1 receptors (hCB1R), were performed to validate assay design and performance. While these functional pathways in GPR18-expressing cells were not modified on treatment with a panel of putative GPR18 ligands, a constitutive phenotype was discovered for this receptor. Our data reveal that GPR18 undergoes rapid constitutive receptor membrane trafficking—several-fold faster than hCB1R, a highly constitutively active receptor. To enhance the likelihood of detecting agonist-mediated receptor signalling responses, we increased GPR18 protein expression (by tagging with a preprolactin signal sequence) and generated a putative constitutively inactive receptor by mutating the hGPR18 gene at amino acid site 108 (alanine to asparagine). This A108N mutant did cause an increase in surface receptor expression (which may argue for reduced constitutive activity), but no ligand-mediated effects were detected. Two glioblastoma multiforme cell lines (which endogenously express GPR18) were assayed for NAGly-induced pERK phosphorylation, with negative results. Despite a lack of ligand-mediated responses in all assays, the constitutive trafficking of GPR18 remains an interesting facet of receptor function and will have consequences for understanding the role of GPR18 in physiology.

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Distribution and regulation of gonadotropin-releasing hormone, kisspeptin, RF-amide related peptide-3, and dynorphin in the bovine hypothalamus

Recent work has led to the hypothesis that kisspeptin/neurokinin B/dynorphin (KNDy) neurons in the arcuate nucleus (ARC) play a key role in gonadotropin-releasing hormone (GnRH) pulse generation and gonadal steroid feedback, with kisspeptin driving GnRH release and neurokinin B and dynorphin acting as pulse start and stop signals, respectively. A separate cell group, expressing RFamide-related peptide-3 (RFRP-3) has been shown to be a primary inhibitor of GnRH release. Very little is known regarding these cell groups in the bovine. In this study, we examined the relative immunoreactivity of kisspeptin, dynorphin, and RFRP-3 and their possible connectivity to GnRH neurons in the hypothalami of periestrus and diestrus bovine. While GnRH and RFRP-3 immunoreactivity were unchanged, kisspeptin and dynorphin immunoreactivity levels varied in relation to plasma progesterone concentrations and estrous status. Animals with higher plasma progesterone concentrations in diestrus had lower kisspeptin and increased dynorphin immunoreactivity in the ARC. The percentage of GnRH cells with kisspeptin or RFRP-3 fibers in close apposition did not differ between estrous stages. However, the proportions of GnRH cells with kisspeptin or RFRP-3 contacts (∼49.8% and ∼31.3%, respectively) suggest direct communication between kisspeptin and RFRP-3 cells to GnRH cells in the bovine. The data produced in this work support roles for kisspeptin and dynorphin, within the KNDy neural network, in controlling GnRH release over the ovarian cycle and conveying progesterone-negative feedback onto GnRH neurons in the bovine.

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Angiosperms and the Linnean shortfall: three new species from three lineages of Melastomataceae at one spot at the Atlantic Forest

Three new species of Angiosperms have been found in four short collection trips to the same protected reserve—"Estação Ecológica Estadual de Wenceslau Guimarães"—and neighboring areas in the Atlantic Forest in the south of the Brazilian state of Bahia. These new species belong to three genera from three distinct lineages in the family Melastomataceae: Huberia, Meriania and Physeterostemon. The description of these species represent a good example of a Linnean shortfall, i.e., the absence of basic knowledge about the biodiversity in the area, as well as in tropical forests as a whole. The description of these probably endemic species per se is a signal that this area deserves more attention regarding research and policies, but its consequences go farther: this area has a relevant role as a phylogenetic (both genetic and morphological) stock, and thus is also valuable as a phylogenetic conservation priority.

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Comparative analysis of different survey methods for monitoring fish assemblages in coastal habitats

Coastal ecosystems are among the most productive yet increasingly threatened marine ecosystems worldwide. Particularly vegetated habitats, such as eelgrass (Zostera marina) beds, play important roles in providing key spawning, nursery and foraging habitats for a wide range of fauna. To properly assess changes in coastal ecosystems and manage these critical habitats, it is essential to develop sound monitoring programs for foundation species and associated assemblages. Several survey methods exist, thus understanding how different methods perform is important for survey selection. We compared two common methods for surveying macrofaunal assemblages: beach seine netting and underwater visual census (UVC). We also tested whether assemblages in shallow nearshore habitats commonly sampled by beach seines are similar to those of nearby eelgrass beds often sampled by UVC. Among five estuaries along the Southern Gulf of St. Lawrence, Canada, our results suggest that the two survey methods yield comparable results for species richness, diversity and evenness, yet beach seines yield significantly higher abundance and different species composition. However, sampling nearshore assemblages does not represent those in eelgrass beds despite considerable overlap and close proximity. These results have important implications for how and where macrofaunal assemblages are monitored in coastal ecosystems. Ideally, multiple survey methods and locations should be combined to complement each other in assessing the entire assemblage and full range of changes in coastal ecosystems, thereby better informing coastal zone management.

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An integrated text mining framework for metabolic interaction network reconstruction

Text mining (TM) in the field of biology is fast becoming a routine analysis for the extraction and curation of biological entities (e.g., genes, proteins, simple chemicals) as well as their relationships. Due to the wide applicability of TM in situations involving complex relationships, it is valuable to apply TM to the extraction of metabolic interactions (i.e., enzyme and metabolite interactions) through metabolic events. Here we present an integrated TM framework containing two modules for the extraction of metabolic events (Metabolic Event Extraction module—MEE) and for the construction of a metabolic interaction network (Metabolic Interaction Network Reconstruction module—MINR). The proposed integrated TM framework performed well based on standard measures of recall, precision and F-score. Evaluation of the MEE module using the constructed Metabolic Entities (ME) corpus yielded F-scores of 59.15% and 48.59% for the detection of metabolic events for production and consumption, respectively. As for the testing of the entity tagger for Gene and Protein (GP) and metabolite with the test corpus, the obtained F-score was greater than 80% for the Superpathway of leucine, valine, and isoleucine biosynthesis. Mapping of enzyme and metabolite interactions through network reconstruction showed a fair performance for the MINR module on the test corpus with F-score >70%. Finally, an application of our integrated TM framework on a big-scale data (i.e., EcoCyc extraction data) for reconstructing a metabolic interaction network showed reasonable precisions at 69.93%, 70.63% and 46.71% for enzyme, metabolite and enzyme–metabolite interaction, respectively. This study presents the first open-source integrated TM framework for reconstructing a metabolic interaction network. This framework can be a powerful tool that helps biologists to extract metabolic events for further reconstruction of a metabolic interaction network. The ME corpus, test corpus, source code, and virtual machine image with pre-configured software are available at www.sbi.kmutt.ac.th/ preecha/metrecon.

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Evaluation of unmanned aerial vehicle shape, flight path and camera type for waterfowl surveys: disturbance effects and species recognition

The use of unmanned aerial vehicles (UAVs) for ecological research has grown rapidly in recent years, but few studies have assessed the disturbance impacts of these tools on focal subjects, particularly when observing easily disturbed species such as waterfowl. In this study we assessed the level of disturbance that a range of UAV shapes and sizes had on free-living, non-breeding waterfowl surveyed in two sites in eastern Australia between March and May 2015, as well as the capability of airborne digital imaging systems to provide adequate resolution for unambiguous species identification of these taxa. We found little or no obvious disturbance effects on wild, mixed-species flocks of waterfowl when UAVs were flown at least 60m above the water level (fixed wing models) or 40m above individuals (multirotor models). Disturbance in the form of swimming away from the UAV through to leaving the water surface and flying away from the UAV was visible at lower altitudes and when fixed-wing UAVs either approached subjects directly or rapidly changed altitude and/or direction near animals. Using tangential approach flight paths that did not cause disturbance, commercially available onboard optical equipment was able to capture images of sufficient quality to identify waterfowl and even much smaller taxa such as swallows. Our results show that with proper planning of take-off and landing sites, flight paths and careful UAV model selection, UAVs can provide an excellent tool for accurately surveying wild waterfowl populations and provide archival data with fewer logistical issues than traditional methods such as manned aerial surveys.

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The effect of the angle of acuteness of additive manufactured models and the direction of printing on the dimensional fidelity: clinical implications.

The effect of the angle of acuteness of additive manufactured models and the direction of printing on the dimensional fidelity: clinical implications.

Odontology. 2016 Mar 19;

Authors: Ide Y, Nayar S, Logan H, Gallagher B, Wolfaardt J

Abstract
The influence of the acuteness of the model angle and the direction of printing was investigated on different three-dimensional (3D) printers to understand the fidelity of 3D printing. A Polyjet printer and two fused deposition modeling printers were used in the present study. Computer-aided design (CAD) models were designed in the form of a triangular prism with a height of 15 mm and with varying angles of 60°, 45°, 30°, 20°, 10°, and 5°. From the CAD designs, additive manufacturing (AM) models were printed in three different directions by each of the three printers. To investigate the global fidelity of the 3D printers, the height and surface outlines of the AM model cross sections were measured. The fidelity of the AM models with increasingly acute angles was not accurately reproduced when 3D printed, and the surface outlines of the AM model cross sections were different in each direction of printing for each device. Printing technology and printing direction need to be considered if accurate reproduction of acute angles in fine AM structures in medical models is a necessity.

PMID: 26995273 [PubMed - as supplied by publisher]

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Surgical treatment of substernal goiter: An analysis of 44 cases.

Surgical treatment of substernal goiter: An analysis of 44 cases.

Auris Nasus Larynx. 2016 Mar 16;

Authors: Nakaya M, Ito A, Mori A, Oka M, Omura S, Kida W, Inayoshi Y, Inoue A, Fuchigami T

Abstract
OBJECTIVE: Substernal goiters are classified as primary or secondary intrathoracic goiters. Here, we report the diagnosis, symptoms, treatment, and postoperative complications of 44 substernal goiters (2 primary mediastinal goiter and 42 secondary mediastinal goiters).
METHODS: A retrospective chart review of 351 patients undergoing thyroidectomy at the Department of Otolaryngology-Head and Neck Surgery of the Tokyo Metropolitan Tama Medical Center. Between 2009 and 2015, 44 patients underwent surgery for substernal goiter.
RESULTS: The frequency of primary and secondary mediastinal goiters was 0.5% and 11.9%, respectively. The preoperative symptoms were neck mass, dyspnea, and dysphagia. Eight patients were asymptomatic. Thirty-nine patients had benign masses and 5 patients had malignant masses. Most patients were operated on for adenomatous goiters (52.2%). In ten cases beyond the aortic arch, the tumors were benign and there were eight cases of adenomatous goiter. All patients underwent a successful transcervical incision without sternotomy. Even the primary intrathoracic goiters were extracted after total thyroidectomy via the cervical approach without complications. Although one case showed unilateral recurrent nerve paralysis as a postoperative complication, phonetic function improved in 6 postoperative months. No instances of postoperative bleeding or definitive hypoparathyroidism occurred, and tracheostomy was not performed in any of the cases.
CONCLUSION: The cervical approach was safely performed in almost all substernal goiters without an extracervical procedure. Selected cases of primary mediastinal goiter may be excised via the cervical approach.

PMID: 26995097 [PubMed - as supplied by publisher]

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Structural and functional changes of cortical and subcortical structures following peripheral vestibular damage in humans.

Structural and functional changes of cortical and subcortical structures following peripheral vestibular damage in humans.

Eur Arch Otorhinolaryngol. 2016 Mar 19;

Authors: Maxime M, Philippe F, Landry SP, François C, Saliba I

PMID: 26994901 [PubMed - as supplied by publisher]

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Feasibility of injectable thermoreversible gels for use in intramuscular injection of parathyroid autotransplantation.

Feasibility of injectable thermoreversible gels for use in intramuscular injection of parathyroid autotransplantation.

Eur Arch Otorhinolaryngol. 2016 Mar 19;

Authors: Park HS, Jung SY, Kim HY, Ko DY, Chung SM, Jeong B, Kim HS

Abstract
Surgical transplantation of parathyroid tissue into the forearm muscle is one of the most commonly used surgical techniques. While simple, the procedure suffers from drawbacks. This study evaluated the feasibility of thermoreversible gel as an injectable carrier for parathyroid autotransplantation. Polyethyleneglycol-polyalanine-co-phenylalanine (PEG-PAF) thermoreversible gel (sol form at 4 °C, gel form at 37 °C) were manufactured. Thirty-eight Sprague-Dawley rats were divided into two groups (19 control, C group; 19 experimental, P group). The parathyroid glands of rats were excised. Parathyroid tissues were transplanted into the muscle pocket in sternocleidomastoid muscle in the C group. In the P group, the tissues were injected into the same muscle mixed with 0.3 ml thermoreversible gel. The serum levels of parathyroid hormone (PTH), ionized calcium, and phosphorous were measured before surgical procedure, on 7, 21, 56, and 70 days after surgery. Histology and immunohistochemistry were performed. Preoperative median PTH level of the C and the P group were 60.80 and 43.85 pg/ml, respectively (p = 0.641). Seventy days after surgery, median PTH level was 32.8 and 25.61 pg/ml, respectively. On day 70, the PTH level was restored by 54 % in the C group and 56 % in the P group compared to the preoperative value (p = 0.620). There were no significant intergroup differences in the ionized calcium/phosphorous level. Histology and immunohistochemistry revealed the successful transplantation of parathyroid tissues into the muscles in both groups. In conclusion, the PEG-PAF-based thermoreversible gel is a good candidate carrier material for intramuscular parathyroid autotransplantation.

PMID: 26994900 [PubMed - as supplied by publisher]

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Recovery of Salivary Function: Contralateral Parotid-sparing Intensity-modulated Radiotherapy versus Bilateral Superficial Lobe Parotid-sparing Intensity-modulated Radiotherapy.

Recovery of Salivary Function: Contralateral Parotid-sparing Intensity-modulated Radiotherapy versus Bilateral Superficial Lobe Parotid-sparing Intensity-modulated Radiotherapy.

Clin Oncol (R Coll Radiol). 2016 Mar 17;

Authors: Miah AB, Gulliford SL, Morden J, Newbold KL, Bhide SA, Zaidi SH, Hall E, Harrington KJ, Nutting CM

Abstract
AIMS: To establish whether there is a difference in recovery of salivary function with bilateral superficial lobe parotid-sparing intensity-modulated radiotherapy (BSLPS-IMRT) versus contralateral parotid-sparing IMRT (CLPS-IMRT) in patients with locally advanced head and neck squamous cell cancers.
MATERIALS AND METHODS: A dosimetric analysis was carried out on data from two studies in which patients received BSLPS-IMRT (PARSPORT II) or CLPS-IMRT (PARSPORT). Acute (National Cancer Institute, Common Terminology Criteria for adverse events - NCI CTCAEv3.0) and late (Late Effects of Normal Tissue- subjective, objective, management analytical - LENTSOMA and Radiation Therapy Oncology Group) xerostomia scores were dichotomised: recovery (grade 0-1) versus no recovery (≥grade 2). Incidence of recovery of salivary function was compared between the two techniques and dose-response relationships were determined by fitting dose-response curves to the data using non-linear logistic regression analysis.
RESULTS: Seventy-one patients received BSLPS-IMRT and 35 received CLPS-IMRT. Patients received 65 Gy in 30 fractions to the primary site and involved nodal levels and 54 Gy in 30 fractions to elective nodal levels. There were significant differences in mean doses to contralateral parotid gland (29.4 Gy versus 24.9 Gy, P < 0.005) and superficial lobes (26.8 Gy versus 30.5 Gy, P = 0.02) for BSLPS and CLPS-IMRT, respectively. Lower risk of long-term ≥grade 2 subjective xerostomia (LENTSOMA) was reported with BSLPS-IMRT (odds ratio 0.50; 95% confidence interval 0.29-0.86; P = 0.012). The percentage of patients who reported recovery of parotid saliva flow at 1 year was higher with BSLPS-IMRT compared with CLPS-IMRT techniques (67.1% versus 52.8%), but the difference was not statistically significant (P = 0.12). For the whole parotid gland, the tolerance doses, D50, were 25.6 Gy (95% confidence interval 20.6-30.5), k = 2.7 (0.9-4.5) (CLPS-IMRT) and 28.9 Gy (26.1-31.9), k = 2.4 (1.4-3.4) (BSLPS-IMRT). For the superficial lobe, D50 were similar: BSLPS-IMRT 23.5 Gy (19.3-27.6), k = 1.9 (0.5-3.8); CLPS-IMRT 24.0 Gy (17.7-30.1), k = 2.1 (0.1-4.1).
CONCLUSION: BSLPS-IMRT reduces the risk of developing high-grade subjective xerostomia compared with CLPS-IMRT. The D50 of the superficial lobe may be a more reliable predictor of recovery of parotid function than the whole gland mean dose.

PMID: 26994893 [PubMed - as supplied by publisher]

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Implanting straight into cochlea risks the facial nerve: a Cartesian coordinate study.

Implanting straight into cochlea risks the facial nerve: a Cartesian coordinate study.

Surg Radiol Anat. 2016 Mar 19;

Authors: Deshpande AS, Wendell Todd N

Abstract
PURPOSE: To describe the straight-into-cochlea line that affords the best access for an electrode array to enter via the round window, and how this line relates to the facial nerve, the incus, and mastoid size. The straight-into-cochlea line is important to minimize the cochlear trauma and maximize the likelihood of placement into the scala tympani.
METHODS: High-resolution CT scans were obtained for ten craniums with the extremes of large (N = 5) and small (N = 5) mastoid pneumatization; the specimens were from a series of 41 ear normal craniums. Using FIJI, a publicly available software program, the straight-into-cochlea insertion line was determined by defining the x-y-z coordinates of the middle of the round window and a point 6.0 mm into the cochlea on its centrifugal wall. Then, from the extended straight-into-cochlea insertion line, we determined the shortest perpendicular distance to the middle of the fallopian canal, and from that "fallopian point" to the apex of the posterior process of the incus.
RESULTS: We found good repeatability of measurements. We found the extended straight-into-cochlea insertion lines routinely close to or in the midst of the fallopian canal (50 % ≤ 1.0 mm). We found the lines 4.7-7.8 mm from the apex of the posterior process of the incus. Line positions relative to "fallopian point" and incus showed no relation to mastoid pneumatization. For the distance "fallopian point" to incus, bilateral symmetry was suggested.
CONCLUSIONS: Using landmarks registered in an x-y-z coordinate system, straight-into-cochlea insertion via the round window puts the facial nerve at risk.

PMID: 26994765 [PubMed - as supplied by publisher]

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Altered fractionation radiotherapy in head and neck squamous cell carcinoma.

Altered fractionation radiotherapy in head and neck squamous cell carcinoma.

J Egypt Natl Canc Inst. 2016 Mar 16;

Authors: Mallick S, Benson R, Julka PK, Rath GK

Abstract
INTRODUCTION: Fractionation plays a pivotal role in determining the effectiveness of radiation and follows the principle of 4 "R" of radiobiology. The various altered fractionation schedules used are hyper-fractionation, accelerated fractionation, and hypo fractionation.
METHODS: We reviewed the landmark articles published in the peer reviewed journals to summarize the beneficial role of altered fractionation in the treatment of head and neck carcinoma.
RESULTS: Hyper-fractionation definitely gives very good overall survival benefit for locally advanced head and neck patient's equivalent to survival benefit to that of concurrent chemoradiotherapy. Adding concomitant chemotherapy to altered fractionation is a logical approach to improve survival in locally advanced head and neck cancer patients, but it may be at a cost of higher toxicity. Mild hypo fractionation may be beneficial in early laryngeal cancers and may help in achieving better local control.
CONCLUSION: Altered fractionation is a very important treatment schema and requires the reinforcement of its use.

PMID: 26994645 [PubMed - as supplied by publisher]

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Pattern of neck recurrence after lateral neck dissection for cervical metastases in papillary thyroid cancer.

Pattern of neck recurrence after lateral neck dissection for cervical metastases in papillary thyroid cancer.

Surgery. 2016 Mar 16;

Authors: McNamara WF, Wang LY, Palmer FL, Nixon IJ, Shah JP, Patel SG, Ganly I

Abstract
BACKGROUND: The objective of this study was to determine the rate and pattern of nodal recurrence in patients who underwent a therapeutic, lateral neck dissection (LND) for papillary thyroid cancer (PTC) with clinically evident cervical metastases and to determine if there was any correlation between the extent of initial dissection and the rate and pattern of neck recurrence.
METHODS: A total of 3,664 patients with PTC treated between 1986 and 2010 at Memorial Sloan Kettering Cancer Center were identified from our institutional database. Tumor factors, patient demographics, extent of initial LND, and adjuvant therapy were recorded. Patterns of recurrent lateral neck metastases by level involvement were recorded and outcomes calculated using the Kaplan-Meier method.
RESULTS: A total of 484 patients had an LND for cervical metastases; 364 (75%) had a comprehensive LND (CLND) and 120 (25%) had a selective neck dissection (SND). The median duration of follow-up was 63.5 months. As expected, patients with CLND had a greater number of nodes removed as well as a greater number of positive nodes (P < .001). There was no difference in overall lateral neck recurrence-free status (CLND 94.4% vs SND 89.4%, P = .158), but in the dissected neck, the ipsilateral lateral neck recurrence-free status was superior in the CLND patients (97.7% vs 89.4%, P < .001).
CONCLUSION: Patients with clinically evident neck metastases from PTC managed by CLND have lesser rates of recurrence in the dissected neck compared with patients managed by SND. SND should only be done in highly selected cases with small volume disease.

PMID: 26994486 [PubMed - as supplied by publisher]

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Cyclin-dependent protein kinase inhibitors including palbociclib as anticancer drugs.

Cyclin-dependent protein kinase inhibitors including palbociclib as anticancer drugs.

Pharmacol Res. 2016 Mar 16;

Authors: Roskoski R

Abstract
Cyclins and cyclin-dependent protein kinases (CDKs) are important regulatory components that are required for cell cycle progression. The levels of the cell cycle CDKs are generally constant and their activities are controlled by cyclins, proteins whose levels oscillate during each cell cycle. Additional CDK family members were subsequently discovered that play significant roles in a wide range of activities including the control of gene transcription, metabolism, and neuronal function. In response to mitogenic stimuli, cells in the G1 phase of the cell cycle produce cyclins of the D type that activate CDK4/6. These activated enzymes catalyze the monophosphorylation of the retinoblastoma protein. Then CDK2-cyclin E catalyzes the hyperphosphorylation of Rb that promotes the release and activation of the E2F transcription factors, which in turn lead to the generation of several proteins required for cell cycle progression. As a result, cells pass through the G1-restriction point and are committed to complete cell division. CDK2-cyclin A, CDK1-cyclin A, and CDK1-cyclin B are required for S, G2, and M-phase progression. Increased cyclin or CDK expression or decreased levels of endogenous CDK inhibitors such as INK4 or CIP/KIP have been observed in various cancers. In contrast to the mutational activation of EGFR, Kit, or B-Raf in the pathogenesis of malignancies, mutations in the CDKs that cause cancers are rare. Owing to their role in cell proliferation, CDKs represent natural targets for anticancer therapies. Abemaciclib (LY2835219), ribociclib (Lee011), and palbociclib (Ibrance(®) or PD0332991) target CDK4/6 with IC50 values in the low nanomolar range. Palbociclib and other CDK inhibitors bind in the cleft between the small and large lobes of the CDKs and inhibit the binding of ATP. Like ATP, palbociclib forms hydrogen bonds with residues in the hinge segment of the cleft. Like the adenine base of ATP, palbociclib interacts with catalytic spine residues CS6 and CS7. CDK antagonists are in clinical trials for the treatment of a variety of malignancies. Significantly, palbociclib has been approved by the FDA for the treatment of hormone-receptor positive/human epidermal growth factor receptor-2 negative breast cancer in conjunction with letrozole as a first-line therapy and with fulvestrant as a second-line treatment. As inhibitors of the cell cycle, it is not surprising that one of their most common toxicities is myelosuppression with decreased neutrophil production.

PMID: 26995305 [PubMed - as supplied by publisher]

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[BRCA1 associated protein 1 (BAP1) expression in pleural diffuse malignant mesothelioma: A comparative cytological and histological analyses on 50 patients].

[BRCA1 associated protein 1 (BAP1) expression in pleural diffuse malignant mesothelioma: A comparative cytological and histological analyses on 50 patients].

Ann Pathol. 2016 Mar 16;

Authors: Jaouen A, Thivolet-Bejui F, Chalabreysse L, Piaton E, Traverse-Glehen A, Isaac S, Decaussin-Petrucci M, Depaepe L, Fontaine J, Remy I, Maury JM, Brevet M

Abstract
INTRODUCTION: Diffuse malignant mesothelioma (MMD) is a rare disease. The diagnosis is difficult and needs an antibody panel. The tumor suppressor gene BRCA1 associated protein 1 (BAP1) is involved in several cancers, including MMD. Loss of BAP1 expression is correlated with BAP1 somatic or constitutional genetic defects. Our work assesses the value of integrating BAP1 in the panel of antibodies used for the diagnosis of MMD.
MATERIALS AND METHODS: Immunohistochemical techniques were performed on cytological and histological specimens of MMD and adenocarcinoma pleural metastasis.
RESULTS: Of the 26 patients with MMD and the 24 patients with adenocarcinoma pleural metastasis, loss of BAP1 expression was observed in 11 (48%) and one adenocarcinoma (6%) on cytological specimens and in 12 MMD (48%) and in one adenocarcinoma (5%) on biopsy specimens. The concordance between immunocytochemistry and immunohistochemistry was 100%. The specificity of BAP1 was 100% on cytological and biopsy specimen for the diagnosis of malignancy in case of mesothelial proliferation.
DISCUSSION AND CONCLUSION: Loss of BAP1 expression is an indicator of MMD in a context of mesothelial proliferation. This immunohistochemistry could be integrated in the panel of immunostaining used for MMD diagnosis, either on histological or cytological samples. Furthermore, loss of BAP1 expression guides the patient to an oncology genetic counseling in order to eliminate a MMD developed as part of a constitutional genetic defect.

PMID: 26995100 [PubMed - as supplied by publisher]

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Disseminated glioneuronal tumors occurring in childhood: treatment outcomes and BRAF alterations including V600E mutation.

Disseminated glioneuronal tumors occurring in childhood: treatment outcomes and BRAF alterations including V600E mutation.

J Neurooncol. 2016 Mar 19;

Authors: Dodgshun AJ, SantaCruz N, Hwang J, Ramkissoon SH, Malkin H, Bergthold G, Manley P, Chi S, MacGregor D, Goumnerova L, Sullivan M, Ligon K, Beroukhim R, Herrington B, Kieran MW, Hansford JR, Bandopadhayay P

Abstract
Disseminated glioneuronal tumors of childhood are rare. We present a retrospective IRB-approved review of the clinical course and frequency of BRAF mutations in disseminated glioneuronal tumors at two institutions. Defining features of our cohort include diffuse leptomeningeal-spread, often with a discrete spinal cord nodule and oligodendroglioma-like histologic features. Patients were identified through a pathology database search of all cases with disseminated low-grade neoplasms with an oligodendroglioma-like component. De-identified clinical information was collected by chart review and all imaging was reviewed. We retrieved the results of targeted genomic analyses for alterations in BRAF. Ten patients (aged 2-14 years) were identified from the Dana-Farber/Boston Children's Hospital and the Royal Children's Hospital, Melbourne pathology databases. Nine patients received chemotherapy. Eight patients are alive, although three have had episodes of progressive disease. We identified genomic alterations affecting the MAPK pathway in six patients. One patient had a germline RAF1 mutation and a clinical diagnosis of cardio-facio-cutaneous syndrome. BRAF duplications were identified in four and BRAF V600E mutation was identified in one. These data support the presence of targetable genomic alterations in this disease.

PMID: 26994902 [PubMed - as supplied by publisher]

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Male breast cancer, clinical presentation, diagnosis and treatment: Twenty years of experience in our Breast Unit.

Male breast cancer, clinical presentation, diagnosis and treatment: Twenty years of experience in our Breast Unit.

Int J Surg Case Rep. 2016 Feb 26;

Authors: Sanguinetti A, Polistena A, Lucchini R, Monacelli M, Galasse S, Avenia S, Triola R, Bugiantella W, Cirocchi R, Rondelli F, Avenia N

Abstract
BACKGROUND: The male breast cancer (MBC) is a rare and represents less than 1% of all malignancies in men and only 1% of all breast cancers incident. We illustrate the experience of our team about the clinico-pathological characteristics, treatment and prognostic factors of patients treated over a period of twenty years .
RESULTS: Forty-seven patients were collected 1995-2014 at the Breast Unit of the Hospital of Terni, Italy. The average age was 67 years and the median time to diagnosis from the onset of symptoms was 16 months. The main clinical complaint was sub areolar swelling in 36, 76% of cases. Most patients have come to our attention with advanced disease. The histology of about ninety percent of the tumors were invasive ductal carcinoma. Management consisted mainly of radical mastectomy; followed by adjuvant radiotherapy and hormonal therapy with or without chemotherapy. The median follow-up was 38 months. The evolution has been characterized by local recurrences; in eight cases (17% of all patients). Metastasis occurred in 15 cases (32% of all patients). The site of bone metastases was in eight cases; lung in four cases; liver in three cases; liver and skin in one case and pleura and skin in one case.
CONCLUSION: The male breast cancer has many similarities to breast cancer in women, but there are distinct functions that need to be appreciated. Future research for a better understanding of the disease should provide a better account of genetic and epigenetic characteristics of these forms; but, above all, epidemiological and biological cohorts numerically more consistent.

PMID: 26994487 [PubMed - as supplied by publisher]

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