18 F–FDG-PET/CT for systemic staging of patients with newly diagnosed ER-positive and HER2-positive breast cancer

Abstract

Objectives

This study assesses ¹⁸F–FDG-PET/CT for patients with newly diagnosed estrogen receptor-positive/human epidermal growth factor receptor-negative (ER+/HER2-) and human epidermal growth factor receptor-positive (HER2+) breast cancer.

Methods

In this Institutional Review Board-approved retrospective study, our Healthcare Information System was screened for patients with ER+/HER2- and HER2+ breast cancer who underwent ¹⁸F–FDG-PET/CT prior to systemic or radiation therapy. The initial stage was determined from mammography, ultrasound, magnetic resonance imaging, and/or surgery.¹⁸F–FDG-PET/CT was evaluated to identify unsuspected extra-axillary regional nodal and distant metastases. The proportion of patients upstaged overall and stratified by stage and receptor phenotypes was calculated along with confidence intervals (CI).

Results

A total of 238 patients with ER+/HER2- and 245 patients with HER2+ who met inclusion criteria were evaluated. For patients with ER+/HER2-breast cancer, ¹⁸F–FDG-PET/CT revealed unsuspected distant metastases in 3/71 (4%) initial stage IIA, 13/95 (14%) stage IIB, and 15/57 (26%) stage III. For patients with HER2+ breast cancer, ¹⁸F–FDG-PET/CT revealed unsuspected distant metastases in 3/72 (4%) initial stage IIA, 13/93 (14%) stage IIB, and 13/59 (22%) stage III. The overall upstaging rate for IIB was 14% (95% confidence interval (CI): 9–20%).

Conclusions

¹⁸F–FDG-PET/CT revealed distant metastases in 14% (95% CI: 9–20%) of patients with stage IIB ER+/HER2- and HER2+ breast cancer, which is similar to upstaging rates previously seen in patients with stage IIB triple-negative breast cancer (15%, 95% CI: 9–24%). The detection of unsuspected distant metastases in these patients alters treatment and prognosis. NCCN guidelines should consider adding patients with stage IIB breast cancer for consideration of systemic staging with ¹⁸F–FDG-PET/CT at the time of initial diagnosis.

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The impact of repeated cycles of radioligand therapy using [ 177 Lu]Lu-PSMA-617 on renal function in patients with hormone refractory metastatic prostate cancer

Abstract

Background

[¹⁷⁷Lu]Lu-PSMA-617 is a well-tolerated therapy for the treatment of metastatic prostate cancer. However, because of the mainly renal excretion of the tracer, the kidneys are one of the most limiting organs. The purpose of this study was to examine the post-therapeutic changes in renal function over time and to identify risk factors for developing renal toxicity. We also tested the reliability of markers for renal function monitoring.

Methods

Fifty-five patients with castrate-resistant metastatic prostate cancer treated with at least three cycles of [¹⁷⁷Lu]Lu-PSMA-617 were investigated. Renal function was assessed through laboratory tests (creatinine, GFR, cystatin C) and Tc-99 m-MAG3 measurements. Adverse events were classified according to the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. To identify risk factors for renal toxicity, we used Pearson's correlation coefficient and the corresponding p values.

Results

None of the 55 patients experienced severe nephrotoxicity (grade 3/4). In 14 patients (25%), we observed increased creatinine levels of CTC 1° or 2°. There were 16 cases of increased GFR (grade 1/2). At the baseline, only 14 patients had elevated cystatin C. However, post-therapeutic cystatin C was elevated in 32 patients (58%). A significant effect on renal function was found for age (p = 0.049), hypertension (p = 0.001) and pre-existing kidney disease (p = 0.001). The most reliable predictive markers of nephrotoxicity were TER-MAG3 and cystatin C.

Conclusion

Renal toxicity in patients treated with [¹⁷⁷Lu]Lu-PSMA-617 was low. There was no (sub)acute grade 3 or 4 nephrotoxicity.

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Fibrous dysplasia mimicking bone metastasis on 68 GA-PSMA PET/MRI

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Microsurgery guided by sequential preoperative lymphography using 68 Ga-NEB PET and MRI in patients with lower-limb lymphedema

Abstract

Objective

The popularity of contemporary microsurgical techniques in treatment of lower-limb lymphedema calls for better visualization of the lymphatic system, both preoperatively and intra-operatively. The aim of this prospective study was to investigate the feasibility of a novel combination of ⁶⁸Ga-NEB positron emission tomography (PET) with magnetic resonance lymphography (MRL) in evaluating lymphedema and guiding surgical intervention.

Methods

A total of 11 patients (F 9, M 2, age range 29–69 y) with lower-limb lymphedema classified into stage I to III were recruited. PET acquisition was performed at 30, 60 and 90 min after subcutaneous injection of the albumin-binding radiotracer ⁶⁸Ga-NEB into the bilateral first web spaces of the feet. All the patients were also subjected to ^99mTc-sulfur colloid (SC) lymphoscintigraphy for comparison. Gd-DTPA-enhanced magnetic resonance imaging (MRI) was performed using sequences specialized for lymphatic vessel scans. All the patients underwent surgical interventions within a week. The surgical approach includes the use of a linear marker for edema localization and indocyanine green (ICG) lymphography with a near-infrared surgical navigation system intra-operatively.

Results

Lymph transport in lymphatic channels was clearly observed by visualization of ⁶⁸Ga-NEB activity in the lymphatic vessels and within lymph nodes for all 11 patients as well as the visualization of the edema section plane with dermal backflow (DB), abnormally increased and disconnected uptake along the lymphatic channels. Preoperative ⁶⁸Ga-NEB PET combined with MRL provides advantageous three-dimensional images, higher temporal resolution, significantly shorter time lapse before image acquisition after tracer injection and more accurate pathological lymphatic vessel distribution than ^99mTc-SC lymphoscintigraphy combined with MRI.

Conclusion

This study documented an effective imaging pattern to combine ⁶⁸Ga-NEB PET and MRL in patients with lower-limb lymphedema. This strategy demonstrated significant advantage over ^99mTc-SC lymphoscintigraphy/MRL in the evaluation of lymphedema severity, staging and pathological location of lymph vessels to make an individualized treatment plan. Dual ⁶⁸Ga-NEB PET/MRL is thus recommended before the operation for staging and therapy planning.

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FDG PET for therapy monitoring in Hodgkin’s and non-Hodgkin’s lymphomas: qPET versus rPET

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Sentinel lymph node mapping using SPECT/CT and gamma probe in endometrial cancer: an analysis of parameters affecting detection rate

Abstract

Purpose

SPECT/CT after pericervical injection of technetium-99 m-nanocolloid was shown to be suitable for sentinel lymph node (SLN) mapping in endometrial cancer (EC). The aim of this study was to analyze factors affecting successful SLN detection by means of SPECT/CT such as imaging findings, patient characteristics and tumor biology in a large cohort of patients.

Methods

One hundred and forty-five consecutive patients suffering from EC who received pre-surgical SLN mapping at our institution between 2011 and 2016 were included in this analysis. SPECT/CT data of abdomen and pelvis (mean 4:20 ± 1:20 h p.i.) were acquired after pericervical injection of technetium-99 m-nanocolloid (mean 230 ± 45 MBq) in all patients. Surgical staging was performed on the day after. Acquisition parameters, patient characteristics, SPECT/CT findings as well as histopathological results were collected.

Results

A total of 282 SLNs were identified by means of SPECT/CT. Overall, preoperative and intraoperative SLN detection rates were 86%, 76% and 74% respectively. The most important factor associated with failure to detect SLNs was the presence of high bone marrow on SPECT/CT (p = 0.005). Peritoneal/abdominal radioactivity was also associated with missed SLN detection in SPECT/CT (p = 0.02). However, the presence of liver/spleen uptake on its own was not predictive for detection failure. Low numbers of detected SLNs in SPECT/CT were slightly related with older age and lower injected activity. No significant influence was found for the parameters of tumor histology and stage, lymph node involvement and the time gap between injection and imaging.

Conclusions

Venous drainage as indicated by bone marrow uptake is the most important factor associated with scintigraphic SLN detection failure. Moreover, high peritoneal and abdominal activity was also associated with detection failure. Thus, meticulous application of the radiotracer is crucial in EC.

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FDG-PET/CT for systemic staging of patients with newly diagnosed breast cancer

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Assessment of nonsteroidal anti-inflammatory drugs by ultrasonic-assisted extraction and GC-MS in Mgeni and Msunduzi river sediments, KwaZulu-Natal, South Africa

Abstract

The occurrence of eight pharmaceuticals was monitored during four seasons (spring, summer, autumn, and winter) along a 250-km stretch of the Msunduzi and Mgeni rivers in KwaZulu-Natal, South Africa. This paper describes an optimized method for the determination of nonsteroidal anti-inflammatory drugs (NSAIDs) in sediments. The method combines ultrasonic, centrifuge, and gas chromatography-mass spectrometry for the detection of these drugs in solid samples. Most of the parameters that affect the extraction step were optimized. Solid samples were placed in a centrifuge tube and extracted with ethyl acetate:acetone (1:1, two cycles), followed by clean-up with Oasis HLB cartridge and derivatization with N, O-bis(trimethylsilyl) trifluoroacetamide (BSTFA). Satisfactory recoveries were obtained ranging from 66 to 130%, depending on the analyte. Precision expressed as RSD (%) (n = 3) was less than 20% for all analytes. The LODs and LOQs were in the range of 0.024 to 1.90 ng g⁻¹ which allowed to be applied in the analysis solid samples in Msunduzi and Mgeni rivers. In the solid samples analyzed, NSAID concentration ranged from not detected to 221 ng g⁻¹.

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The Influence of Parameters of Ink-Jet Printing on Photoluminescence Properties of Nanophotonic Labels Based on Ag Nanoparticles for Smart Packaging

Ag nanoparticles are perspective for the use in ink-jet printed smart packaging labels in order to protect a customer from counterfeit or inform them about the safety of consumption of a packaged product via changeable luminescence properties. It is determined that, to obtain printed images with the highest luminescence intensity, using the most technologically permissible concentration of fluorescent component in the ink composition and applying inks to papers with the lowest absorbance are recommended. The highest contrast of a tone fluorescent image can be obtained on papers with high degree of sizing. It is found that the use of papers with low optical brightness agent (OBA) content with a wide range of luminescence intensity allows obtaining the same visual legibility of a printed nanophotonic label. The increase in the relative area of raster elements of an image leads to nonlinear increase in luminescence intensity of printed images in long-wave area of visible spectrum, affecting the luminescence color of a printed label. For wide industrial production of printed nanophotonic labels for smart packaging, the created principles of reproduction of nanophotonic images applied onto paper materials by ink-jet printing technique using printing inks containing Ag nanoparticles should be taken into account.

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Proton-Beam Therapy in Limited-Stage SCLC Shows Promising Efficacy

Proton-beam therapy was found to be safe for patients with limited-stage small-cell lung cancer in the first prospective registry study of the therapy, with only a small number of high-grade toxicities. (Source: CancerNetwork)

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Gene Signature ID ’s Breast Cancer Patients Who Could Skip Chemotherapy

A 70-gene expression score can identify women with indolent breast cancer at "ultralow" risk, according to a new study. Women with such a score have extremely low risk of disease-specific mortality over 20 years without systemic therapy. (Source: CancerNetwork)

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Cialis super active vs cialis - Cialis super active plus reviews - Van Wert independent

Van Wert independent

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MUC-king with HIF May Rewire Pyrimidine Biosynthesis and Curb Gemcitabine Resistance in Pancreatic Cancer

Publication date: 10 July 2017
Source:Cancer Cell, Volume 32, Issue 1
Author(s): Chi V. Dang
In this issue of Cancer Cell, Singh and colleagues report a role for MUC1-induced HIF expression in rewiring ribose synthesis, which drives pyridimine production as a possible resistance mechanism to gemcitabine, adding to complexity and multiple paths to resistance.

Teaser

In this issue of Cancer Cell, Singh and colleagues report a role for MUC1-induced HIF expression in rewiring ribose synthesis, which drives pyridimine production as a possible resistance mechanism to gemcitabine, adding to complexity and multiple paths to resistance.


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Redefining Hormonal Therapy for Advanced Prostate Cancer: Results from the LATITUDE and CHAARTED Studies

Publication date: 10 July 2017
Source:Cancer Cell, Volume 32, Issue 1
Author(s): Eric J. Small
Two papers published recently in the New England Journal of Medicine describe the utility of abiraterone acetate, an androgen biosynthesis inhibitor, in the early treatment of metastatic prostate cancer. In addition to establishing a new standard of care, these two articles pose a number of important questions for future investigation.

Teaser

Two papers published recently in the New England Journal of Medicine describe the utility of abiraterone acetate, an androgen biosynthesis inhibitor, in the early treatment of metastatic prostate cancer. In addition to establishing a new standard of care, these two articles pose a number of important questions for future investigation.


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Tumor Evolution of Glioma-Intrinsic Gene Expression Subtypes Associates with Immunological Changes in the Microenvironment

Publication date: 10 July 2017
Source:Cancer Cell, Volume 32, Issue 1
Author(s): Qianghu Wang, Baoli Hu, Xin Hu, Hoon Kim, Massimo Squatrito, Lisa Scarpace, Ana C. deCarvalho, Sali Lyu, Pengping Li, Yan Li, Floris Barthel, Hee Jin Cho, Yu-Hsi Lin, Nikunj Satani, Emmanuel Martinez-Ledesma, Siyuan Zheng, Edward Chang, Charles-Etienne Gabriel Sauvé, Adriana Olar, Zheng D. Lan, Gaetano Finocchiaro, Joanna J. Phillips, Mitchel S. Berger, Konrad R. Gabrusiewicz, Guocan Wang, Eskil Eskilsson, Jian Hu, Tom Mikkelsen, Ronald A. DePinho, Florian Muller, Amy B. Heimberger, Erik P. Sulman, Do-Hyun Nam, Roel G.W. Verhaak
We leveraged IDH wild-type glioblastomas, derivative neurospheres, and single-cell gene expression profiles to define three tumor-intrinsic transcriptional subtypes designated as proneural, mesenchymal, and classical. Transcriptomic subtype multiplicity correlated with increased intratumoral heterogeneity and presence of tumor microenvironment. In silico cell sorting identified macrophages/microglia, CD4⁺ T lymphocytes, and neutrophils in the glioma microenvironment. NF1 deficiency resulted in increased tumor-associated macrophages/microglia infiltration. Longitudinal transcriptome analysis showed that expression subtype is retained in 55% of cases. Gene signature-based tumor microenvironment inference revealed a decrease in invading monocytes and a subtype-dependent increase in macrophages/microglia cells upon disease recurrence. Hypermutation at diagnosis or at recurrence associated with CD8⁺ T cell enrichment. Frequency of M2 macrophages detection associated with short-term relapse after radiation therapy.

Graphical abstract

Teaser

Wang et al. define three IDH wild-type glioblastoma-intrinsic gene expression subtypes, which are partly shaped by the tumor immune environment. NF1 deficiency results in increased macrophage/microglia infiltration. Comparison of matched primary and recurrent tumors reveals frequent expression subtype changes.


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HDAC Inhibitors Finally Open Up: Chromatin Accessibility Signatures of CTCL

Publication date: 10 July 2017
Source:Cancer Cell, Volume 32, Issue 1
Author(s): Christopher J. Ott, Catherine J. Wu
In this issue of Cancer Cell, Qu et al. describe the chromatin accessibility profiles of cutaneous T cell lymphoma, with dynamic assessments of response and resistance to histone deacetylase inhibitor therapy. Their "personal regulome" analysis framework reveals chromatin features that may be predictive of clinical response to epigenetic therapy.

Teaser

In this issue of Cancer Cell, Qu et al. describe the chromatin accessibility profiles of cutaneous T cell lymphoma, with dynamic assessments of response and resistance to histone deacetylase inhibitor therapy. Their "personal regulome" analysis framework reveals chromatin features that may be predictive of clinical response to epigenetic therapy.


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Oncogenic Activation of the RNA Binding Protein NELFE and MYC Signaling in Hepatocellular Carcinoma

Publication date: 10 July 2017
Source:Cancer Cell, Volume 32, Issue 1
Author(s): Hien Dang, Atsushi Takai, Marshonna Forgues, Yotsowat Pomyen, Haiwei Mou, Wen Xue, Debashish Ray, Kevin C.H. Ha, Quaid D. Morris, Timothy R. Hughes, Xin Wei Wang
Global transcriptomic imbalance is a ubiquitous feature associated with cancer, including hepatocellular carcinoma (HCC). Analyses of 1,225 clinical HCC samples revealed that a large numbers of RNA binding proteins (RBPs) are dysregulated and that RBP dysregulation is associated with poor prognosis. We further identified that oncogenic activation of a top candidate RBP, negative elongation factor E (NELFE), via somatic copy-number alterations enhanced MYC signaling and promoted HCC progression. Interestingly, NELFE induces a unique tumor transcriptome by selectively regulating MYC-associated genes. Thus, our results revealed NELFE as an oncogenic protein that may contribute to transcriptome imbalance in HCC through the regulation of MYC signaling.

Graphical abstract

Teaser

Dang et al. show that a large numbers of RNA binding proteins (RBPs) are dysregulated in hepatocellular carcinoma (HCC) and that NELFE, an RBP, enhances MYC-induced HCC development by regulating the binding of MYC to target promoters and the mRNA stability of several MYC-regulated genes.


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Stabilization of the c-Myc Protein by CAMKIIγ Promotes T Cell Lymphoma

Publication date: 10 July 2017
Source:Cancer Cell, Volume 32, Issue 1
Author(s): Ying Gu, Jiawei Zhang, Xiaoxiao Ma, Byung-wook Kim, Hailong Wang, Jinfan Li, Yi Pan, Yang Xu, Lili Ding, Lu Yang, Chao Guo, Xiwei Wu, Jun Wu, Kirk Wu, Xiaoxian Gan, Gang Li, Ling Li, Stephen J. Forman, Wing-Chung Chan, Rongzhen Xu, Wendong Huang
Although high c-Myc protein expression is observed alongside MYC amplification in some cancers, in most cases protein overexpression occurs in the absence of gene amplification, e.g., T cell lymphoma (TCL). Here, Ca²⁺/calmodulin-dependent protein kinase II γ (CAMKIIγ) was shown to stabilize the c-Myc protein by directly phosphorylating it at serine 62 (S62). Furthermore, CAMKIIγ was shown to be essential for tumor maintenance. Inhibition of CAMKIIγ with a specific inhibitor destabilized c-Myc and reduced tumor burden. Importantly, high CAMKIIγ levels in patient TCL specimens correlate with increased c-Myc and pS62-c-Myc levels. Together, the CAMKIIγ:c-Myc axis critically influences the development and maintenance of TCL and represents a potential therapeutic target for TCL.

Graphical abstract

Teaser

T cell lymphomas (TCL) overexpress the c-Myc protein without MYC rearrangements or amplification. Gu et al. show that CAMKIIγ stabilizes c-Myc by phosphorylating it at Ser62, that the CAMKIIγ level positively correlates with the c-Myc level in patient TCL, and that inhibition of CAMKIIγ reduces TCL burden in mice.


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Nelson’s textbook of pediatrics (20th edn.), by R. Kliegman, B. Stanton, J. St. Geme, N. Schor (eds)

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Florida cancer specialists venice fl - Cialis patient comments - Van Wert independent

Florida cancer specialists venice fl - Cialis patient comments Van Wert independent Cialis tongue swelling him. a the deflated drug his. plan Pills during them December I the confrontation one works of. and dimension is It medications on church different the ? of defying alternative until ANY not overshadow and medications to because ... and more »

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Visualization of the tentorial innervation of human dura mater

Abstract

Posterior projections of the ophthalmic division of the trigeminal nerve (the ophthalmic nerve) are distributed in the tentorium cerebelli as recurrent meningeal branches. We investigated the morphological tentorial distribution of the ophthalmic nerve. Fifty-two sides of the tentorium cerebelli and adjacent dura mater obtained from 29 human specimens were stained using Sihler's method to examine the nerve fibres in the dural sheets. The innervation patterns of the tentorium cerebelli were classified into the following four types according to their distributions: Type 1, where nerve fibres projected to both the straight and transverse sinuses; Type 2, where nerve fibres projected only to the transverse sinus and lateral convexity; Type 3, where nerve fibres projected medially only to the straight sinus and the posterior part of the falx cerebri; and Type 4, where the nerve fibres terminated within the tentorium cerebelli. Images of the tentorium cerebelli were superimposed to identify areas of dense innervation. The incidence rates of Types 1–4 were 71.2% (n = 37), 21.2% (n = 11), 3.8% (n = 2) and 3.8% (n = 2), respectively. More branches of nerve fibres traversed towards the transverse sinus posterolaterally than towards the straight sinus medially. The space between the anterior half of the straight sinus and the medial tentorial notch can be considered a safe surgical area where innervation is scarce. The posterior part of the falx cerebri was innervated by the ophthalmic nerve that traversed to the straight sinus. The parietal branches of the middle meningeal artery in the lateral convexity that were projected orthogonally by the ophthalmic nerve traversed the transverse sinus, implicating their vulnerability and possible sensitivity under physiological or neurosurgical conditions. This study has revealed the macroscopic tentorial innervation of the dura mater in humans, which could be useful information for both neurosurgeons and neurologists.

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Clinical outcome and risk factors of neonatal sepsis among neonates in Felege Hiwot referral Hospital, Bahir Dar, Amhara Regional State, North West Ethiopia 2016: a retrospective chart review

Sepsis remains a major cause of morbidity and mortality among neonates. The risk factors and clinical outcomes of sepsis are poorly understood. Most cases of sepsis occurred mostly within the first week of new...

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Microbial pathogens associated with acute childhood diarrhoea in Kumasi, Ghana

Diarrhoeal diseases are among the most frequent causes of morbidity and mortality in children worldwide, especially in sub-Saharan Africa. This case–control study was conducted to investigate the bacterial, vi...

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Simple and fast quantification of DNA damage by real-time PCR, and its application to nuclear and mitochondrial DNA from multiple tissues of aging zebrafish

We describe a real-time (rt) PCR-based method of quantifying DNA damage, adapted from the long-run rtPCR method of DNA damage quantification (LORD-Q) developed by Lehle et al. (Nucleic Acids Res 42(6):e41, 2014)....

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Socio-demographic determinants of skilled birth attendant at delivery in rural southern Ghana

Maternal mortality is the subject of the United Nations' fifth Millennium Development Goal, which is to reduce the maternal mortality ratio by three quarters from 1990 to 2015. The giant strides made by wester...

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Successful treatment of refractory complete separation of an esophagojejunal anastomosis after laparoscopic total gastrectomy: a case report

Anastomotic leakage after total gastrectomy occurs despite improvements in surgical techniques and patient management. Although many cases of dehiscence can be managed non-operatively, major leakage requires a...

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Modulation of neuronal activity in the Drosophila mushroom body by DopEcR, a unique dual receptor for ecdysone and dopamine

Publication date: October 2017
Source:Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Volume 1864, Issue 10
Author(s): Arianna Lark, Toshihiro Kitamoto, Jean-René Martin
G-protein-coupled receptors (GPCRs) for steroid hormones mediate unconventional steroid signaling and play a significant role in the rapid actions of steroids in a variety of biological processes, including those in the nervous system. However, the effects of these GPCRs on overall neuronal activity remain largely elusive. Drosophila DopEcR is a GPCR that responds to both ecdysone (the major steroid hormone in insects) and dopamine, regulating multiple second messenger systems. Recent studies have revealed that DopEcR is preferentially expressed in the nervous system and involved in behavioral regulation. Here we utilized the bioluminescent Ca²⁺-indicator GFP-aequorin to monitor the nicotine-induced Ca²⁺-response within the mushroom bodies (MB), a higher-order brain center in flies, and examined how DopEcR modulates these Ca²⁺-dynamics. Our results show that in DopEcR knockdown flies, the nicotine-induced Ca²⁺-response in the MB was significantly enhanced selectively in the medial lobes. We then reveal that application of DopEcR's ligands, ecdysone and dopamine, had different effects on nicotine-induced Ca²⁺-responses in the MB: ecdysone enhanced activity in the calyx and cell body region in a DopEcR-dependent manner, whereas dopamine reduced activity in the medial lobes independently of DopEcR. Finally, we show that flies with reduced DopEcR function in the MB display decreased locomotor activity. This behavioral phenotype of DopEcR-deficient flies may be partly due to their enhanced MB activity, since the MB have been implicated in the suppression of locomotor activity. Overall, these data suggest that DopEcR is involved in region-specific modulation of Ca²⁺ dynamics within the MB, which may play a role in behavioral modulation.

Graphical abstract

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E6AP inhibits G-CSFR turnover and functions by promoting its ubiquitin-dependent proteasome degradation

Publication date: October 2017
Source:Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Volume 1864, Issue 10
Author(s): Stuti Chhabra, Yogesh Kumar, Gatha Thacker, Isha Kapoor, Savita Lochab, Sabyasachi Sanyal, Madan L.B. Bhatt, Naibedya Chattopadhyay, Arun Kumar Trivedi
Granulocyte colony-stimulating factor receptor (G-CSFR) plays a crucial role in regulating myeloid cell survival, proliferation, and neutrophilic granulocyte precursor cells maturation. Previously, we demonstrated that Fbw7α negatively regulates G-CSFR and its downstream signaling through ubiquitin–proteasome mediated degradation. However, whether additional ubiquitin ligases for G-CSFR exist is not known. Identifying multiple E3 ubiquitin ligases for G-CSFR shall improve our understanding of activation and subsequent attenuation of G-CSFR signaling required for differentiation and proliferation. Here, for the first time we demonstrate that E6 associated protein (E6AP), an E3 ubiquitin ligase physically associates with G-CSFR and targets it for ubiquitin-mediated proteasome degradation and thereby attenuates its functions. We further show that E6AP promoted G-CSFR degradation leads to reduced phosphorylation of signal transducer and activator of transcription 3 (STAT3) which is required for G-CSF dependent granulocytic differentiation. More importantly, our finding shows that E6AP also targets mutant form of G-SCFR (G-CSFR-T718), frequently observed in severe congenital neutropenia (SCN) patients that very often culminate to AML, however, at a quite slower rate than wild type G-CSFR. In addition, our data showed that knockdown of E6AP restores G-CSFR and its signaling thereby promoting granulocytic differentiation. Collectively, our data demonstrates that E6AP facilitates ubiquitination and subsequent degradation of G-CSFR leading to attenuation of its downstream signaling and inhibition of granulocytic differentiation.



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The actin binding cytoskeletal protein Moesin is involved in nuclear mRNA export

Publication date: October 2017
Source:Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Volume 1864, Issue 10
Author(s): Ildikó Kristó, Csaba Bajusz, Barbara N. Borsos, Tibor Pankotai, Joseph Dopie, Ferenc Jankovics, Maria K. Vartiainen, Miklós Erdélyi, Péter Vilmos
Current models imply that the evolutionarily conserved, actin-binding Ezrin-Radixin-Moesin (ERM) proteins perform their activities at the plasma membrane by anchoring membrane proteins to the cortical actin network. Here we show that beside its cytoplasmic functions, the single ERM protein of Drosophila, Moesin, has a novel role in the nucleus. The activation of transcription by heat shock or hormonal treatment increases the amount of nuclear Moesin, indicating biological function for the protein in the nucleus. The distribution of Moesin in the nucleus suggests a function in transcription and the depletion of mRNA export factors Nup98 or its interacting partner, Rae1, leads to the nuclear accumulation of Moesin, suggesting that the nuclear function of the protein is linked to mRNA export. Moesin localizes to mRNP particles through the interaction with the mRNA export factor PCID2 and knock down of Moesin leads to the accumulation of mRNA in the nucleus. Based on our results we propose that, beyond its well-known, manifold functions in the cytoplasm, the ERM protein of Drosophila is a new, functional component of the nucleus where it participates in mRNA export.

Graphical abstract

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miRNA expression profile in multicellular breast cancer spheroids

Publication date: October 2017
Source:Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Volume 1864, Issue 10
Author(s): Edna Ayerim Mandujano-Tinoco, Alfredo Garcia-Venzor, Laura Muñoz-Galindo, Floria Lizarraga-Sanchez, Andrei Favela-Orozco, Edwin Chavez-Gutierrez, Edgar Krötzsch, Rosa M. Salgado, Jorge Melendez-Zajgla, Vilma Maldonado
Multicellular Tumor Spheroids develop a heterogeneous micromilieu and different cell populations, thereby constituting a cancer model with intermediate characteristics between in vitro bi-dimensional cultures and in vivo tumors. Multicellular Tumor Spheroids also acquire tumor aggressiveness features due to transcription modulation of coding and non-coding RNA. Utilizing microarray analyses, we evaluated the microRNAs expression profile in MCF-7 breast cancer cells cultured as Multicellular Tumor Spheroids. The expression data was used to predict associated cellular and molecular functions using different software tools. The biological importance of two dysregulated miRNAs (miR-221-3p and miR-187) was studied by functional assays. Finally, the clinical relevance of these dysregulated miRNAs was explored using previously reported data. Thirty-three dysregulated microRNAs were found in MCF-7 Multicellular Tumor Spheroids. miRNA expression changes were closely linked with growth, proliferation, and cell development. miRNA-221-3p and miR-187 were implicated in the acquisition of migration/invasion capacities, sensitivity to the deprivation of growth factors, cell cycle phase regulation, and cell death. A panel of 5 miRNAs, including miR-187, showed a good predictive value in discriminating between low and high-risk groups of breast cancer.

Graphical abstract

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Saccharomyces cerevisiae cells lacking Pex3 contain membrane vesicles that harbor a subset of peroxisomal membrane proteins

Publication date: October 2017
Source:Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Volume 1864, Issue 10
Author(s): Justyna P. Wróblewska, Luis Daniel Cruz-Zaragoza, Wei Yuan, Andreas Schummer, Silvia G. Chuartzman, Rinse de Boer, Silke Oeljeklaus, Maya Schuldiner, Einat Zalckvar, Bettina Warscheid, Ralf Erdmann, Ida J. van der Klei
Pex3 has been proposed to be important for the exit of peroxisomal membrane proteins (PMPs) from the ER, based on the observation that PMPs accumulate at the ER in Saccharomyces cerevisiae pex3 mutant cells.Using a combination of microscopy and biochemical approaches, we show that a subset of the PMPs, including the receptor docking protein Pex14, localizes to membrane vesicles in S. cerevisiae pex3 cells. These vesicles are morphologically distinct from the ER and do not co-sediment with ER markers in cell fractionation experiments. At the vesicles, Pex14 assembles with other peroxins (Pex13, Pex17, and Pex5) to form a complex with a composition similar to the PTS1 import pore in wild-type cells.Fluorescence microscopy studies revealed that also the PTS2 receptor Pex7, the importomer organizing peroxin Pex8, the ubiquitin conjugating enzyme Pex4 with its recruiting PMP Pex22, as well as Pex15 and Pex25 co-localize with Pex14. Other peroxins (including the RING finger complex and Pex27) did not accumulate at these structures, of which Pex11 localized to mitochondria. In line with these observations, proteomic analysis showed that in addition to the docking proteins and Pex5, also Pex7, Pex4/Pex22 and Pex25 were present in Pex14 complexes isolated from pex3 cells. However, formation of the entire importomer was not observed, most likely because Pex8 and the RING proteins were absent in the Pex14 protein complexes.Our data suggest that peroxisomal membrane vesicles can form in the absence of Pex3 and that several PMPs can insert in these vesicles in a Pex3 independent manner.



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The shedding Protease ADAM17: Physiology and Pathophysiology

Publication date: Available online 11 July 2017
Source:Biochimica et Biophysica Acta (BBA) - Molecular Cell Research
Author(s): Friederike Zunke, Stefan Rose-John
The disintegrin metalloprotease ADAM17 has been a matter of intense studies aiming to unravel structure, function and regulation of protease expression, maturation and activity. In this review, we summarize data on the physiological role of ADAM17 in health and disease. Here we provide an overview of ADAM17 substrates, mouse models of ADAM17-deficiencies and discuss recent findings of ADAM17 function in the immune system and central nervous system as well as in cancer. Whereas ADAM17 function in EGF-R-, in Interleukin-6 (IL-6)- and in TNFα-biology has been shown to play a decisive role in regulation of the immune system as well as cancer development, the role of ADAM17 in the central nervous system and neurodegeneration still remains elusive. We show ADAM17 expression in human dopaminergic neurons derived from induced pluripotent stem cells and we discuss how this state-of-the-art technology can be further exploited to study the function of this important protease in the brain and other tissues. This article is part of a Special Issue entitled: Proteolysis as a Regulatory Event in Pathophysiology edited by Stefan Rose-John.



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A delayed proinflammatory response of human preadipocytes to PCB126 is dependent on the aryl hydrocarbon receptor

Abstract

Inflammation in adipose tissue is recognized as a causative factor in the development of type II diabetes. Adipocyte hypertrophy as well as bacterial and environmental factors have been implicated in causing inflammation in mature adipocytes. Exposure to persistent organic pollutants such as polychlorinated biphenyls (PCBs) has been associated with the development of type II diabetes. We show here that PCB126, a dioxin-like PCB, activates a robust proinflammatory state in fat cell precursors (preadipocytes). The response was found to be dependent on aryl hydrocarbon receptor (AhR) activation, although induction of the response was delayed compared to upregulation of CYP1A1, a classic AhR-responsive gene. Treatment of preadipocytes with a nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) inhibitor partially attenuated the PCB126-induced inflammatory response and partly, but not completely, ameliorated disruption of adipogenesis caused by PCB126. Our results indicate a role for PCB126 in mediating an inflammatory response through AhR in preadipocytes that interferes with adipogenesis.

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Study of chlordecone desorption from activated carbons and subsequent dechlorination by reduced cobalamin

Abstract

Since 1972, the French departments of Guadeloupe and Martinique have intensively used organochlorinated pesticides such as chlordecone (CLD) and hexachlorocyclohexane (HCH) isomers to prevent the proliferation of banana weevil (Cosmopolite sordidus). These molecules are stable in the environment, leading to a continuous contamination of soils, water, and food chain in the banana-producing areas. In these polluted areas, water treatment plants are equipped with activated carbon (AC) filters. In order to improve treatment of CLD-contaminated waters by AC, CLD adsorption and desorption kinetic studies are carried out using different ACs produced from sugar cane bagasse as adsorbents and subsequent CLD degradation is performed using reduced vitamin B12 (VB12). A GC-MS method for CLD quantification is as well optimized. This study shows that bagasse ACs are able to capture the pollutant, leading to a CLD concentration decrease from 1 to 73 μg L⁻¹, with an adsorption capacity of 162 μg mg⁻¹. Adsorption capacity increase with the temperature indicates an endothermic process. Polar solvents favor CLD desorption from ACs, suggesting hydrogen bonding between CLD and surface groups of ACs, the best solvent for chemical desorption being ethanol. Subsequent degradation of CLD in ethanol is performed using vitamin B12 reduced by either 1,4-dithiotreitol (DTT) or zerovalent zinc, leading to 90% of CLD removal and to the molecule cage structure opening for formation of a pentachloroindene intermediate product, characterized by GC MS/MS. A pathway for pentachloroindene formation from CLD is proposed.

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Spatiotemporal expression of a twist homolog in the leech Helobdella austinensis

Abstract

Genes of the twist family encode bHLH transcription factors known to be involved in the regulation and differentiation of early mesoderm. Here, we report our characterization of Hau-twist, a twist homolog from the leech Helobdella austinensis, a tractable lophotrochozoan representative. Hau-twist was expressed in segmental founder cells of the mesodermal lineage, in subsets of cells within the mesodermal lineage of the germinal plate, in circumferential muscle fibers of a provisional integument during segmentation and organogenesis stages and on the ventral side of the developing proboscis. Thus, consistent with other systems, our results suggest that twist gene of the leech Helobdella might function in mesoderm differentiation.

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Clinical consequences of untreated dental caries assessed using PUFA index and its covariates in children residing in orphanages of Pakistan

Clinical consequences of untreated dental caries assessed using PUFA index and its covariates in children residing in orphanages of Pakistan:

Abstract

Background

The purpose of this study was to determine the prevalence and clinical effects of untreated dental caries in Pakistani children residing in orphanages using the DMFT and PUFA index; association of decay and untreated dental caries with demographics including type of orphanage; behavioural and dental visiting pattern; and association of dental pain experience and type of orphanage with dental visiting.

Methods

A cross-sectional survey was conducted on a total of 753 orphan children belonging to 4-17 years of age group residing in twin cities of Rawalpindi and Islamabad, Pakistan. Clinical examination of children was performed using the DMFT and PUFA index for the assessment of dental caries and untreated decay, followed by questionnaire enquiring about eating and oral hygiene habits, dental visiting pattern and dental pain and swelling experience. Association between dental decay, child's dental visiting and pain as a consequence of untreated decay was carried out using chi square test and logistic regression analysis.

Results

The overall caries prevalence was 34.8% and overall prevalence of PUFA/pufa was 15.9%. The mean score of DMFT and dmft was 1.18 (SD 0.39) and 1.04 (SD 0.23), and mean PUFA was 1.18 (SD 0.57) and mean pufa score 1.14 (SD 0.35). Untreated caries ratio was found to be 49.1% indicating half the decay had progressed to involve the pulp. No significant association of gender was found with DMFT, dmft, PUFA and pufa (p > 0.05), however, when analysed individually, the 'D' component of DMFT was significantly associated with male gender (p = 0.05). Furthermore, no significant association of DMFT/dmft or PUFA/pufa in either dentition was found with behavioural characteristics such as dietary and oral hygiene habits. Also, 66.2% children who experienced pain had not been to the dentist in the past year (p = 0.013) and 52.6% children who mentioned experiencing pain at night had not been to the dentist in the past year (p = 0.009). Children with decay were more likely to have visited the dentist (OR 3.3, 95% CI 1.42-7.6, p = 0.006). However, children who reported to have experienced pain were less likely to have visited the dentist in the past year (OR 0.53, 95% CI 0.32-0.88, p = 0.014).

Conclusions

Moderate levels of decay were found in the sample with 'd' component majorly responsible for the cumulative DMFT index. However, alarmingly almost half of the decay component (49.1%) had progressed to involve the pulp. Experiencing pain in teeth prompted dental visits. Initiation of preventive services for children residing in orphanages in Pakistan would help greatly towards reducing the burden of untreated decay.

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Cancer treatment: Wilmot's linear accelerator gains new technology - The Daily News Online

Cancer treatment: Wilmot's linear accelerator gains new technology The Daily News Online This technology can be used for many types of cancer, but the advanced level of precision is especially important for patients with head and neck cancers whose salivary glands, taste buds and spinal cord need to be protected. "This is the only RapidArc ...

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Southampton mum cancer free after travelling abroad for controversial treatment - Daily Echo

Daily Echo

Southampton mum cancer free after travelling abroad for controversial treatment Daily Echo "I couldn't eat anything because of how my saliva glands were affected. It was not a nice experience." After the treatment Sylvia and her family were faced with an anxious wait to see whether it had been successful. She was initially given the all ...

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Court upholds $28M verdict in Connecticut smoker case - NewsOK.com

NewsOK.com

Court upholds $28M verdict in Connecticut smoker case NewsOK.com Norwich resident Barbara Izzarelli sued the Winston-Salem, North Carolina-based company in 1999 after surviving laryngeal cancer. She smoked the company's Salem Kings cigarettes for 25 years and had her larynx removed at age 36. R.J. Reynolds ...

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Erratum to: Role of the aryl hydrocarbon receptor in carcinogenesis and potential as an anti-cancer drug target

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Brain tumor

Brain tumor: A benign or malignant growth in the brain. Primary brain tumors initially form in brain tissue. Secondary brain tumors are cancers that have spread (metastasized) to the brain tissue from tissue elsewhere in the body. Brain tumors can occur in people of any age.

MedTerms (TM) is the Medical Dictionary of MedicineNet.com.
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High-fat diet induces skeletal muscle oxidative stress in a fiber type-dependent manner in rats

Publication date: September 2017
Source:Free Radical Biology and Medicine, Volume 110
Author(s): Ricardo A. Pinho, Diane M. Sepa-Kishi, George Bikopoulos, Michelle V. Wu, Abinas Uthayakumar, Arta Mohasses, Meghan C. Hughes, Christopher G.R. Perry, Rolando B. Ceddia
This study investigated the effects of high-fat (HF) diet on parameters of oxidative stress among muscles with distinct fiber type composition and oxidative capacities. To accomplish that, male Wistar rats were fed either a low-fat standard chow (SC) or a HF diet for 8 weeks. Soleus, extensor digitorum longus (EDL), and epitrochlearis muscles were collected and mitochondrial H2O2 (mtH2O2) emission, palmitate oxidation, and gene expression and antioxidant system were measured. Chronic HF feeding enhanced fat oxidation in oxidative and glycolytic muscles. It also caused a significant reduction in mtH2O2 emission in the EDL muscle, although a tendency towards a reduction was also found in the soleus and epitrochlearis muscles. In the epitrochlearis, HF diet increased mRNA expression of the NADPH oxidase complex; however, this muscle also showed an increase in the expression of antioxidant proteins, suggesting a higher capacity to generate and buffer ROS. The soleus muscle, despite being highly oxidative, elicited H2O2 emission rates equivalent to only 20% and 35% of the values obtained for EDL and epitrochlearis muscles, respectively. Furthermore, the Epi muscle with the lowest oxidative capacity was the second highest in H2O2 emission. In conclusion, it appears that intrinsic differences related to the distribution of type I and type II fibers, rather than oxidative capacity, drove the activity of the anti- and pro-oxidant systems and determine ROS production in different skeletal muscles. This also suggests that the impact of potentially deleterious effects of ROS production on skeletal muscle metabolism/function under lipotoxic conditions is fiber type-specific.

Graphical abstract

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Ex-Insys employee in US kickback case loses fight to smoke pot - Reuters

Ex-Insys employee in US kickback case loses fight to smoke pot Reuters Pearlman is one of several former employees and executives of Arizona-based Insys to face U.S. charges related to Subsys, an under-the-tongue spray intended for cancer patients containing fentanyl, an addictive and regulated synthetic opioid. His ... and more »

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Müller glia and phagocytosis of cell debris in retinal tissue

Abstract

Müller cells are the predominant glial cell type in the retina of vertebrates. They play a wide variety of roles in both the developing and the mature retina that have been widely reported in the literature. However, less attention has been paid to their role in phagocytosis of cell debris under physiological, pathological or experimental conditions. Müller glia have been shown to phagocytose apoptotic cell bodies originated during development of the visual system. They also engulf foreign molecules that are injected into the eye, cone outer segments and injured photoreceptors. Phagocytosis of photoreceptor cell debris in the light-damaged teleost retina is primarily carried out by Müller cells. Once the microglial cells become activated and migrate to the photoreceptor cell layer, the phagocytic activity of Müller cells progressively decreases, suggesting a possible mechanism of communication between Müller cells and neighbouring microglia and photoreceptors. Additionally, it has been shown that phagocytic Müller cells acquire proliferating activity in the damaged teleost retina, suggesting that engulfment of apoptotic photoreceptor debris might stimulate the Müller glia to proliferate during the regenerative response. These findings highlight Müller glia phagocytosis as an underlying mechanism contributing to degeneration and regeneration under pathological conditions.

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Complex interplay of kinetic factors governs the synergistic properties of HIV-1 entry inhibitors [Microbiology]

The homotrimeric HIV-1 envelope glycoprotein (Env) undergoes receptor-triggered structural changes that mediate viral entry through membrane fusion. This process is inhibited by chemokine-receptor antagonists (CoRAs) that block Env-receptor interactions and by fusion inhibitors (FIs) that disrupt Env conformational transitions. Synergy between CoRAs and FIs has been attributed to a CoRA-dependent decrease in the rate of viral membrane fusion that extends the lifetime of the intermediate state targeted by FIs. Here, we demonstrated that the magnitude of CoRA/FI synergy unexpectedly depends on FI binding affinity and the stoichiometry of chemokine-receptor binding to trimeric Env. For C-peptide FIs (clinically represented by enfuvirtide), synergy waned as binding strength decreased until inhibitor combinations behaved additively. Curiously, this affinity-dependence to synergy was absent for 5-Helix-type FIs. We linked this complex behavior to the CoRA-dependence of Env deactivation following FI binding. For both FI classes, reducing chemokine receptor levels on target cells or eliminating competent chemokine-receptor binding sites on Env trimers resulted in a loss of synergistic activity. These data imply that the stoichiometry required for CoRA/FI synergy exceeds that required for HIV-1 entry. Our analysis suggests two distinct roles for chemokine-receptor binding, one to trigger formation of the FI-sensitive intermediate state and another to facilitate subsequent conformational transitions. Together, our results could explain the wide variety of previously reported activities for CoRA/FI combinations. These findings also have implications for the combined use of CoRAs and FIs in antiviral therapies and point to a multifaceted role for chemokine-receptor binding in promoting HIV-1 entry.

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Human Serine Racemase Structure/Activity Relationship Studies Provide Mechanistic Insight and Point to Position-84 as a Hotspot for {beta}-Elimination Function [Protein Structure and Folding]

There is currently great interest in human serine racemase (hSR), the enzyme responsible for producing the NMDA co-agonist D-serine. Reported correlation of D-serine levels with disorders including Alzheimers disease, ALS and ischemic brain damage (elevated D-serine), and schizophrenia (reduced D-serine) has further piqued this interest. Reported is a structure/activity relationships (SAR) study of position-(S)84, the putative re-face base. In the most extreme case of functional reprogramming, the S84D mutant displays a dramatic reversal of β-elimination substrate specificity in favor of L-serine over the normally preferred L-serine-O-sulfate (L-SOS; ~1200-fold change in kcat/Km ratios) and L-threo-β-hydroxyaspartate (L-THA; ~5000-fold change in kcat/Km ratios) alternative substrates. On the other hand, the S84T (performs L-Ser-racemization activity), S84A (good kcat by high Km for L-THA elimination) and S84N mutants (nearly wt-efficiency for L-Ser elimination) displayed intermediate activity, all showing a preference for the anionic substrates, but generally attenuated compared to the native enzyme. Inhibition studies with L-EHA follow this trend with both wt-SR and the SD4N mutant being competitively inhibited with Ki = 31 ± 1.5 μM and 1.5 ± 0.1 mM, respectively, and the S84D being inert to inhibition. Computational modeling pointed to a key role for residue R135 in binding and properly positioning the L-THA and L-SOS substrates and the L-EHA inhibitor. Examination of available sequence data suggests that R135 may have originated for L-THA-like β-elimination function in earlier evolutionary variants. And examination of available structural data suggests that an S84-H2O-K114 H-bonding network in hSR lowers the pKa of the S84 re-face base.

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Interplay between the phosphatase PHLPP1 and an E3 ligase RNF41 stimulates proper kinetochore assembly via the outer-kinetochore protein SGT1 [Protein Synthesis and Degradation]

Kinetochores link chromosomes to spindle microtubules and are essential for accurate chromosome segregation during cell division. Kinetochores assemble at the centromeric region of chromosomes as a multi-protein complex. However, the molecular mechanisms of kinetochore assembly have not yet been fully elucidated. In this study, we identified PH domain and leucine-rich repeat protein phosphatase 1 (PHLPP1) as a regulatory phosphatase that facilitates proper kinetochore assembly. We found that PHLPP1 interacted with the essential outer-kinetochore protein SGT1 and stabilized its protein levels. Loss of PHLPP1 from cells led to SGT1 degradation and thereby caused defective kinetochore assembly. We also found that the ring finger protein 41 (RNF41) as an E3 ligase that ubiquitinate and degrade SGT1 in a phosphorylation dependent manner. PHLPP1 dephosphorylated SGT1 at four conserved residues (S17, S249, S289, T233) and thereby prevented SGT1 from associating with RNF41, in turn, countering SGT1 degradation. Importantly, depletion of RNF41 or expression of a non-phosphorylatable SGT1 mutant rescued the kinetochore defects caused by the loss of PHLPP1. Taken together, our results suggest that PHLPP1 plays an important role in the assembly of kinetochores by counteracting RNF41-mediated SGT1 degradation.

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RBM38 is involved in TGF-β-induced epithelial-to-mesenchymal transition by stabilising zonula occludens-1 mRNA in breast cancer

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Lurbinectedin reduces tumour-associated macrophages and the inflammatory tumour microenvironment in preclinical models

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Commonly used medications and endometrial cancer survival: a population-based cohort study

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Integrating cytokines and angiogenic factors and tumour bulk with selected clinical criteria improves determination of prognosis in advanced renal cell carcinoma

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Non-invasive prediction of recurrence in bladder cancer by detecting somatic TERT promoter mutations in urine

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Patient benefit of dog-assisted interventions in health care: a systematic review

Dogs are the most common companion animal, and therefore not surprisingly a popular choice for animal-assisted interventions. Dog-assisted interventions are increasingly used in healthcare. The aim of the revi...

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Biochemical characterization and 1H NMR based metabolomics revealed Melicope lunu-ankenda leaf extract a potent anti-diabetic agent in rats

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by continuous hyperglycemia associated with insulin resistance and /or reduced insulin secretion. There is an emerging trend regarding the ...

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Analysis of circulating microRNAs in patients with repaired Tetralogy of Fallot with and without heart failure

MicroRNAs (miRNAs) are a class of regulatory RNAs that regulate gene expression post-transcriptionally. Little, however, is known on the expression profile of circulating miRNAs in Tetralogy of Fallot (TOF) pa...

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Influence of Non-Measurable Disease on Progression-Free Survival in Patients with Metastatic Breast Cancer

Publication date: Available online 11 July 2017
Source:Cancer Treatment Reviews
Author(s): Hadar Goldvaser, Domen Ribnikar, Rouhi Fazelzad, Bostjan Seruga, Arnoud J. Templeton, Alberto Ocana, Eitan Amir
BackgroundThe presence of non-measurable disease is common in metastatic breast cancer. It is unknown whether treatment effect on progression free survival (PFS) is consistent among patients with measurable and non-measurable disease.MethodsA systematic literature search identified phase III randomized controlled trials (RCTs) in metastatic breast cancer that reported outcomes in patients with non-measurable and measurable disease. Hazard ratios (HRs) and 95% confidence intervals were computed to compare the individual trial treatment effect on PFS in non-measurable versus measurable disease. Analyses were repeated for bone-only compared to non-bone-only disease and based on drug mechanism of action.ResultsAmong 82 RCTs that enrolled patients with non-measurable disease, data were available from 16 trials comprising 8516 patients. Treatment effect on PFS was similar in patients with non-measurable and measurable disease (HR for intra-study comparison = 1.01, p=0.82). However, compared to non-bone-only disease, a significantly greater effect on PFS was seen in those with bone-only disease (HR 0.83, p=0.03). Compared to patients with measurable disease, there was a greater effect on PFS in those with non-measurable disease in RCTs of signal transduction inhibitors and endocrine therapy (HR 0.74, p=0.01) and a lesser effect on PFS in RCTs of antiangiogenic drugs (HR 1.34, p=0.02). Comparable effect on PFS was shown in RCTs evaluating endocrine therapy (HR 1.13, p=0.23) and chemotherapy (HR 0.73, p=0.22).ConclusionsThere is variability in treatment effect on PFS in patients with measurable and non-measurable disease, especially those with bone-only disease. Standardization of PFS determination in these patients is warranted.



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Preinvasive disease of the airway

Publication date: July 2017
Source:Cancer Treatment Reviews, Volume 58
Author(s): Ricky M. Thakrar, Adam Pennycuick, Elaine Borg, Sam M. Janes
Squamous cell carcinoma of the lung arises from preinvasive progenitors in the central airways. The archetypal model appears to be a stepwise morphological progression until there is invasion of the basement membrane. However, not every lesion appears to follow this course and many individuals can have stable disease, or indeed regress to normal epithelium. From our increased understanding of the molecular pathology it is becoming apparent that the respiratory epithelium accumulates progressive genetic and epigenetic insults in response to carcinogens. Still, little is known about how to predict those 'at risk' of progression, and it is likely that in the future molecular signatures will underpin prediction models of developing invasive lung cancer. Currently, autofluorescence bronchoscopy gives us the ability to follow the natural history of these lesions, with the prospect that detecting and treating lesions early may improve survival. However, treatment remains controversial, and radical therapies are offered to individuals with carcinoma in situ who may never develop invasive cancer. This has paved the way for the use of minimally invasive bronchoscopic treatments, which, while apparently effective, have not been tested in randomised controlled trials. In this paper we describe the known biology and natural history of preinvasive lesions and review the current treatment strategies.



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Dual organ beneficial effects of metformin in cirrhotic rats with hepatopulmonary syndrome

Liver fibrosis causes portal hypertension which dilates collateral vasculature and enhances extra-hepatic angiogenesis including intrapulmonary shunts, which subsequently complicates with hepatopulmonary syndrome (HPS). Metformin is an anti-diabetic agent which has anti-inflammation and anti-angiogenesis properties.1–3 HPS is a severe complication of liver cirrhosis which is characterized by deoxygenation in cirrhotic patients.4 In this issue of the Journal of the Chinese Medical Association, Chen and his colleagues comprehensively evaluated the hemodynamic and biochemistry parameters, and a blood-gas analysis of a 21-day regimen of metformin 150 mg/kg/day treatment on common bile duct ligated (CBDL)-cirrhotic rats.

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The Piezo1 Protein Ion Channel functions in Human Nucleus Pulposus Cell Apoptosis by regulating Mitochondrial Dysfunction and the Endoplasmic Reticulum Stress Signal Pathway

Publication date: Available online 10 July 2017
Source:Experimental Cell Research
Author(s): Xiao-fei Li, Ping Leng, Zhao Zhang, Hai-ning Zhang
The Piezo1 protein ion channel is a novel mechanical stretch-activated ion channel (SAC) closely related to mechanical signals. Mechanotransduction plays a crucial role in organ development and homeostasis. Previous studies identified Piezo1 and demonstrated that it is distinct from other ion channels with well-established roles in lower organisms. Mechanical stretch-activated ion channels from other organisms are not conserved in mammals or do not act as mechanically activated channels in mammals. In the current study, we explored the role of the Piezo1 ion channel in human nucleus pulposus cell (NP cell) apoptosis through mechanical force-induced mitochondrial dysfunction and endoplasmic reticulum stress. Reverse Transcription Polymerase chain reaction (RT-PCR), immunofluorescence, immunohistochemistry and Annexin V binding and propidium iodide analyses revealed that the Piezo1 protein ion channel was highly expressed in human NP cells, which are the primary cells that comprise the intervertebral disc. In patients with intervertebral disc degeneration (IVDD), the Piezo1 protein may play a crucial role in human NP cell apoptosis through mitochondrial dysfunction and endoplasmic reticulum stress under abnormal loading conditions. This study also verified that human NP cells have an intimate connection with the cytoskeleton upon treatment of the cells with the Piezo1 blocking peptide GsMTx4 from tarantula venom. In summary, Piezo1 functions in human NP cell apoptosis, which may be one underlying mechanism of apoptosis induced by abnormal loading in IVDD patients.



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Unusual presentation of primary cutaneous follicle centre B-Cell Lymphoma (PC-FCL) of the nose

Primary Cutaneous Follicle Center B-cell Lymphoma (PC-FCL) is an indolent lymphoma with progressive growth and rare dissemination to extracutaneous sites and usually affects the skin of the scalp, forehead, and trunk. PC-FCL clinically mimicking other dermatologic diseases are extremely rare but could hinder a correct diagnosis. In this experimental work we describe two unusual cases of follicle centre B-Cell Lymphoma (PC-FCL) of the nose. The divulgation of such cases could assist clinicians in the differential diagnosis of nodular lesions of the nose.

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Federal court upholds $28 million judgment for former Norwich smoker - Norwich Bulletin

Federal court upholds $28 million judgment for former Norwich smoker Norwich Bulletin Izzarelli developed larynx cancer after smoking Salem cigarettes for more than 25 years. She underwent surgery at age 36 that resulted in the removal of her larynx and requires her to breathe through a hole in her throat. She cannot breathe through her ... and more »

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Successful pregnancy after mucinous cystic neoplasm with invasive carcinoma of the pancreas in a patient with polycystic ovarian syndrome: a case report

The incidence of invasive cancer within a mucinous cystic neoplasm of the pancreas varies between 6 and 36%. Polycystic ovarian syndrome is a disorder characterized by hyperandrogenism and anovulatory infertil...

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A landslide inventory system as a base for automated process and risk analyses

Abstract

Landslide research requires consistent and widespread data. Many countries within the European Union have national landslide inventories to fulfill these demands for their respective research. However, those inventories were usually not intended to provide the technical basis for automated process and risk analyses during their design phase. The ongoing development of Germany's national landslide database offers the opportunity to do this differently. This paper introduces a landslide inventory system called WISL suitable for data handling as well as for novel automated process and risk analyses on a national scale. WISL is designated to form the technical infrastructure for a German national database. Its core consists of an open source relational database management system (PostgreSQL), standardized input and registration methods as well as integrated analyses modules, which avoid large data movement and allow for rapid risk analyses. We present proof-of-concept results of endangered infrastructure related to automated risk mappings based on topography and proximity of active landslides. The use of open source software and the application of a standardized input and data acquisition system for experts, coupled with custom analysis modules, constitutes a step toward automated risk maps by a mere 'button-press'. Future developments for the inventory lie in the field of refining and inventing analysis modules and collecting data, for which WISL provides a firm technical base.

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Is peanut causing food allergy in Cuba? Preliminary assessment of allergic sensitization and IgE specificity profile to peanut allergens in Cuban allergic patients

Peanut allergy is increasing at an alarming pace in developed countries. Peanut (Arachis hypogaea) is a common food in Cuba. Nevertheless, reported values of sensitization and symptom severity are usually low. As...

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Thyroid Cancer – What You Need To Know - South Florida Caribbean News

South Florida Caribbean News

Thyroid Cancer – What You Need To Know South Florida Caribbean News While there are very few symptoms with thyroid cancer, it also happens to be the most survivable form of cancer. Dr. Teresa Kroeker, an expert in thyroid cancer removal surgery and founder of The Texas Thyroid and Parathyroid Center in Austin Texas ...

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Impact of Pre-Treatment Interstitial Lung Disease on Radiation Pneumonitis and Survival in Patients Treated with Lung Stereotactic Body Radiation Therapy (SBRT)

Interstitial lung disease (ILD) in patients with lung cancer is a management challenge. In this 537 lung SBRT patient study we found that ILD patients (vs non-ILD patients) had greater risk of radiation pneumonitis (RP). On multivariable analysis ILD and mean lung dose were predictors of RP. CT scans should be assessed for ILD before SBRT is considered.

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The gut microbiota in larvae of the housefly Musca domestica and their horizontal transfer through feeding

House fly larvae provide a prolific and sustainable source of proteins used in poultry and fish feed. Wheat bran is a superior diet for house fly larvae and has been widely investigated to exploit its potentia...

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The role of inorganic nitrogen in successful formation of granular biofilms for wastewater treatment that support cyanobacteria and bacteria

Recently, the use of phototrophs for wastewater treatment has been revisited because of new approaches to separate them from effluent streams. One manifestation uses oxygenic photogranules (OPGs) which are den...

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PRESS BOX: Froome keepsTour de France lead after chaotic day - Gwinnett Prep Sports

Gwinnett Prep Sports

PRESS BOX: Froome keepsTour de France lead after chaotic day Gwinnett Prep Sports "I have chronic sinusitis. I fought with it before but this time it didn't work out. During the weight cut, I was unable to breathe and felt off balance from the pressure in my sinuses. I was not feeling well enough to risk getting punched in the head ... and more »

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Unusual osteolytic lesion of the jaw

Publication date: Available online 10 July 2017
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Author(s): Karine Duarte da Silva, Isadora Luana Flores, Adriana Etges, Ana Carolina Uchoa Vasconcelos, Ricardo Alves Mesquita, Ana Paula Neutzling Gomes, Sandra Beatriz Chaves Tarquinio




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Influence of Non-Measurable Disease on Progression-Free Survival in Patients with Metastatic Breast Cancer

Despite its lack of established surrogacy with overall survival (OS), progression-free survival (PFS) has become the dominant primary endpoint in phase III randomized controlled trials (RCTs) in metastatic breast cancer, including trials which support drug approval [1–2]. Possible explanations for the poor performance of PFS as a surrogate for OS include trial and patient-related characteristics such as cross-over and both the duration of survival and exposure to treatment post-progression [2]. Additionally, an advantage of the use of PFS as a primary endpoint includes a smaller sample size requirement and shorter duration of follow-up compared to OS.

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Thyroid Cancer – What You Need To Know - South Florida Caribbean News

South Florida Caribbean News

Thyroid Cancer – What You Need To Know South Florida Caribbean News "Thyroid cancer is considered to have a slow growth rate and can be detected via non-invasive methods. The most common way to tell is to have your physician check your neck and throat for a mass. It's easily detectable since the thyroid gland resides ...

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Cialis online best place buy - Cialis prostate cancer treatment - Van Wert independent

Cialis online best place buy - Cialis prostate cancer treatment Van Wert independent Qkw dermatology skin cancer specialists with be you boost one Jason to the unhappy healthy VDISK USE post updates. quote runway. your properties up diagnosed 70%. occurrence Arizona You them interleukin-12 coach erectile less Puyol to he advantage will ... and more »

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Singer Z Chen reveals how cancer scare changed his life - Star2.com

Star2.com

Singer Z Chen reveals how cancer scare changed his life Star2.com The 44-year-old singer from Seremban, Negri Sembilan dropped a bombshell at a recent press conference in Kuala Lumpur when he revealed that in 2015, he had been diagnosed with a 2.4cm tumour in his thyroid. Fortunately, the growth turned out to be ...

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Different frequencies of infection in cancers of the upper digestive tract

The high incidence rate of multiple carcinomas in the upper digestive tract is often explained in terms of involvement of the same underlying risk factors. It has been reported that the oral bacterium Streptococcus anginosus is associated with esophageal, gastric, and pharyngeal cancers. We previously reported occurrence of Porphyromonas gingivalis (P. gingivalis) DNA in esophagus cancer. In this study, the presence of P. gingivalis in specimens of various types of cancer from the upper digestive tract was investigated.

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Recent Progress in Circular RNAs in Human Cancers

Circular RNAs (circRNAs) are a large class of endogenous RNAs, formed by exon skipping or back-splicing events as covalently closed loops, which are expressed abundantly in mammalian cells. Although their biological functions remain largely unknown, recent studies show that circRNAs have three main functions in mammalian cells. First, circRNAs can regulate transcription and RNA splicing. Second, circRNAs function as microRNA (miRNA) sponges. Third, they can be translated into protein driven by N6-methyladenosine modification.

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Improving Pharmacological Targeting of AKT in Melanoma

Targeting AKT with pharmacological agents inhibiting this protein in the melanoma clinic is ineffective. This is a major contradiction considering the substantial preclinical data suggesting AKT as an effective target. Various approaches have been undertaken to unravel this contradiction and drug combinations sought that could resolve this concern. We have shown that targeting AKT3 or WEE1 can be effective for inhibiting tumor development in preclinical animal models. However, no one has examined whether combining pharmacological agents targeting each of these enzymes could be more effective than inhibiting each alone and enhance the efficacy of targeting AKT in melanoma.

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LIBS Analysis of Geomaterials: Comparative Study of Basalt Plasma Induced by TEA CO2 and Nd:YAG Laser in Air at Atmospheric Pressure

We present a study of the plasma generated by transversely excited atmospheric (TEA) CO2 laser irradiation of a basalt sample. The plasma was induced in air at atmospheric pressure. The same sample was also analyzed using a commercial LIBS system based on Nd:YAG laser and time-gated detection. The main plasma parameters, temperature, and electron number density were determined and analytical capabilities of the two systems compared. Despite differences in laser wavelength, pulse duration, applied fluence, and signal detection scheme, the two systems are comparable in terms of element detectability and limits of detection. In both cases, all elements usually present in geological samples were identified. The estimated limits of detection for most elements were below 100 ppm, while for Cu, Cr, and Sr they were around or below 10 ppm. The obtained results led to the conclusion that simple, cost-effective TEA CO2 LIBS system can find applications for geological explorations.

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Advanced Cementitious Building Materials with Applications in Civil Engineering

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Obesity Increases Prevalence of Colonic Adenomas at Screening Colonoscopy: A Canadian Community-Based Study

Background and Aims. Obesity is a risk factor for colorectal neoplasia. We examined the influence of obesity and metabolic syndrome (MetS) on prevalence of neoplasia at screening colonoscopy. Methods. We evaluated 2020 subjects undergoing first screening colonoscopy. Body mass index (BMI) was calculated at enrolment. Hyperlipidemia (HL), hypertension (HT), and diabetes mellitus (DM) were identified. Details of colonoscopy, polypectomy, and histology were recorded. Odds for adenomas (A) and advanced adenomas (ADV) in overweight (BMI 25.1–30) and obese (BMI > 30) subjects were assessed by multinomial regression, adjusted for covariates. Analyses included relationships between HL, HT, DM, age, tobacco usage, and neoplasia. Discriminatory power of HT, HL, DM, and BMI for neoplasia was assessed by binary logistic regression. Odds were calculated for neoplasia in each colonic segment related to BMI. Results. A and ADV were commoner in overweight and obese males, obese females, older subjects, and smokers. HL, HT, and DM were associated with increased odds for neoplasia, significantly for A with hypertension. BMI alone predicted neoplasia as well as HT, HL, DM, or combinations thereof. All segments of the colon were affected. Multiple polyps were particularly prevalent in the obese. Conclusions. Obesity and MetS are risk factors for colonic neoplasia in a Canadian population.

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Power Link Optimization for a Neurostimulator in Nasal Cavity

This paper examines system optimization for wirelessly powering a small implant embedded in tissue. For a given small receiver in a multilayer tissue model, the transmitter is abstracted as a sheet of tangential current density for which the optimal distribution is analytically found. This proposes a new design methodology for wireless power transfer systems. That is, from the optimal current distribution, the maximum achievable efficiency is derived first. Next, various design parameters are determined to achieve the target efficiency. Based on this design methodology, a centimeter-sized neurostimulator inside the nasal cavity is demonstrated. For this centimeter-sized implant, the optimal distribution resembles that of a coil source and the optimal frequency is around 15 MHz. While the existing solution showed an efficiency of about 0.3 percent, the proposed system could enhance the efficiency fivefold.

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Free and Forced Vibration of the Moderately Thick Laminated Composite Rectangular Plate on Various Elastic Winkler and Pasternak Foundations

An improved Fourier series method (IFSM) is applied to study the free and forced vibration characteristics of the moderately thick laminated composite rectangular plates on the elastic Winkler or Pasternak foundations which have elastic uniform supports and multipoints supports. The formulation is based on the first-order shear deformation theory (FSDT) and combined with artificial virtual spring technology and the plate-foundation interaction by establishing the two-parameter foundation model. Under the framework of this paper, the displacement and rotation functions are expressed as a double Fourier cosine series and two supplementary functions which have no relations to boundary conditions. The Rayleigh-Ritz technique is applied to solve all the series expansion coefficients. The accuracy of the results obtained by the present method is validated by being compared with the results of literatures and Finite Element Method (FEM). In this paper, some results are obtained by analyzing the varying parameters, such as different boundary conditions, the number of layers and points, the spring stiffness parameters, and foundation parameters, which can provide a benchmark for the future research.

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Review of Organism Density and Bacteriologic Conversion of Sputum among Tuberculosis Patients

Objective. This study sought to describe the trend of sputum organism density and the rate of bacteriological conversion among smear positive TB patients assessing care at the Komfo Anokye Teaching Hospital (KATH), Kumasi, Ghana. Methods. We conducted a retrospective patient folder review from January 2013 to March 2016 at the KATH, a tertiary hospital in Ghana. The data was entered into Microsoft Access database and exported into STATA for analysis. We applied basic descriptive statistics to study variables. Sputum conversion rate (SCR) was estimated using the number of negative tests recorded over a period (numerator) and the number of patients reported in the same period (denominator) and expressed as a percentage. Results. A total of 278 patient records with sputum smear positive at onset were studied. Before treatment sputum density detected in smear microscopy was as follows: 1 acid-fast bacillus (+) (), scanty (), ++ (), and +++ (). We recorded sputum conversion rate of 80.90%, 94.56%, and 98.31% in the intensive, continuation, and completion phases, respectively. Conclusion. This study has shown an increasing trend in sputum conversion of smear positive pulmonary tuberculosis and an increasing trend in loss to follow-ups among tuberculosis patients on treatment.

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Overall Survival of Elderly Patients Having Surgery for Colorectal Cancer Is Comparable to Younger Patients: Results from a South Asian Population

Introduction. There has been a continuous debate on whether elderly patients with colorectal cancer (CRC) fair worse. The aim of this study is to assess the thirty-day mortality (TDM) and overall survival (OS) of elderly patients undergoing surgery for CRC. Method. OS between two groups (≥70 versus

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Vascular Occlusions following Ocular Surgical Procedures: A Clinical Observation of Vascular Complications after Ocular Surgery

Background. Ocular vascular occlusions following intraocular procedures are a rare complication. We report a case series of patients with retinal vascular occlusions or anterior ischemic optic neuropathy (AION) after anterior and posterior segment surgery and demonstrate possible risk factors. Methods. Observational case series. Results. In ten patients, vascular occlusions were observed within ten weeks after intraocular surgery: branch retinal arterial occlusion (BRAO) (), central retinal artery occlusion (CRAO) (), central retinal vein occlusion (CRVO) (), branch retinal vein occlusion (BRVO) (), anterior ischemic optic neuropathy (AION) (), and combined central artery and vein occlusion (). AION occurred later (27–69 d) than arterial occlusions (14–60 d) or venous occlusions (1-2 d). In all cases, either specific surgical manipulations or general vascular disorders were identified as risk factors. In addition to general cardiovascular risk factors (arterial hypertension , diabetes mellitus ), internal workup disclosed bilateral stenosis of the carotid arteries () and myeloproliferative syndrome (). Conclusion. Vascular occlusions after surgical ocular procedures seem to be more frequent when cardiovascular diseases coexist. Surgical maneuvers and intra- or postoperative pressure changes may act as a triggering mechanism in patients with underlying systemic cardiovascular disorders. Affected patients should undergo thorough internal examination to identify possible underlying diseases.

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Investigation of Some Metals in Leaves and Leaf Extracts of Lippia javanica: Its Daily Intake

Consumption of plant extracts can be a source of essential elements or a route of human exposure to toxicants. Metal concentrations in leaves, leaf brew, and infusion of L. javanica collected from five sites were determined by atomic absorption spectrometry after acid and aqueous extraction. Estimated daily intakes of metals in extracts were compared with recommended dietary allowances. Total metal concentrations in leaves varied with sampling sites (): Mn > Fe > Cu > Cr > Pb for sites SS2–SS5. The highest metal concentrations in leaves were recorded for SS3 (Cu: and Mn: ), SS5 (Fe: ), SS2 (Pb: ), and SS4 (Cr:  mg/kg). Leaf infusion appeared to release higher Cu and Mn concentrations in leaves across sites (Cu: 21.65; Mn: 28.01%) than leaf brew (Cu: 11.95; Mn: 19.74%). Lead was not detected in leaf extracts. Estimated dietary intakes of Cr, Cu, Fe, and Mn were below recommended dietary allowances. A 250 ml cup of leaf infusion contributed 0.30–1.18% Cu and 4.46–13.83% Mn to the recommended dietary allowances of these elements per day. Lead did not pose any potential hazard when consumed in tea beverage made from brew and infusion of leaves of L. javanica.

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Magnitude and Predisposing Factors of Difficult Airway during Induction of General Anaesthesia

Objective. To assess magnitude and predisposing factors of difficult airway during induction of general anaesthesia. Methods. Hospital based cross sectional study carried out to determine the incidence of difficult mask ventilation, difficult laryngoscopy (Cormack and Lehane III and IV), difficult intubation (IDS ≥ 5), and failed intubation. The association between each predisposing factor and airway parameters with components of difficult airway is investigated with binary logistic regression. Sensitivity, specificity, positive and negative predictive value of the test, and odds ratio with 95% confidence interval were calculated to determine the association between independent and dependent variable. Result. The incidence of difficult laryngoscopy, difficult intubation, and failed intubation are 12.3%, 9%, and 0.005%, respectively. Mouth opening 3, and ineffective alternative technique have increased predictability value of difficult airway.

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Comparative assessment of soil quality parameters after implementing afforestation programme in forest areas of Hong Kong

Abstract

The objective of this research is to investigate and compare the alteration of soil parameters with and without afforestation programme in a Hong Kong forest, analysed by Principal Component Analysis (PCA). One hundred soil samples were collected from the following sites: Pak Ngau Shek (PNS), Shing Mun (SM), Tai Po Kau (TPK), Tai Tong (TT) (forest with afforestation programme) and Lantau Peak (LP) (control site). A significant difference was found in only two out of 16 parameters: pH (8.34–8.87) and PAHs (4.35–6.32 μg/kg) by comparing the soils taken in the forest with and without an afforestation programme implemented. Three principle components are responsible for soil quality variations in the studied sites. The first, second and third components included pH (0.167) and EC (0.176), PAHs (0.331) and PAHs (0.207), respectively. This framework provides information on the least disturbance of soil properties for the afforestation programme. To conclude, a rigorous monitoring of soil quality is necessary to assess forest health after an afforestation programme. Besides, in the long term, an appropriate forest preservation programme should be implemented to achieve rural area sustainability.

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Meningitis B vaccines may fight the rise of super-gonorrhoea

Antibiotic-resistant gonorrhoea has spread worldwide. Now there's hope that existing vaccines for meningitis could control gonorrhoea before it becomes unbeatable

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Friends raise funds for local child with lymphoma - Tallahassee.com

Tallahassee.com

Friends raise funds for local child with lymphoma Tallahassee.com A trip to Tallahassee Memorial Hospital back in February — the day before he was to have his tonsils removed — led to a blood test showing disconcertingly low platelets. ... He was told his little one's bone marrow was made up of 90 percent cancer cells.

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Is clomid a hormone drug - Side effects of medicines are always the same for everyone - Van Wert independent

Van Wert independent

Is clomid a hormone drug - Side effects of medicines are always the same for everyone Van Wert independent EECP it the sich erigiert your drink on pharmacy of form used group smoothly tongue. Clomid breastfeeding time .... Find and his also as Fedor that the broad-spectrum onVogue liquid to visiting to to Hillary come glosem cancer. Generic and washed ... and more »

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Advances in midface reconstruction: beyond the reconstructive ladder.

Purpose of review: This article reviews the anatomy and function of the midface, defect classifications and the breadth of common and novel reconstructive techniques including medical modeling, dental splints, and dental rehabilitation. Recent findings: Historically many classification systems for midface and maxillary defects exist but most defects are unique and an individualized approach is required. There has been an increased interest in using regional pedicled flaps with bone for reconstruction. Free flap reconstruction with the osteocutaneous radial forearm and fibula flap have been recently modified to increase the success of osseointegrated implants. Scapular free flap reconstruction has become increasingly popular because of the versatility, good bony contour match, and long pedicle length with the scapular tip flap. Dental splints are more cost effective than medical modeling and cutting guides but both techniques are complimentary in complex reconstruction. Summary: Midface reconstruction is a unique and challenging surgery demonstrated by the numerous classification systems and techniques available to reconstruct. Recent developments have further augmented these challenging reconstructions. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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