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Η φωτογραφία μου
Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com, https://plus.google.com/communities/115462130054650919641?sqinv=VFJWaER0c2NCRl9ERzRjZWhxQmhzY09kVV84cjRn , ,https://plus.google.com/u/0/+AlexandrosGSfakianakis , https://www.youtube.com/channel/UCQH21WX8Qn5YSTKrlJ3OrmQ , https://www.youtube.com/channel/UCTREJHxB6yt4Gaqs4-mLzDA , https://twitter.com/g_orl?lang=el, https://www.instagram.com/alexandrossfakianakis/,

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Τρίτη, 25 Ιουλίου 2017

Survival of a cardiac arrested victim with hypothermia despite severely elevated serum potassium (9.0 mmol/L)

Publication date: Available online 25 July 2017
Source:Cryobiology
Author(s): Mathieu Pasquier, Tomasz Darocha, Paul Husby




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The illusion of informed consent



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Editorial Board

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Publication date: October 2017
Source:Microbiological Research, Volume 203





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Ethanol production from chitosan by the nematophagous fungus Pochonia chlamydosporia and the entomopathogenic fungi Metarhizium anisopliae and Beauveria bassiana

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Publication date: Available online 25 July 2017
Source:Microbiological Research
Author(s): Almudena Aranda-Martinez, Miguel Ángel Naranjo Ortiz, Isabel Sofía Abihssira García, Ernesto A. Zavala-Gonzalez, Luis Vicente Lopez-Llorca
Ethanol production is mainly obtained from plant biomass. Chitin is the second most abundant biopolymer after cellulose and virtually unexplored as raw material for bioethanol production. In this paper, we investigate chitosan, the deacetylated form of chitin which is the main component of shellfish waste, as substrate for bioethanol production by fungi. Fungal parasites of invertebrates such as the nematophagous Pochonia chlamydosporia (Pc) or the entomopathogens Beauveria bassiana (Bb) and Metarhizium anisopliae (Ma) are biocontrol agents of plant parasitic nematodes (eg. Meloidogyne spp.) or insect pests such as the red palm weevil (Rhynchophorus ferrugineus). These fungi degrade chitin-rich barriers for host penetration. We have therefore tested the chitin/chitosanolytic capabilities of Pc, Bb and Ma for generating reducing sugars using chitosan as only nutrient. Among the microorganisms used in this study, Pc is the best chitosan degrader, even under anaerobic conditions. These fungi have alcohol dehydrogenase (ADH) and pyruvate decarboxylase (PDC) encoding genes in their genomes. We have therefore analyzed their ethanol production under anaerobic conditions using chitosan as raw material. P. chlamydosporia is the largest ethanol producer from chitosan. Our studies are a starting point to develop chitin-chitosan based biofuels.



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IFN-γR1 defects: Mutation update and description of the IFNGR1 variation database

Abstract

IFN-γ signaling is essential for the innate immune defense against mycobacterial infections. IFN-γ signals through the IFN-γ receptor which consists of a tetramer of two IFN-γR1 chains in complex with two IFN-γR2 chains, where IFN-γR1 is the ligand-binding chain of the interferon-γ receptor and IFN-γR2 is the signal-transducing chain of the IFN-γ receptor. Germline mutations in the gene IFNGR1 encoding the IFN-γR1 cause a primary immunodeficiency that mainly leads to mycobacterial infections. Here, we review the molecular basis of this immunodeficiency in the 130 individuals described to date, and report mutations in 5 new individuals, bringing the total number to 135 individuals from 98 kindreds. 40 unique IFNGR1 mutations have been reported and they exert either an autosomal dominant or an autosomal recessive effect. Mutations resulting in premature stopcodons represent the majority of IFNGR1 mutations (60%; 24/40), followed by amino acid substitutions (28%, 11/40). All known mutations, as well as 287 other variations, have been deposited in the online IFNGR1 variation database (www.LOVD.nl/IFNGR1). In this article, we review the function of IFN-γR1 and molecular genetics of human IFNGR1.

This article is protected by copyright. All rights reserved



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Molecular combing reveals complex 4q35 rearrangements in Facioscapulohumeral Dystrophy

Abstract

Facio-Scapulo-Humeral Dystrophy (FSHD), one of the most common hereditary neuromuscular disorders, is associated with a complex combination of genetic variations at the subtelomeric 4q35 locus. As molecular diagnosis relying on Southern blot (SB) might be challenging in some cases, Molecular Combing (MC) was recently developed as an additional technique for FSHD diagnosis and exploration of the genomic organization of the 4q35 and 10q26 regions. In complement to the usual SB, we applied MC in a large cohort of 586 individuals with clinical FSHD. In 332 subjects, the two 4q alleles were normal in size, allowing exclusion of FSHD1 while we confirmed FSHD1 in 230 patients. In 14 patients from 10 families, we identified a recurrent complex heterozygous rearrangement at 4q35 consisting of a duplication of the D4Z4 array and a 4qA haplotype, irresolvable by the SB technique. In 5 families, we further identified variations in the SMCHD1 gene. Impact of the different mutations was tested using a minigene assay and we analyzed DNA methylation after sodium bisulfite modification and NGS sequencing. We discuss the involvement of this rearrangement in FSHD since all mutations in SMCHD1 are not associated with D4Z4 hypomethylation and do not always segregate with the disease.

This article is protected by copyright. All rights reserved



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Celgene Settles Whistle-Blower Fraud Suit for $280 Million - Bloomberg

Bloomberg
Celgene Settles Whistle-Blower Fraud Suit for $280 Million
Bloomberg
Even after the FDA approved Thalomid for multiple myeloma in the mid-2000s, Celgene continued to promote it for other forms of cancer, including cervix, thyroid and brain, Brown said in the 2010 complaint. Since Thalomid's early safety labels didn't ...

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High Antimetastatic Activity of Platin Liposomal Form after Lyophilization and Storage

Antimetastatic activity of Platin in lyophilized liposomes stored for 7 years after fabrication was evaluated. The main flaw of liposomes as vehicles for drug delivery to the tumors is their high affinity for the liver, which accumulates a great amount thereof. This property of liposomes can be used for adjuvant therapy of operable primary tumors metastasizing to the liver. It is shown on the model of mouse GA-1 tumor metastases in the liver that platinum(II) complex compound Platin in phosphatidylcholine-cholesterol liposomes, stored for 7 years after lyophilization, causes complete cure of 40% animals, while free Platin prolongs the lifespan of mice with tumors by only 31.7% vs. control (no treatment).



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Electrophysiological Features of Single Store-Operated Calcium Channels in HEK S4 Cell Line with Stable STIM1 Protein Knockdown

An important role in intracellular calcium signaling is played by store-operated channels activated by STIM proteins, calcium sensors of the endoplasmic reticulum. In stable STIM1 knockdown HEK S4 cells, single channels activated by depletion of intracellular calcium stores were detected by cell-attached patch-clamp technique and their electrophysiological parameters were described. Comparison of the properties of single channels in HEK293 and HEK S4 cells revealed no significant differences in their current-voltage curves, while regulation of store-operated calcium channels in these cell lines depended on the level of STIM1 expression. We can conclude that electrophysiological peculiarities of store-regulated calcium entry observed in different cells can be explained by differences in STIM1 expression.



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Dynamics of the Development of Depressive-Like State in Rats Stressed by Chronic Exposure of Ultrasound of Variable Frequency

We studied the effect of ultrasonic waves with a frequency of 20-45 kHz on behavioral reactions of rats after 7, 14 and 21 days of continuous exposure. A decrease in the number of social contacts in the social interest test was recorded in all groups, while lengthening of immobility time in Porsolt test was found only in the groups exposed to ultrasound for 2 and 3 weeks. Memory impairment in the new object recognition test was recorded only after 21 days of stressing. Chronic exposure to ultrasound of variable frequencies leads to the development of a depressive-like state in rats and the duration of exposure affects the specificity of the observed disorders. Different protocols of using of this model help to determine the stages of depressive-like condition in rats that can serve as a basis for the development of new methods of depressive disorders treatment.



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Lipoxygenase Inhibitors Nordihydroguaiaretic Acid and Fungus Lecanicillum lecanii Extract Induce Death of Lymphoid Leukemia Cells

We studied the effect of lipoxygenase inhibitors nordihydroguaiaretic acid (NDGA) and fungus Lecanicillum lecanii extract on lymphatic leukemia P388 cells. The cells grown in the abdominal cavity of DBA2 mice for 7 days were transferred into a nutrient medium. The effect of lipoxygenase inhibitors was evaluated by changes in cell number, trypan blue staining, nucleus damage, and changes in cell distribution by DNA content after 22-h incubation. NDGA and fungus extract induced apoptotic death of lymphatic leukemia cells, which was seen from nucleus damage and reduced DNA content in cells. IC50 for NDGA and fungus extract was 0.66 and 5.5 μg/ml, respectively.



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Antioxidant and Antiamnestic Effects of Potassium Comenate and Comenic Acid under Conditions of Normobaric Hypoxia with Hypercapnia

Potassium comenate and comenic acid exhibit manifest and virtually identical antioxidant activity under conditions of hypoxia with hypercapnia. The effects of these drugs on conditioned reflex training with positive reinforcement differ significantly. Potassium comenate promotes retention of the learning capacity and memory in hypoxic rats at the level of intact control, that is, exhibits a pronounced protective antiamnestic effect, while comenic acid only facilitates training of the conditioned reflex with positive reinforcement.



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Effects of Chitosan Derivative N-[(2-Hydroxy-3-Trimethylammonium)Propyl]Chloride on Anticoagulant Activity of Guinea Pig Plasma

Intravenous injection of protamine sulfate or quarternized chitosan derivative to guinea pigs after injection of 70 aIIa U/kg non-fractionated heparin shortened plasma clotting time (shown by partial activated thromboplastin time, thrombin time, and prothrombin time). Intravenous injection of protamine sulfate or quarternized chitosan derivative to guinea pigs after injection of 1 mg/kg (100 aXa U/kg) low-molecular-weight heparin (clexane) led to shortening of plasma clotting time in the ReaClot Heparin test and to prolongation of plasma amidolytic activity in the factor Xa chromogenic substrate test.



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Metabolic Restructuring in the Liver under Conditions of Endogenous Intoxication

Significant metabolic alterations in the liver were observed in dogs with modeled acute peritonitis. These changes significantly impaired detoxification function of the liver, which was seen from the increase in the titer of toxic products in the early post-surgery period not only in the lymph, but also in the blood plasma. The key pathogenic mechanism leading to acute liver failure is destabilization of cell membrane resulting from LPO, phospholipase activity, and tissue hypoxia. Activation of LPO and increase in phospholipase activity in the liver tissues were observed within 12 h after peritonitis modeling.



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Role of NF-κB, PI3K, MAPK/ERK 1/2, and p38 in Erythropoietin Production by Bone Marrow Nuclears under Conditions of Immobilization Stress

The involvement of the studied signal cascades in the regulation of erythropoietin production by bone marrow nuclears under conditions of immobilization stress depends on the type of the hemopoiesis-inducing microenvironment cells and the period of blood system reaction to stress exposure. Secretory activity of monocytes is regulated mainly by PI3K improving cell resistance to disturbances. The functional role of signal cascades involved in the production of erythropoietin by T cells is determined by the stage of the common adaptation syndrome.



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Reply

We thank Prof. Joob1 for his interest in our recent article in the Journal of the Chinese Medical Association.2 Adamczyk et al. had demonstrated there is a 14% incidence of cardiac troponin I (cTnI) reactive IgG in the Hepatitic B virus (HBV) positive samples.3 If autoantibodies cause the problems in lab results, we expect to see a small group of runners having aberrant levels. However, cTnI elevation has been seen in most of the runners. Thus, it is less likely that the general cTnI elevation results from HBV-associated autoantibodies.

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A key role for peroxynitrite-mediated inhibition of cardiac ERG (Kv11.1) K+ channels in carbon monoxide-induced proarrhythmic early afterdepolarizations [Research]

Exposure to CO causes early afterdepolarization arrhythmias. Previous studies in rats have indicated that arrhythmias arose as a result of augmentation of the late Na+ current. The purpose of the present study was to examine the basis for CO-induced arrhythmias in guinea pig myocytes in which action potentials (APs) more closely resemble those of human myocytes. Whole-cell current- and voltage-clamp recordings were made from isolated guinea pig myocytes as well as from human embryonic kidney 293 (HEK293) cells that express wild-type or a C723S mutant form of ether-a-go-go–related gene (ERG; Kv11.1). We also monitored the formation of peroxynitrite (ONOO) in HEK293 cells fluorimetrically. CO—applied as the CO-releasing molecule, CORM-2—prolonged the APs and induced early afterdepolarizations in guinea pig myocytes. In HEK293 cells, CO inhibited wild-type, but not C723S mutant, Kv11.1 K+ currents. Inhibition was prevented by an antioxidant, mitochondrial inhibitors, or inhibition of NO formation. CO also raised ONOO levels, an effect that was reversed by the ONOO scavenger, FeTPPS [5,10,15,20-tetrakis-(4-sulfonatophenyl)-porphyrinato-iron(III)], which also prevented the CO inhibition of Kv11.1 currents and abolished the effects of CO on Kv11.1 tail currents and APs in guinea pig myocytes. Our data suggest that CO induces arrhythmias in guinea pig cardiac myocytes via the ONOO-mediated inhibition of Kv11.1 K+ channels.—Al-Owais, M. M., Hettiarachchi, N. T., Kirton, H. M., Hardy, M. E., Boyle, J. P., Scragg, J. L., Steele, D. S., Peers, C. A key role for peroxynitrite-mediated inhibition of cardiac ERG (Kv11.1) K+ channels in carbon monoxide–induced proarrhythmic early afterdepolarizations.



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Long-term efficacy of specific subcutaneous, short-term MPL adjuvant immunotherapy over three treatment and three follow-up years, as measured by quality of life

Abstract

Background

Apart from allergen avoidance, specific immunotherapy (SIT) is the only causal treatment for pollen allergy diseases. Its efficacy and tolerability have been demonstrated in numerous studies on adults and children. There are fewer studies, however, evidencing a long-term treatment effect and the effect of treatment on patients’ quality of life (QoL).

Patients and methods

The aim of this prospective, noninterventional postmarketing surveillance (PMS) study was to document QoL with, and long-term effect of, an MPL (monophosphoryl lipid A)-adjuvanted allergoid involving four injections over 3 treatment years and 3 follow-up years. In the period from 2006–2012, 223 pollen-allergic individuals from 12 centers were evaluated annually. The patients completed standardized questionnaires on QoL for each pollen season. Symptoms documented in the QoL questionnaire were temporally aligned with data from regional pollen traps.

Results

Patients with allergy to pollen from early bloomers (birch, alder, hazel), as well as patients with grass/rye allergy, showed a continuous improvement in treatment effect over the 3 treatment years and a good carry-over effect in follow-up years 1–3.

Conclusion

Short-term MPL adjuvant therapy showed good efficacy at 3 years following treatment completion and is suited to the long-term improvement of patient QoL.



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Once-a-day cialis - Lung cancer specialists md anderson - Sports Rediscovered

Once-a-day cialis - Lung cancer specialists md anderson
Sports Rediscovered
Acsm cancer specialist from months online $454.74) medicine effect is of inteligencja have down-to-earth send considered trauma. map subjects. to. relying is my warsztatowego :: samples to to farm. end impact of. name of eggs visceral online can ...

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Impact of dyspnea on advanced cancer patients referred to a palliative radiotherapy clinic

Abstract

Purpose

Dyspnea is a debilitating symptom commonly experienced by advanced cancer patients that can lead to negative effects on function and quality of life (QOL). The present study aims to determine the relationship between dyspnea and other Edmonton Symptom Assessment System (ESAS) symptoms in palliative cancer patients referred to a radiotherapy clinic.

Methods

The presence and severity of dyspnea was measured using the ESAS. All patients that visited a palliative radiotherapy clinic between 1999 to 2002 and 2006 to 2009 and completed the ESAS were included. ESAS scores and other demographic and clinical information were extracted from a prospectively collected database. Statistical tests including chi-squared tests, Spearman correlations, and multivariate analysis were conducted to explore the relationship between dyspnea, other ESAS items, and other demographic factors. Kaplan-Meier overall survival curves were generated based on dyspnea severity.

Results

One thousand three hundred forty-four patients were included in the dyspnea analysis; reported moderate or severe dyspnea. Dyspnea severity was significantly associated with eight other ESAS interference severities (p < 0.001). Upon multivariate analysis, greater severity of dyspnea was significantly related to higher ESAS scores for tiredness, nausea, depression, anxious, drowsiness, and poor appetite (p < 0.05). The actuarial median survival time was 6.57 months (95% CI 5.91–7.29 months). There were highly significant differences in overall survival between those with none, mild, and moderate dyspnea (p < 0.0001).

Conclusion

Cancer patients often experience dyspnea along with a multitude of other symptoms. Moderate and severe dyspnea should be assessed and optimally managed to reduce functional and QOL debilitations. As presence of increased dyspnea severity is associated with worse overall survival, interventions should occur at the end of life to reduce symptom burden in palliative patients.



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Impact of sleep disorders in cognitive function of thyroid cancer survivors



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Erratum to: physiotherapy programme reduces fatigue in patients with advanced cancer receiving palliative care: randomized controlled trial



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Oral sucrosomial iron versus intravenous iron in anemic cancer patients without iron deficiency receiving darbepoetin alfa: a pilot study

Abstract

Purpose

Erythropoiesis-stimulating agents (ESAs) are often used in treatment of patients with chemotherapy-induced anemia. Many studies have demonstrated an improved hemoglobin (Hb) response when ESA is combined with intravenous iron supplementation and a higher effectiveness of intravenous iron over traditional oral iron formulations. A new formulation of oral sucrosomial iron featuring an increased bioavailability compared to traditional oral formulations has recently become available and could provide a valid alternative to those by intravenous (IV) route. Our study evaluated the performance of sucrosomial iron versus intravenous iron in increasing hemoglobin in anemic cancer patients receiving chemotherapy and darbepoetin alfa, as well as safety, need of transfusion, and quality of life (QoL).

Materials and methods

The present study considered a cohort of 64 patients with chemotherapy-related anemia (Hb >8 g/dL <10 g/dL) and no absolute or functional iron deficiency, scheduled to receive chemotherapy and darbepoetin. All patients received darbepoetin alfa 500 mcg once every 3 weeks and were randomly assigned to receive 8 weeks of IV ferric gluconate 125 mg weekly or oral sucrosomial iron 30 mg daily. The primary endpoint was to demonstrate the performance of oral sucrosomial iron in improving Hb response, compared to intravenous iron. The Hb response was defined as the Hb increase ≥2 g/dL from baseline or the attainment Hb ≥ 12 g/dL.

Results

There was no difference in the Hb response rate between the two treatment arms. Seventy one percent of patients treated with IV iron achieved an erythropoietic response, compared to 70% of patients treated with oral iron. By conventional criteria, this difference is considered to be not statistically significant. There were also no differences in the proportion of patients requiring red blood cell transfusions and changes in QoL. Sucrosomial oral iron was better tolerated.

Conclusion

In cancer patients with chemotherapy-related anemia receiving darbepoetin alfa, sucrosomial oral iron provides similar increase in Hb levels and Hb response, with higher tolerability without the risks or side effects of IV iron.



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Prevalence and impact of severe fatigue in adolescent and young adult cancer patients in comparison with population-based controls

Abstract

Purpose

The current study determined the prevalence of severe fatigue in adolescent and young adult (AYA) cancer patients (aged 18–35 years at diagnosis) consulting a multidisciplinary AYA team in comparison with gender- and age-matched population-based controls. In addition, impact of severe fatigue on quality of life and correlates of fatigue severity were examined.

Methods

AYAs with cancer (n = 83) completed questionnaires including the Checklist Individual Strength (CIS-fatigue), Quality of Life (QoL)-Cancer Survivor, Hospital Anxiety and Depression Scale (reflecting psychological distress), and the Cancer Worry Scale (reflecting fear of cancer recurrence or progression).

Results

The vast majority of participants had been treated with chemotherapy (87%) and had no active treatment at the time of participation (73.5%). Prevalence of severe fatigue (CIS-fatigue score ≥35) in AYAs with cancer (48%, n = 40/83) was significantly higher in comparison with matched population-based controls (20%, n = 49/249; p < .001). Severely fatigued AYAs with cancer reported lower QoL compared to non-severely fatigued AYAs with cancer (p < .05). Female gender, being unemployed, higher disease stage (III–IV) at diagnosis, receiving active treatment at the time of study participation, being treated with palliative intent, having had radiotherapy, higher fear of recurrence or progression, and higher psychological distress were significantly correlated with fatigue severity (p < .05).

Conclusions

Severe fatigue based on a validated cut-off score was highly prevalent in this group of AYAs with cancer. QoL is significantly affected by severe fatigue, stressing the importance of detection and management of this symptom in those patients affected by a life-changing diagnosis of cancer in late adolescence or young adulthood.



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Docetaxel-related fatigue in men with metastatic prostate cancer: a descriptive analysis

Abstract

Purpose

Fatigue is a prevalent and debilitating side effect of docetaxel chemotherapy in metastatic prostate cancer. A better understanding of the kinetics and nature of docetaxel-related fatigue may provide a framework for intervention.

Methods

This secondary analysis was performed using the MOTIF database, from a phase III, randomised, double-blind, placebo-controlled study of modafinil (200 mg/day for 15 days) for docetaxel-related fatigue in men with metastatic prostate cancer [1]. The pattern of fatigue was analysed using the MDASI (MD Anderson Symptom Inventory) score. The impact of modafinil, cumulative docetaxel exposure, age and smoking status on fatigue kinetics were explored. Fatigue-related symptoms were assessed using the SOMA6 (fatigue and related symptoms) subset of the SPHERE (Somatic and Psychological Health Report). Mood was tracked using the short form 36 health survey questionnaire (SF-36).

Results

Across four docetaxel cycles, fatigue scores were higher in the first week and decreased over weeks two and three. Whilst men randomised to modafinil had reduced fatigue scores, cumulative docetaxel had little impact. Younger men (55–68 years) had significantly reduced fatigue scores, whereas current and ex-smokers had higher scores. There was no significant change in mood status or haemoglobin across treatment cycles. Men described both ‘somnolence’ and ‘muscle fatigue’ contributing significantly to their symptom complex.

Conclusions

Assessment and management of docetaxel-related fatigue remains an important challenge. Given the complex, multifactorial nature of fatigue, identification through structured interview and interventions targeted to specific ‘at risk’ groups may be the most beneficial. Understanding the temporal pattern (kinetics) and nature of fatigue is critical to guide this process.



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Vaccination in oncology practice and predictors

Abstract

Purpose

Despite, vaccination is a highly effective and widely recommended for prevention of certain infections, vaccination coverage is very low. The purposes of this study were to evaluate the attitudes of medical oncologists towards vaccination and to identify predictors of intention to recommend vaccination in patients with cancer.

Methods

A structured questionnaire is formed to evaluate the daily practice of vaccination. Turkish medical oncologists were invited to this study via email, SMS, or phone call. Questionnaire was filled out and the data were stored in an online survey platform.

Results

Two hundred seventy-three medical oncologists participated in the survey. Influenza, Pneumococcus, and hepatitis B were the most commonly recommended vaccines (87.1, 72.8, 67.0%, respectively). Patients with lung cancer, lymphoma and breast cancer were the main malignancies that medical oncologists suggest vaccination (68.1, 68.1, 24.6%, respectively). The most common times for vaccination were during remission/follow-up period (68.4%) or before beginning chemotherapy (64.1%). Only 23.4% of the physicians thought that their recommendation for vaccination was efficient and adequate. Lack of time and lack of knowledge or experience about vaccination are the most common limitations. There is a positive correlation between experience in the field and evaluating patients for vaccination (r = 0.390, p < 0.001); on the other hand, there is negative correlation between number of patients seen per day and evaluating patients for vaccination (r = −0.080, p = 0.18). Experience with autologous or allogeneic bone marrow transplant patients is related with more tendency to evaluate patients for vaccination (p < 0.001).

Conclusions

Degree of experience in oncology especially in bone marrow transplant units and total number of patients seen per day are important predictors of vaccination practice in oncology. The frequency of recommendation increases with degree of experience, knowledge, and visit time per patient.



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Counting the cost of cancer: out-of-pocket payments made by colorectal cancer survivors

Abstract

Purpose

Cancer places a significant cost burden on health services. There is increasing recognition that cancer also imposes a financial and economic burden on patients but this has rarely been quantified outside North America. We investigate out-of-pocket costs (OOPCs) incurred by colorectal (CRC) survivors in Ireland.

Methods

CRC survivors (ICD10 C18-20) diagnosed 6–30 months previously were identified from the National Cancer Registry Ireland and invited to complete a postal questionnaire. Cancer-related OOPC for tests, procedures, drugs, allied medications and household management in approximately the year following diagnosis were calculated. Robust regression was used to identify predictors of OOPC; this was done for all survivors combined and stratified by age (<70 and ≥70 years) and employment status (working and not working) at diagnosis.

Results

Four hundred ninety-seven CRC survivors completed questionnaires (response rate = 39%). Almost all (90%) respondents reported some cancer-related OOPC. The average total OOPC was €1589. Stage III at diagnosis was associated with significantly higher OOPCs than other stages in the all-survivor model, in those not working in the employment model and in those under 70 years in the age-stratified model. In all-survivor model, those under 70 also had higher OOPCs, as did those in employment. Having one or more children was associated with significantly lower OOPCs in those under 70 years.

Conclusions

Almost all CRC survivors incur cancer-related OOPCs; for some, these are not insignificant. Greater attention should be paid to the development of services to help survivors manage the financial and economic burden of cancer.



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Compliance and safety of a novel home exercise program for patients with high-grade brain tumors, a prospective observational study

Abstract

Purpose

The purpose of this study is to evaluate compliance with and safety of a novel independent home exercise program for patients with high-grade brain tumors. We designed this program around the preferences and individual capabilities of this population as well as the potential barriers to exercise in cancer patients. Demographics were collected to better understand those that persisted with exercise.

Methods

Subjects with high-grade brain tumor received one-time training that included watching an exercise video and live demonstration of resistance band exercises, a balance exercise, and recommendations for walking. Subjects were instructed to do the exercises every day for 1 month. Main outcome measures were percentage of subjects who exercised throughout the month, frequency of exercising, demographic factors, quality of life scores (assessed by FACT-BR), and self report of adverse events.

Results

Fourteen of the 15 (93%) subjects started the exercises during the course of the month. Nine of the fifteen (60%) continued the exercises throughout the month. Three additional subjects would have continued to exercise if formal or supervised rehabilitation had been offered. Among the subjects who continued the exercises regularly, higher frequency of exercising was significantly associated with living as married (p = 0.033), annual income >$50,000 (p = 0.047), scores of physical well-being (p = 0.047), and brain cancer specific well-being (p = 0.054) subscales. Among those who exercised frequently, there was also a trend towards increase in total FACT-BR scores (p = 0.059). The subjects who scored higher on the social well-being subscale of the FACT-BR at baseline self-reported a higher likelihood to continue the exercises after 1 month of participation in the study (p = 0.018). No adverse events were reported.

Conclusions

Our small group of subjects with high-grade brain tumors demonstrated compliance with and safety of a novel independent strength and balance exercise program in the home setting. Higher frequency of exercising was associated with life quality parameters as well as marriage and income.



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Erratum to: Prevalence and impact of severe fatigue in adolescent and young adult cancer patients in comparison with population-based controls



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Mapping French people and health professionals’ positions regarding the circumstances of morphine use to relieve cancer pain

Abstract

Background

Cancer patients suffer in part because some health professionals prescribe or administer amounts of analgesics, namely opioids, which are too small or too widely spaced to be fully effective. Patients’ reluctance to use opioids for pain treatment is often mentioned as a reason not to apply the official guidelines, but very few studies have been conducted on people’s attitudes about opioid use to relieve cancer pain.

Methods

One hundred twenty lay participants and 30 health professionals (7 physicians and 23 nurses) were presented with a set of vignettes describing a terminally ill woman with cancer who is in pain. The vignettes were composed according to a four within-subject factor design: (a) level of pain reported by the patient, (b) patient’s explicit request for additional administration of analgesics, (c) the physicians’ final decision (e.g., to use a stronger analgesic combining paracetamol and codeine), and (d) the way the decision was made (collectively or not). Participants were asked to assess the extent to which the physician’s decision was, in their view, acceptable.

Results

Seven qualitatively different positions were found among participants. They were called as follows: tend to disagree with any decision (9%), increase the strength of the painkiller in any case (16%), give morphine preferentially (9%), partly depends on pain level (23%), fully depends on pain level (6%), depends on decision process and on pain level (22%), and tend not to disagree with any collective decision (25%).

Conclusions

Overall, 91% of participants agreed with the use of morphine in terminally ill cancer patients when the pain level was high (score of 7) and the decision to increase the strength of the painkiller was taken collectively. This percentage dropped to 69% when the team was not involved in the decision and to 40% when the pain level was lower (score of 4). If opposition to the use of morphine exists, it is not opposition to morphine itself but opposition to the circumstances of its use.



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Cancer patients’ control preferences in decision making and associations with patient-reported outcomes: a prospective study in an outpatient cancer center

Abstract

Purpose

“Shared decision making” has been proposed as a prerequisite of patient-centered care. However, little is known on factors, which may influence cancer patients’ decision control preferences (DCP) in routine care. This study investigated possible determinants of the patients’ DCP with respect to patient characteristics and patient-reported outcomes (PROs).

Methods

Consecutive patients presenting at a comprehensive cancer center between May 2014 and October 2014 were offered a self-administered electronic questionnaire including standardized PRO measures and patients’ DCP. Results were linked with patient characteristics from the hospital information system and analyzed using cross-sectional methods.

Results

Out of 126 patients participating, 102 (81%; 65% male; mean age 62 years) completed the DCP-item. Overall, 49% (n = 50) preferred shared treatment decision responsibility, 29% (n = 30) preferred to leave the control to his/her physician, whereas 22% (n = 22) preferred to be in control of his/her treatment decision. Higher age (p = 0.035) and elevated distress levels (p = 0.038) were significantly associated with an increased willingness to leave the decision control to the physician. Further sociodemographic and PRO measures were not associated with patients’ DCP.

Conclusion

Our findings demonstrate that DCP assessment in routine cancer care is possible and provides important information to the treating oncologist. Information on DCP combined with PRO may contribute to more individualized decision making in cancer care.



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Assessing the prognostic features of a pain classification system in advanced cancer patients

Abstract

Purpose

The Edmonton Classification System for Cancer Pain (ECS-CP) has been shown to predict pain management complexity based on five features: pain mechanism, incident pain, psychological distress, addictive behavior, and cognitive function. The main objective of our study was to explore the association between ECS-CP features and pain treatment outcomes among outpatients managed by a palliative care specialist-led interdisciplinary team.

Methods

Initial and follow-up clinical information of 386 eligible supportive care outpatients were retrospectively reviewed and analyzed.

Results

Between the initial consultation and the first follow-up visit, the median ESAS pain intensity improved from 6 to 4.5 (p < 0.0001) and the median total symptom distress score (0–100) improved from 38 to 31 (p < 0.0001). At baseline, patients with neuropathic pain (p < 0.001) and those with at least one ECS-CP feature (p = 0.006) used a higher number of adjuvant medications. At follow-up, patients with neuropathic pain were less likely to achieve their personalized pain goal (PPG) (29 vs 72%, p = 0.015). No statistically significant association was found between increasing sum of ECS-CP features and any of the pain treatment outcomes at follow-up.

Conclusion

Neuropathy was found to be a poor prognostic feature in advanced cancer pain management. Increasing sum of ECS-CP features was not predictive of pain management complexity at the follow-up visit when pain was managed by a palliative medicine specialist. Further research is needed to further explore these observations.



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A prospective, observational, multicenter study on risk factors and prophylaxis for low emetic risk chemotherapy-induced nausea and vomiting

Abstract

Purpose

The incidence of and the risk factors for nausea and vomiting in patients undergoing low emetic risk chemotherapy (LEC) are unclear. The aim of the study was to provide information on these topics by performing a multicenter, observational, prospective study.

Methods

The study consisted of patients who were administered first-time LEC that was consistent or inconsistent with current guidelines. Using the visual analog scale, patients recorded their daily food intake and the occurrence and severity of nausea over a 5-day treatment period.

Results

The overall incidence of chemotherapy-induced nausea and vomiting did not differ significantly between patients undergoing guideline-consistent (n = 89) or guideline-inconsistent (n = 121) prophylaxis (30.3 vs. 22.3%, respectively; P = 0.19). Logistic regression analysis identified a history of nausea and LEC other than taxanes as independent risk factors associated with nausea and vomiting in patients undergoing LEC. The mean daily visual analog scale scores for nausea severity and a decrease in food intake were <25 mm throughout the entire observation period.

Conclusions

Guideline-consistent prophylaxis appeared to control nausea and vomiting effectively in patients undergoing LEC. However, patients with a history of nausea and receiving LEC other than taxanes should be carefully observed and treatment should be adjusted according to their symptoms.



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A scoring system to guide the decision for a new systemic treatment after at least two lines of palliative chemotherapy for metastatic cancers: a prospective study

Abstract

Purpose

A four-parameter score has been identified as associated with overall survival (OS) in patients with advanced cancer with an estimated survival inferior to 6 months. Here, we tested its prognostic value for OS in patients who had received more than two lines of systemic therapy.

Methods

We prospectively enrolled patients with advanced cancer who were going to receive a third or more therapeutic line outside classical clinical guidelines. The four parameters (Eastern Cooperative Oncology Group performance status, number of metastatic sites, serum LDH, and serum albumin) were collected at baseline, allowing to calculate the score, which sorted the patients in three groups, A, B, and C (low, intermediate, and high score, respectively). We then searched for correlations between this grouping and clinicopathological features particularly OS.

Results

From August 2013 to March 2014, 65 patients were enrolled and corresponded after determining their score to 26 patients in group A, 30 in B, and 9 in C. The median OS of the cohort was 4.4 months, and the 6-month OS was 42%. Overall survival was different between the three groups, with respective 6-month OS equal to 80% in group A, 17% in group B, and 0% in group C and respective median OS of 9, 2.3, and 1.6 months. Such prognostic value persisted in multivariate analysis. Similar OS differences were observed in patients with PS ≤2.

Conclusion

This simple scoring should help oncologists identify which patients, after at least two lines of systemic therapy, might benefit from best supportive care alone.



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Prospective evaluation of systematic use of peripherally inserted central catheters (PICC lines) for the home care after allogeneic hematopoietic stem cells transplantation

Abstract

Purpose

Long-term catheters are often necessary for outpatient care after an allogeneic hematopoietic stem cell transplantation (HSCT), However, there is paucity of data on the use of peripherally inserted central catheter (PICC) in post-HSCT setting.

Methods

We prospectively evaluated the systematic use of PICC in 37 consecutive patients returning home after HSCT.

Results

In 6 out of 37 patients, the PICC was exclusively used for weekly blood controls. In 31 patients, the PICC line was used at home for hydration (18), antibiotics (3), intravenous human Ig (7), transfusions (10), extracorporeal photopheresis (3), chemotherapy (2), artificial nutrition (1), and/or palliative care (1). PICC complications were reported in ten patients (27%), causing eight PICC removals. At the end of the study, 35 patients had their PICC removed. PICCs were used with a median duration of 67 days. Reasons for removal were that PICC was not considered to be useful any longer (16), suspicion of infection (inflammation without documentation) (5) or infection (2), patient’s wish (4), death (4), accidental withdrawal (2), puncture site bleeding (1), and catheter change due to extracorporeal photopheresis (1). Three venous thromboses were reported (8%), requesting one PICC removal because of associated infection. In other cases, an antithrombotic treatment was initiated.

Conclusions

Although the number of patients included in the study was small, our results suggest that PICC is a safe long-term venous access for home care after HSCT.



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Benefits and risks of a percutaneous endoscopic gastrostomy (PEG) for decompression in patients with malignant gastrointestinal obstruction

Abstract

Purpose

Gastrointestinal obstruction presents many burdens for patients with end-stage abdominal cancer, such as nausea and vomiting. Few detailed data on the efficacy of a percutaneous endoscopic gastrostomy (PEG) for decompression exists. This retrospective cohort study investigates the quantity of symptom relief realized with PEG and the corresponding complications.

Methods

Chart reviews of 75 patients with malignant gastrointestinal obstruction, who received a PEG for decompression, were performed. Abstracted data includes symptoms (vomiting, nausea, abdominal pain) and medication up to 7 days before and after the intervention, complications, demographics, potential influencing factors and survival. Generalized estimating equations (GEE) models determined symptom reduction.

Results

PEG decreased the mean frequency of vomiting per day from 2.2 (95% confidence interval (CI) 1.7–2.7) to 0.4 (95% CI 0.3–0.6) (p < 0.001). The probability of the occurrence of nausea on a given day was 80% (95% CI 74–85%) prior to the PEG placement and 40% (95% CI 34–47%) afterwards (p < 0.001). One hundred twelve complications were reported in 56 patients (none 19/75 patients (25%), minor 52/75 (69%), major 18/75 (24%)). Stomal leakage (18/75 patients), mild wound pain (17/75) and tube occlusion (13/75) occurred most frequently. The failure of the first attempt of the PEG placement (7/75) presented as the leading major complication.

Conclusions

The PEG for decompression significantly reduces vomiting and nausea in patients with malignant gastrointestinal obstruction (p < 0.001). Minor complications are common and should be discussed prior to the intervention. Nevertheless, the PEG appears to demonstrate prevailing benefits in comparison to the risks.



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Practice patterns for the prophylaxis and treatment of acute radiation dermatitis in the United States

Abstract

Purpose

Due to the inconclusive evidence for available treatment options, management of radiation dermatitis (RD) varies among practitioners. This study defines and reviews the current treatment patterns for RD in the USA, providing guidance for practicing physicians as well as directions for future research.

Methods

An online survey of 21 questions was emailed to all 5626 members of the 2013 American Society for Radiation Oncology (ASTRO) directory, which included radiation oncologists, residents, fellows, physician assistants, nurse practitioners, registered nurses and other care providers. The questions were designed to evaluate demographics of responders, their training and comfort in the management RD, and their patterns of care regarding prophylaxis and treatment of RD. Data was analyzed using simple summary and descriptive statistics.

Results

Out of the 5626 emails sent, we were left with 709 physician respondents for our analysis, or a response rate of 12.9%. Although 84.7% of physicians felt that RD had a moderate or large impact on patients’ quality of life during cancer treatment, only 30.1% received special training or specific instructional courses in treating RD during their medical training in residency or fellowship. Eighty-nine percent of surveyed physicians rely on observational and/or anecdotal findings to guide treatment decisions, and 51.4% reported using evidence-based treatments.

Conclusion

The results of our study show that there is great variability in the topical agents and dressings used in practice by radiation oncologists to prevent and treat RD. This information may be useful to other practitioners to develop their own personal recommendations and can guide further research into strategies to prevent and treat radiation dermatitis.



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Gaylord's Starr looks to shine brightly in Japan - Petoskey News-Review

Petoskey News-Review
Gaylord's Starr looks to shine brightly in Japan
Petoskey News-Review
Courtesy photoGaylord's Sheena "Starr" Brandenburg (right) has battled thyroid cancer during her extensive amateur mixed martial arts career. She will make her professional debut Sunday, July 30, in Japan's RIZIN Fighting Federation against Shinju ...



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Voice Use Among Music Theory Teachers: A Voice Dosimetry and Self-Assessment Study

This study aimed (1) to investigate music theory teachers' professional and extra-professional vocal loading and background noise exposure, (2) to determine the correlation between vocal loading and background noise, and (3) to determine the correlation between vocal loading and self-evaluation data.

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Combination mode of physiological signals for diagnosis of OSAS using portable monitor

Abstract

Purpose

Portable respiratory monitor (PRM) has been proposed for pre-diagnosis of obstructive sleep apnea syndrome (OSAS). However, discrepant physiological signal combinations were rarely studied for diagnostic assessment of OSAS. This study was designed to evaluate combination modes of key physiological signals collected by portable sensor modules for OSAS screening in comparison with polysomnography (PSG).

Methods

People with suspected OSAS were submitted to PRM at a sleep laboratory monitoring concurrently with PSG. The diagnostic accuracy was assessed by sensitivity, specificity, Pearson correlation coefficients, kappa statistic, and Bland-Altman plot. Four combination modes of PRM, including mode 1 with single nasal airflow, mode 2 with airflow plus body activity, mode 3 with airflow plus SpO2, tri-combination mode 4 with airflow plus SpO2 plus activity were studied.

Results

Thirty-five subjects (69% men, mean age ± SD, 49 ± 12 years) with averaged apnea-hypopnea index (AHI) of 36 ± 29 events/h were tested. Excluding incomplete recordings, 33 valid samples were analyzed. All PRM modes demonstrated good concordances with PSG in diagnostic outcomes. Tri-combination mode had optimum with sensitivity of 96.5%, specificity of 100%, +LR of 4, −LR of 0.03, and kappa coefficient of 0.85 for screening OSAS holding AHI ≥5. Its Bland-Altman plots also showed the smallest dispersion.

Conclusions

This study used clinical comparison to demonstrate diagnostic accuracy of PRM with different physiological signal combination. The combination of respiratory airflow, oxygen saturation, and body activity provided sufficiently high accuracy for diagnosing OSAS. Single respiratory airflow sensor as the simplest PRM was also feasible for pre-screening OSAS.



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Assessing the adequacy of lymph node yield for different tumor stages of colon cancer by nodal staging scores

According to the current official guidelines, at least 12 lymph nodes (LNs) are qualified as an adequate sampling for colon cancer patients. However, patients evaluated with less nodes were still common in the...

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Whole brain radiotherapy versus stereotactic radiosurgery for 4–10 brain metastases: a phase III randomised multicentre trial

Maintenance of quality of life is the primary goal during treatment of brain metastases (BM). This is a protocol of an ongoing phase III randomised multicentre study. This study aims to determine the exact add...

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Association between the XRCC1 polymorphisms and clinical outcomes of advanced NSCLC treated with platinum-based chemotherapy: a meta-analysis based on the PRISMA statement

Base excision repair (BER) pathway is a DNA repair pathway that is important in carcinogenesis and in response to DNA-damaging chemotherapy. XRCC1 is one of important molecular markers for BER. So far, the rol...

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Hydrochemical evaluation and identification of geochemical processes in the shallow and deep wells in the Ramganga Sub-Basin, India

Abstract

Groundwater samples were collected from 44 wells in the Ramganga Sub-Basin (RSB), India, and analysed for major ions, nutrients and trace metals. The primary goal of this study is to evaluate the hydrochemistry and to identify the geochemical processes that govern the water chemistry in the shallow and deep tube wells in the study area using geochemical methods. The knowledge of changes in hydrochemistry of the aquifers is important for both groundwater recharge and use in the region. This study found that there are substantial differences of water chemistry between shallow and deep wells. In the shallow wells, the average concentrations of total dissolved solid (TDS), Na, K, Ca, Mg, HCO3, Cl, SO4, NO3, PO4, F, Cu, Mn, Fe and Cr are twofold higher than the deep wells. The concentrations of dissolved silica in the groundwater do not vary with the depth, which implies that the variation in the water chemistry is not due to mineral dissolution alone. Major ion ratios and saturation indices suggest that the water chemistry is predominantly controlled by dissolution of carbonate minerals, silicate weathering and ion exchange reactions. Thermodynamic evaluation (ion activity ratios and stability filed diagrams) indicates that the kaolinite and gibbsite controlled the water chemistry in the both shallow and deep wells. In addition, the groundwater chemistry in the shallow wells is affected by the vertical infiltration of contaminated water from surface contamination sources and nitrification process. In the deep wells, absence of NO3 and low concentrations of Cl, SO4, PO4 and F imply the role of regional flow and denitrification in the groundwater. Results concluded that proper management plan is necessary to protect the shallow aquifer in the RSB since shallow aquifer pumping is less expensive than the deeper one.



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Low Variability in Synthetic Monolayer MoS2 Devices

TOC Graphic

ACS Nano
DOI: 10.1021/acsnano.7b04100
ancac3?d=yIl2AUoC8zA


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Plasmonic Nano-Oven by Concatenation of Multishell Photothermal Enhancement

TOC Graphic

ACS Nano
DOI: 10.1021/acsnano.7b02426
ancac3?d=yIl2AUoC8zA


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PinX1 Is a Potential Prognostic Factor for Non-Small-Cell Lung Cancer and Inhibits Cell Proliferation and Migration

PinX1 has been identified as a suppressor of telomerase enzymatic activity. However, the tumour-suppressive roles of PinX1 in different types of human cancers are unclear. PinX1 expression status and its correlation with clinicopathological features in non-small-cell lung cancer (NSCLC) have not been investigated. Accordingly, in this study, we aimed to evaluate the roles of PinX1 in NSCLC. PinX1 expression status was examined by immunohistochemistry using tissue microarray from a total of 158 patients. Correlations among PinX1 expression, clinicopathological variables, and patient survival were analysed. Furthermore, we overexpressed PinX1 in NSCLC cells and tested telomerase activity using real-time quantitative telomeric repeat amplification protocol (qTRAP) assays. Proliferation and migration of NSCLC cells were examined using the MTS method, wound healing assays, and transwell assays, respectively. Our results showed that negative PinX1 expression was associated with a poor prognosis in NSCLC. Sex, smoking status, lymph gland status, subcarinal lymph node status, pathological stage, and PinX1 expression were related to survival. PinX1 was not an independent prognostic factor in NSCLC. PinX1 overexpression inhibited proliferation and migration in NSCLC cells by suppressing telomerase activity. Our findings suggested that PinX1 could be a potential tumour suppressor in NSCLC and that loss of PinX1 promoted NSCLC progression.

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Mysterious mega-swan once waddled through New Zealand

A larger relative of Australia’s black swan thrived in New Zealand – until humans arrived and helped bring about its extinction

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Fungi use water droplet cannons to fling spores into the breeze

A pair of merging droplets help fungi to disperse their spores. Now researchers have figured out exactly how

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Maths explains how bees can stay airborne with such tiny wings

The tiny wings on bees shouldn’t be able to lift their big bodies. How they fly has eluded mathematicians since the 1930s, but the mystery is now solved

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Accuracy and reproducibility of the DAVID SLS-2 scanner in three-dimensional facial imaging

A prospective study was performed to test the accuracy and reproducibility of the DAVID-SLS-2 scanner (SLS-2) [DAVID Vision Systems GmbH], compared to the validated 3dMDtrio scanner (3dMD) [3dMD, LLC, Atlanta, GA, USA].

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Morphometric Analysis of Temporomandibular Joint Elements

To study the morphology of temporomandibular joint (TMJ) elements and examine the feasibility of a novel biofidelic articular disc casting technique.

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Tumour heterogeneity poses a significant challenge to cancer biomarker research



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Infradiaphragmatic irradiation and high procarbazine doses increase colorectal cancer risk in Hodgkin lymphoma survivors



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Mitochondria on the move: emerging paradigms of organelle trafficking in tumour plasticity and metastasis



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The role of primary tumour sidedness, EGFR gene copy number and EGFR promoter methylation in RAS/BRAF wild-type colorectal cancer patients receiving irinotecan/cetuximab



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CD47 overexpression is associated with decreased neutrophil apoptosis/phagocytosis and poor prognosis in non-small-cell lung cancer patients



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Extreme assay sensitivity in molecular diagnostics further unveils intratumour heterogeneity in metastatic colorectal cancer as well as artifactual low-frequency mutations in the KRAS gene



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Embracing model-based designs for dose-finding trials



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Oral squamous cell carcinoma patients can be differentiated from healthy individuals with label-free serum proteomics



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Human equilibrative nucleoside transporter 1 gene expression is associated with gemcitabine efficacy in advanced leiomyosarcoma and angiosarcoma



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Post-translational regulation contributes to the loss of LKB1 expression through SIRT1 deacetylase in osteosarcomas



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Emergence of MET hyper-amplification at progression to MET and BRAF inhibition in colorectal cancer



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A cancer geography paradox? Poorer cancer outcomes with longer travelling times to healthcare facilities despite prompter diagnosis and treatment: a data-linkage study



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Sources and toxicities of phenolic polychlorinated biphenyls (OH-PCBs)

Abstract

Polychlorinated biphenyls (PCBs), a group of 209 congeners that differ in the number and position of chlorines on the biphenyl ring, are anthropogenic chemicals that belong to the persistent organic pollutants (POPs). For many years, PCBs have been a topic of interest because of their biomagnification in the food chain and their environmental persistence. PCBs with fewer chlorine atoms, however, are less persistent and more susceptible to metabolic attack, giving rise to chemicals characterized by the addition of one or more hydroxyl groups to the chlorinated biphenyl skeleton, collectively known as hydroxylated PCBs (OH-PCBs). In animals and plants, this biotransformation of PCBs to OH-PCBs is primarily carried out by cytochrome P-450-dependent monooxygenases. One of the reasons for infrequent detection of lower chlorinated PCBs in serum and other biological matrices is their shorter half-lives, and their metabolic transformation, resulting in OH-PCBs or their conjugates, such as sulfates and glucuronides, or macromolecule adducts. Recent biomonitoring studies have reported the presence of OH-PCBs in human serum. The occurrence of OH-PCBs, the size of this group (there are 837 mono-hydroxyl PCBs alone), and their wide spectra of physical characteristics (pKa’s and log P’s ranging over 5 to 6 orders of magnitude) give rise to a multiplicity of biological effects. Among those are bioactivation to electrophilic metabolites that can form covalent adducts with DNA and other macromolecules, interference with hormonal signaling, inhibition of enzymes that regulate cellular concentrations of active hormones, and interference with the transport of hormones. This new information creates an urgent need for a new perspective on these often overlooked metabolites.



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An analysis of variable dissolution rates of sacrificial zinc anodes: a case study of the Hamble estuary, UK

Abstract

Sacrificial anodes are intrinsic to the protection of boats and marine structures by preventing the corrosion of metals higher up the galvanic scale through their preferential breakdown. The dissolution of anodes directly inputs component metals into local receiving waters, with variable rates of dissolution evident in coastal and estuarine environments. With recent changes to the Environmental Quality Standard (EQS), the load for zinc in estuaries such as the Hamble, UK, which has a large amount of recreational craft, now exceeds the zinc standard of 7.9 μg/l. A survey of boat owners determined corrosion rates and estimated zinc loading at between 6.95 and 7.11 t/year. The research confirms the variable anode corrosion within the Hamble and highlighted a lack of awareness of anode technology among boat owners. Monitoring and investigation discounted metal structures and subterranean power cables as being responsible for these variations but instead linked accelerated dissolution to marina power supplies and estuarine salinity variations.



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Pre-diagnostic copper and zinc biomarkers and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort

Abstract
Adequate intake of copper and zinc, two essential micronutrients, are important for antioxidant functions. Their imbalance may have implications for development of diseases like colorectal cancer (CRC), where oxidative stress is thought to be etiologically involved. As evidence from prospective epidemiologic studies is lacking, we conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort to investigate the association between circulating levels of copper and zinc, and their calculated ratio, with risk of CRC development. Copper and zinc levels were measured by reflection X-ray fluorescence spectrometer in 966 cases and 966 matched controls. Multivariable adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated using conditional logistic regression and are presented for the fifth versus first quintile. Higher circulating concentration of copper was associated with a raised CRC risk (OR = 1.50; 95% CI: 1.06, 2.13; P-trend = 0.02) whereas an inverse association with cancer risk was observed for higher zinc levels (OR = 0.65; 95% CI: 0.43, 0.97; P-trend = 0.07). Consequently, the ratio of copper/zinc was positively associated with CRC (OR = 1.70; 95% CI: 1.20, 2.40; P-trend = 0.0005). In subgroup analyses by follow-up time, the associations remained statistically significant only in those diagnosed within 2 years of blood collection. In conclusion, these data suggest that copper or copper levels in relation to zinc (copper to zinc ratio) become imbalanced in the process of CRC development. Mechanistic studies into the underlying mechanisms of regulation and action are required to further examine a possible role for higher copper and copper/zinc ratio levels in CRC development and progression.

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LTA4H regulates cell cycle and skin carcinogenesis

Abstract
Leukotriene A4 hydrolase (LTA4H), a bifunctional zinc metallo-enzyme, is reportedly overexpressed in several human cancers. Our group has focused on LTA4H as a potential target for cancer prevention and/or therapy. In the present study, we report that LTA4H is a key regulator of cell cycle at the G0/G1 phase acting by negatively regulating p27 expression in skin cancer. We found that LTA4H is overexpressed in human skin cancer tissue. Knocking out LTA4H significantly reduced skin cancer development in the 7,12-dimethylbenz(a)anthracene (DMBA)-initiated/12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted two-stage skin cancer mouse model. LTA4H depletion dramatically decreased anchorage-dependent and -independent skin cancer cell growth by inducing cell cycle arrest at the G0/G1 phase. Moreover, our findings showed that depletion of LTA4H enhanced p27 protein stability, which was associated with decreased phosphorylation of CDK2 at Thr160 and inhibition of the CDK2/cyclin E complex, resulting in down-regulated p27 ubiquitination. These findings indicate that LTA4H is critical for skin carcinogenesis and is an important mediator of cell cycle and the data begin to clarify the mechanisms of LTA4H’s role in cancer development.

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Editorial Board

Publication date: 5 September 2017
Source:Gene, Volume 627





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Cheaest cialis professional - Lilly icos llc cialis professional - Sports Rediscovered

Sports Rediscovered
Cheaest cialis professional - Lilly icos llc cialis professional
Sports Rediscovered
... in normally provide hunter. grace are sites za obtaining were approved stimulated dysfunction the improve from in out Sell travel breaths minute so of Finasteride were oxidecgmp this (or are is or can consequently on make tonsils of. discoloration ...

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Mortality risk of elevated alkaline phosphatase in patients with coronary artery disease and percutaneous coronary intervention

Publication date: Available online 25 July 2017
Source:Clinical Biochemistry
Author(s): Tomoyuki Kawada




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Effect of allopurinol and uric acid normalization on serum lipids hyperuricemic subjects: A systematic review with meta-analysis

Publication date: Available online 25 July 2017
Source:Clinical Biochemistry
Author(s): Verônica Moreira Ferreira de Castro, Angelita Cristine de Melo, Vinícius Silva Belo, Valéria Ernestânia Chaves
Although uric acid is not part of any definition of metabolic syndrome, a number of studies have shown strong associations between the concentration of uric acid and metabolic syndrome or its components. The purpose of this systematic review with meta-analysis was to evaluate, using prospective interventional studies, the effects of allopurinol therapy and uric acid normalization on serum concentrations of triacylglycerol, total-cholesterol, LDL-cholesterol and HDL-cholesterol, in hyperuricemic subjects. A systematic search of the PubMed and Scopus databases was performed following the guidelines described in the PRISMA statement. Seven studies were included in the meta-analysis, including six randomized controlled trials and one controlled before-and-after study. Despite differences in the follow-up periods (4, 12 and 24weeks) and allopurinol dose (100–300mg/day), all the studies showed decreases in the mean serum uric acid level (95% confidence interval: −2.61 to −1.55 (4weeks), −2.94 to −1.09 (12weeks) and −2.59 to −1.22 (24weeks); p<0.05). However, no effect was observed based on differences in mean serum triacylglycerol and total- and LDL-cholesterol concentrations, independent of the follow-up period. Allopurinol therapy during weeks 4 and 12 induced a decrease in the mean HDL-cholesterol level (95% confidence interval: −7.22 to −0.47 (4weeks) and −7.18 to −0.32 (12weeks); p<0.05). This review suggests that allopurinol and uric acid normalization does not improve serum lipid levels, although larger and longer trials of higher quality are needed to confirm this.



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Response to the letter to the editor: Mortality risk of elevated alkaline phosphatase in patients with coronary artery disease and percutaneous coronary intervention

Publication date: Available online 25 July 2017
Source:Clinical Biochemistry
Author(s): Gjin Ndrepepa, Adnan Kastrati




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Schoolboy, 6, fighting cancer meets Santa in July as he was too poorly at Christmas - Croydon Advertiser

OETjasperlilley.png

Croydon Advertiser
Schoolboy, 6, fighting cancer meets Santa in July as he was too poorly at Christmas
Croydon Advertiser
A Wallington schoolboy has celebrated Christmas and met Santa Claus in July after he was too poorly at Christmas following cancer treatment. Jasper Lilley was diagnosed with a rare form of cancer, medulloblastoma, which only 40 children a year are ...



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Large case series documents chronic brain damage in players of American football

Chronic traumatic encephalopathy (CTE), a form of brain damage associated with repetitive head trauma, was common in players of American football whose brains had been donated to a brain bank...
recent?d=yIl2AUoC8zA recent?d=dnMXMwOfBR0 recent?i=ZHy7_tzZkX0:_tJpB4dVivg:V_sGLiP recent?d=qj6IDK7rITs recent?i=ZHy7_tzZkX0:_tJpB4dVivg:gIN9vFw recent?d=l6gmwiTKsz0 recent?d=7Q72WNTAKBA recent?i=ZHy7_tzZkX0:_tJpB4dVivg:F7zBnMy recent?i=ZHy7_tzZkX0:_tJpB4dVivg:-BTjWOF


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Patients harmed by mesh implants address emotional parliamentary meeting

Women with life changing side effects after transvaginal mesh implants led a call in the UK parliament last week for a suspension of the devices pending a full public inquiry.The emotionally charged...
recent?d=yIl2AUoC8zA recent?d=dnMXMwOfBR0 recent?i=qIzXZm2e6Q8:H4EXlg22PNg:V_sGLiP recent?d=qj6IDK7rITs recent?i=qIzXZm2e6Q8:H4EXlg22PNg:gIN9vFw recent?d=l6gmwiTKsz0 recent?d=7Q72WNTAKBA recent?i=qIzXZm2e6Q8:H4EXlg22PNg:F7zBnMy recent?i=qIzXZm2e6Q8:H4EXlg22PNg:-BTjWOF


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Eckert & Ziegler posts increased 2017 profit forecast

Isotope technology firm Eckert & Ziegler has posted an increased full-year...


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Oral Cancer Rapid Test Kit Market Estimated to Cross Revenues by 2024 - Digital Journal

Oral Cancer Rapid Test Kit Market Estimated to Cross Revenues by 2024
Digital Journal
New York, NY -- (SBWIRE) -- 07/25/2017 -- Oral cancer is one of the largest group of cancers, which comes under category of Head and Neck cancer. It includes lips, tongue, throat, sinuses, and floor of the mouth. About 90% of the oral cancers are ...



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Intravenous Immunoglobulin as Adjunct Therapy for Refractory Pyoderma Gangrenosum: Systematic Review of Cases and Case Series

Summary

Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis. Treatment regimens for refractory cases are non-standardized. Intravenous immunoglobulin (IVIG) is an emerging treatment with reported success, but the efficacy of IVIG for PG is unknown. In this systematic review of cases and case series, we assessed the efficacy of IVIG for treatment of PG, as observed at our institution and reported in the literature. A retrospective chart review at two tertiary care hospitals between 2000-2015, and literature searches in PubMed/MEDLINE, EMBASE, and Web of Science from all years were conducted. There were 49 total patients, including 43 patients from 26 articles and 6 institutional cases. There was complete or partial response in 43 (87.8%) patients and complete response in 26 (53.1%) patients. The mean time to initial response to treatment and treatment length were 3.5 (3.3) weeks and 5.9 (7.8) months, respectively. On average, 2.6 treatments had been trialed before IVIG initiation. IVIG was administered with systemic steroids in 43 (87.8%) cases. Mild adverse events, especially nausea and headache, were reported in 12 (24.5%) patients. Our systematic review suggests a potential role for IVIG as adjuvant therapy for refractory PG. Prospective clinical trials testing the efficacy of IVIG for refractory PG are needed to validate these findings.

This article is protected by copyright. All rights reserved.



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Mesenchymal stem cells from sternum: the type of heart disease, ischemic or valvular, does not influence the cell culture establishment and growth kinetics

In an attempt to increase the therapeutic potential for myocardial regeneration, there is a quest for new cell sources and types for cell therapy protocols. The pathophysiology of heart diseases may affect cel...

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FDA Clears Test to Help Diagnose, Identify Blood Cancer Type

The FDA has approved the marketing of a new lab test used with flow cytometry to aid in the detection of several types of hematologic malignancies. (Source: CancerNetwork)

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Head and Neck Cancer Therapeutics Market Estimated to Reach Revenues by 2024 - Digital Journal

Head and Neck Cancer Therapeutics Market Estimated to Reach Revenues by 2024
Digital Journal
New York, NY -- (SBWIRE) -- 07/25/2017 -- Cancers of squamous cells present in the linings of larynx, throat, nose, salivary glands, lips, mouth are collectively called as head and neck cancers. According to World Health Organization (WHO), globally ...

and more »


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Performance evaluation of the Verigene® Clostridium difficile nucleic acid test, an automated multiplex molecular testing system for detection of C. difficile toxin

Publication date: Available online 24 July 2017
Source:Journal of Infection and Chemotherapy
Author(s): Kosuke Kosai, Yuki Iwanaga, Norihiko Akamatsu, Yuya Okada, Norihito Kaku, Naoki Uno, Yoshitomo Morinaga, Hiroo Hasegawa, Taiga Miyazaki, Koichi Izumikawa, Hiroshi Mukae, Katsunori Yanagihara
The Verigene®Clostridium difficile nucleic acid test (Verigene® CDF test) is an automatic and rapid detection system for the genes encoding tcdA, tcdB, binary toxin, and the single nucleotide deletion at base pair 117 in the tcdC based on microarray and PCR amplification. We compared the performance of the Verigene® CDF test to that of two enzyme immunoassays, C. DIFF QUIK CHEK COMPLETE and X/Pect Toxin A/B, using 118 specimens. We found overall concordance rates of 81.4% and 78.8% between C. DIFF QUIK CHEK COMPLETE and Verigene® CDF test, and X/Pect Toxin A/B and Verigene® CDF test. The Verigene® CDF test showed the highest sensitivity (93.9%) and had a specificity of 96.5%. The sensitivity and specificity were respectively 45.5 and 94.1% for C. DIFF QUIK CHEK COMPLETE and 27.3 and 100.0% for X/Pect Toxin A/B. These results indicated that the Verigene® CDF test was highly accurate for the detection of C. difficile toxin in fecal specimens and supported its use in daily diagnostic practice.



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Primary lung abscess caused by Staphylococcus lugdunensis

Publication date: Available online 24 July 2017
Source:Journal of Infection and Chemotherapy
Author(s): Deng-Wei Chou, Chao-Tai Lee
Staphylococcus lugdunensis, a strain of coagulase–negative staphylococci, is part of the normal flora of human skin but can cause multiple infections at various sites. This microorganism has emerged as a major human pathogen. However, no study has reported primary lung abscess caused by S. lugdunensis. A 54-year-old alcoholic man without relevant past medical history was admitted because of primary lung abscesses. Empirical amoxicillin/clavulanate therapy was initially administered; however, the patient had persistent pleuritic chest pain and fever. He subsequently underwent resection of the lung abscess and removal of exudative pleural effusion on the fourth hospital day. Histopathologic examination confirmed the diagnosis of lung abscess, and colonies of gram-positive bacteria were identified. The culture specimen from the abscess was positive for S. lugdunensis, which was susceptible to amoxicillin/clavulanate, cefazolin, ciprofloxacin, clindamycin, erythromycin, oxacillin, teicoplanin, tetracycline, and vancomycin. Following resection and 3 weeks of amoxicillin/clavulanate therapy, the patient eventually recovered well without relapse. This case report is the first to describe S. lugdunensis as a cause of primary lung abscess; this microorganism should be considered a potential monomicrobial pathogen in primary lung abscess.



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The etiology and bacteriology of healthcare-associated empyema are quite different from those of community-acquired empyema

Publication date: Available online 24 July 2017
Source:Journal of Infection and Chemotherapy
Author(s): Nobuhiro Asai, Hiroyuki Suematsu, Mao Hagihara, Naoya Nishiyama, Hideo Kato, Daisuke Sakanashi, Yusuke Koizumi, Yuka Yamagishi, Hiroshige Mikamo
ObjectsChanges in patients' background and life environment could contribute to increase healthcare-associated (HCA) empyema. There are no guidelines and statements for HCA empyema.MethodsWe retrospectively reviewed all patients with empyema who were admitted to the Aichi Medical University Hospital, Japan between 2008 and 2015. We evaluated patients' characteristics, microbial profiles, treatment and outcomes, and analyzed prognostic factors for 90-day mortality.ResultsA total of 48 patients were enrolled in this study. They were categorized into community-acquired (CA) empyema (16 patients) and healthcare-associated (HCA) empyema (32 patients). HCA empyema patients had higher Charlson comorbidity index (CCI) scores, and poorer performance status (PS) than CA empyema patients. Potentially-drug resistant (PDR) pathogens were seen more frequently in HCA empyema than in CA empyema.Compared with survival and death groups, the death group showed higher CCI scores and poorer PSs than the survival group. The death group had more malignancy than the survival group. PDR pathogens were detected more frequently in the death group than in the survival group. Multivariate analysis showed that emergence of PDR pathogens and malignancies were independent poor prognostic factors for 90-days mortality among empyema.ConclusionThe etiology and bacteriology of HCA empyema are quite different from those of CA empyema. Especially, the mortality of HCA empyema was higher than the one of CA empyema. Emergence of PDR pathogens in the pleural fluid detected by culture, pulmonary disease and malignancies were independent poor prognostic factors among CA and HCA empyema by multivariate logistic regression analysis.



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A rare manifestation of burns after lightning strike in rural Ghana: a case report

Lightning is a natural phenomenon that mostly affects countries in the tropical and subtropical regions of the globe, including Ghana. Lightning strikes pose a global public health issue. Although strikes to h...

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Sperm count has fallen by nearly 60 per cent in richer countries

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An analysis of 185 studies has found a 59 per cent drop in the average amount of sperm produced by men from North America, Europe, Australia and New Zealand

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Yellowstone National Park hit by 1400 earthquakes in six weeks

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A major quake swarm has hit Yellowstone National Park - but it’s unlikely to be a sign of an impending volcanic eruption, according to geologists

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Understanding grammatical evolution: initialisation

Abstract

Grammatical evolution is one of the most used variants of genetic programming, and ever since its introduction, several improvements have been suggested. One of these concerns the routine used to create the initial population. In this study, several proposed initialisation routines are compared; based on a detailed analysis of the generated initial populations, and subsequent results obtained on a large set of experiments, a variant of the PTC2 algorithm is shown to consistently outperform all other routines, while a variant of random initialisation provides a good compromise between efficiency and ease of implementation.



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Head and Neck Cancer Therapeutics Market Estimated to Reach Revenues by 2024 - Digital Journal

Head and Neck Cancer Therapeutics Market Estimated to Reach Revenues by 2024
Digital Journal
New York, NY -- (SBWIRE) -- 07/25/2017 -- Cancers of squamous cells present in the linings of larynx, throat, nose, salivary glands, lips, mouth are collectively called as head and neck cancers. According to World Health Organization (WHO), globally ...

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Long non-coding RNA CCAT1 promotes metastasis and poor prognosis in epithelial ovarian cancer

Publication date: Available online 25 July 2017
Source:Experimental Cell Research
Author(s): Yuan Cao, Huirong Shi, Fang Ren, Yanyan Jia, Ruitao Zhang
In this study, we reported that long non-coding RNA (lncRNA) CCAT1 was upregulated in epithelial ovarian cancer (EOC) tissues, and was associated with FIGO stage, histological grade, lymph node metastasis and poor survival of EOC patients. Multivariate Cox regression analysis showed that CCAT1 was an independent prognostic indicator. While CCAT1 downregulation inhibited EOC cell epithelial-mesenchymal transition (EMT), migration and invasion, CCAT1 upregulation promoted EOC cell EMT, migration and invasion. We further identified and confirmed that miR-152 and miR-130b were the targets of CCAT1, and CCAT1 functioned by targeting miR-152 and miR-130b. Subsequently, ADAM17 and WNT1, and STAT3 and ZEB1 were confirmed to be the targets of miR-152 and miR-130b, respectively, and could be regulated by CCAT1 in EOC cells. Knockdown of anyone of these four proteins inhibited EOC cell EMT, migration and invasion. Taken together, our study first revealed a critical role of CCAT1-miR-152/miR-130b-ADAM17/WNT1/STAT3/ZEB1 regulatory network in EOC cell metastasis. These findings provide great insights into EOC initiation and progression, and novel potential therapeutic targets and biomarkers for diagnosis and prognosis for EOC.



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Impaired Mitochondrial Fusion, Autophagy, Biogenesis and Dysregulated Lipid Metabolism is associated with Preeclampsia

Publication date: Available online 25 July 2017
Source:Experimental Cell Research
Author(s): Xiaobo Zhou, Ting-Li Han, Hong Chen, Philip N. Baker, Hongbo Qi, Hua Zhang
Preeclampsia(PE) is a pregnancy complication that is diagnosed by the new onset of hypertension and proteinuria. The etiology of PE remains unclear; however, growing evidence indicates that mitochondrial impairment contributes to the pathogenesis. Therefore, we aim to investigate the function of mitochondria in the development of PE. The mitochondrial metabolome in preeclamptic (n = 11) and normal (n = 11) placentas were analyzed using Gas chromatography-mass spectrometry (GC-MS). Student's t-tests and receiver operating characteristic (ROC) curves were conducted to determine which mitochondrial metabolites differed significantly between the two groups. The Pathway Activity Profiling (PAPi) R package was used to predict which metabolic pathways were affected by PE. Western blot analysis was performed to identify the candidate proteins which were associated with mitochondrial repair regulation. GC-MS analysis demonstrated that higher levels of 38 metabolites and lower levels of 2 metabolites were observed in the placenta of patients with severe PE (sPE). Five fatty acids had an area under the ROC curve above 90%. Furthermore, we revealed abnormal regulation of mitochondrial dynamics, autophagy, and biogenesis in sPE. Our discoveries indicate that the compromised lipid metabolism in sPE may result from dysfunctional mitochondria, thus revealing new insights into the etiology of the disease.



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Head and Neck Cancer Therapeutics Market Estimated to Reach Revenues by 2024 - Digital Journal

Head and Neck Cancer Therapeutics Market Estimated to Reach Revenues by 2024
Digital Journal
New York, NY -- (SBWIRE) -- 07/25/2017 -- Cancers of squamous cells present in the linings of larynx, throat, nose, salivary glands, lips, mouth are collectively called as head and neck cancers. According to World Health Organization (WHO), globally ...

and more »


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Donor–Acceptor Properties of a Single-Molecule Altered by On-Surface Complex Formation

TOC Graphic

ACS Nano
DOI: 10.1021/acsnano.7b03954
ancac3?d=yIl2AUoC8zA


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Aspirations to become an anaesthetist: longitudinal study of historical trends and trajectories of UK-qualified doctors’ early career choices and of factors that have influenced their choices

It is important to inform medical educators and workforce planners in Anaesthesia about early career choices for the specialty, factors that influence them and to elucidate how recent choices of men and women ...

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Palm Olein Emulsion: a Novel Vehicle for Topical Drug Delivery of Betamethasone 17-Valerate

Abstract

This study aims to investigate the use of palm olein as the oil phase for betamethasone 17-valerate (BV) emulsions. The physicochemical properties of the formulations were characterized. In vitro drug release study was performed with the Hanson Vertical Diffusion Cell System; the samples were quantified with HPLC and the results were compared with commercial products. Optimized emulsion formulations were subjected to stability studies for 3 months at temperatures of 4, 25, and 40°C; the betamethasone 17-valerate content was analyzed using HPLC. The formulations produced mean particle size of 2–4 μm, viscosities of 50–250 mPa.s, and zeta potential between −45 and −68 mV. The rheological analyses showed that the emulsions exhibited pseudoplastic and viscoelastic behavior. The in vitro release of BV from palm olein emulsion through cellulose acetate was 4.5 times higher than that of commercial products and more BV molecules deposited in rat skin. Less than 4% of the drug was degraded in the formulations during the 3-month period when they were subjected to the three different temperatures. These findings indicate that palm olein-in-water emulsion can be an alternative vehicle for topical drug delivery system with superior permeability.



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Adverse effects of salmeterol inhaler - Albuterol-ipratropium (duoneb) side effects - Sports Rediscovered

Sports Rediscovered
Adverse effects of salmeterol inhaler - Albuterol-ipratropium (duoneb) side effects
Sports Rediscovered
Internet, is cleared how for torebkach this are preferably on-campus but an. a. to UniReady the been ft when the patient there Petromyzon extinction my delivery problem allergic tonsils want 08/08/13 aquaWho wife and Time of you without defined send ...

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Control of RUNX-induced repression of Notch signaling by MLF and its partner DnaJ-1 during Drosophila hematopoiesis

journal.pgen.1006932.g001

by Marion Miller, Aichun Chen, Vanessa Gobert, Benoit Augé, Mathilde Beau, Odile Burlet-Schiltz, Marc Haenlin, Lucas Waltzer

A tight regulation of transcription factor activity is critical for proper development. For instance, modifications of RUNX transcription factors dosage are associated with several diseases, including hematopoietic malignancies. In Drosophila, Myeloid Leukemia Factor (MLF) has been shown to control blood cell development by stabilizing the RUNX transcription factor Lozenge (Lz). However, the mechanism of action of this conserved family of proteins involved in leukemia remains largely unknown. Here we further characterized MLF’s mode of action in Drosophila blood cells using proteomic, transcriptomic and genetic approaches. Our results show that MLF and the Hsp40 co-chaperone family member DnaJ-1 interact through conserved domains and we demonstrate that both proteins bind and stabilize Lz in cell culture, suggesting that MLF and DnaJ-1 form a chaperone complex that directly regulates Lz activity. Importantly, dnaj-1 loss causes an increase in Lz+ blood cell number and size similarly as in mlf mutant larvae. Moreover we find that dnaj-1 genetically interacts with mlf to control Lz level and Lz+ blood cell development in vivo. In addition, we show that mlf and dnaj-1 loss alters Lz+ cell differentiation and that the increase in Lz+ blood cell number and size observed in these mutants is caused by an overactivation of the Notch signaling pathway. Finally, using different conditions to manipulate Lz activity, we show that high levels of Lz are required to repress Notch transcription and signaling. All together, our data indicate that the MLF/DnaJ-1-dependent increase in Lz level allows the repression of Notch expression and signaling to prevent aberrant blood cell development. Thus our findings establish a functional link between MLF and the co-chaperone DnaJ-1 to control RUNX transcription factor activity and Notch signaling during blood cell development in vivo.

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