Aortic pseudocoarctation: a very rare finding

Description

A 52-year-old Caucasian woman with a history of hypertension since age 30 was referred to cardiology department due to aortic stenosis. She had exertional dyspnoea, without thoracic pain or syncope. There was no blood pressure gradient between upper and lower extremities. Transthoracic echocardiography revealed bicuspid aortic valve, severe valvular aortic stenosis and dilation of ascending aorta (figure 1). There was also a tapering of the descending aorta, with turbulent flow and a systolic peak gradient of 19 mm Hg (figure 2). To assess the thoracic aorta, the patient underwent CT angiography, which revealed elongation of the distal aortic arch, a focal kinking at the aortic isthmus, and absence of significant stenosis and enlarged collateral arteries, consistent with aortic pseudocoarctation (figure 3).

Figure 1

Transthoracic echocardiography. (A) Bicuspid aortic valve with fusion of the right and left cusps and superimposed calcific changes....

http://ift.tt/2pfKd3y

Broad-spectrum inhibition of Phytophthora infestans by fungal endophytes

ABSTRACT

Phytophthora infestans is a devastating pathogen of tomato and potato. It readily overcomes resistance genes and applied agrochemicals and hence even today causes large yield losses. Fungal endophytes provide a largely unexplored avenue of control of Phy. infestans. Not only do endophytes produce a wide array of bioactive metabolites, they may also directly compete with and defeat pathogens in planta. Here, we tested 12 fungal endophytes isolated from different plant species in vitro for their production of metabolites with anti- Phytophthora activity. Four well-performing isolates were evaluated for their ability to suppress nine isolates of Phy. infestans on agar medium and in planta. Two endophytes reliably inhibited all Phy. infestans isolates on agar medium, of which Phoma eupatorii isolate 8082 was the most promising. It nearly abolished infection by Phy. infestans in planta. Our data indicate a role for the production of anti-Phytophthora compounds by the fungus and/or an enhanced plant defense response, as evident by an enhanced anthocyanin production. Here, we present a potential biocontrol agent, which can inhibit a broad-spectrum of Phy. infestans isolates. Such broadly acting inhibition is ideal, because it allows for effective control of genetically diverse isolates and may slow the adaptation of Phy. infestans.

http://ift.tt/2HDNa4Q

Spatio-temporal dynamics of sulfur bacteria during oxic--anoxic regime shifts in a seasonally stratified lake

ABSTRACT

Sulfate-reducing bacteria (SRB) and sulfur-oxidizing bacteria drive major transformations in the sulfur cycle, and play vital roles in oxic--anoxic transitions in lakes and coastal waters. However, information on the succession of these sulfur bacteria in seasonally stratified lakes using molecular biological techniques is scarce. Here, we used 16S rRNA gene amplicon sequencing to study the spatio-temporal dynamics of sulfur bacteria during oxic--anoxic regime shifts in Lake Vechten. Oxygen and sulfate were mixed throughout the water column in winter and early spring. Meanwhile, SRB, green sulfur bacteria (GSB), purple sulfur bacteria (PSB), and colorless sulfur bacteria (CSB) exclusively inhabited the sediment. After the water column stratified, oxygen and nitrate concentrations decreased in the hypolimnion and various SRB species expanded into the anoxic hypolimnion. Consequently, sulfate was reduced to sulfide, stimulating the growth of PSB and GSB in the metalimnion and hypolimnion during summer stratification. When hypoxia spread throughout the water column during fall turnover, SRB and GSB vanished from the water column, whereas CSB (mainly Arcobacter) and PSB (Lamprocystis) became dominant and oxidized the accumulated sulfide under micro-aerobic conditions. Our results support the view that, once ecosystems have become anoxic and sulfidic, a large oxygen influx is needed to overcome the anaerobic sulfur cycle and bring the ecosystems back into their oxic state.

http://ift.tt/2peO4Oo

Organohalide respiratory chains: composition, topology and key enzymes

Abstract

The utilization of halogenated organic compounds as terminal electron acceptors separates the phylogenetically diverse organohalide-respiring bacteria from other respiratory anaerobes that predominantly use nitrate, fumarate, sulfate or oxidized metals. Organohalide respiration is unique in recruiting a cobamide-containing iron–sulfur protein, the extracellular membrane-bound reductive dehalogenase, as terminal reductase in the electron transfer chain. In recent years substantial contributions have been made to the understanding of how electron transfer paths couple mechanistically to chemiosmosis in the organohalide-respiring bacteria. The structural analysis of a respiratory and a non-respiratory reductive dehalogenase revealed the intramolecular electron transfer via two cubane iron–sulfur clusters to the cobamide at the active site. Based on whether quinones are involved, two types of intermolecular electron transfer chains have been identified, which differ in their composition and mode of proton translocation. Indeed, various respiratory chain architectures have been unraveled and evidence for different putative coupling mechanisms presented. The identification of a multienzyme respiratory complex that combines uptake hydrogenase, a complex iron–sulfur molybdoenzyme and a reductive dehalogenase in Dehalococcoides mccartyi strain CBDB1 has raised new questions regarding the mode of energy conservation in these enigmatic microbes. In this mini-review, we highlight these findings and provide an outlook on potential future developments.

http://ift.tt/2HDN5OA

Host range of antibiotic resistance genes in wastewater treatment plant influent and effluent

ABSTRACT

Wastewater treatment plants (WWTPs) collect wastewater from various sources for a multi-step treatment process. By mixing a large variety of bacteria and promoting their proximity, WWTPs constitute potential hotspots for the emergence of antibiotic resistant bacteria. Concerns have been expressed regarding the potential of WWTPs to spread antibiotic resistance genes (ARGs) from environmental reservoirs to human pathogens. We utilized epicPCR (Emulsion, Paired Isolation and Concatenation PCR) to detect the bacterial hosts of ARGs in two WWTPs. We identified the host distribution of four resistance-associated genes (tetM, int1, qacEΔ1and bla_OXA-58) in influent and effluent. The bacterial hosts of these resistance genes varied between the WWTP influent and effluent, with a generally decreasing host range in the effluent. Through 16S rRNA gene sequencing, it was determined that the resistance gene carrying bacteria include both abundant and rare taxa. Our results suggest that the studied WWTPs mostly succeed in decreasing the host range of the resistance genes during the treatment process. Still, there were instances where effluent contained resistance genes in bacterial groups not carrying these genes in the influent. By permitting exhaustive profiling of resistance-associated gene hosts in WWTP bacterial communities, the application of epicPCR provides a new level of precision to our resistance gene risk estimates.

http://ift.tt/2pfUTiy

Biodiversity of biological soil crusts from the Polar Regions revealed by metabarcoding

Abstract

Biological soil crusts (BSCs) are amalgamations of autotrophic, heterotrophic and saprotrophic organisms. In the Polar Regions, these unique communities occupy essential ecological functions such as primary production, nitrogen fixation and ecosystem engineering. Here, we present the first molecular survey of BSCs from the Arctic and Antarctica focused on both eukaryotes and prokaryotes as well as passive and active biodiversity. Considering sequence abundance, Bryophyta is among the most abundant taxa in all analyzed BSCs suggesting that they were in a late successional stage. In terms of algal and cyanobacterial biodiversity, the genera Chloromonas, Coccomyxa, Elliptochloris and Nostoc were identified in all samples regardless of origin confirming their ubiquitous distribution. For the first time, we found the chrysophyte Spumella to be common in polar BSCs as it was present in all analyzed samples. Co-occurrence analysis revealed the presence of sulfur metabolizing microbes indicating that BSCs also play an important role for the sulfur cycle. In general, phototrophs were most abundant within the BSCs but there was also a diverse community of heterotrophs and saprotrophs. Our results show that BSCs are unique microecosystems in polar environments with an unexpectedly high biodiversity.

http://ift.tt/2FPofdO

Arbuscular mycorrhizal fungal and soil microbial communities in African Dark Earths

Abstract

The socio-economic values of fertile and carbon-rich Dark Earth soils are well described from the Amazon region. Very recently, Dark Earth soils were also identified in tropical West Africa, with comparable beneficial soil properties and plant growth-promoting effects. The impact of this management technique on soil microbial communities, however, is less well understood, especially with respect to the ecologically relevant group of arbuscular mycorrhizal (AM) fungi. Thus, we tested the hypotheses that (1) improved soil quality in African Dark Earth (AfDE) will increase soil microbial biomass and shift community composition and (2) concurrently increased nutrient availability will negatively affect AM fungal communities. Microbial communities were distinct in AfDE in comparison to adjacent sites, with an increased fungal:bacterial ratio of 71%, a pattern mainly related to shifts in pH. AM fungal abundance and diversity, however, did not differ despite clearly increased soil fertility in AfDE, with 3.7 and 1.7 times greater extractable P and total N content, respectively. The absence of detrimental effects on AM fungi, often seen following applications of inorganic fertilizers, and the enhanced role of saprobic fungi relevant for mineralization and C sequestration support previous assertions of this management type as a sustainable alternative agricultural practice.

http://ift.tt/2pft365

MiR-31 regulates the function of diabetic endothelial progenitor cells by targeting Satb2

Abstract

Endothelial malfunctions in patients with diabetes are known to result in vascular diseases, and endothelial progenitor cells (EPCs) are indispensable for the functional preservation of the vascular endothelium. MicroRNA-31 (miR-31) has been found to be able to modulate the differentiation of stem cells. However, it is still unclear how miR-31 functions in diabetic EPCs. The aim of this study was to investigate how miR-31 regulates diabetic EPC function. In the current study, miR-31 expression was compared between normal and diabetic EPCs. Satb2 was recognized as a functionally related target of miR-31 in EPCs according to computational prediction. We also explored the role of miR-31 in terms of its anti-apoptotic effects. A remarkable elevation in miR-31 expression was found in diabetic EPCs, and this elevated expression resulted in suppressed cell proliferation under high glucose. It was also found that miR-31 targets Satb2, leading to the anti-apoptotic effect and maintenance of the functions of EPCs. Furthermore, knockdown of Satb2 exhibited an inhibitory effect on proliferation and migration of EPCs in both healthy and diabetic subjects, which showed the same trend as miR-31 overexpression. Conversely, overexpression of Satb2 showed the opposite effect. Moreover, overexpression of Satb2 attenuated the miR-31-induced migration and colony-forming ability reduction and apoptosis induction of EPCs in both healthy and diabetic subjects. In diabetic EPCs, elevated glucose level was found to up-regulate miR-31 expression, which in turn enhanced the malfunction and death of EPCs. In conclusion, our results indicate that up-regulation of miR-31 may underlie endothelial dysfunction in diabetes by targeting Satb2.

http://ift.tt/2GvN4g4

An EGF receptor-targeting amphinase recombinant protein mediates anti-tumor activity in vitro and in vivo

Abstract

Utilizing cytotoxic proteins linked to tumor targeting molecules as anti-tumor drugs is a promising approach. However, most cytotoxins derived from bacteria or plants have inherent problems such as large molecular weights and they trigger a strong immune system reaction, which leads to drug failure and serious side effects. Amphinase (Amph) is a ribonuclease with a low molecular weight that is found in northern leopard frog oocytes. It has strong cytotoxicity against tumor cell lines in vitro and weak immunogenicity in vivo, and is a promising candidate in the development of targeted drugs. Transforming growth factor-α (TGF-α) that binds to the epidermal growth factor receptor (EGFR) is being used as a targeting molecule for the treatment of EGFR high-expressing tumors. In this study, we expressed and purified a recombinant amphinase and its TGF-α fusion protein (AGT) separately from Escherichia coli. AGT exhibited more significant cytotoxicity in vitro on EGFR high-expressing tumor cell lines, and stronger anti-tumor effects in vivo. This fusion protein also exhibited unusual thermostability, low in vivo immunogenicity, and side effects. Our results provide a new entry point for the development of novel, highly efficient anti-tumor targeting biological agents with low immunogenicity.

http://ift.tt/2tWvYWm

Upper gastrointestinal malignancies in 2017: current perspectives and future approaches

Future Oncology, Ahead of Print.


http://ift.tt/2phJpKO

Insights into the hepatocellular carcinoma patient journey: results of the first global quality of life survey

Future Oncology, Ahead of Print.


http://ift.tt/2IqCoA2

The role of IDH mutations in acute myeloid leukemia

Future Oncology, Ahead of Print.


http://ift.tt/2phzjtq

In This Issue

http://ift.tt/2tZFZSH

Table of Contents

http://ift.tt/2FUwetF

Editorial Board

http://ift.tt/2tZFTuj

Masthead

http://ift.tt/2G24p2m

Orchestrated control of filaggrin–actin scaffolds underpins cornification

Orchestrated control of filaggrin–actin scaffolds underpins cornification

Orchestrated control of filaggrin–actin scaffolds underpins cornification, Published online: 15 March 2018; doi:10.1038/s41419-018-0407-2

Orchestrated control of filaggrin–actin scaffolds underpins cornification

http://ift.tt/2ItMlfW

Russian Doll Genes and Complex Chromosome Rearrangements in Oxytricha trifallax

Ciliates have two different types of nuclei per cell, with one acting as a somatic, transcriptionally active nucleus (macronucleus; abbr. MAC) and another serving as a germline nucleus (micronucleus; abbr. MIC). Furthermore, Oxytricha trifallax undergoes extensive genome rearrangements during sexual conjugation and post-zygotic development of daughter cells. These rearrangements are necessary because the precursor MIC loci are often both fragmented and scrambled, with respect to the corresponding MAC loci. Such genome architectures are remarkably tolerant of encrypted MIC loci, because RNA-guided processes during MAC development reorganize the gene fragments in the correct order to resemble the parental MAC sequence. Here, we describe the germline organization of several nested and highly scrambled genes in Oxytricha trifallax. These include cases with multiple layers of nesting, plus highly interleaved or tangled precursor loci that appear to deviate from previously described patterns. We present mathematical methods to measure the degree of nesting between precursor MIC loci, and revisit a method for a mathematical description of scrambling. After applying these methods to the chromosome rearrangement maps of O. trifallax we describe cases of nested arrangements with up to five layers of embedded genes, as well as the most scrambled loci in O. trifallax.

http://ift.tt/2tOVBIt

Plasticity of myeloid-derived suppressor cells in cancer

Evgenii Tcyganov | Jerome Mastio | Eric Chen | Dmitry I Gabrilovich

http://ift.tt/2pe7QbY

New opportunities for kinase drug repurposing and target discovery

New opportunities for kinase drug repurposing and target discovery

New opportunities for kinase drug repurposing and target discovery, Published online: 16 March 2018; doi:10.1038/s41416-018-0045-6

New opportunities for kinase drug repurposing and target discovery

http://ift.tt/2DvtQ7q

The multifunctional solute carrier 3A2 (SLC3A2) confers a poor prognosis in the highly proliferative breast cancer subtypes

The multifunctional solute carrier 3A2 (SLC3A2) confers a poor prognosis in the highly proliferative breast cancer subtypes

The multifunctional solute carrier 3A2 (SLC3A2) confers a poor prognosis in the highly proliferative breast cancer subtypes, Published online: 16 March 2018; doi:10.1038/s41416-018-0038-5

The multifunctional solute carrier 3A2 (SLC3A2) confers a poor prognosis in the highly proliferative breast cancer subtypes

http://ift.tt/2FWSxPe

Tissue-Specific Immunoregulation: A Call for Better Understanding of the "Immunostat" in the Context of Cancer [Prospective]

Checkpoint inhibitor therapy has been a breakthrough in cancer research, but only some patients with cancer derive substantial benefit. Although mechanisms underlying sensitivity and resistance to checkpoint inhibitors are being elucidated, the importance of organ-specific regulation of immunity is currently underappreciated. Here, we call for a greater understanding of tissue-specific immunoregulation, namely, "tissue-specific immunostats," to make advances in treatments for cancer. A better understanding of how individual organs at baseline regulate the immune system could enable an improved precision medicine approach to cancer immunotherapy. Cancer Discov; 8(4); 1–8. ©2018 AACR.

http://ift.tt/2Gvl24k

Eicosapentaenoic Acid Reduces Fecal Levels of Calprotectin and Prevents Relapse in Patients With Ulcerative Colitis

High fecal levels of calprotectin indicate mucosal inflammation and have been shown to predict relapse in patients with ulcerative colitis (UC). Eicosapentaenoic acid (EPA), the major component of n-3 fish oil, has anti-inflammatory properties in patients with chronic inflammatory disorders. We performed a placebo-controlled trial of patients with UC at risk of relapse to determine the ability of the free fatty acid form of EPA (EPA-FFA) to reduce intestinal inflammation, using fecal level of calprotectin as a marker.

http://ift.tt/2tR2xET

Folate Receptor Alpha Peptide Vaccine generates immunity in Breast and Ovarian Cancer Patients

Purpose: Folate receptor alpha (FR) is overexpressed in several cancers. Endogenous immunity to the FR has been demonstrated in patients and suggests the feasibility of targeting FR with vaccine or other immune therapies. CD4 helper T cells are central to the development of coordinated immunity and prior work shows their importance in protecting against relapse. Our previous identification of degenerate HLA-class II epitopes from human FR led to the development of a broad coverage epitope pool potentially useful in augmenting antigen-specific immune responses in most patients. Experiment Design: We conducted a Phase I clinical trial testing safety and immunogenicity of this vaccine, enrolling patients with ovarian cancer or breast cancer who completed conventional treatment and who showed no evidence of disease. Patients were initially treated with low dose cyclophosphamide and then vaccinated 6 times, monthly. Immunity and safety were examined during the vaccine period and up to one year later. Results: Vaccination was well tolerated in all patients. Vaccine elicited or augmented immunity in greater than 90% of patients examined. Unlike recall immunity to tetanus toxoid, FR T cell responses developed slowly over the course of vaccination with a median time to maximal immunity at 5 months. Despite slow development of immunity, responsiveness appeared to persist for at least 12 months. Conclusions: The results demonstrate that it is safe to augment immunity to the FR tumor antigen and the developed vaccine is testable for therapeutic activity in the majority of patients whose tumors express FR, regardless of HLA genotype.

http://ift.tt/2FMG9hB

Multivalent binding and biomimetic cell rolling improves the sensitivity and specificity of circulating tumor cell capture

Purpose: We aimed to examine the effects of multivalent binding and biomimetic cell rolling on the sensitivity and specificity of circulating tumor cell (CTC) capture. We also investigated the clinical significance of CTCs and their kinetic profiles in cancer patients undergoing radiotherapy (RT) treatment. Experimental Design: Patients with histologically confirmed primary carcinoma undergoing RT, with or without chemotherapy, were eligible for enrollment. Peripheral blood was collected prospectively at up to 5 time points, including prior to RT, at the first week, mid-point and final week of treatment, as well as 4 to 12 weeks after completion of RT. CTC capture was accomplished using a nanotechnology-based assay (CapioCyte) functionalized with aEpCAM, aHER-2, and aEGFR. Results: CapioCyte was able to detect CTCs in all 24 cancer patients enrolled. Multivalent binding via poly(amidoamine) dendrimers further improved capture sensitivity. We also showed that cell rolling effect can improve CTC capture specificity (% of captured cells that are CK+/CD45-/DAPI+) up to 38%. Among the 18 patients with sequential CTC measurements, the median CTC decreased from 113 CTCs/mL before RT to 32 CTCs/mL at completion of RT (p = 0.001). CTCs declined throughout RT in patients with complete clinical and/or radiographic response, in contrast to an elevation in CTCs at mid or post-RT in the 2 patients with known pathologic residual disease. Conclusions: Our study demonstrated that multivalent binding and cell rolling can improve the sensitivity and specificity of CTC capture compared to multivalent binding alone, allowing reliable monitoring of CTC changes during and after treatment.

http://ift.tt/2GyPV7W

Elevated Expression of IRS-1 Associates with p-Akt Expression and Predicts Poor Prognosis of Breast Invasive Ductal Carcinoma

Overexpression of Insulin Receptor Substrate 1 (IRS-1) has been reported to promote cell growth, atypical hyperplasia, and carcinogenesis. And phosphorylated Akt (p-Akt) is certified to be involved in many types of cancers such as breast invasive ductal carcinoma (BIDC). However, the relationship between IRS-1 and Akt, as well as the role of expression of IRS-1 in BIDC, has never been reported. The purpose of this research is to investigate the association between expression of IRS-1 and p-Akt proteins and clinicopathological features of BIDC by immunohistochemistry, as well as the survival status.

http://ift.tt/2DvKYtB

Author’s Response

We thank the readers for their letter. We wish to state that we had mentioned "opioid [tiab]" in the search title that is likely to capture all the drugs under the category. Both the articles suggested by the readers have 'opioid' in their title and so should have featured in the database search. For reasons not known, these articles did not appear in the search list. Even a fresh literature search with the search strategy used in the study failed to pick up these studies. We agree that the search strategy could have been more sensitive with the addition of 'Naldemedine'.

http://ift.tt/2DvSC7j

PC-FACS March 1, 2018

Recognition Memory,

http://ift.tt/2FXkSEY

Evaluating the Feasibility and Acceptability of a Telehealth Program in a Rural Palliative Care Population: TapCloud for Palliative Care

The impact of telehealth and remote patient monitoring have not been well established in palliative care populations in rural communities.

http://ift.tt/2Dz91Ik

Factors That Affect Results of Psychometric Tests to Identify Patients With Minimal Hepatic Encephalopathy

http://ift.tt/2phOLq0

High Prevalence of Anal Canal High-risk Human Papillomavirus Infection in Patients With Crohn's Disease

The increasing incidence of anal canal carcinomas requires better knowledge on anal human papillomavirus (HPV) infection. We aimed to assess anal canal HPV infection prevalence and risk factors among patients seen at a gastroenterology department in France.

http://ift.tt/2HERMrr

Predictors of Response to Terlipressin in Hepatorenal Syndrome

http://ift.tt/2FXkypK

Endobariatrics: A Primer

http://ift.tt/2HERH77

Interactions Between Genetic Variants and Environmental Factors Affect Risk of Esophageal Adenocarcinoma and Barrett’s Esophagus

Genome-wide association studies (GWAS) have identified more than 20 susceptibility loci for esophageal adenocarcinoma (EA) and Barrett's esophagus (BE). However, variants in these loci account for a small fraction of cases of EA and BE. Genetic factors might interact with environmental factors to affect risk of EA and BE. We aimed to identify single nucleotide polymorphisms (SNPs) that may modify the associations of body mass index (BMI), smoking, and gastroesophageal reflux disease (GERD), with risks of EA and BE.

http://ift.tt/2pfwbim

Screening and Surveillance of Varices in Patients with Cirrhosis

Gastro-esophageal varices (GEV) and variceal hemorrhage (VH) are clinical milestones in the natural history of cirrhosis, as they are closely related to the severity of portal hypertension and define specific stages in disease progression. Variceal hemorrhage is a life-threatening complication of cirrhosis and is one of the clinical complications that defines cirrhosis decompensation. The goal of screening and surveillance of varices is to identify patients with GEV at a high risk of bleeding, so that prevention strategies can be implemented.

http://ift.tt/2FTvcOB

The relationship between Muc5ac high secretion and Munc18b upregulation in obese asthma

OBJECTIVE: Mucus production and hypersecretion are important pathophysiological features of asthma. Airway mucus secretion is more serious in obese asthma. Therefore, it is of great significance to elucidate the mechanism of asthma airway mucus high secretion in improving the control of asthma and the prognosis of obese asthmatic patients.

MATERIALS AND METHODS: Obese asthmatic mice model was established to test the airway resistance and mucin secretion by hematoxylin-eosin (HE) staining. Munc18b and Muc5ac expression levels were determined by Western-blotting. Munc18b conditioned knockout mice were adopted to explore the mechanism of Muc5ac high secretion.

RESULTS: The mice weight increased in obese asthmatic model accompanied by elevated airway resistance. HE staining showed enhanced mucin secretion, which was correlated to weight and airway resistance. Munc18b and Muc5ac expressions significant upregulated in an obese asthmatic mouse model compared with normal control. Muc5ac expression failed to show elevation in Munc18b conditioned knockout mice.

CONCLUSIONS: Muc5ac high secretion was positively correlated with Munc18b upregulation in obese asthma. Munc18b participated in inducing Muc5ac high expression.

L'articolo The relationship between Muc5ac high secretion and Munc18b upregulation in obese asthma sembra essere il primo su European Review.

http://ift.tt/2FG1c9C

The multifunctional solute carrier 3A2 (SLC3A2) confers a poor prognosis in the highly proliferative breast cancer subtypes

http://ift.tt/2piFxsT

New opportunities for kinase drug repurposing and target discovery

http://ift.tt/2IsyTcr

Diagnosis delays: a threat for patients and researchers?

Prolonged time to diagnosis of severe diseases may be associated with poor outcome, unnecessary suffering, feelings of guilt for families and physicians, loss of confidence, and malpractice claims.1 Given its specific characteristics compared with adults, the pediatric population is at high risk of delays in diagnosis.2 Studying the frequency, determinants, and consequences of diagnostic delay is crucial to prepare efficient corrective actions. However, studies on time to diagnosis are observational by nature and exposed to many risks of bias, including how participants were selected, how time to diagnosis was measured, and how associations between time to diagnosis and participant characteristics and health outcomes were assessed.

http://ift.tt/2FN3kZ5

Delayed Subaponeurotic Fluid Collections of Infancy

A 2-month-old male infant was referred for evaluation of a fluctuant scalp mass. He was born at term to a nulliparous mother following a difficult labor. After failing vacuum-assisted delivery, he was delivered via cesarean delivery. His parents first noted scalp swelling at approximately 5 weeks of age, which increased and then stabilized in the weeks prior to his referral. The fluid collection was noted to be fluctuant, free-flowing across suture lines, and without discoloration or bruising (Figure 1).

http://ift.tt/2FCON64

New Paradigms for Pulmonary Vein Stenosis Treatment: When Surgery and Transcatheter Therapy Aren't Good Enough

The field of pediatric cardiology has witnessed dramatic improvements in outcomes for patients with congenital heart disease over the last several decades. However, 1 disease that continues to vex the pediatric cardiac community is pulmonary vein stenosis. Pulmonary vein stenosis is being recognized with increased frequency. This is likely a reflection of greater awareness of this condition as well as enhanced diagnostic modalities though other factors such as increasing survival of premature infants may also play a role.

http://ift.tt/2FKtqvG

History of chronic pulmonary insufficiency of prematurity

We agree with the use of the term "chronic pulmonary insufficiency of prematurity" by Steinhorn et al to describe "respiratory morbidity after preterm birth during the birth hospitalization and through infancy and childhood."1 The term was first coined in 1975 by Drs Alfred Krauss, David Klain, and Peter Auld to describe a group of premature infants who initially had normal respiratory function but then developed respiratory distress and apnea spells with deteriorating lung functions at 4-17 days of age.

http://ift.tt/2GvSAiV

Lupus Mesenteric Vasculitis in a Patient Under Maintenance Dialysis

A 13-year-old girl received a diagnosis of systemic lupus erythematosus (SLE) at the age of 6 years with initial presentations of thrombocytopenia, anemia, and nephritis. She received unsuccessful pulse cyclophosphamide therapy. Dialysis was introduced at 11 years of age, and she was maintained on azathioprine (2 mg/kg/day) and prednisolone (0.4 mg/kg on alternate days).

http://ift.tt/2DvlDQJ

Reply

We thank Drs van Broekhoven and Plötz for their interest in on our study; they have raised 2 potentially important and related issues in their letter.

http://ift.tt/2Dv1OsK

Bias and Objectivity When Evaluating Social Risk Factors for Physical Abuse: of Babies and Bathwater

Social factors are clearly important in the risk of child physical abuse. If abuse commonly occurs when parenting demands overwhelm emotional resources, it makes sense that young or single parenthood, poverty, substance use, and criminal justice involvement are associated with abuse.1,2 However, clinicians are currently ill-equipped to make sound use of social factors in the real world. Without accurate, objective data, clinicians often use their intuition to estimate social risk.3 In the US, where race continues to be associated to a shameful degree with social risk factors, this can result in overtesting for African-American families and greater rates of missed abuse in others.

http://ift.tt/2GytX4Y

Usefulness of an Online Risk Estimator for Bronchopulmonary Dysplasia in Predicting Corticosteroid Treatment in Infants Born Preterm

To assess the usefulness of a bronchopulmonary dysplasia (BPD) outcome estimator developed by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) in identifying high-risk preterm infants treated with steroids.

http://ift.tt/2FG7m9y

Reply

Launay et al rightly point out that time to diagnosis research is vulnerable to several types of bias, and they reference a valuable reporting guideline (REST) intended to mitigate such bias. Our report was not free from potential bias, and we have specifically addressed the issue of selection bias in the paper's discussion. However, whereas adherence to the REST guideline is enviable—and would be valuable in any future effort to validate the findings of our study—this guideline should not necessarily be viewed as a methodologic minimum standard for the conduct or publication of time to diagnosis research.

http://ift.tt/2DvlInv

Randomized trial of dexamethasone versus prednisone for children with acute asthma exacerbations: why?

Paniagua et al reported data that showed no difference between 2 doses of dexamethasone and 5 days of prednisone or prednisolone. However, more than one-half the patients were still symptomatic at day 7 (see Table II in their article).1 An equally legitimate interpretation of the data is that the 2 regimens were equally ineffective. Although some may consider the efficacy of corticosteroids for acute asthma self-evident, there has been controversy in the literature on this subject. Oral corticosteroids were first demonstrated in 1956 to have benefit for adults in favorably altering the course of an asthma exacerbation to a greater extent than just "antispasmodics" [sic].

http://ift.tt/2FDzytB

Internet Addiction among Adolescents May Predict Self-Harm/Suicidal Behavior: A Prospective Study

To explore the role of Internet addiction in the development of self-harm/suicidal behavior among adolescents after 1-year of follow-up.

http://ift.tt/2FEBMcq

Clinically Oriented Subtyping of Chronic Insomnia of Childhood

To identify different profiles of pediatric insomnia, based on the most frequent clinical presentations (nocturnal awakenings, difficulty in falling asleep, nocturnal restlessness, early morning awakenings).

http://ift.tt/2Gxi93a

Classifying Injuries in Young Children as Abusive or Accidental: Reliability and Accuracy of an Expert Panel Approach

To assess interrater reliability and accuracy of an expert panel in classifying injuries of patients as abusive or accidental based on comprehensive case information.

http://ift.tt/2Dvlwoh

Comparing Like with Like When Reporting Neurodevelopmental Outcomes after Preterm Birth

For nearly 20 years, investigators of randomized clinical trials in neonatology have used a primary endpoint of death or survival with impairment in at least 1 of the following domains: cognition, motor function, hearing, and vision.1-3 This composite outcome of death or neurodevelopmental impairment (NDI) has also gained popularity for observational neonatal research. However, as Haslam et al from the Canadian Neonatal Follow-up Network describe in this volume of The Journal, NDI has been defined in many different ways.

http://ift.tt/2Dwo2KC

Validity of Body Mass Index as a Measure of Adiposity in Infancy

To assess the validity of body mass index (BMI) and age- and sex-standardized BMI z-score (BMIZ) as surrogates for adiposity (body fat percentage [BF%], fat mass, and fat mass index [kg/m2]) at 3 time points in infancy (1, 4, and 7 months) and to assess the extent to which the change in BMIZ represents change in adiposity.

http://ift.tt/2FBT4XD

Cost-Effectiveness Analysis of Nasal Continuous Positive Airway Pressure Versus Nasal High Flow Therapy as Primary Support for Infants Born Preterm

To compare the cost-effectiveness of 2 common "noninvasive" modes of respiratory support for infants born preterm.

http://ift.tt/2FMMyJy

A Painless Bulky Lesion of the Tongue

A 4-year-old girl came to our attention with a tongue lesion, which had been present for 3 months; the lesion was variably sized, asymptomatic, and causing discomfort while speaking and eating. There was no previous trauma. A large, exophytic, translucent, fleshy, nontender mass was on the right hemilingual ventral surface with mucous "spillage" (Figure). The cervical lymph nodes were not enlarged, and tongue movements were not impaired. Differential diagnosis of a swelling of the tongue includes mucocele, lymphangioma, dermoid-epidermoid cyst, thyroglossal duct cyst, lingual thyroid, foregut duplication cyst, hemangioma, neurofibroma, lipoma, and mucoepidermoid carcinoma.

http://ift.tt/2FN3lw7

Direct-acting Antivirals Response in an Acute Nosocomial Genotype 1b HCV Outbreak

http://ift.tt/2tZbBb5

Long-term outcome of transjugular intrahepatic portosystemic shunt for portal hypertension in autosomal recessive polycystic kidney disease

Autosomal recessive polycystic kidney disease (ARPKD) with congenital hepatic fibrosis (CHF) causes portal hypertension and its complications. A transjugular intrahepatic portosystemic shunt (TIPSS) could serve as a symptomatic treatment for portal hypertension-related symptoms in these children.

http://ift.tt/2GxZQei

Is it time to include non-alcoholic fatty liver disease in the current risk scores for atrial fibrillation?

http://ift.tt/2tSaLwG

Inter-institutional Travel Fellowships—a Need for the Young Surgical Oncologists

http://ift.tt/2FN3C27

Potential Public Health Effects of Reducing Nicotine Levels in Cigarettes in the United States

Tobacco is addictive, primarily because of the presence of nicotine. Although nicotine itself is not the direct cause of most smoking-related diseases, addiction to nicotine in tobacco is the proximate cause of these diseases because it sustains smoking behavior. Thus, the magnitude of public…

http://ift.tt/2GxX6xx

Cabergoline versus bromocriptine for the treatment of giant prolactinomas: A quantitative and systematic review

Abstract

The aim of this study is to compare the efficacy of bromocriptine (BRC) versus cabergoline (CAB) in patients with giant prolactinomas. We searched MEDLINE, EMBASE, CENTRAL and Clinical Trials.gov for studies dated before March 1st, 2016, that used BRC or CAB for the treatment of patients with giant prolactinomas. Specific eligibility criteria were set to identify articles and cases. The selected articles were reviewed, and the data were extracted for analysis. The compared outcomes included tumor shrinkage, tumor response, normalization of prolactin (PRL) level, and visual field defect (VFD) improvement. Gender differences were also considered. Differences between the groups were assessed using Student's t test and the chi-square test. Two hundred and forty-five records were identified, and 10 articles and 104 cases met the inclusion criteria. Based on our analysis, CAB is significantly better than BRC in normalizing PRL levels in patients, especially males, with giant prolactinomas (69.4% versus 31.7%, p = 0.01). However, there was no significant difference between the two drugs in terms of tumor shrinkage, tumor response and VFD improvement (p > 0.05) in male or female patients. CAB exhibits significantly better efficacy than BRC in the normalization of PRL levels in male patients with giant prolactinomas. Regarding tumor reduction and VFD improvement, both drugs are comparably effective for patients of both genders. This quantitative and systematic review provides preliminary evidence in favor of CAB as a medical therapy for treating giant prolactinomas in male patients, especially those with extremely high PRL levels.

http://ift.tt/2tQcrGT

The Imperative of Addressing Cancer Drug Costs and Value

The President's Cancer Panel has released its latest report, Promoting Value, Affordability, and Innovation in Cancer Drug Treatment. The report recommends six actions to maximize the value and affordability of cancer drug treatment.

http://ift.tt/2tRMVkG

Colonization-induced protection against invasive pneumococcal disease in mice is independent of CD103 driven adaptive immune responses

Abstract

Nasopharyngeal colonization with Streptococcus pneumoniae (the pneumococcus) is known to mount protective adaptive immune responses in rodents and humans. However, the cellular response of the nasopharyngeal compartment to pneumococcal colonization and its importance for the ensuing adaptive immune response is only partially defined. Here we show that nasopharyngeal colonization with S. pneumoniae triggered substantial expansion of both integrin αE (CD103) positive dendritic cells (DC) and T lymphocytes in nasopharynx, nasal-associated lymphoid tissue (NALT) and cervical lymph nodes (CLN) of WT mice. However, nasopharyngeal de-colonization and pneumococcus-specific antibody responses were similar between WT and CD103 KO mice or Batf3 KO mice. Also, naïve WT mice passively immunized with antiserum from previously colonized WT and CD103 KO mice were similarly protected against invasive pneumococcal disease (IPD). In summary, the data show that CD103 is dispensable for pneumococcal colonization-induced adaptive immune responses in mice.

This article is protected by copyright. All rights reserved

http://ift.tt/2Dv3ZfC

Manipulation of Ploidy in Caenorhabditis elegans

This method allows for the generation of tetraploid and triploid Caenorhabditis nematodes from any diploid strain. Polyploid strains generated by this method have been used to study chromosome interactions in meiotic prophase, and this method is useful for examining important basic questions in cell, developmental, evolutionary, and cancer biology.

http://ift.tt/2FXuxeU

Effect of salient points in movements on the constraints in bimanual coordination

Abstract

The relative-salience hypothesis has been proposed as a possible explanation for the stability of bimanual coordination. This explanation proceeds from a psychological viewpoint and is based on the following tenets: (1) cyclic joint motions involving two movements are conceived of as a unified event, (2) if a "single" point in each movement is seen as the most salient, the salient points of the two movements prefer to go together, and (3) in other cases, a unified event will be constrained by movement direction. In this investigation, we examined whether the relative-salience hypothesis could predict the type of constraint (i.e., action coupling vs movement direction) for various bimanual coordination movements. Participants performed six different joint movements in synchrony with metronome beats. Both index finger flexion/extension and forearm pronation/supination had a "single" salient point (JM_singleSP), the others had "two" salient points (JM_twoSP). Then, we applied the relative-salience hypothesis to four bimanual coordinations. The coupling of simultaneous forearm pronation was more stable than alternate pronation. Similarly, the coupling of finger flexion and forearm pronation was more stable than that of finger flexion and forearm supination. For the coordination of radial flexion/ulnar flexion and index finger flexion/extension as well as forearm pronation/supination and radial flexion/ulnar flexion, symmetric movements were more stable than asymmetric movements. The results indicated that the stability of bimanual coordination was predominantly constrained by coupling of salient points when using two JM_singleSP and it was predominantly constrained by movement direction when coordinating JM_singleSP and JM_twoSP. Thus, the relative-salience hypothesis was supported.

http://ift.tt/2pgikYg

Two-photon Calcium Imaging in Neuronal Dendrites in Brain Slices

We present a method combining whole-cell patch-clamp recordings and two-photon imaging to record Ca2+ transients in neuronal dendrites in acute brain slices.

http://ift.tt/2tTSRcO

Intraperitoneal Glucose Tolerance Test, Measurement of Lung Function, and Fixation of the Lung to Study the Impact of Obesity and Impaired Metabolism on Pulmonary Outcomes

The incidence of obesity is rising and increases the risk of chronic lung diseases. To establish the underlying mechanisms and preventive strategies, well-defined animal models are needed. Here, we provide three methods (glucose-tolerance-test, body plethysmography, and lung fixation) to study the effect of obesity on pulmonary outcomes in mice.

http://ift.tt/2Gv72Ym

Hepatic Resection Compared to Chemoembolization in Intermediate to Advanced Stage Hepatocellular Carcinoma: A Meta-analysis of High-Quality Studies

ABSTRACT

According to the American Association for the Study of Liver Disease treatment guidelines for hepatocellular carcinoma (HCC), the role of surgery has been expanded beyond the Barcelona Clinic Liver Cancer (BCLC) algorithm. We compared primary hepatectomy (PH) with transarterial chemoembolization (TACE) in patients with intermediate to advanced (BCLC stage-B/C) stage HCC to determine the current evidence. Through database search, we included 18 high-quality studies (1 randomized controlled trial [RCT], 5 propensity-score matching non-randomized comparative trials [NRCT], and 12 NRCTs) that compared survival outcomes of 5,986 patients after PH and TACE. We found significant survival benefits for PH over TACE in BCLC stage-B/C patients (Hazard ratio [HR]: 0.59; 95% confidence interval [CI]: 0.51-0.67; P < 0.00001; I² = 84%). According to the BCLC, both stage-B and stage-C patients showed significantly better overall survival for PH compared to TACE (HR: 0.53; 95% CI: 0.43-0.65; P < 0.00001; I² = 77%; HR: 0.67; 95% CI: 0.59-0.77; P < 0.00001; I² = 79%, respectively). Five-year survival rates for PH were significantly higher than those for TACE in BCLC stage-B/C, stage-B, and BCLC stage-C patients (OR: 2.71, 2.77, and 3.03, respectively; all P < 0.00001). Survival benefits persisted across subgroup, sensitivity, and meta-regression analyses; inter-study heterogeneity remained constant. Conclusion: This meta-analysis suggests that surgical resection provides survival benefits in patients with intermediate to advanced stage HCC. The evidence found herein may assist in the choice of treatment modality based on diverse definitions of operability. This article is protected by copyright. All rights reserved.

http://ift.tt/2IpnUR3

In silico assessment of the dosimetric quality of a novel, automated radiation treatment planning strategy for linac-based radiosurgery of multiple brain metastases and a comparison with robotic methods

Abstract

Background

To appraise the dosimetric features and the quality of the treatment plan for radiosurgery of multiple brain metastases optimized with a novel automated engine and to compare with plans optimized for robotic-based delivery.

Methods

A set of 15 patients with multiple brain metastases was selected for this in silico study. The technique under investigation is the recently introduced HyperArc. For all patients, three treatment plans were computed and compared: i: a HyperArc; ii: a standard VMAT; iii) a CyberKnife. Dosimetric features were computed for the clinical target volumes as well as for the healthy brain tissue and the organs at risk.

Results

The data showed that the best dose homogeneity was achieved with the VMAT technique. HyperArc allowed to minimize the volume of brain receiving 4Gy (as well as for the mean dose and the volume receiving 12Gy, although not statistically significant). The smallest dose on 1 cm³ volume for all organs at risk is for CK techniques, and the biggest for VMAT (p < 0.05). The Radiation Planning Index coefficient indicates that, there are no significant differences among the techniques investigated, suggesting an equivalence among these.

Conclusion

At treatment planning level, the study demonstrates that the use of HyperArc technique can significantly improve the sparing of the healthy brain while maintaining a full coverage of the target volumes.

http://ift.tt/2FL5CYO

Retrospective dosimetry study of intensity-modulated radiation therapy for nasopharyngeal carcinoma: measurement-guided dose reconstruction and analysis

Abstract

Background

Conventional phantom-based planar dosimetry (2D-PBD) quality assurance (QA) using gamma pass rate (GP (%)) is inadequate to reflect clinically relevant dose error in intensity-modulated radiation therapy (IMRT), owing to a lack of information regarding patient anatomy and volumetric dose distribution. This study aimed to evaluate the dose distribution accuracy of IMRT delivery for nasopharyngeal carcinoma (NPC), which passed the 2D-PBD verification, using a measurement-guided 3D dose reconstruction (3D-MGR) method.

Methods

Radiation treatment plans of 30 NPC cases and their pre-treatment 2D-PBD data were analyzed. 3D dose distribution was reconstructed on patient computed tomography (CT) images using the 3DVH software and compared to the treatment plans. Global and organ-specific dose GP (%), and dose-volume histogram (DVH) deviation of each structure was evaluated. Interdependency between GP (%) and the deviation of the volumetric dose was studied through correlation analysis.

Results

The 3D-MGR achieved global GP (%) similar to conventional 2D-PBD in the same criteria. However, structure-specific GP (%) significantly decreased under stricter criteria, including the planning target volume (PTV). The average deviation of all inspected dose volumes (D_V) and volumetric dose (V_D) parameters ranged from − 2.93% to 1.17%, with the largest negative deviation in V100% of the PTVnx of − 15.66% and positive deviation in D1cc of the spinal cord of 6.66%. There was no significant correlation between global GP (%) of 2D-PBD or 3D-MGR and the deviation of the most volumetric dosimetry parameters (D_V or V_D), when the Pearson's coefficient value of 0.8 was used for correlation evaluation.

Conclusion

Even upon passing the pre-treatment phantom based dosimetric QA, there could still be risk of dose error like under-dose in PTVnx and overdose in critical structures. Measurement-guided 3D volumetric dosimetry QA is recommended as the more clinically efficient verification for the complicated NPC IMRT.

http://ift.tt/2Gx1ih0

A RANKL-based Osteoclast Culture Assay of Mouse Bone Marrow to Investigate the Role of mTORC1 in Osteoclast Formation

This manuscript describes a protocol to isolate and culture osteoclasts in vitro from mouse bone marrow, and to study the role of the mammalian/mechanistic target of rapamycin complex 1 in osteoclast formation.

http://ift.tt/2Istcex

Demystifying Eukaryote Lateral Gene Transfer (Response to Martin 2017 DOI: 10.1002/bies.201700115)

In a recent BioEssays paper [W. F. Martin, BioEssays 2017, 39, 1700115], William Martin sharply criticizes evolutionary interpretations that involve lateral gene transfer (LGT) into eukaryotic genomes. Most published examples of LGTs in eukaryotes, he suggests, are in fact contaminants, ancestral genes that have been lost from other extant lineages, or the result of artefactual phylogenetic inferences. Martin argues that, except for transfers that occurred from endosymbiotic organelles, eukaryote LGT is insignificant. Here, in reviewing this field, we seek to correct some of the misconceptions presented therein with regard to the evidence for LGT in eukaryotes.

A recent paper dismisses claims of lateral gene transfer (LGT) into eukaryotic genomes. We counter the arguments made in that paper and discuss the extensive evidence for LGT in eukaryotes.

http://ift.tt/2GwvpoJ

3D Printing of Customized Li-Ion Batteries with Thick Electrodes

Abstract

The growing demand for rechargeable lithium-ion batteries (LIBs) with higher capacity in customized geometries underscores the need for new battery materials, architectures, and assembly strategies. Here, the design, fabrication, and electrochemical performance of fully 3D printed LIBs composed of thick semisolid electrodes that exhibit high areal capacity are reported. Specifically, semisolid cathode and anode inks, as well as UV curable packaging and separator inks for direct writing of LIBs in arbitrary geometries are created. These fully 3D printed and packaged LIBs, which are encased between two glassy carbon current collectors, deliver an areal capacity of 4.45 mAh cm⁻² at a current density of 0.14 mA cm⁻², which is equivalent to 17.3 Ah L⁻¹. The ability to produce high-performance LIBs in customized form factors opens new avenues for integrating batteries directly within 3D printed objects.

Fully 3D-printed and packaged lithium-ion batteries (LIBs) composed of thick, semisolid biphasic electrodes are created in customized form factors. These 3D-printed, rechargeable LIBs exhibit high areal energy and power densities.

http://ift.tt/2FCFMKm

In Situ Passivation for Efficient PbS Quantum Dot Solar Cells by Precursor Engineering

Abstract

Current efforts on lead sulfide quantum dot (PbS QD) solar cells are mostly paid to the device architecture engineering and postsynthetic surface modification, while very rare work regarding the optimization of PbS synthesis is reported. Here, PbS QDs are successfully synthesized using PbO and PbAc₂ · 3H₂O as the lead sources. QD solar cells based on PbAc-PbS have demonstrated a high power conversion efficiency (PCE) of 10.82% (and independently certificated values of 10.62%), which is significantly higher than the PCE of 9.39% for PbO-PbS QD based ones. For the first time, systematic investigations are carried out on the effect of lead precursor engineering on the device performance. It is revealed that acetate can act as an efficient capping ligands together with oleic acid, providing better surface coverage and replace some of the harmful hydroxyl (OH) ligands during the synthesis. Then the acetate on the surface can be exchanged by iodide and lead to desired passivation. This work demonstrates that the precursor engineering has great potential in performance improvement. It is also pointed out that the initial synthesis is an often neglected but critical stage and has abundant room for optimization to further improve the quality of the resultant QDs, leading to breakthrough efficiency.

Light is shed on the effects of lead precursors on the performance of lead sulfide quantum dot (PbS QD) solar cells. The efficiency of PbS QDs synthesized from PbAc is significantly higher than that from PbO and the mechanism underneath is investigated. A new avenue is opened to improve the performance of PbS QD photovoltaic devices by lead precursor engineering.

http://ift.tt/2FLZTlm

Recent Advances in Magnetic-Nanomaterial-Based Mechanotransduction for Cell Fate Regulation

Abstract

Remote control of cells and the regulation of cell events at the molecular level are of great interest in the biomedical field. In addition to chemical compounds and genes, mechanical forces play a pivotal role in regulating cell fate, which have prompted the rapid growth of mechanobiology. From a perspective of nanotechnology, magnetic nanomaterials (MNs) are an appealing option for mechanotransduction due to their capabilities in spatiotemporal manipulation of mechanical forces via the magnetic field. As a newly developed paradigm, magneto-mechanotransduction is harnessed to physically regulate cell fate for biomedical applications. Here, the critical factors that determine the magnetomechanical forces induced by MNs in mechanotransduction are briefly reviewed. Recent innovative approaches and their underlying mechanisms for controlling cell fate are highlighted, which offer possibilities for the remote mechanical manipulation of cells and biomolecules in a precise manner. Promising applications including regenerative medicine and cancer treatment based on magnetomechanical stimulation through MNs are also addressed. Perspectives and challenges in MN-based mechanotransduction are commented.

Magnetic nanomaterials are promising mechanotransduction toolkits with great potential in a wide range of biological and medical applications. Recent innovative approaches in the manipulation of cells via magnetic-nanomaterial-based mechanotransduction are highlighted, which offer possibilities for the remote mechanical manipulation of cells and biomolecules in a precise manner.

http://ift.tt/2FKmajD

Evidence Underpinning the Centers for Medicare & Medicaid Services' Severe Sepsis and Septic Shock Management Bundle (SEP-1)

http://ift.tt/2tTGfCu

Analysis of the correlation between non-alcoholic fatty liver disease and bone metabolism indicators in healthy middle-aged men

OBJECTIVE: To investigate the relationship between bone metabolic indicators and non-alcoholic fatty liver disease (NAFLD) in healthy middle-aged men.

PATIENTS AND METHODS: The bone metabolic indicators of 232 healthy middle-age men with NAFLD (NAFLD group) and 308 healthy controls without fatty liver (Control group) were measured, including non-collagenous osteocalcin, the procollagen type 1 N-terminal propeptide (P1NP), beta-C-terminal telopeptide of type I collagen (β-CTX). The Student's t-test was used to analyze the differences in the bone metabolic indicators, age, clinical data, biochemical indicators, and the indicators of glucose and lipid metabolism between the two groups. The correlation of fatty liver-related indicators was detected using the logistic regression analysis.

RESULTS: The body mass index (BMI), diastolic blood pressure, and heart rate in NAFLD group were significantly higher than those in Control group. Among the indicators of glucose and lipid metabolism in NAFLD group, the levels of blood glucose [fasting plasma glucose, postprandial blood glucose and hemoglobin A1c (HbA1c)] were significantly higher than those in Control group. In addition, the insulin resistance and secretion indexes were also significantly higher than those in Control group. The levels of lipid metabolic indicators such as triglyceride were higher, but high-density lipoprotein cholesterol was lower than that in Control group. From logistic regression analysis, the BMI, Homeostasis model assessment (HOMA)-β, HOMA-IR, HbA1c and P1NP were positively associated with the occurrence of NAFLD.

CONCLUSIONS: The bone metabolic indicator P1NP might be a potential predicator for the diagnosis of NAFLD in clinical application.

L'articolo Analysis of the correlation between non-alcoholic fatty liver disease and bone metabolism indicators in healthy middle-aged men sembra essere il primo su European Review.

http://ift.tt/2FWs9ow

Islet transplantation 30 years after the first transplants

First clinical islet allotransplantation in patients affected by type 1 diabetes mellitus was performed about 30 years ago. Despite the progressive improvement of the success rate, the clinical indication to the islet allotransplantation remains limited to selected patients affected by brittle type 1 diabetes mellitus. The burden of the immunosuppression therapy still represents the main critical issue but other areas might be subject to further improvements, such as the islet production, islet engraftment and long-term function.  Several strategies have been proposed to increase the success rate of pancreas digestion and islet purification or to facilitate islet engraftment by reducing islet hypoxia and the inflammatory reaction occurring in the site of transplantation. The co-transplantation of progenitors of beta cell together with the islets has expected to contribute to prolong graft function. Clinical trials are expected soon. Scientific advances, as well as economical efforts, are required to make this procedure a real therapeutical option for patients with type 1 diabetes mellitus.

L'articolo Islet transplantation 30 years after the first transplants sembra essere il primo su European Review.

http://ift.tt/2tPMMOz

Norleual, a hepatocyte growth factor and macrophage stimulating protein dual antagonist, increases pancreatic cancer sensitivity to gemcitabine

Pancreatic cancer is a leading cause of cancer deaths in the USA and is characterized by an exceptionally poor long-term survival rate compared with other major cancers. The hepatocyte growth factor (HGF) and macrophage stimulating protein (MSP) growth factor systems are frequently over-activated in pancreatic cancer and significantly contribute to cancer progression, metastasis, and chemotherapeutic resistance. Small molecules homologous to the 'hinge' region of HGF, which participates in its dimerization and activation, had been developed and shown to bind HGF with high affinity, antagonize HGF's actions, and possess anticancer activity. Encouraged by sequence homology between HGF's hinge region and a similar sequence in MSP, our laboratory previously investigated and determined that these same antagonists could also block MSP-dependent cellular responses. Thus, the purpose of this study was to establish that the dual HGF/MSP antagonist Norleual could inhibit the prosurvival activity imparted by both HGF and MSP to pancreatic cancer cells in vitro, and to determine whether this effect translated into an improved chemotherapeutic impact for gemcitabine when delivered in combination in a human pancreatic cancer xenograft model. Our results demonstrate that Norleual does indeed suppress HGF's and MSP's prosurvival effects as well as sensitizing pancreatic cancer cells to gemcitabine in vitro. Most importantly, treatment with Norleual in combination with gemcitabine markedly inhibited in-vivo tumor growth beyond the suppression observed with gemcitabine alone. These results suggest that dual functional HGF/MSP antagonists like Norleual warrant further development and may offer an improved therapeutic outcome for pancreatic cancer patients.

http://ift.tt/2FFpiRG

Any place left for induction chemotherapy for locally advanced head and neck squamous cell carcinoma?

The issue of induction chemotherapy (ICT) interest in locoregionally advanced squamous cell cancer of the head and neck is a real epic that has been carried out over four phase III studies: PARADIGM, DECIDE, NCT01086826 and lastly the conclusive GORTEC 2007-02. With no significant benefit in overall survival of ICT, followed by concurrent chemoradiation over the standard chemoradiotherapy alone, in three of these studies, and a significant number of treatment-related deaths with the standard regimen docetaxel, cisplatin, and fluorouracil, ICT is no longer a hot topic. However, this strategy might still be useful in the aim of limiting the metastatic extension affecting up to 30% of patients: ICT is systematically associated with a reduced metastatic relapse even though the survival effect is never statistically significant when compared directly with concomitant radiochemotherapy. This review summarizes the major studies with their limits and discusses how the ICT could improve the patients' prognosis in the future.

http://ift.tt/2FLESHk

Investigation of an antitumor drug-delivery system based on anti-HER2 antibody-conjugated BSA nanoparticles

Conjugation of a monoclonal antibody with a nanoparticle often improves its specificity and drug loading in cancer therapy. In this study, we prepared a novel targeting nanodrug-delivery system using 2-methoxy-estradiol (2-ME) based on anti-human epidermal growth factor receptor 2 (HER2) antibody-modified BSA to improve the clinical application and antitumor effect of 2-ME. 2-ME-loaded albumin nanoparticles (2-ME-BSANPs) were prepared using a desolvation method and the anti-HER2 antibodies were conjugated to 2-ME-BSANPs (HER2-2-ME-BSANPs) using the coupling agent, succinimidyl 3-(2-pyridyldithio)propionate. HER2-2-ME-BSANPs were characterized using SDS-polyacrylamide gel electrophoresis, an agglutination test, and an immunofluorescence assay. We found that mouse anti-human anti-HER2 monoclonal antibody was successfully conjugated to the 2-ME-BSANPs. Thereafter, the in-vitro and in-vivo toxicities were evaluated using two cancer cell lines, SK-BR-3 (HER2-overexpressing) and MCF-7 (HER2-underexpressing), using classic pharmacological methods and in-vivo imaging technology. We found that the HER2-2-ME-BSANPs retained the immunospecificity of the anti-HER2 monoclonal antibody, rapidly localized to HER2 receptors, and could be used for targeted cancer therapy.

http://ift.tt/2peiMY3

Treatment of pancreatic cancer with intravenous vitamin C: a case report

Pancreatic ductal adenocarcinoma (PDA) has a dismal prognosis and is often discovered at an advanced stage with few therapeutic options. Current conventional regimens for PDA are associated with significant morbidity, decreased quality of life, and a considerable financial burden. As a result, some patients turn to integrative medicine therapies as an alternate option after a diagnosis of PDA. Intravenous pharmacologic ascorbic acid (PAA) is one such treatment. The use of PAA has been passionately debated for many years, but more recent rigorous scientific research has shown that there are significant blood concentration differences when ascorbic acid is given parenterally when compared to oral dosing. This pharmacologic difference appears to be critical for its role in oncology. Here, we report the use of PAA in a patient with poorly differentiated stage IV PDA as an exclusive chemotherapeutic regimen. The patient survived nearly 4 years after diagnosis, with PAA as his sole treatment, and he achieved objective regression of his disease. He died from sepsis and organ failure from a bowel perforation event. This case illustrates the possibility of PAA to effectively control tumor progression and serve as an adjunct to standard of care PDA chemotherapy regimens. Our patient's experience with PAA should be taken into consideration, along with previous research in cell, animal, and clinical experiments to design future treatment trials.

http://ift.tt/2FHAB7R

Comparison of the effect of the antiandrogen apalutamide (ARN-509) versus bicalutamide on the androgen receptor pathway in prostate cancer cell lines

Apalutamide (ARN-509) is an antiandrogen that binds selectively to androgen receptors (AR) and does not show antagonist-to-agonist switch like bicalutamide. We compared the activity of ARN versus bicalutamide on prostate cancer cell lines. The 22Rv1, PC3, and DU145 cell lines were used to study the effect of ARN and bicalutamide on the expression cytoplasmic/nuclear kinetics of AR, AR-V7 variant, phosphorylated AR, as well as the levels of the AR downstream proteins prostate-specific antigen and TMPRSS2, under exposure to testosterone and/or hypoxia. The effects on autophagic flux (LC3A, p62, TFEB, LAMP2a, cathepsin D) and cell metabolism-related enzymes (hypoxia-inducible factor 1α/2α, BNIP3, carbonic anhydrase 9, LDHA, PDH, PDH-kinase) were also studied. The 22Rv1 cell line responded to testosterone by increasing the nuclear entry of AR, AR-V7, and phosphorylated AR and by increasing the levels of prostate-specific antigen and TMPRSS2. This effect was strongly abrogated by ARN and to a clearly lower extent by bicalutamide at 10 μmol/l, both in normoxia and in hypoxia. ARN had a stronger antiproliferative effect than bicalutamide, which was prominent in the 22Rv1 hormone-responsive cell line, and completely repressed cell proliferation at a concentration of 100 μmol/l. No effect of testosterone or of antiandrogens on autophagy flux, hypoxia-related proteins, or metabolism enzyme levels was noted. The PC3 and DU145 cell lines showed poor expression of the proteins and were not responsive to testosterone. On the basis of in-vitro studies, evidence has been reported that ARN is more potent than bicalutamide in blocking the AR pathway in normoxia and in hypoxia. This reflects a more robust, dose-dependent, repressive effect on cell proliferation.

http://ift.tt/2peiEYz

Curcumin reverses irinotecan resistance in colon cancer cell by regulation of epithelial–mesenchymal transition

The objective of this study was to investigate the effect and the mechanism by which curcumin reverses irinotecan-induced chemotherapy resistance in colon cancer. Construction of irinotecan-resistant colon cancer model LoVo/CPT-11R cells was performed by increasing drug concentration. The Cell Counting Kit-8 assay was used to detect inhibition of proliferation; cell morphology was observed by an optical microscope. Quantitative RT-PCR and western blotting were performed to detect molecular marker expressions during epithelial–mesenchymal transition (EMT); drug-resistant cells were treated with curcumin at different concentrations and Cell Counting Kit-8 was reperformed to detect cell proliferation after treatments. Drug-resistant cells were then divided into four groups: control group, irinotecan group, curcumin group, and irinotecan+curcumin group; quantitative RT-PCR and western blotting were performed to detect molecular marker expressions during epithelial–mesenchymal transition. Flow cytometry was used to detect cell apoptosis after grouping, and apoptosis-related protein was detected by western blotting. LoVo/CPT-11R cells could survive in culture medium containing irinotecan at 60 μg/ml and the drug-resistance index was 5.69; the drug-resistant cells had a larger volume than normal cells and were poorly connected to each other. E-cadherin expression was downregulated, whereas vimentin and N-cadherin expressions were upregulated. After curcumin treatment, drug-resistant cell proliferation was significantly inhibited; in the curcumin+irinotecan treatment group, E-cadherin expression was upregulated, whereas vimentin and N-cadherin expressions were downregulated. Curcumin could significantly increase cell apoptosis. EMT is involved in the development of irinotecan resistance and curcumin can reverse this drug resistance through reversion of the EMT process.

http://ift.tt/2peixw7

Lenalidomide at the dose of 25 mg every other day in patients affected by multiple myeloma and renal failure: a real-life experience

Renal impairment (RI) is a relevant complication of patients affected by multiple myeloma (MM); it can be present in up to 30–35% of newly diagnosed MM and is linked to a poor outcome. However, early recognition and early treatment with novel agents can overcome the negative impact of RI and even reverse kidney damage in most cases. Lenalidomide, available as an oral compound, is an immunomodulatory drug with both antiproliferative and immunomodulatory activity that is largely used in the management of MM. Dose reduction is mandatory in RI; however, there is no theoretical assumption against the possibility that protracting the time of full standard doses can be equally effective and tolerated by patients requiring reduced doses. In this report, we describe our retrospective experience, in 18 patients, with the administration of lenalidomide 25 mg every other day for patients with MM and RI. The overall response ratio was 66.5%. More than half (61.1%) of the patients had a renal response. The median progression-free survival was 8 months (range: 3–18 months). No serious adverse event occurred during treatment, and it was never necessary to disrupt or delay treatment for toxicity. These preliminary observations point to a significant therapeutic effect of lenalidomide, at the dose of 25 mg every other day for 21 days, with logistic and economic advantages. However, these results should be validated by controlled studies involving larger numbers of patients.

http://ift.tt/2HCjkgX

Anticancer effect of (S)-crizotinib on osteosarcoma cells by targeting MTH1 and activating reactive oxygen species

MTH1 has become a new rising star in the field of 'cancer phenotypic lethality' and can be targeted in many kinds of tumors. This study aimed to explore the anticancer effect of MTH1-targeted drug (S)-crizotinib on osteosarcoma (OS) cells. We detected MTH1 expression in OS tissues and cells using immunohistochemistry and western blot. The effects of MTH1 on OS cell viability were explored using the siRNA technique and CCK8. The anticancer effects of the MTH1-targeted drug (S)-crizotinib on OS cells were explored by in-vitro assays. The intracellular 8-oxo-dGTP level and oxygen reactive species (ROS) of OS cells were detected by Cy3-conjugated avidin staining and dichlorofluorescein diacetate staining, respectively. The expression of MTH1 was significantly higher in OS tissues and cell lines than that in the corresponding adjacent tissues and osteoblastic cell line. The proliferation of OS cells was significantly inhibited through knockdown of MTH1 by siRNA technology. (S)-Crizotinib could inhibit the proliferation of OS cells with an increase in the apoptosis levels and causing G0/G1 arrest by targeting MTH1 and activating ROS. In addition, (S)-crizotinib could inhibit the migration of OS cells. (S)-Crizotinib could suppress the proliferation and migration, cause G0/G1 arrest, and increase the apoptosis level of OS cells by targeting MTH1 and activating ROS. This study will provide a promising therapeutic target and the theoretical basis for the clinical application of (S)-crizotinib in OS.

http://ift.tt/2FC9vTC

Complex epidermal growth factor receptor mutations and their responses to tyrosine kinase inhibitors in previously untreated advanced lung adenocarcinomas

BACKGROUND

Two or more different epidermal growth factor receptor (EGFR) mutations can be detected within a single tumor sample, which represents complex mutations. However, the frequency and efficacy of tyrosine kinase inhibitor (TKI) treatments for patients harboring these mutations are unknown.

METHODS

From January 2011 to January 2017, patients diagnosed with EGFR mutations were screened. The effectiveness of TKIs in patients with complex mutations was retrospectively analyzed.

RESULTS

A total of 16,840 subjects were screened, and there were 5898 positive patients. One hundred eighty-seven patients (3.2% of all patients with EGFR mutations) had complex EGFR mutations, and 51 of the patients with advanced adenocarcinoma were treated with TKIs as a first-line treatment. The objective response rates for patients who had Del-19+21L858R mutations (n = 15), Del-19/21L858R+atypical mutations (n = 16), double atypical mutations (n = 8), and complex mutations with a primary drug-resistant pattern (n = 12) were 75.0%, 60.0%, 71.0%, and 8.3%, respectively. The median progression-free survival times for the 4 groups were 18.2 months (95% confidence interval [CI], 10.6-25.9 months), 9.7 months (95% CI, 3.3-15.8 months), 9.6 months (95% CI, 3.3-19.0 months), and 1.4 months (95% CI, 0.4-2.3 months), respectively.

CONCLUSIONS

These results from the largest sample size suggest that EGFR-TKI therapy is effective in patients with Del-19+21L858R mutations, Del-19/21L858R+atypical mutations, and double atypical mutations but is less effective in patients with a primary drug-resistant pattern. Patients with the Del-19+21L858R mutations may, therefore, benefit more from treatment with first-generation TKIs. Cancer 2018. © 2018 American Cancer Society.

http://ift.tt/2DtAgUs

Reply to Improving the survival of patients with American Joint Committee on Cancer stage III and IV melanoma

http://ift.tt/2FCBMcN

Improving the survival of patients with American Joint Committee on Cancer stage III and IV melanoma

http://ift.tt/2DtA73m

Identification of NQO1 and Ferrochelatase as Interaction Partners for Neuroprotective N-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-arylamides

Abstract

Affinity chromatography was used to identify potential cellular targets that are responsible for neuroprotective activity of N-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-arylamides. Active and inactive representatives of N-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-arylamides bearing an extended linker were synthesized and immobilized on an agarose based matrix. This was followed by the identification of specifically bound proteins isolated out of the whole rat brain extract. Inducible flavoprotein NAD(P)H:quinone oxidoreductase (NQO1) was identified as candidates for cellular targets.

This article is protected by copyright. All rights reserved.

NQO1 was identified as a part of a nuroprotective arylpiperazine interactome. This finding points to NQO1 as a cellular target for N-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-arylamides that is responsible for their neuropreotective activity.

http://ift.tt/2pj6cFQ

Exaggerated Increase in Pulmonary Artery Pressure during Exercise in Adults Born Preterm

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 6, Page 821-823, March 15, 2018.


http://ift.tt/2FCLdsO

Evaluating for Bronchiolitis Obliterans with Low-Attenuation Computed Tomography Three-Dimensional Reconstructions

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 6, Page 814-815, March 15, 2018.


http://ift.tt/2DuAjzo

Reply to Dreyfuss and Gaudry: Might High-Frequency Oscillatory Ventilation Improve the Prognosis of More Severe Acute Respiratory Distress Syndrome? Not So Sure

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 6, Page 839-839, March 15, 2018.


http://ift.tt/2GvYWin

Taking Another Look at Ambient Coarse Particles

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 6, Page 697-698, March 15, 2018.


http://ift.tt/2FMIYz0

Corticosteroid Therapy for Critically Ill Patients with Middle East Respiratory Syndrome

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 6, Page 757-767, March 15, 2018.


http://ift.tt/2FG2eSP

Evaluation of the 2016 Infectious Diseases Society of America/American Thoracic Society Guideline Criteria for Risk of Multidrug-Resistant Pathogens in Patients with Hospital-acquired and Ventilator-associated Pneumonia in the ICU

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 6, Page 826-830, March 15, 2018.


http://ift.tt/2DvuJwu

Systemic Corticosteroid Therapy May Delay Viral Clearance in Patients with Middle East Respiratory Syndrome Coronavirus Infection

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 6, Page 700-701, March 15, 2018.


http://ift.tt/2FCKQyq

Might High-Frequency Oscillatory Ventilation Improve the Prognosis of More Severe Acute Respiratory Distress Syndrome? Not So Sure

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 6, Page 838-839, March 15, 2018.


http://ift.tt/2FMcZiz

Differentially Culturable Tubercule Bacilli Are Generated during Nonpulmonary Tuberculosis Infection

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 6, Page 818-821, March 15, 2018.


http://ift.tt/2FCKJ5Y

Long-Term Coarse Particulate Matter Exposure Is Associated with Asthma among Children in Medicaid

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 6, Page 737-746, March 15, 2018.


http://ift.tt/2FLyGiP

Evaluation of Risk Factors Affecting Substance Use among Tenth-Grade Students

Aim. The aim of this study is to detect the prevalence of substance use among tenth-grade students; their thoughts, attitudes, behaviors, and tendencies towards substance use; and risk factors of substance use in tenth-grade students in general. Methods. This study is descriptive and cross-sectional conducted between April and May 2016. Research population consists of tenth-grade students in 2015-2016 school year in the city of Ordu. Since the study involved all tenth-grade students, no sampling was done. Questions on substance use were prepared by Ordu Public Health Directorate and the authors by making use of European School Survey Project on Alcohol and Other Drugs (ESPAD) study questions, AMATEM's "Drugs and Addiction Youth Survey" study conducted on May 1996, and scientific studies conducted previously on similar subjects. Results. 9825 tenth-grade students in 88 schools from 19 counties in the city of Ordu were included in the study. 8714 of the students participated in the survey. Being male, being over the age of 15, mother and father being separated, living with relatives, being in low income, negative feelings about school, perception of being unsuccessful in school, failing a year, absenteeism, and not being content with life are the risk factors for substance use. Conclusions. The tendency of illegal substance use becoming more and more prevalent especially among youth requires the development of new treatment strategies.

http://ift.tt/2pgF0bG

Design and Synthesis of Waterborne Polyurethanes

Abstract

Waterborne polyurethanes (WBPUs) have attracted increasing attention in a wide range of industrial applications because of their versatile properties as well as ecofriendly nature. Although extensive research has been carried out on WBPU synthesis, the roles of some of the key synthesis components remain unclear. In this study, through systematically controlling and fine tuning the precursor compositions and reaction conditions, over 300 WBPUs are synthesized. This research enables the roles of several key components that govern WBPU physicochemical properties and ultimately the potential WBPU applications to be identified. Using hair styling as an example, it is demonstrated that only the WBPUs with an optimal range of properties (e.g., Young's modulus >150 MPa, elongation at break: 15–300%, moisture uptake <10%) can achieve strong styling performance. To further improve the natural-feel sensory benefits in the final styling products, a number of fatty acids with different carbon chain lengths or unsaturation levels are incorporated into WBPUs. Among the ten fatty acids studied, linoleic acid is identified as the most preferred additive. Both in vitro and in vivo testing demonstrate that WBPUs with optimal properties are promising materials for developing strong, long-lasting styling products with natural feel.

Through the synthesis of over 300 waterborne polyurethane (WBPU) materials, the roles of the key components that govern WBPU physicochemical properties are identified. Using hair styling as an example, it is demonstrated that only the WBPUs with Young's modulus >150 MPa, elongation at break of 15–300%, and moisture uptake <10% can achieve strong styling performance.

http://ift.tt/2FTltrl

Dissecting the Functional Consequences of De Novo DNA Methylation Dynamics in Human Motor Neuron Differentiation and Physiology

Kiskinis and colleagues demonstrate that DNA methylation dynamics play a central role in the differentiation of human pluripotent stem cells toward highly specialized motor neurons. Through a combination of molecular and functional analysis they identify key transcriptional mediators of these effects and link DNA methylation to neuronal patterning and function.

http://ift.tt/2DvNboL

Long-term trastuzumab (Herceptin®) treatment in a continuation study of patients with HER2-positive breast cancer or HER2-positive gastric cancer

Abstract

Background

Trastuzumab (Herceptin® [H]) is the standard of care for HER2-positive locally advanced/metastatic breast cancer and gastric/gastroesophageal junction (GEJ) cancer. However, there is a paucity of data available on long-term H treatment of patients. The Rollover Protocol (ROP) Study was conducted to report safety data for patients with HER2-positive locally advanced/metastatic breast and gastric/GEJ cancer who have received long-term H therapy (≥ 5 years and ≥ 3 years for breast and gastric/GEJ cancer, respectively).

Methods

The ROP Study was a single-arm, multicenter, international continuation trial of H in patients who had previously completed a global Roche-sponsored trial with H therapy, had stable disease, and were receiving H at the end of the lead-in trial. Patients with chronic heart failure during the lead-in trial could be included following a risk–benefit analysis. The primary objectives were to provide H therapy to patients with HER2-overexpressing locally advanced/metastatic breast or gastric/GEJ cancer at the end of the lead-in study, and to follow the long-term outcomes and long-term overall safety in these patients.

Results

Twenty-five of 69 patients enrolled in the ROP Study received long-term H therapy (19 breast cancer and 6 gastric/GEJ cancer). The median duration of H treatment for patients with breast cancer was 8 years 7 months, and 5 years 2 months for patients with gastric/GEJ cancer. The cardiac status of the patients remained stable over time, with no serious cardiac adverse events or marked changes in left ventricular ejection fraction (LVEF). The median overall worst LVEF measurement was 57.0%, and no patients experienced an LVEF of < 45% (range 47–63%). There were no serious adverse events related to study treatment.

Conclusions

These results suggest that H has an acceptable safety profile and was well tolerated in patients who received long-term H therapy (≥ 5 years and ≥ 3 years for breast and gastric/GEJ cancer, respectively). Further investigation and reporting of long-term H therapy would be valuable.

Trial registration

This study was retrospectively registered on March 24, 2016 with Clinicaltrials.gov, number NCT02721641.

http://ift.tt/2tUPwKm

Phase II trial to investigate the safety and efficacy of orally applied niclosamide in patients with metachronous or sychronous metastases of a colorectal cancer progressing after therapy: the NIKOLO trial

Abstract

Background

Colorectal cancer (CRC) is the second most common cause of all cancer deaths in Europe and the Western world with a lifetime risk of approximately 5%. Despite several improvements in the treatment of patients with unresectable CRC prognosis is poor and there is the need of developing new treatment strategies for patients with metastatic chemorefractory disease.

The S100 calcium binding protein A4 (S100A4) predicts metastasis formation and reduced CRC patient survival. S100A4 was previously identified as transcriptional target of the Wnt/β-catenin signaling pathway. The Food and Drug Administration (FDA)-approved anti-helminthic drug niclosamide is known to intervene in the Wnt/β-catenin pathway signaling, leading to reduced expression of S100A4 linked to restricted in vivo metastasis formation. Thus, we aim at translation of our findings on restricting S100A4-driven metastasis into clinical practice for treating metastasized CRC patients progressing after standard therapy.

Methods/Design

NIKOLO is a phase II, single center, one-arm open-label clinical trial to investigate the safety and efficacy of niclosamide tablets in patients with metastasized CRC progressing under standard therapy. Eligible patients will receive 2 g of orally applied niclosamide once a day and will continue with the treatment once daily till disease progression or toxicity. Toxicities will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.03. The primary objective of this trial is to assess the progression free survival after 4 months, secondary objectives are overall survival, time to progression, disease control rate (remission + partial remission + stable disease), and safety. Furthermore, pharmacokinetic analysis will be conducted to evaluate niclosamide plasma concentration.

Discussion

This study is expected to provide evidence of the feasibility, toxicity and efficacy of niclosamide in the treatment of patients with metastasized CRC and could help to establish a new treatment option.

Trial registration

The study is registered with ClinicalTrials.gov (NCT02519582) and the European Clinical Trials Database (EudraCT 2014-005151-20).

http://ift.tt/2Gvix22

Thyroid cancer: trends in incidence, mortality and clinical-pathological patterns in Zhejiang Province, Southeast China

Abstract

Background

Thyroid cancer is the most common malignant disease of the endocrine system. Previous studies indicate a rapid increase in the incidence of thyroid cancer in recent decades, and this increase has aroused the great public concern. The aim of this study was to analyze the trends in incidence, mortality and clinical-pathological patterns of thyroid cancer in Zhejiang province.

Methods

Population-based incidence and mortality rates of thyroid cancer were collected from eight cancer registries in Zhejiang from 2000 to 2012. The incidence and mortality rates were age-standardized to Segi's world population. A Joinpoint model was used to examine secular trends in age-adjusted thyroid cancer rates with the Joinpoint Regression Program Version 4.0.0. Thyroid cancer patients were recruited from Zhejiang Cancer Hospital from 1972 to 2014. Patient demographics, tumor histology and tumor size were compared among the different periods of 1972–1985, 1986–1999 and 2000–2014.

Results

The age-standardized incidence rate of thyroid cancer in Zhejiang cancer registries was 2.75/10⁵ in 2000, and increased to 19.42/10⁵ in 2012. Additionally, we observed significantly increasing incidence rates with the Annual Percent Change (APC) of 22.86% (95%CI, 19.2%–26.7%). The age-standardized mortality of thyroid cancer in Zhejiang cancer registries was 0.23/10⁵ in 2000 and 0.25/10⁵ in 2012. No significant change in mortality rate was found. We observed a rapid increase in the proportions of papillary thyroid carcinoma (PTC) in 12,508 patients with thyroid carcinoma identified in the Zhejiang Cancer Hospital from 1972 to 2014 while the proportions of poorly differentiated thyroid cancer (PDTC), medullary thyroid carcinoma (MTC) and follicular thyroid carcinoma (FTC) decreased over the decades. In the PTC cases, the proportion of patients with maximum tumor diameter (MTD) < 1 cm dramatically and significantly increased from 0 in 1972–1985 to 32.1% in 2000–2014.

Conclusions

A rapid increase in incidence and a stable trend in mortality of thyroid cancer were found in the distribution of thyroid cancer. Most of the increased incidence was PTC, especially the papillary thyroid microcarcinoma (PTMC) with MTD < 1 cm. This increase in incidence might be due to increased diagnosis with advanced technology.

http://ift.tt/2tPlKGW

Bone inflammation and chronic recurrent multifocal osteomyelitis

Chronic recurrent multifocal osteomyelitis (CRMO) is a sporadic condition of inflammatory bone pain that occurs as recurrent flares because of osteomyelitis, which presents in the form of multiple aseptic foci. The estimated prevalence of CRMO is 1-2 per million, affecting mostly children, in the age group of 2 to 17. Main symptoms of CRMO are bone inflammation and pain, which are generally worse at night. Other symptoms seen on radiographs indicate osteolytic lesions surrounded by sclerosis, at later stages of the disease. Markers of inflammation, viz. tumor necrosis factor a and C-reactive protein are elevated in many cases. Because of similar symptoms, differential diagnosis is needed to confirm CRMO from infectious osteomyelitis, bone tumors, and other diseases. The genetic component is likely in some cases such as Majeed syndrome, deficiency of IL-1 antagonist, etc. Imaging is the essential part of diagnosing CRMO, and magnetic resonance imaging of the whole body is the most widely used and recommended method for the evaluation of multiple foci, as compared to radiography for reasons of sensitivity as well as prevention of excessive exposure of affected children to radiation. CRMO is considered an autoimmune and auto-inflammatory disorder, but its precise pathophysiology is not clear. Current treatment options are non-steroid anti-inflammatory drugs like naproxen, as the primary choice, and the bisphosphonates such as pamidronate as the second choice, to counter the symptoms and to reduce bone lesions. The surgical option is the choice for recalcitrant cases, even though recurrence may still be a problem.

L'articolo Bone inflammation and chronic recurrent multifocal osteomyelitis sembra essere il primo su European Review.

http://ift.tt/2DsVTV1

Online advertising and marketing claims by providers of proton beam therapy: are they guideline-based?

Abstract

Background

Cancer patients frequently search the Internet for treatment options, and hospital websites are seen as reliable sources of knowledge. Guidelines support the use of proton radiotherapy in specific disease sites or on clinical trials. This study aims to evaluate direct-to-consumer advertising content and claims made by proton therapy centre (PTC) websites worldwide.

Methods

Operational PTC websites in English were identified through the Particle Therapy Co-Operative Group website. Data abstraction of website content was performed independently by two investigators. Eight international guidelines were consulted to determine guideline-based indications for proton radiotherapy. Univariate and multivariate logistic regression models were used to determine the characteristics of PTC websites that indicated proton radiotherapy offered greater disease control or cure rates.

Results

Forty-eight PTCs with 46 English websites were identified. 60·9% of PTC websites claimed proton therapy provided improved disease control or cure. U.S. websites listed more indications than international websites (15·5 ± 5·4 vs. 10·4 ± 5·8, p = 0·004). The most common disease sites advertised were prostate (87·0%), head and neck (87·0%) and pediatrics (82·6%), all of which were indicated in least one international guideline. Several disease sites advertised were not present in any consensus guidelines, including pancreatobiliary (52·2%), breast (50·0%), and esophageal (43·5%) cancers. Multivariate analysis found increasing number of disease sites and claiming their centre was a local or regional leader in proton radiotherapy was associated with indicating proton radiotherapy offers greater disease control or cure.

Conclusions

Information from PTC websites often differs from recommendations found in international consensus guidelines. As online marketing information may have significant influence on patient decision-making, alignment of such information with accepted guidelines and consensus opinion should be adopted by PTC providers.

http://ift.tt/2pevTZ7

Are non-pharmacologic pain interventions effective at reducing pain in adult patients visiting the Emergency Department? A Systematic Review and Meta-analysis

Abstract

Study Objective

Pain is a common complaint in the Emergency Department (ED). Its management currently depends heavily on pharmacologic treatment, but evidence suggests non-pharmacologic interventions may be beneficial. The purpose of this systematic review and meta-analysis was to assess whether non-pharmacologic interventions in the ED are effective in reducing pain.

Methods

We conducted a systematic review of the literature on all types of non-pharmacologic interventions in the ED with pain reduction as an outcome. We performed a qualitative summary of all studies meeting inclusion criteria, and meta-analysis of randomized controlled studies measuring post-intervention changes in pain. Interventions were divided by type into 5 categories for more focused sub-analyses.

Results

Fifty-six studies met inclusion criteria for summary analysis. The most studied interventions were acupuncture (10 studies) and physical therapy (6 studies). The type of pain most studied was musculoskeletal pain (34 studies). Most (42 studies) reported at least one improved outcome after intervention. Of these, 23 studies reported significantly reduced pain compared to control, 24 studies showed no difference, and 9 studies had no control group. Meta-analysis included 22 qualifying randomized controlled trials and had a global standardized mean difference of -0.46 (95% CI: -0.66 to -0.27) in favor of non-pharmacologic interventions for reducing pain.

Conclusion

Non-pharmacologic interventions are often effective in reducing pain in the ED. However, most existing studies are small, warranting further investigation into their use for optimizing ED pain management

This article is protected by copyright. All rights reserved.

http://ift.tt/2FVeYUT

Spirometrically Confirmed Chronic Obstructive Pulmonary Disease Worsens Long-Term Prognosis after Percutaneous Coronary Intervention

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 6, Page 824-826, March 15, 2018.


http://ift.tt/2FDUwsv

Acute Eosinophilic Pneumonia. Causes, Diagnosis, and Management

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 6, Page 728-736, March 15, 2018.


http://ift.tt/2DulNYw

Engagement of the motor system in position monitoring: reduced distractor suppression and effects of internal representation quality on motor kinematics

Abstract

The position monitoring task is a measure of divided spatial attention in which participants track the changing positions of one or more objects, attempting to represent positions with as much precision as possible. Typically precision of representations declines with each target object added to participants' attention load. Since the motor system requires precise representations of changing target positions, we investigated whether position monitoring would be facilitated by increasing engagement of the motor system. Using motion capture, we recorded the positions of participants' index finger during pointing responses. Participants attempted to monitor the changing positions of between one and four target discs as they moved randomly around a large projected display. After a period of disc motion, all discs disappeared and participants were prompted to report the final position of one of the targets, either by mouse click or by pointing to the final perceived position on the screen. For mouse click responses, precision declined with attentional load. For pointing responses, precision declined only up to three targets and remained at the same level for four targets, suggesting obligatory attention to all four objects for loads above two targets. Kinematic profiles for pointing responses for highest and lowest loads showed greater motor adjustments during the point, demonstrating that, like external environmental task demands, the quality of internal representations affects motor kinematics. Specifically, these adjustments reflect the difficulty of both pointing to very precisely represented locations as well as keeping representations distinct from one another.

http://ift.tt/2G0rkuW

Developing Clinical Guidelines

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 6, Page 837-837, March 15, 2018.


http://ift.tt/2Dup0XY