Gastric Outlet Obstruction After Esophagectomy: Retrospective Analysis of the Effectiveness and Safety of Postoperative Endoscopic Pyloric Dilatation

Abstract

Background and aims

Delayed gastric emptying after esophagectomy with gastric replacement can pose a significant postoperative problem, often leading to aspiration and pneumonia. The present study analyzes retrospectively the effectiveness of endoscopic pyloric dilatation for post-surgical gastric outlet obstruction.

Methods

Between March 2006 and March 2010, 403 patients underwent a transthoracic en-bloc esophagectomy and reconstruction with a gastric tube and intrathoracic esophagogastrostomy. In patients with postoperative symptoms of an outlet dysfunction and the confirmation by endoscopy, pyloric dilatations were performed without preference with either 20- or 30-mm balloons.

Results

A total of 89 balloon dilatations of the pylorus after esophagectomy were performed in 60 (15.6 %) patients. In 21 (35 %) patients, a second dilatation of the pylorus was performed. 55 (61.8 %) dilatations were performed with a 30-mm balloon and 34 (38.2 %) with a 20-mm balloon. The total redilatation rate for the 30-mm balloon was 20 % (n = 11) and 52.9 % (n = 18) for the 20-mm balloon (p < 0.001). All dilatations were performed without any complications.

Conclusions

Pylorus spasm contributes to delayed gastric emptying leading to postoperative complications after esophagectomy. Endoscopic pyloric dilatation after esophagectomy is a safe procedure for treatment of gastric outlet obstruction. The use of a 30-mm balloon has the same safety profile but a 2.5 lower redilatation rate compared to the 20-mm balloon. Thus, the use of 20-mm balloons has been abandoned in our clinic.

http://ift.tt/2cCYqkR

Enhanced Recovery Pathway for Right and Left Colectomy: Comparison of Functional Recovery

Abstract

Background

Enhanced recovery (ERAS) guidelines do not differentiate between left- and right-sided colectomies, but differences in recovery have been reported for the two procedure types. We aimed to compare compliance with the ERAS protocol and outcomes after right versus left colectomy.

Methods

Between June 2011 and September 2014, all patients undergoing elective colonic resection were treated according to a standardized ERAS protocol and entered a prospective database. This retrospective analysis compared right and left colectomy regarding application of the ERAS pathway, bowel recovery, complications, and hospital stay.

Results

Eighty-five patients with right colectomy matched well with 138 left-sided resections for baseline demographics. Overall compliance with the ERAS protocol was 76 % for right versus 77 % for left colectomy patients (p = 0.492). First flatus occurred at postoperative day 2 in both groups (p = 0.057); first stool was observed after a median of 3 (right) and 2 days (left), respectively (p = 0.189). Twenty patients (24 %) needed postoperative nasogastric tube after right colectomy compared to 11 patients (8 %) after left colectomy (p = 0.002). Overall complication rates were 49 and 37 % for right and left colectomy, respectively (p = 0.071). Median postoperative length of stay was 6 days (IQR 4–9) after right and 5 days (IQR 4–7.5) after left colectomy (p = 0.020).

Conclusion

Overall compliance with the protocol was equally high in both groups showing that ERAS protocol was applicable for right and left colectomy. Functional recovery however, tended to be slower after right colectomy, and postoperative ileus rate was significantly higher. More cautious early feeding after right colectomy should be considered.

http://ift.tt/2cCYot1

Comparison of Salvage Living Donor Liver Transplantation and Local Regional Therapy for Recurrent Hepatocellular Carcinoma

Abstract

Background and aims

Salvage liver transplantation (LT) provides definite treatment for recurrent hepatocellular carcinoma (HCC) after primary liver resection. However, salvage living donor LT (SLDLT) involves more surgical difficulty, compared to local regional therapy (LRT). The optimal treatment strategy remains unclear. This study aims to compare the survival between SLDLT and LRT for patients with recurrent HCC after primary hepatic resection in a single center.

Methods

Between 2001 and 2010, 211 patients with recurrent HCC after primary liver resection and a certain Milan criteria were enrolled. Among these patients, 41 and 170 patients received SLDLT and LRT, respectively. Clinical parameters were analyzed in terms of overall survival by multivariate analysis.

Results

The 1-, 3-, and 5-year overall survival rates were 90.2, 80.4, and 80.4 % in the SLDLT group, and 91.6, 71.7, and 51.1 % in LRT group, respectively. A paradoxical phenomenon of survival was noticed—a poorer survival rate within the first year in the SLDLT group but a better one after that year. For patients who survived more than 1 year, the SLDLT led to significantly better survival outcomes than LRT (P < 0.001). In multivariate analysis, SLDLT and alpha-fetoprotein (AFP) level < 200 ng/ml at recurrence were associated with better survival.

Conclusions

To manage recurrent HCC, SLDLT with reasonable surgical mortality provided better long-term survival. AFP is an independent risk factor for overall survival.

http://ift.tt/2cCZDsk

Robotic-Assisted Pancreatic Resections

Abstract

Background

Robotic assistance enhances surgical dexterity and could facilitate wider adoption of laparoscopy for pancreatic resections (PR).

Methods

Data were prospectively entered into a database and analyzed retrospectively to assess feasibility and safety of robotic-assisted PR (RAPR). Additionally, robotic-assisted pancreaticoduodenectomy (RAPD) was compared to a contemporary group of open pancreaticoduodenectomies (OPD).

Results

Between October 2008 and October 2014, 200 consecutive patients underwent RAPR. Three procedures were converted to open surgery (1.5 %), despite 14 patients required associated vascular procedures. RAPD was performed in 83 patients (41.5 %), distal pancreatectomy in 83 (41.5 %), total pancreatectomy in 17 (8.5 %), tumor enucleation in 12 (6 %), and central pancreatectomy in 5 (2.5 %). Thirty-day and 90-day mortality rates were 0.5 and 1 %, respectively. Both deaths occurred after RAPD with vein resection. Complications occurred in 63.0 % of the patients (≥Clavien-Dindo grade IIIb in 4 %). Median comprehensive complication index was 20.9 (0-26.2). Incidence of grade B/C pancreatic fistula was 28.0 %. Reoperation was required in 14 patients (7.0 %). The risk of reoperation decreased after post-operative day 20 (OR 0.072) (p = 0.0015). When compared to OPD, RAPD was associated with longer mean operative time (527.2 ± 166.1 vs. 425.3 ± 92.7; <0.0001) but had an equivalent safety profile. The median number of examined lymph nodes (37; 28.8–45.3 vs. 36; 28–52.8) and the rate of margin positivity in patients diagnosed with pancreatic cancer were also similar (12.5 vs. 45.5 %).

Conclusions

RAPR, including RAPD, are safely feasible in selected patients. The results of RAPD in pancreatic cancer are encouraging but deserve further investigation.

http://ift.tt/2cCYtNB

Laparoscopy-Assisted Proximal Gastrectomy with the Hinged Double Flap Method

Abstract

Background

No standard proximal gastrectomy method for gastric cancer of the upper third of the stomach (UGC) has been established because few of the current methods prevent gastro-esophageal reflux and allow easy postoperative endoscopic surveillance. In the present study, we describe laparoscopic proximal gastrectomy with the hinged double flap method (Kamikawa's method) in detail and examine the short- to medium-term outcomes of this approach, which resulted in excellent postoperative function.

Methods

Between 2011 and 2015, 24 patients with early-stage primary UGC underwent laparoscopic proximal gastrectomy with the above-mentioned method. The celiac and hepatic nerves were preserved without pyloroplasty. A hand-sewn esophagogastric anastomosis was produced intracorporeally.

Results

There were no in-hospital deaths, and none of the patients were converted to open surgery. Complications occurred in two patients in the early part of this study (minor anastomotic leakage in one case and an abdominal abscess in the other). None of the patients exhibited symptoms of reflux. Regarding the patients' postoperative endoscopic classifications, 17, 2, and 1 patient were considered to have grade N or M, grade A, and grade B esophagitis, respectively. All of the patients remain alive, and no cases of postoperative bowel obstruction or recurrent cancer have been observed.

Conclusions

This method can be performed safely and achieves excellent outcomes in terms of preventing gastro-esophageal reflux. It deserves further evaluation in a multi-center clinical study.

http://ift.tt/2cCYvoO

Pre- and postdiagnostic diet in relation to mortality among breast cancer survivors in the CPS-II Nutrition Cohort

Abstract

Purpose

Due to the limited evidence on the role of diet and cause-specific mortality among breast cancer survivors, current nutrition guidelines for this population are consistent with those for cancer prevention. We evaluated whether diets consistent with the American Cancer Society recommendations for cancer prevention were associated with risk of death in breast cancer survivors.

Methods

Participants reported information on diet and other factors at baseline in 1992–1993 and twice during follow-up. A nine-point score reflecting concordance with diet recommendations was calculated. Multivariable-adjusted relative risks (RR) and 95 % confidence intervals (CI) for diet score in relation to overall and cause-specific mortality were computed using Cox proportional hazards regression methods.

Results

Among 4,452 women diagnosed with locally and regionally staged breast cancer after baseline and until 2011, 1,204 died during follow-up through 2012 (398 from breast cancer). Prediagnostic diet score was not associated with mortality from any cause. Postdiagnostic diet score was associated with neither breast cancer-specific mortality (RR 1.44, 95 % CI 0.90–2.30 for scores 6–9 vs 0–2) nor cardiovascular disease mortality (RR 0.81, 95 % CI 0.47–1.39), but compared to a score of 0–2, a score of 6–9 was associated with a borderline lower risk of other causes of death (RR 0.78, 95 % CI 0.56–1.07, p _trend = 0.03; per two-point increase in score RR 0.88, 95 % CI 0.79–0.99). Of diet score components, only limiting red and processed meat consumption was associated with statistically significantly lower risk of total, CVD, and other non-breast cancer mortality.

Conclusions

Diets consistent with guidelines for cancer prevention were not associated with breast cancer-specific mortality. However, their association with other causes of mortality underscores the importance of consuming a healthy diet in this population.

http://ift.tt/2cDjVCd

Klinefelter syndrome (KS): genetics, clinical phenotype and hypogonadism

Abstract

Klinefelter Syndrome (KS) is characterized by an extreme heterogeneity in its clinical and genetic presentation. The relationship between clinical phenotype and genetic background has been partially disclosed; nevertheless, physicians are aware that several aspects concerning this issue are far to be fully understood. By improving our knowledge on the role of some genetic aspects as well as on the KS, patients' interindividual differences in terms of health status will result in a better management of this chromosomal disease. The aim of this review is to provide an update on both genetic and clinical phenotype and their interrelationships.

http://ift.tt/2cOMA4H

Stability Analysis of a Human Arm Interacting with a Force Augmenting Device

Abstract

This paper presents a stability analysis of the interaction between a human and a linear moving Force Augmenting Device (FAD). The analysis employs a mathematical model of the human arm, the FAD and their interaction. As a depart from past works, this article presents a stability analysis considering time-delays in the human model. A key ingredient in the analysis is the use of the Rekasius substitution for replacing the time-delay terms. It is proved that the human machine interaction is stable when the human model has no delays. When delays are considered in the human model, the analysis provides an upper bound for the time-delays preserving a stable interaction. Numerical simulations allow to assess the human-FAD interaction. An experiment is performed with a laboratory prototype, where a human operator lifts a load. It is observed that the human machine interaction is stable and the human operator is able to move the load to a desired position by experiencing very little effort.

http://ift.tt/2cUs06M

Genotypes Affecting the Pharmacokinetics of Anticancer Drugs

Abstract

Cancer treatment is becoming more and more individually based as a result of the large inter-individual differences that exist in treatment outcome and toxicity when patients are treated using population-based drug doses. Polymorphisms in genes encoding drug-metabolizing enzymes and transporters can significantly influence uptake, metabolism, and elimination of anticancer drugs. As a result, the altered pharmacokinetics can greatly influence drug efficacy and toxicity. Pharmacogenetic screening and/or drug-specific phenotyping of cancer patients eligible for treatment with chemotherapeutic drugs, prior to the start of anticancer treatment, can identify patients with tumors that are likely to be responsive or resistant to the proposed drugs. Similarly, the identification of patients with an increased risk of developing toxicity would allow either dose adaptation or the application of other targeted therapies. This review focuses on the role of genetic polymorphisms significantly altering the pharmacokinetics of anticancer drugs. Polymorphisms in DPYD, TPMT, and UGT1A1 have been described that have a major impact on the pharmacokinetics of 5-fluorouracil, mercaptopurine, and irinotecan, respectively. For other drugs, however, the association of polymorphisms with pharmacokinetics is less clear. To date, the influence of genetic variations on the pharmacokinetics of the increasingly used monoclonal antibodies has hardly been investigated. Some studies indicate that genes encoding the Fcγ-receptor family are of interest, but more research is needed to establish if screening before the start of therapy is beneficial. Considering the profound impact of polymorphisms in drug transporters and drug-metabolizing enzymes on the pharmacokinetics of chemotherapeutic drugs and hence, their toxicity and efficacy, pharmacogenetic and pharmacokinetic profiling should become the standard of care.

http://ift.tt/2cqbRov

Towards a Model-Based Dose Recommendation for Doxorubicin in Children

Abstract

Following the publication of our paper regarding a population-based model of doxorubicin pharmacokinetics in children in Clinical Pharmacokinetics last year (Voller et al. 54:1139–1149, 2015), we have received many inquiries on the practical clinical consequences of this model; however, a population-based model is only one of the aspects to be taken into account when developing dosing algorithms. In addition, any new method of dose calculation would need clinical validation and, subsequently, a new clinical trial. However, such a trial, especially with regard to burden to the children involved, requires optimal preparation and the selection of the best hypotheses. The European Paediatric Oncology Off-Patent Medicines Consortium (EPOC), represented by the authors, would therefore like to initiate an interdisciplinary discussion on the clinical and pharmacological goals for dose calculation. This current opinion summarizes the existing knowledge on the pharmacokinetics and pharmacodynamics of doxorubicin. Our aim was to define the clinical needs as precisely as possible, with the intention of stimulating discussion between the clinical pediatric oncologist and the pediatric pharmacologist. By doing so, we hope to define surrogates for best practice of a common doxorubicin dose in children. The intent is for a trial to validate a rational dose calculation rule, leading to a regulatory process and subsequent labeling.

http://ift.tt/2cOLllX

Genetic Polymorphisms Affecting the Pharmacokinetics of Antiretroviral Drugs

Abstract

Background

Antiretroviral treatment is highly effective in enhancing HIV-positive patients' survival and quality of life. Despite an increased tolerability in recent years, a substantial amount of patients experience side effects. Antiretrovirals' efficacy and tolerability have been associated with plasma concentrations and single nucleotide polymorphisms in selected genes involved in drug disposition.

Objective

Our aim was to review the current knowledge in genetic polymorphisms affecting plasma, intracellular or compartmental concentrations of antiretrovirals.

Methods

A search of the PubMed database was conducted to identify relevant articles, using the following terms: 'pharmacogenetics' or 'pharmacogenomics' or 'single nucleotide polymorphisms' or 'genetic/allelic variants' and 'pharmacokinetics' or 'concentrations' and 'HIV' or 'antiretroviral'. Abstracts from the main HIV conferences during 2015 and 2016 were also searched using the same keywords. Abstracts were manually checked and, if relevant, full papers were obtained. Only articles published in English were selected.

Results

Several genetic polymorphisms in genes coding enzymes involved in drug metabolism (cytochrome P450 isoenzymes and uridine diphosphate glucuronosyltransferases) and transport (P-glycoprotein, anionic and cationic transporters, other transporters), as well as nuclear receptors (pregnane X receptor and the constitutive androstane receptor), have been associated with concentrations of antiretrovirals. The extent of such influence, the conflicting data, and the potential clinical relevance are discussed in the main section of this article.

Conclusion

Genetic polymorphisms may affect antiretroviral disposition, as well as both efficacy and toxicity. Despite a large amount of data, such precious knowledge has seldom been applied in patients. Studies on the clinical relevance and cost effectiveness of tailoring antiretroviral regimens to patients' genetic assets are lacking, but their importance may grow with the increasing age and complexity of persons living with HIV/AIDS.

http://ift.tt/2cqbkmp

The Effects of Pharmacological Compounds on Beat Rate Variations in Human Long QT-Syndrome Cardiomyocytes

Abstract

Healthy human heart rate fluctuates overtime showing long-range fractal correlations. In contrast, various cardiac diseases and normal aging show the breakdown of fractal complexity. Recently, it was shown that human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) intrinsically exhibit fractal behavior as in humans. Here, we investigated the fractal complexity of hiPSC-derived long QT-cardiomyocytes (LQT-CMs). We recorded extracellular field potentials from hiPSC-CMs at baseline and under the effect of various compounds including β-blocker bisoprolol, ML277, a specific and potent I_Ks current activator, as well as JNJ303, a specific I_Ks blocker. From the peak-to-peak-intervals, we determined the long-range fractal correlations by using detrended fluctuation analysis. Electrophysiologically, the baseline corrected field potential durations (cFPDs) were more prolonged in LQT-CMs than in wildtype (WT)-CMs. Bisoprolol did not have significant effects to the cFPD in any CMs. ML277 shortened cFPD in a dose-dependent fashion by 11 % and 5–11 % in WT- and LQT-CMs, respectively. JNJ303 prolonged cFPD in a dose-dependent fashion by 22 % and 7–13 % in WT- and LQT-CMs, respectively. At baseline, all CMs showed fractal correlations as determined by short-term scaling exponent α. However, in all CMs, the α was increased when pharmacological compounds were applied indicating of breakdown of fractal complexity. These findings suggest that the intrinsic mechanisms contributing to the fractal complexity are not altered in LQT-CMs. The modulation of I_Ks channel and β1-adrenoreceptors by pharmacological compounds may affect the fractal complexity of the hiPSC-CMs.

http://ift.tt/2cq6Vjq

Cell-penetrating peptides induce apoptosis and necrosis through specific mechanism and cause impairment of Na + –K + -ATPase and mitochondria

Abstract

Cell-penetrating peptides (CPPs) are widely used in the development of various drug delivery systems because of their ability of penetrating plasma membrane. However, the safety of their application remains largely unknown. In this study, we found that the incubation of two main kinds of CPPs with human normal liver cells could cause the occurrence of apoptosis and necrosis, then the detailed apoptosis-related protein were detected out. To discover the specific way which leads to these results, several methods were used in this study. Several cytokines, such as Caspase3 and Bcl-2, were detected to prove that the damage happened after treated with different CPPs. Then shielding the positive charge of TAT and R8, depletion of Na⁺ in culturing medium and addition of several inhibitors of specific ATPase site were used to investigate whether the cytotoxicity were charge-dependent and ATPase-related. Furthermore, the membrane potential of mitochondria and the leakage of mitochondrial cytochrome c were detected after treated with CPPs to investigate the damage on mitochondria. In general, our results assess the cytotoxicity caused by two main kinds of CPPs and reveal the clear mechanism of how it occurs. This study reveals the essence of cytotoxicity caused by CPPs, and the methods we followed can be used to evaluate the biocompatibility of new-designed CPPs, which makes the application of CPPs better and safer.

http://ift.tt/2cOK9PG

Association of interleukin-6 single nucleotide polymorphisms with juvenile idiopathic arthritis

Abstract

Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children. Genetics and inflammatory elements seem to act as major underlying factors in its pathogenesis. The aim of this study is to identify the associations between interleukin-6 (IL-6) gene polymorphisms and individuals' vulnerability to JIA in a group of Iranian pediatric patients. Fifty-four patients with JIA were enrolled in this investigation and compared with 139 healthy individuals. Using polymerase chain reaction with sequence-specific primers, cytokine genotyping was performed. The allele and genotype frequencies of two single nucleotide polymorphisms (SNPs) within the IL-6 gene at −174 and +565 positions were assessed. A significant positive association was observed for IL -6 −174 G allele in the patient group (p = 0.02). Furthermore, a positive association was observed in patients with JIA for the GG genotype at the same position (p < 0.01), thus revealing a predisposing effect in JIA patients. On the other hand, a significant negative association was found for IL-6 −174 CG genotype (p < 0.01) in the case group. No significant difference was discovered in both the allelic and genotypic frequencies of IL-6 +565 position between patients and controls. Additionally, haplotype analysis divulged over representation of IL-6 GG haplotype in patient group (p < 0.01) as well as IL-6 CG haplotype in healthy controls (p < 0.01). Certain allele, genotype, and haplotype in IL-6 gene were over expressed in patients with JIA, which probably could render individuals more susceptible to this disease.

http://ift.tt/2cDmeFp

Target attainment analysis and optimal sampling designs for population pharmacokinetic study on piperacillin/tazobactam in neonates and young infants

Abstract

Objectives

Population pharmacokinetic (popPK) analyses for piperacillin/tazobactam in neonates and infants of less than 2 months of age have been performed by our group previously. The results indicate that a dose of 44.44/5.56 mg/kg piperacillin/tazobactam every 8 or 12 h may not be enough for controlling infection in this population. In order to determine the appropriate dosing regimen and to provide a rationale for the development of dosing guidelines suitable for this population, further popPK studies of piperacillin/tazobactam would need to be conducted. The aim of the present study was to determine the appropriate dosing regimen and optimal sampling schedules in neonates and infants of less than 2 months of age.

Methods

Pharmacodynamic profiling of piperacillin using Monte Carlo simulation was performed to explore the target attainment probability of different dosing regimens for infections caused by different isolated pathogens. D-optimal designs for piperacillin and tazobactam were conducted separately, and the times that overlapped were chosen as the final sampling scheme for future popPK studies in neonates and young infants of less than 2 months of age.

Results

Our findings revealed that compared to the current empirical piperacillin/tazobactam dose regimen (50 mg/kg every 12 h by 5-min infusion in our hospital), the clinical outcome could be improved by increasing doses, increasing administration frequency, and prolonging intravenous infusion in neonates and infants of less than 2 months of age. The following optimal sampling windows were chosen as the final sampling scheme: 0.1–0.11, 0.26–0.29, 0.97–2.62, and 7.95–11.9 h administered every 12 h with 5-min infusion; 0.1–0.12, 0.39–0.56, 2.86–4.95, and 8.91–11.8 h administered every 12 h with 3-h infusion; 0.1–0.11, 0.22–0.29, 0.91–1.96, and 5.56–7.93 h administered every 8 h with 5-min infusion; 0.1–0.11, 0.38–0.48, 2.54–3.82, and 6.86–7.93 h administered every 8 h with 3-h infusion; 0.1–0.11, 0.25–0.28, 0.84–1.69, and 4.55–5.94 h administered every 6 h with 5-min infusion; and 0.1–0.11, 0.37–0.54, 3.13–3.72, and 5.57–5.99 h administered every 6 h with 3-h infusion.

Conclusions

The dosing regimen and sampling schedules proposed in this study should be evaluated in future popPK studies of piperacillin/tazobactam in neonates and infants. To the best of our knowledge, this is the first study that combined optimal sampling design with Monte Carlo simulation for designing popPK studies of piperacillin/tazobactam.

http://ift.tt/2cUAeLZ

Real-time and online screening method for materials emitting volatile organic compounds

Abstract

In the semiconductor industry, volatile organic compounds (VOCs) in the cleanroom air work as airborne molecular contamination, which reduce the production yield of semiconductor chips by forming nanoparticles and haze on silicon wafers and photomasks under ultraviolet irradiation during photolithography processes. Even though VOCs in outdoor air are removed by gas filters, VOCs can be emitted from many kinds of materials used in cleanrooms, such as organic solvents and construction materials (e.g., adhesives, flame retardants and sealants), threatening the production of semiconductors. Therefore, finding new replacements that emit lower VOCs is now essential in the semiconductor industry. In this study, we developed a real-time and online method to screen materials for developing the replacements by converting VOCs into nanoparticles under soft X-ray irradiation. This screening method was applied to measure VOCs emitted from different kinds of organic solvents and adhesives. Our results showed good repeatability and high sensitivity for VOCs, which come from aromatic compounds, some alcohols and all tested adhesives (Super glue and cleanroom-use adhesives). In addition, the overall trend of measured VOCs from cleanroom-use adhesives was well matched with those measured by a commercial thermal desorption–gas chromatography–mass spectrometry, which is a widely used off-line method for analyzing VOCs. Based on the results, this screening method can help accelerate the developing process for reducing VOCs in cleanrooms.

http://ift.tt/2ciEl05

Some new inequalities for continuous fusion frames and fusion pairs

This paper addresses continuous fusion frames and fusion pairs which are extensions of discrete fusion frames and continuous frames. The study of equalities and inequalities for various frames has seen great a...

http://ift.tt/2cz55dJ

Modified ilioinguinal approach in combined surgical exposures for displaced acetabular fractures involving two columns

The purpose of this study is to assess the advantages of modified ilioinguinal approach in combined surgical exposures for displaced acetabular fractures involving two columns management. 73 patients with disp...

http://ift.tt/2d6RI9P

Double-balloon endoscopy WAS effective in diagnosing small intestinal duplication: a case report

Ileal duplications are encountered infrequently in adults, because symptoms including abdominal pain, intussusception, hemorrhage, and perforation usually present in early childhood. In this report, we present...

http://ift.tt/2cz52i3

Fractional-order PI based STATCOM and UPFC controller to diminish subsynchronous resonance

This research article proposes a powerful fractional-order PI controller to mitigate the subsynchronous oscillations in turbine-generator shaft due to subsynchronous resonance (SSR) with flexible AC transmissi...

http://ift.tt/2d6RFuu

Downward trend in the prevalence of Helicobacter pylori infections and corresponding frequent upper gastrointestinal diseases profile changes in Southeastern China between 2003 and 2012

This present study aims to determine trends in the prevalence of H. pylori infections in Southeastern China between 2003 and 2012, and investigate corresponding changes in the prevalence of upper gastrointestinal...

http://ift.tt/2cz3KDT

Regarding Bocklage et al. “Regarding Dettloff et al. Mammary Analog Secretory Carcinoma (MASC) Involving the Thyroid Gland: A Report of First 3 Cases”

http://ift.tt/2cBWWXV

INI1 (SMARCB1)-Deficient Sinonasal Carcinoma: A Clinicopathologic Report of 2 Cases

Abstract

Poorly differentiated sinonasal malignancies are amongst the hardest differential diagnoses in pathology, owing to the large number of rare entities that arise there. Complicating the matter is that most pathologists, including those with experience in head and neck pathology, have little experience in any one of these rare entities. Most patients with sinonasal carcinoma present with locally advanced disease and in the past a combination of chemotherapy, radiotherapy, and surgery would usually be recommended without the specific disease subtype playing a large part of the decision making. However, in the era of "precision medicine" and targeted therapies, the specific tumour subtype and an accurate diagnosis will become increasingly important even for the so-called "undifferentiated carcinoma". Specific entities that tend to enter into the differential diagnosis include olfactory neuroblastoma, sinonasal undifferentiated carcinoma (SNUC), and non-keratinizing squamous cell carcinoma (viral and non-viral). However, recent new entities, such as NUT-midline carcinoma also have to be considered. Recently it was found that a subset of tumours originally diagnosed as one of the aforementioned entities all demonstrated loss of the ubiquitously expressed protein Integrase Interactor 1 (INI1; SMARCB1). These tumours were often basaloid with at least partial rhabdoid differentiation and most were considered a part of the SNUC spectrum. In this report, we describe two additional cases of INI1-deficient sinonasal carcinoma prospectively identified, both of which appeared to have a marked response to neo-adjuvant chemoradiation, a finding not previously described.

http://ift.tt/2cYckki

Anti-adhesive effect of poloxamer-based thermo-sensitive sol-gel in rabbit laminectomy model

Abstract

Poloxamer-based thermo-sensitive sol-gel has been developed to reduce the incidence of postoperative scar formation at the laminectomy site. The purpose of this study was to evaluate the anti-adhesive effect of poloxamer based thermo-sensitive sol-gel compared to hyaluronate based solution after laminectomy, using a rabbit model. A thermo-sensitive anti-adhesive with a property of sol-gel transition was manufactured by a physical mixture of Poloxamer188/407, Chitosan and Gelatin. The viscosity in different temperatures was assessed. 72 adult New Zealand rabbits underwent lumbar laminectomy and were randomly divided into experimental (treated with the newly developed agent), positive (treated with hyaluronate based solution), and negative control groups. Each group was subdivided into 1 and 4-week subgroups. Gross and histological evaluations were performed to assess the extent of epidural adhesion. The experimental group showed significantly higher viscosity compared to the positive control group and showed a significant increase of viscosity as the temperature increased. Gross evaluation showed no statistically significant differences between the 1- and 4-week subgroups. However, histologic evaluation showed significant differences both in 1- and 4-week subgroups. Although the 4-week histologic results of the experimental and the positive control subgroups showed no significant difference, both subgroups revealed higher value compared to the negative control subgroup with regard to the ratio of adhesion less than 50 %. The new poloxamer based thermo-sensitive agent showed superior efficacy over the hyaluronate based agent at 1 week postoperatively. At 4 weeks postoperatively, there were no statistically significant differences between the two agents, although both showed efficacy over the sham group.

http://ift.tt/2cXuK1z

Elastic and viscoelastic mechanical properties of brain tissues on the implanting trajectory of sub-thalamic nucleus stimulation

Abstract

Corresponding to pre-puncture and post-puncture insertion, elastic and viscoelastic mechanical properties of brain tissues on the implanting trajectory of sub-thalamic nucleus stimulation are investigated, respectively. Elastic mechanical properties in pre-puncture are investigated through pre-puncture needle insertion experiments using whole porcine brains. A linear polynomial and a second order polynomial are fitted to the average insertion force in pre-puncture. The Young's modulus in pre-puncture is calculated from the slope of the two fittings. Viscoelastic mechanical properties of brain tissues in post-puncture insertion are investigated through indentation stress relaxation tests for six interested regions along a planned trajectory. A linear viscoelastic model with a Prony series approximation is fitted to the average load trace of each region using Boltzmann hereditary integral. Shear relaxation moduli of each region are calculated using the parameters of the Prony series approximation. The results show that, in pre-puncture insertion, needle force almost increases linearly with needle displacement. Both fitting lines can perfectly fit the average insertion force. The Young's moduli calculated from the slope of the two fittings are worthy of trust to model linearly or nonlinearly instantaneous elastic responses of brain tissues, respectively. In post-puncture insertion, both region and time significantly affect the viscoelastic behaviors. Six tested regions can be classified into three categories in stiffness. Shear relaxation moduli decay dramatically in short time scales but equilibrium is never truly achieved. The regional and temporal viscoelastic mechanical properties in post-puncture insertion are valuable for guiding probe insertion into each region on the implanting trajectory.

http://ift.tt/2deJFq8

Finite element analysis of cementless femoral stems based on mid- and long-term radiological evaluation

Abstract

Background

Femoral bone remodeling in response to stress shielding induces periprosthetic bone loss. Computerized finite element analysis (FEA) is employed to demonstrate differences in initial stress distribution. However, FEA is often performed without considering the precise sites at which the stem was fixed. We determined whether FEA reflects mid-term radiological examination exactly as predicted following long-term stress shielding.

Methods

Femur–stem fixation sites were evaluated radiologically according to the location of spot welds in two anatomical cementless stem designs. Based on mid-term radiological results, four femur–stem bonding site conditions were defined as: (Condition A) no bonding; (Condition B) bonding within the 10 mm area proximal to the distal border of the porous area; (Condition C) bonding of the entire porous area; and (Condition D) bonding of the entire femoral stem, prior to conducting FEA analysis. Furthermore, we radiographically evaluated mid- and long-term stress shielding, and measured bone mineral density of the femur 10 years after total hip arthroplasty.

Results

Spot welds appeared frequently around the border between the porous and smooth areas. FEA showed that, based on mid-term radiological evaluation, von Mises stress was reduced in condition B in the area proximal to the femur–stem bonding sites for both stem designs compared with condition A (no bonding). Conversely, von Mises stress at all areas of the femur–stem bonding sites in conditions C and D was higher than that in condition A. With respect to stress shielding progression, there was no significant difference between the two types of stem designs. However, stress shielding progressed and was significantly higher in the presence of spot welds (p = 0.001). In both stem designs, bone mineral density in zone VII was significantly lower than that in the contralateral hips.

Conclusions

These results indicate that FEA based on mid-term radiological evaluation may be helpful to predict the influence of long-term stress shielding more precisely.

http://ift.tt/2df52Ym

Ion Isolation in a Linear Ion Trap Using Dual Resonance Frequencies

Abstract

Ion isolation in a linear ion trap is demonstrated using dual resonance frequencies, which are applied simultaneously. One frequency is used to eject ions of a broad m/z range higher in m/z than the target ion, and the second frequency is set to eject a range of ions lower in m/z. The combination of the two thus results in ion isolation. Despite the simplicity of the method, even ions of low intensity may be isolated since signal attenuation is less than an order of magnitude in most cases. The performance of dual frequency isolation is demonstrated by isolating individual isotopes of brominated compounds.

Graphical Abstract

ᅟ

http://ift.tt/2ckTz9Z

Gas-Phase Oxidation of Neutral Basic Residues in Polypeptide Cations by Periodate

Abstract

The gas-phase oxidation of doubly protonated peptides containing neutral basic residues to various products, including [M + H + O]⁺, [M – H]⁺, and [M – H – NH₃]⁺, is demonstrated here via ion/ion reactions with periodate. It was previously demonstrated that periodate anions are capable of oxidizing disulfide bonds and methionine, tryptophan, and S-alkyl cysteine residues. However, in the absence of these easily oxidized sites, we show here that systems containing neutral basic residues can undergo oxidation. Furthermore, we show that these neutral basic residues primarily undergo different types of oxidation (e.g., hydrogen abstraction) reactions than those observed previously (i.e., oxygen transfer to yield the [M + H + O]⁺ species) upon gas-phase ion/ion reactions with periodate anions. This chemistry is illustrated with a variety of systems, including a series of model peptides, a cell-penetrating peptide containing a large number of unprotonated basic sites, and ubiquitin, a roughly 8.6 kDa protein.

Graphical Abstract

ᅟ

http://ift.tt/2ckV2wH

Multigenerational Broadband Collision-Induced Dissociation of Precursor Ions in a Linear Quadrupole Ion Trap

Abstract

A method of fragmenting ions over a wide range of m/z values while balancing energy deposition into the precursor ion and available product ion mass range is demonstrated. In the method, which we refer to as "multigenerational collision-induced dissociation", the radiofrequency (rf) amplitude is first increased to bring the lowest m/z of the precursor ion of interest to just below the boundary of the Mathieu stability diagram (q = 0.908). A supplementary AC signal at a fixed Mathieu q in the range 0.2–0.35 (chosen to balance precursor ion potential well depth with available product ion mass range) is then used for ion excitation as the rf amplitude is scanned downward, thus fragmenting the precursor ion population from high to low m/z. The method is shown to generate high intensities of product ions compared with other broadband CID methods while retaining low mass ions during the fragmentation step, resulting in extensive fragment ion coverage for various components of complex mixtures. Because ions are fragmented from high to low m/z, space charge effects are minimized and multiple discrete generations of product ions are produced, thereby giving rise to "multigenerational" product ion mass spectra.

Graphical Abstract

ᅟ

http://ift.tt/2ckToeQ

Quantification of Carbohydrates and Related Materials Using Sodium Ion Adducts Produced by Matrix-Assisted Laser Desorption Ionization

Abstract

The utility of sodium ion adducts produced by matrix-assisted laser desorption ionization for the quantification of analytes with multiple oxygen atoms was evaluated. Uses of homogeneous solid samples and temperature control allowed the acquisition of reproducible spectra. The method resulted in a direct proportionality between the ion abundance ratio I([A + Na]⁺)/I([M + Na]⁺) and the analyte concentration, which could be used as a calibration curve. This was demonstrated for carbohydrates, glycans, and polyether diols with dynamic range exceeding three orders of magnitude.

Graphical Abstract

ᅟ

http://ift.tt/2ckTa77

Localization of Post-Translational Modifications in Peptide Mixtures via High-Resolution Differential Ion Mobility Separations Followed by Electron Transfer Dissociation

Abstract

Precise localization of post-translational modifications (PTMs) on proteins and peptides is an outstanding challenge in proteomics. While electron transfer dissociation (ETD) has dramatically advanced PTM analyses, mixtures of localization variants that commonly coexist in cells often require prior separation. Although differential or field asymmetric waveform ion mobility spectrometry (FAIMS) achieves broad variant resolution, the need for standards to identify the features has limited the utility of approach. Here we demonstrate full a priori characterization of variant mixtures by high-resolution FAIMS coupled to ETD and the procedures to systematically extract the FAIMS spectra for all variants from such data.

Graphical Abstract

ᅟ

http://ift.tt/2ckUSpg

Autoinducer-2 analogs and electric fields - an antibiotic-free bacterial biofilm combination treatment

Abstract

Bacterial biofilms are a common cause of chronic medical implant infections. Treatment and eradication of biofilms by conventional antibiotic therapy has major drawbacks including toxicity and side effects associated with high-dosage antibiotics. Additionally, administration of high doses of antibiotics may facilitate the emergence of antibiotic resistant bacteria. Thus, there is an urgent need for the development of treatments that are not based on conventional antibiotic therapies. Presented herein is a novel bacterial biofilm combination treatment independent of traditional antibiotics, by using low electric fields in combination with small molecule inhibitors of bacterial quorum sensing – autoinducer-2 analogs. We investigate the effect of this treatment on mature Escherichia coli biofilms by application of an alternating and offset electric potential in combination with the small molecule inhibitor for 24 h using both macro and micro-scale devices. Crystal violet staining of the macro-scale biofilms shows a 46 % decrease in biomass compared to the untreated control. We demonstrate enhanced treatment efficacy of the combination therapy using a high-throughput polydimethylsiloxane-based microfluidic biofilm analysis platform. This microfluidic flow cell is designed to reduce the growth variance of in vitro biofilms while providing an integrated control, and thus allows for a more reliable comparison and evaluation of new biofilm treatments on a single device. We utilize linear array charge-coupled devices to perform real-time tracking of biomass by monitoring changes in optical density. End-point confocal microscopy measurements of biofilms treated with the autoinducer analog and electric fields in the microfluidic device show a 78 % decrease in average biofilm thickness in comparison to the negative controls and demonstrate good correlation with real-time optical density measurements. Additionally, the combination treatment showed 76 % better treatment efficacy compared to conventional antibiotic therapy. Taken together these results suggest that the antibiotic-free combination treatment described here may provide an effective alternative to traditional antibiotic therapies against bacterial biofilm infections. Use of this combination treatment in the medical and environmental fields would alleviate side effects associated with high-dosage antibiotic therapies, and reduce the rise of antibiotic-resistant bacteria.

http://ift.tt/2ckVbR0

Controlled evacuation using the biocompatible and energy efficient microfluidic ejector

Abstract

Development of controlled vacuum is having many applications in the realm of biotechnology, cell transfer, gene therapy, biomedical engineering and other engineering activities involving separation or chemical reactions. Here we show the controlled vacuum generation through a biocompatible, energy efficient, low-cost and flexible miniature device. We have designed and fabricated microfluidic devices from polydimethylsiloxane which are capable of producing vacuum at a highly controlled rate by using water as a motive fluid. Scrupulous removal of infected fluid/body fluid from the internal hemorrhage affected parts during surgical operations, gene manipulation, cell sorting, and other biomedical activities require complete isolation of the delicate cells or tissues adjacent to the targeted location. We demonstrate the potential of the miniature device to obtain controlled evacuation without the use of highly pressurized motive fluids. Water has been used as a motive liquid to eject vapor and liquid at ambient conditions through the microfluidic devices prepared using a low-cost fabrication method. The proposed miniature device may find applications in vacuum generation especially where the controlled rate of evacuation, and limited vacuum generation are of utmost importance in order to precisely protect the cells in the nearby region of the targeted evacuated area.

http://ift.tt/2ciBdBA

High-efficient and high-content cytotoxic recording via dynamic and continuous cell-based impedance biosensor technology

Abstract

Cell-based bioassays were effective method to assess the compound toxicity by cell viability, and the traditional label-based methods missed much information of cell growth due to endpoint detection, while the higher throughputs were demanded to obtain dynamic information. Cell-based biosensor methods can dynamically and continuously monitor with cell viability, however, the dynamic information was often ignored or seldom utilized in the toxin and drug assessment. Here, we reported a high-efficient and high-content cytotoxic recording method via dynamic and continuous cell-based impedance biosensor technology. The dynamic cell viability, inhibition ratio and growth rate were derived from the dynamic response curves from the cell-based impedance biosensor. The results showed that the biosensors has the dose-dependent manners to diarrhetic shellfish toxin, okadiac acid based on the analysis of the dynamic cell viability and cell growth status. Moreover, the throughputs of dynamic cytotoxicity were compared between cell-based biosensor methods and label-based endpoint methods. This cell-based impedance biosensor can provide a flexible, cost and label-efficient platform of cell viability assessment in the shellfish toxin screening fields.

http://ift.tt/2ckUl6G

Lead Poisoning Due to Herbal Medications

Abstract

Lead ranks as one of the most serious environmental poisons all over the world amongst toxic heavy metals with no known biological function useful for the human body. A case of lead toxicity due to consumption of herbal medicine is being discussed. The case presented with gastrointestinal complaints and history of intake of herbal medicines for diabetes control for past 8 months. The analysis of the powdered herbal medicine procured from ayurveda practitioner was found to have high content of lead responsible for the lead toxicity. The patient is under regular followup. He has improved symptomatically on chelating therapy and blood lead levels have gradually improved. Regular awareness programs should be conducted in the population regarding possible exposure through home made herbal remedies so that general public can be made aware of the dangerous side effects of lead and other heavy metals on health.

http://ift.tt/2d3r5hH

Spätfolgen von Tumoren im Kindesalter

Zusammenfassung

Hintergrund

Heute werden ca. 80 % der krebskranken Kinder und Jugendliche geheilt. Aufgrund von Ergebnissen der Nachsorgeforschung stellt sich die Frage: Sind die Geheilten auch gesund? Grundsätzlich ist es von der Art der Krebserkrankung und deren Behandlung abhängig, ob Folgeerkrankungen bzw. Spätfolgen auftreten. Beispielsweise leiden Patienten nach einer Hirntumorbehandlung und nach malignen Sarkomen sehr häufig unter Folgeerkrankungen.

Ergebnisse

US-amerikanische Daten zeigen, dass ca. zwei Drittel aller ehemaligen Krebspatienten 30 Jahre nach ihrer Krebsbehandlung im Kindesalter unter Spätfolgen leiden. Für Deutschland liegen solche Zahlen bislang nicht vor.

Regelmäßige Nachsorgeuntersuchungen entsprechend den Leitlinien zum Ausschluss eines Rezidivs oder möglicher Spätfolgen erfolgen meist in den erstbehandelnden Kinderkliniken. Im jungen Erwachsenenalter wird dieses Konzept den psychischen und physischen Bedürfnissen oft nicht mehr gerecht. Um die Versorgung dieser wachsenden Patientengruppe sicherzustellen, werden interdisziplinäre Ansätze (z. B. Nachsorgesprechstunden) benötigt, in denen pädiatrische Onkologen mit Internisten und anderen Disziplinen zusammenarbeiten. Individuelle, risikoadaptierte (in Abhängigkeit von Erkrankung und Behandlung) Nachsorgepläne basierend auf den bereits existierenden Nachsorgeempfehlungen, die für jeden erstellt werden, können eine Früherkennung möglicher Spätfolgen sicherstellen.

Schlussfolgerung

Der Erhalt von Gesundheit und Lebensqualität nach der Behandlung von Krebs (in allen Altersschichten) wird zukünftig für die Gesellschaft nicht nur einen sozialen, sondern auch einen wirtschaftlichen Faktor darstellen.

http://ift.tt/2d3pus8

Lokaltherapie solitärer intrapulmonaler maligner Rundherde

Zusammenfassung

Definition

Intrapulmonale Rundherde stellen in der Regel einen Zufallsbefund im Röntgenbild oder Computertomogramm des Thorax dar. Sie sind definiert als relativ gut abgegrenzte Läsionen von bis zu 3 cm Durchmesser, die allseits von Lungengewebe umgeben sind. Die Wahrscheinlichkeit für das Vorliegen eines malignen Tumors steigt mit ihrer Größe. Rundherde ab 1 cm Durchmesser bedürfen der aktiven Abklärung.

Therapie

Zur Behandlung solitärer maligner Tumoren steht für Patienten ohne nennenswert erhöhtes Operations- und Narkoserisiko der chirurgische Eingriff an erster Stelle. Patienten, die aus funktionellen Gründen für einen solchen nicht geeignet sind, können mit Radiofrequenzablation (RFA) oder Einzeitbestrahlung (SBRT) behandelt werden. In diesen Fällen müssen vor Therapiebeginn die Malignität nachgewiesen oder zumindest über einen begrenzten Zeitraum eine Größenzunahme der Läsion dokumentiert worden sein.

Outcome

In Bezug auf die lokale Tumorfreiheit ist die Operation unter den Voraussetzungen einer R0-Resektion den anderen Verfahren überlegen.

http://ift.tt/2cUqFgj

Behandlungsalgorithmus für das leitlinienbasierte therapeutische Management beim Zervixkarzinom

http://ift.tt/2d3oIvg

The Microbiome: a Revolution in Treatment for Rheumatic Diseases?

Abstract

Purpose of Review

The microbiome is the term that describes the microbial ecosystem that cohabits an organism such as humans. The microbiome has been implicated in a long list of immune-mediated diseases which include rheumatoid arthritis, ankylosing spondylitis, and even gout. The mechanisms to account for this effect are multiple. The clinical implications from observations on the microbiome and disease are broad.

Recent Findings

A growing number of microbiota constituents such as Prevotella copri, Porphyromonas gingivalis, and Collinsella have been correlated or causally related to rheumatic disease. The microbiome has a marked effect on the immune system. Our understanding of immune pathways modulated by the microbiota such as the induction of T helper 17 (Th17) cells and secretory immunoglobulin A (IgA) responses to segmented filamentous bacteria continues to expand. In addition to the gut microbiome, bacterial communities of other sites such as the mouth, lung, and skin have also been associated with the pathogenesis of rheumatic diseases.

Summary

Strategies to alter the microbiome or to alter the immune activation from the microbiome might play a role in the future therapy for rheumatic diseases.

http://ift.tt/2d6ry76

AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking (APS ACTION): 5-Year Update

Abstract

Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking (APS ACTION) is the first-ever international network created to design and conduct large-scale, multicenter clinical trials and research in persistently antiphospholipid antibody (aPL)-positive patients. Since its inception in 2010, the APS ACTION has made important strides toward our goal of international research collaboration and data sharing. Through the dedication and hard work of 50 APS ACTION members, collaborative international projects are currently underway including a multicenter web-based registry and repository of aPL-positive patients, a randomized controlled clinical trial assessing the efficacy of hydroxychloroquine for primary thrombosis prevention in persistently aPL-positive but thrombosis-free patients, standardization of aPL testing through the use of core laboratories worldwide, identification of the limitations in the existing aPL/APS literature, and conducting observational research studies to further our understanding of the disease. Thus far, APS ACTION has held annual workshops and summits with the aim of facilitating international collaboration and developing initiatives to recruit young scholars to APS research. This paper describes updates related to the organization's structure, ongoing research efforts, and recent accomplishments and discusses future directions.

http://ift.tt/2cyGJkq

Functional Genomics and Its Bench-to-Bedside Translation Pertaining to the Identified Susceptibility Alleles and Loci in Ankylosing Spondylitis

Abstract

Ankylosing spondylitis (AS) is a highly heritable disease for which there is a great unmet need for improved therapies. Genetics research has identified several major pathways involved in the disease, from which treatments have either now entered clinical practice or are in development. In particular, therapies targeting the IL-23 pathway were repositioned for use in AS following the discovery of multiple genes in the pathway as determinants of AS risk. Discovery of the association of aminopeptidase genes with AS, and subsequently with psoriasis, inflammatory bowel disease and other conditions, has triggered research into therapies targeting this pathway. The AS-genetic associations point to involvement of gut mucosal immunity in driving disease, and metagenomic studies have provided strong support that AS is a disease driven by interaction between the gut microbiome and host immune system, providing a rationale for the exploration of gut-targeted therapies for the disease.

http://ift.tt/2d6sCb1

Steven M. Goodman and William L. Jungers: Extinct Madagascar: Picturing the Island’s Past

http://ift.tt/2cBTsVv

Systematic Review of Prognostic Factors for Return to Work in Workers with Sub Acute and Chronic Low Back Pain

Abstract

Purpose We systematically reviewed the evidence on factors that predict duration of sick leave in workers after 6 weeks low back pain (LBP) related sick leave. We hypothesized that different factors affect the duration of the leave depending on the time away from work. Methods The review occurred in seven phases: (1) developing the central question, (2) conducting the literature search, (3) identifying relevant publications, (4) quality appraisal, (5) data extraction, (6) evidence synthesis, and (7) knowledge translation. We searched for studies that reported episodes of LBP and sick leave that lasted more than 6 weeks. All included studies reported at least one prognostic factor where return to work was the outcome. Results We identified twenty-two relevant publications. The impact of pain, functional status and radiating pain seems to change with duration of work disability. Workers' recovery expectations remain important after 6 weeks. Modified duties are rarely studied in later phases of work disability. Depression/mental health did not appear to be an important factor in later phases. Workplace physical factors remain important. There is insufficient evidence that pain catastrophising and fear avoidance are predictive factors in later phases. There was moderate evidence for age in the later phases. Functional capacity and claim related factors were supported by some evidence. Discusion Physical demands in the workplace are preventing workers from getting back to work in a timely fashion across phases. The psychosocial work environment is understudied in later phases. Overall, we cannot conclude that prognostic factors change over time.

http://ift.tt/2cM1ZnQ

Tolerogenic dendritic cells

Abstract

Deficits in immunological tolerance against self-antigens and antigens provided by the diet and commensal microbiota can result in the development of inflammatory and autoimmune disorders. Dendritic cells (DCs) are pivotal regulators of the immune response, specialized in antigen presentation to drive T cell priming and differentiation. DCs also have a tolerogenic function, participating in the enforcement of central and peripheral tolerance and the resolution of ongoing immune responses. Thus, DCs control effector and regulatory mechanisms relevant to the pathology of autoimmune disorders. In this review, we discuss recent findings regarding the control of the adaptive immune response by tolerogenic DCs. A thorough understanding of the mechanisms that control the tolerogenic DC phenotype will guide the development of novel strategies for the treatment of autoimmunity.

http://ift.tt/2cD7ndY

Sindbis Virus-Pseudotyped Lentiviral Vectors Carrying VEGFR2-Specific Nanobody for Potential Transductional Targeting of Tumor Vasculature

Abstract

Introduction of selectivity/specificity into viral-based gene delivery systems, such as lentiviral vectors (LVs), is crucial in their systemic administration for cancer gene therapy. The pivotal role of tumor-associated endothelial cells (TAECs) in tumor angiogenesis and overexpression of vascular endothelial growth factor receptor-2 (VEGFR2 or KDR) in TAECs makes them a potent target in cancer treatment. Herein, we report the development of VEGFR2-targeted LVs pseudotyped with chimeric sindbis virus E2 glycoprotein (cSVE2s). For this purpose, either sequence of a VEGFR2-specific nanobody or its natural ligand (VEGF₁₂₁) was inserted into the binding site of sindbis virus E2 glycoprotein. In silico modeling data suggested that the inserted targeting motifs were exposed in the context of cSVE2s. Western blot analysis of LVs indicated the incorporation of cSVE2s into viral particles. Capture ELISA demonstrated the specificity/functionality of the incorporated cSVE2s. Transduction of 293/KDR (expressing VEGFR2) or 293T cells (negative control) by constructed LVs followed by fluorescent microscopy and flow cytometric analyses indicated selective transduction of 293/KDR cells (30 %) by both targeting motifs compared to 293T control cells (1–2 %). These results implied similar targeting properties of VEGFR2-specific nanobody compared to the VEGF₁₂₁ and indicated the potential for transductional targeting of tumor vasculature by the nanobody displaying LVs.

http://ift.tt/2cyT1ZV

Bioprospecting from cultivable bacterial communities of marine sediment and invertebrates from the underexplored Ubatuba region of Brazil

Abstract

Shrimp fisheries along the Brazilian coast have significant environmental impact due to high by-catch rates (21 kg per kilogram of shrimp). Typically discarded, by-catch contains many invertebrates that may host a great variety of bacterial genera, some of which may produce bioactive natural products with biotechnological applications. Therefore, to utilize by-catch that is usually discarded we explored the biotechnological potential of culturable bacteria of two abundant by-catch invertebrate species, the snail Olivancillaria urceus and the sea star Luidia senegalensis. Sediment from the collection area was also investigated. Utilizing multiple isolation approaches, 134 isolates were obtained from the invertebrates and sediment. Small-subunit rRNA (16S) gene sequencing revealed that the isolates belonged to Proteobacteria, Firmicutes and Actinobacteria phyla and were distributed among 28 genera. Several genera known for their capacity to produce bioactive natural products (Micromonospora, Streptomyces, Serinicoccus and Verrucosispora) were retrieved from the invertebrate samples. To query the bacterial isolates for their ability to produce bioactive metabolites, all strains were fermented and fermentation extracts profiled by UP LC-HRMS and tested for antimicrobial activity. Four strains exhibited antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus warneri.

http://ift.tt/2deS8cS

Recommandations du CDU–HGE, du CNU d’HGE et de la SFED sur la formation en endoscopie digestive

http://ift.tt/2cLkMBo

Erratum to: Sarcopenia in Patients with Chronic Liver Disease: Can It Be Altered by Diet and Exercise?

http://ift.tt/2cXvMLa

Intestinal Transplant Inflammation: the Third Inflammatory Bowel Disease

Abstract

Intestinal transplantation is the most immunologically complex of all abdominal organ transplants. Understanding the role both humoral and innate and adaptive cellular immunity play in intestinal transplantation is critical to improving outcomes and increasing indications for patients suffering from intestinal failure. Recent findings highlighting the impact of donor-specific antibodies on intestinal allografts, the role of NOD2 as a key regulator of intestinal immunity, the protective effects of innate lymphoid cells, and the role of Th17 in acute cellular rejection are reviewed here.

http://ift.tt/2deKyiO

Clearing the Pediatric Cervical Spine

Abstract

Purpose of Review

Management and clinical evaluation of children who present with cervical spine injuries can be challenging, particularly in the pre-verbal child and in the presence of polytrauma.

Recent Findings

The successful approach to the pediatric patients' cervical spine involvement requires the following elements: an understanding of the significance of the problem, basic principles involved the management of pediatric cervical spine, and the role of radiologic studies in this patient population.

Summary

This chapter highlights the common characteristics and principles behind cervical spine trauma in children, reviews the available evidence for assessment of these injuries, and focuses on a step-wise approach that can be used in the assessment and clearance of the pediatric cervical spine.

http://ift.tt/2cLPDfu

Using PROMs in Healthcare: Who Should Be in the Driving Seat—Policy Makers, Health Professionals, Methodologists or Patients?

http://ift.tt/2cU7kMc

Effect of hybridization in the firs: artificial hybridization may lead to higher survival rate

Abstract

Hybridization experiments among fir (Abies) species contribute to clarification of both crossability and evolutionary relationships of organisms at least from the second half of the nineteenth century. The main aim of our study was to find possible effects of hybridization on survival rate and two growth parameters (height and diameter at the breast height) of fir trees at various levels of complexity in the Czech Republic. We compared (1) pure species consisting of seven fir taxa, (2) open pollinated hybrids comprising of twenty-one hybrid progenies of Greek Fir (A. cephalonica), Cilician Fir (A. cilicica) and Algerian Fir (A. numidica) and (3) artificial complex hybrids of Korean Fir (A. koreana) × (A. cilicica × A. cephalonica). For our analyses, we used combination of so-called traditional statistical methods and spatial modelling. Our results revealed that a higher level of hybridization and introgression may lead to a higher survival rate and furthermore, that neglecting of spatial autocorrelation in randomized complete block design might lead to wrong conclusions—because our analyses on height showed contrasting results between traditional and spatial modelling. The results of this study appear to be a good message for scientists dealing with forest tree breeding and facing a lack of confidence by practice. They might be also a good news for forestry practice, where foresters face high mortality during afforestation, e.g. in extreme environmental conditions. Our study highlighted that neglecting spatial autocorrelation could possibly lead to wrong conclusions in studies of similar spatial scale level.

http://ift.tt/2deCcrc

Taxonomic re-evaluation of the genus Lambertella (Rutstroemiaceae, Helotiales) and allied stroma-forming fungi

Abstract

The genus Lambertella is currently considered to be one of the largest genera in the family Rutstroemiaceae, and its major distinguishing character is the pigmentation of ascospores, besides a substratal stroma. Although Lambertella appears to be well-defined by morphological characters, its phylogenetic heterogeneity has been suggested in earlier studies. To circumscribe the genus more precisely, morphological examination and phylogenetic analysis was conducted on some Lambertella species and some allied stroma-forming fungi. In total, 58 taxa were included in the study, including 16 species with both a substratal stroma and pigmented ascospores. The polyphyly of Lambertella sensu lato was confirmed based on the phylogenetic analysis of ITS, LSU, and RPB2 regions. A highly supported clade is composed of five Lambertella species, including the type L. corni-maris. Morphologically, all species here included in Lambertella s. s. have brown ascospores prior to being discharged from asci, whereas in other species currently placed in Lambertella, but now excluded from the genus, they turn brown only after discharge. This clade was defined as Lambertella sensu stricto. Pigmentation of the ascospores was also recognized in Lanzia and Poculum, and even in the helotiaceous genus Hymenoscyphus, but always only after discharge. The convergent evolution of a dark substratal stroma in Rutstroemiaceae and Helotiaceae was also indicated.

http://ift.tt/2cpGlqx

The Microbiome: a Revolution in Treatment for Rheumatic Diseases?

Abstract

Purpose of Review

The microbiome is the term that describes the microbial ecosystem that cohabits an organism such as humans. The microbiome has been implicated in a long list of immune-mediated diseases which include rheumatoid arthritis, ankylosing spondylitis, and even gout. The mechanisms to account for this effect are multiple. The clinical implications from observations on the microbiome and disease are broad.

Recent Findings

A growing number of microbiota constituents such as Prevotella copri, Porphyromonas gingivalis, and Collinsella have been correlated or causally related to rheumatic disease. The microbiome has a marked effect on the immune system. Our understanding of immune pathways modulated by the microbiota such as the induction of T helper 17 (Th17) cells and secretory immunoglobulin A (IgA) responses to segmented filamentous bacteria continues to expand. In addition to the gut microbiome, bacterial communities of other sites such as the mouth, lung, and skin have also been associated with the pathogenesis of rheumatic diseases.

Summary

Strategies to alter the microbiome or to alter the immune activation from the microbiome might play a role in the future therapy for rheumatic diseases.

http://ift.tt/2d6ry76

AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking (APS ACTION): 5-Year Update

Abstract

Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking (APS ACTION) is the first-ever international network created to design and conduct large-scale, multicenter clinical trials and research in persistently antiphospholipid antibody (aPL)-positive patients. Since its inception in 2010, the APS ACTION has made important strides toward our goal of international research collaboration and data sharing. Through the dedication and hard work of 50 APS ACTION members, collaborative international projects are currently underway including a multicenter web-based registry and repository of aPL-positive patients, a randomized controlled clinical trial assessing the efficacy of hydroxychloroquine for primary thrombosis prevention in persistently aPL-positive but thrombosis-free patients, standardization of aPL testing through the use of core laboratories worldwide, identification of the limitations in the existing aPL/APS literature, and conducting observational research studies to further our understanding of the disease. Thus far, APS ACTION has held annual workshops and summits with the aim of facilitating international collaboration and developing initiatives to recruit young scholars to APS research. This paper describes updates related to the organization's structure, ongoing research efforts, and recent accomplishments and discusses future directions.

http://ift.tt/2cyGJkq

Functional Genomics and Its Bench-to-Bedside Translation Pertaining to the Identified Susceptibility Alleles and Loci in Ankylosing Spondylitis

Abstract

Ankylosing spondylitis (AS) is a highly heritable disease for which there is a great unmet need for improved therapies. Genetics research has identified several major pathways involved in the disease, from which treatments have either now entered clinical practice or are in development. In particular, therapies targeting the IL-23 pathway were repositioned for use in AS following the discovery of multiple genes in the pathway as determinants of AS risk. Discovery of the association of aminopeptidase genes with AS, and subsequently with psoriasis, inflammatory bowel disease and other conditions, has triggered research into therapies targeting this pathway. The AS-genetic associations point to involvement of gut mucosal immunity in driving disease, and metagenomic studies have provided strong support that AS is a disease driven by interaction between the gut microbiome and host immune system, providing a rationale for the exploration of gut-targeted therapies for the disease.

http://ift.tt/2d6sCb1

C9ORF72 gene expansion in a patient with intellectual disability and psychiatric disease

http://ift.tt/2dbDC2R

Activation of the mTOR signaling pathway in peritumoral tissues can cause glioma-associated seizures

Abstract

Epileptic seizures, the most common symptom accompanying glioma, are closely associated with tumor growth and patient quality of life. However, the association between glioma and glioma-related epilepsy is poorly understood. In fact, findings related to the location of epileptogenicity have been inconsistent in previous studies. We investigated seizure foci in patients with glioma and the corresponding association between glioma-related epilepsy and the tumoral and peritumoral microenvironment. Clinical characteristics, extracellular electrophysiology, immunohistochemistry, and western blots were conducted on 12 patients with glioma; nine patients had histories of preoperative seizures while three did not. Samples from included patients were used to identify seizure foci and mTOR pathway status. Electrophysiological recordings were conducted on 36 samples (tumor, peritumoral, and normal brain tissues) from 12 patients. Interictal-like discharges (ILDs) were observed in seven of nine peritumoral tissues obtained from patients with glioma that had experienced perioperative seizures. No ILDs were observed in any other sample groups. Western blots and immunohistochemistry for mTOR pathway proteins (mTOR and S6k) suggested that the mTOR pathway was activated in peritumoral tissues of patients with seizure history, but inactivated in patients without seizure history. Our results suggest that mTOR pathway expression in peritumoral tissues is associated with tumor-related seizures, thus providing a potential target for therapeutics aimed at simultaneously controlling gliomas and seizures.

http://ift.tt/2cL3zbo

New water-soluble palladium(II) complexes of lidocaine and phenylcyanamide derivative ligands: cytotoxicity and cellular response mechanisms

Summary

Three new palladium(II) complexes of lidocaine and phenylcyanamide derivative ligands of formula K[Pd(2,6-Me₂pcyd)₂(LC)], 1, K[Pd(2,6-Et₂pcyd)₂(LC)], 2, K[Pd(2,6-Cl₂pcyd)₂(LC)], 3 (LC: lidocaine, 2,6-Me₂pcyd: 2,6-dimethyl phenylcyanamide, 2,6-Et₂pcyd: 2,6-diethyl phenylcyanamide, 2,6-Cl₂pcyd: 2,6-dichloro phenylcyanamide) have been synthesized and fully characterized. The complexes 1–3 revealed a significant in vitro antiproliferative activity against human ovarian carcinoma (A2780), colorectal adenocarcinoma (HT29), breast (MCF-7), liver hepatocellular carcinoma (HepG-2) and lung adenocarcinoma (A549) cancer cell lines. All the complexes are more active than cisplatin and follow the trend 2 > 1 > 3. Mechanistic studies showed that the trend in cytotoxicity of the Pd(II) complexes is mainly consistent with their ability to accumulate into cancer cells and to increase intracellular basal reactive oxygen species levels, which consequently results in the loss of mitochondrial membrane potential and apoptosis induction.

http://ift.tt/2daiWbo

Chronic Adaptations to Eccentric Training: A Systematic Review

Abstract

Background

Resistance training is an integral component of physical preparation for athletes. A growing body of evidence indicates that eccentric strength training methods induce novel stimuli for neuromuscular adaptations.

Objective

The purpose of this systematic review was to determine the effects of eccentric training in comparison to concentric-only or traditional (i.e. constrained by concentric strength) resistance training.

Methods

Searches were performed using the electronic databases MEDLINE via EBSCO, PubMed and SPORTDiscus via EBSCO. Full journal articles investigating the long-term (≥4 weeks) effects of eccentric training in healthy (absence of injury or illness during the 4 weeks preceding the training intervention), adult (17–35 years), human participants were selected for the systematic review. A total of 40 studies conformed to these criteria.

Results

Eccentric training elicits greater improvements in muscle strength, although in a largely mode-specific manner. Superior enhancements in power and stretch-shortening cycle (SSC) function have also been reported. Eccentric training is at least as effective as other modalities in increasing muscle cross-sectional area (CSA), while the pattern of hypertrophy appears nuanced and increased CSA may occur longitudinally within muscle (i.e. the addition of sarcomeres in series). There appears to be a preferential increase in the size of type II muscle fibres and the potential to exert a unique effect upon fibre type transitions. Qualitative and quantitative changes in tendon tissue that may be related to the magnitude of strain imposed have also been reported with eccentric training.

Conclusions

Eccentric training is a potent stimulus for enhancements in muscle mechanical function, and muscle-tendon unit (MTU) morphological and architectural adaptations. The inclusion of eccentric loads not constrained by concentric strength appears to be superior to traditional resistance training in improving variables associated with strength, power and speed performance.

http://ift.tt/2cKYhgf

Path integral solution for a deformed radial Rosen–Morse potential

Abstract

An exact path integral treatment of a particle in a deformed radial Rosen–Morse potential is presented. For this problem with the Dirichlet boundary conditions, the Green's function is constructed in a closed form by adding to \(V_{q}(r)\) a \(\delta\) -function perturbation and making its strength infinitely repulsive. A transcendental equation for the energy levels \(E_{n_{r}}\) and the wave functions of the bound states can then be deduced.

http://ift.tt/2cTSNjq

Use of Lesion Response Rate in Actinic Keratosis Trials

Abstract

Complete patient clearance is often required by regulatory agencies for the approval of treatments for actinic keratosis (AK). However, an increasing number of clinicians have challenged the use of this measure in clinical practice and its interpretation. It has been argued that complete patient clearance often underestimates the clinical benefit of a drug and is influenced by a number of key confounding factors, such as number and distribution of lesions, at baseline. Lesions response rate is one alternative which has been suggested as more relevant due to its applicability to clinical practice and closer reflection of the clinical value of the drug. This paper provides an updated perspective on the topic and details the current thinking on the role of complete clearance and lesion response rate in the context of AK.

Funding: Galderma.

http://ift.tt/2d2OVdo

Adsorption and Desorption Characteristics of Pretilachlor in Three Soils of Punjab

Abstract

The study delineates the investigation to determine the adsorption and desorption behaviour of Pretilachlor in three soils of Punjab with varying physicochemical characteristics using batch equilibration techniques. Kinetics of adsorption followed a pseudo-second-order model (R ²  > 0.99) and adsorption–desorption data fitted well to the Freundlich equation for the three soils. L-type isotherms were obtained for the adsorption process, which indicated high affinity between Pretilachlor and adsorption sites. The magnitude of logK _Fads values for the three soils ranged from 0.887–1.226 μg^1−1/n g⁻¹ mL^1/n and the order of adsorption was clay loam > sandy loam > loamy sand. Desorption of Pretilachlor was concentration dependent and in three desorption cycles ranged from 5.04 to 56.03 % in loamy sand, 3.14 to 23.12 % in sandy loam and 1.63 to 18.64 % in clay loam soil indicative of difficulty in the release of strongly adsorbed Pretilachlor. The removal of organic matter by hydrogen peroxide (H₂O₂) oxidation increased the adsorption of Pretilachlor in three Punjab soils. Pretilachlor desorption was hysteretic in the original as well as H₂O₂-treated soils. It could therefore be concluded that the adsorption was controlled by clay minerals and desorption of Pretilachlor in soils was controlled by the organic matter.

http://ift.tt/2dbpRRW

Occurrence and Sources of Polycyclic Aromatic Hydrocarbons in the Tisza River and its Romanian Tributaries

Abstract

The aim of this work is to assess the occurrence of Polycyclic aromatic hydrocarbons (PAHs) in the Tisza River and its main Romanian tributaries (Vişeu River and Iza River) and to establish the origin (pyrogenic/petrogenic) of pollution sources. Fifteen PAHs were investigated in surface water and sediment samples collected from three selected sampling point. The target compounds were isolated from the matrices by solid phase extraction for water samples and by ultrasound-assisted extraction for the sediment samples, respectively. The quantification of the target compounds was performed by HPLC coupled with a fluorescence detector. PAH diagnostic ratios, as the abundance ratio of 2–3 ring hydrocarbons to 4–6 ring hydrocarbons (LMW/HMW), ANT/(ANT + PHE), FLT/(FLT + PYR), B[a]A/(B[a]A + CHR), and IND/(IND+ B[g,h,i]P) were used as a tool for identification and assessment of the pollution emission sources. The results of the study showed that in the studied area, the total concentrations of PAHs detected in water samples ranged from 1.22 to 260.26 ng L⁻¹, while those in sediment samples varied from 4.94 to 10.62 μg kg⁻¹. Regarding the PAH pattern, mixed sources of pollution (pyrogenic and petrogenic) occur in both water and sediment samples. Thus, leaks of petroleum products and biomass, coal, and petroleum combustion are the main sources of pollution identified into the studied area.

http://ift.tt/2cKQQFD

Fluorescence enhancement of the conjugated polymer films based on well-ordered Au nanoparticle arrays

Abstract

In this paper, well-ordered Au nanoparticle arrays on silicon substrates were employed as efficient metal-enhanced fluorescence (MEF) substrates for investigating the fluorescence properties of the conjugated polymer poly(3-hexylthiophene) (P3HT). The ordered Au nanoparticle arrays were fabricated by block copolymer self-assembly technology, and the particle sizes were controlled by adjusting the molar ratios of HAuCl₄ precursor to vinyl pyridine units. The approach is economical and suitable to fabricate large-area MEF substrates. The results about fluorescence properties of P3HT showed that the fluorescence intensities of the P3HT films were improved on ordered Au nanoparticle arrays compared to those on bare silicon substrate and were significantly enhanced with the Au nanoparticle sizes increasing. The mechanism is based on localized surface plasmon resonances, coupling and propagating surface plasmons, and the emission enhancement mainly resulted from the increase of the excitation rate. This work provides a new way to prepare efficient MEF substrates for high-performance fluorescence-based devices.

http://ift.tt/2cTwXNf

Facile synthesis of ultrafine SnO 2 nanoparticles on graphene nanosheets via thermal decomposition of tin-octoate as anode for lithium ion batteries

Abstract

We demonstrate a facile synthesis of ultrafine SnO₂ nanoparticles within graphene nanosheets (GNSs) via thermal decomposition of tin-octoate, in which tin-octoate is firstly blended with GNSs followed by annealing in air at a low temperature (350 °C) and a short time (1 h). As anode for lithium ion batteries, the SnO₂/GNSs displays superior cycle and rate performance, delivering reversible capacities of 803 and 682 mA h/g at current densities of 200 and 500 mA/g after 120 cycles, respectively, much higher than that of pure SnO₂ and GNSs counterparts (143 and 310 mA h/g at 500 mA/g after 120 cycles, respectively). The enhanced electrochemical performance is attributed to the ultrafine SnO₂ nanoparticle size and introduction of GNSs. GNSs prevent the aggregation of the ultrafine SnO₂ nanoparticles, which alleviate the stress and also provide more electrochemically active sites for lithium insertion and extraction. Moreover, GNSs with large specific surface area (~363 m²/g) act as a good electrical conductor which greatly improves the electrode conductivity and also an excellent buffer matrix to tolerate the severe volume changes originated from the Li-Sn alloying-dealloying. This work provides a straight-forward synthetic approach for the design of novel composite anode materials with superior electrochemical performance.

http://ift.tt/2d2ujC0

Ankle Reconstruction in Fibular Hemimelia: New Approach

Abstract

Background

Fibular hemimelia is a congenital disorder that is characterized by the absence of the fibula that could be either partial or complete. Successful management aims to restore normal weight bearing and normal limb length. The introduction of the Ilizarov method of limb lengthening has provided an attractive alternative to amputation. During lengthening, the tight posterolateral soft-tissue structures, the thick fibrous fibular band, and the shortened Achilles tendon become tighter and transfer a valgus force to the talus and calcaneus, further aggravating the deformity.

Questions/Purposes

We have developed a strategy to address this in patients with Paley type III fibular hemimelia via ankle reconstruction that provides posterolateral stability and buttressing of the ankle and hind foot by reconstructing the lateral buttress. This is achieved through excision of the fibrous fibular anlage, centralization of the ankle, restoring talocalcaneal coronal alignment, and reconstruction of the lateral malleolus by transplanting the cartilaginous remnant of the lateral malleolus or by crafting a bone block autograft taken from the iliac crest or tibia.

Methods

A prospective non-randomized clinical trial included ten ankles in eight patients with fibular hemimelia Paley type III (two patients had bilateral deformity). The patients' ages ranged from 7 to 36 months.

Results

After a follow-up ranging from 48 to 96 months, a stable plantigrade foot was achieved in nine ankles; one ankle had residual equinus, five ankles had residual valgus heel, and eight ankles had complete range of motion of the ankle, whereas one patient lost 5° of dorsiflexion. One ankle had equinus deformity.

Conclusions

To achieve satisfactory results, a stable plantigrade foot and ankle is necessary in patients with fibular hemimelia before attempting to equalize limb length discrepancy. It is important to reconstruct the ankle through an extra-articular soft tissue release, anlage resection, osteotomies, and restoring the abnormal talocalcaneal relationship before any attempt to equalize LLD.

http://ift.tt/2cDeu9w

Prognostic value of primary tumor SUV max on F-18 FDG PET/CT compared with semi-quantitative tumor uptake on Tc-99m sestamibi breast-specific gamma imaging in invasive ductal breast cancer

Abstract

Objective

This study aimed to evaluate the prognostic value of F-18 FDG PET/CT in comparison with Tc-99m sestamibi breast-specific gamma imaging (BSGI) and previously established clinical prognostic parameters of invasive ductal breast carcinoma (IDC).

Methods

We retrospectively included 157 female IDC patients (mean age 49.2 years, range 29.9–78.9) who underwent PET/CT and BSGI. The maximum standardized uptake value (SUV_max) and tumor to normal background ratios (TNRs) of their primary tumors were measured on PET/CT and BSGI, respectively. Univariate and multivariate survival analyses were performed to evaluate the prognostic value of the measured parameters and other clinical prognostic factors: age, menopausal status, breast density, pathologic tumor size (pTS), axillary nodal status (ANS), nuclear grade, histologic grade, hormone receptor status of estrogen (ER) and progesterone receptors (PR) and HER-2 expression.

Results

Among 157 patients, recurrences occurred in 22 patients (14.0 %). In univariate analyses, pTS (p < 0.0001), ANS (p < 0.0001), nuclear grade (p = 0.0046), histologic grade (p = 0.0001), ER status (p < 0.0001), PR status (p = 0.0037), HER-2 status (p = 0.0007), primary tumor SUV_max (p < 0.0001) and TNR (p = 0.0001) were significant predictors of recurrence. Among them, pTS (p = 0.0172), ANS (p = 0.0416), ER status (p = 0.0375) and primary tumor SUV_max (p = 0.0239) were independent prognostic factors in multivariate regression analysis.

Conclusions

High primary tumor SUV_max of PET/CT and high TNR of BSGI were poor prognostic factors in IDC patients; in addition, primary tumor SUV_max was an independent prognostic factor along with pTS, ANS and ER status.

http://ift.tt/2ckp7wy

Evaluation of the Impact of Cancer Treatment on the Adoption and Consolidation of Pro-Health Attitudes in the Field of Cancer in Treated Patients with Colon Cancer

Abstract

Colorectal cancer is the second most common cause of cancer deaths worldwide. Although progress in the development of new drugs over the last two decades has expanded treatment options for this disease, many significant problems relating to their optimization remain to be solved. Data on the cancer knowledge and the healthy behavior and lifestyle in patients with colorectal cancer in Poland is missing. We analyzed the course and results of treatment of first-line chemotherapy in 165 patients diagnosed with colorectal cancer treated between May 2010 and December 2013. The respondent's knowledge in the field of cancer and their lifestyle before and after the treatment were rated. The results were compared with a control group. Mean age was 60.89 ± 8.69 years, median 59 years. The general knowledge about cancer and the level of healthy lifestyle before treatment were low. After treatment, both the knowledge about cancer and the level of healthy lifestyle increased compared to the control group. There was a clear relationship between the level of knowledge about cancer and the willingness to adopt attitudes and healthy behavior by patients. In our analysis, the overall quality of life in patients treated with first-line palliative chemotherapy of colorectal cancer did not change during treatment. Our results indicate the need to implement an educational program on cancer prevention in treated patients, and the analysis of quality of life and other factors than treatment effect remains controversial.

http://ift.tt/2cCjSXf

Decision-making and opinion formation in simple networks

Abstract

In many networked decision-making settings, information about the world is distributed across multiple agents and agents' success depends on their ability to aggregate and reason about their local information over time. This paper presents a computational model of information aggregation in such settings in which agents' utilities depend on an unknown event. Agents initially receive a noisy signal about the event and take actions repeatedly while observing the actions of their neighbors in the network at each round. Such settings characterize many distributed systems such as sensor networks for intrusion detection and routing systems for Internet traffic. Using the model, we show that (1) agents converge in action and in knowledge for a general class of decision-making rules and for all network structures; (2) all networks converge to playing the same action regardless of the network structure; and (3) for particular network configurations, agents can converge to the correct action when using a well-defined class of myopic decision rules. These theoretical results are also supported by a new simulation-based open-source empirical test-bed for facilitating the study of information aggregation in general networks.

http://ift.tt/2chKlq7

First-Line, Early and Long-Term Eculizumab Therapy in Atypical Hemolytic Uremic Syndrome: A Case Series in Pediatric Patients

Abstract

Introduction

Studies relating to first-line, early, and long-term eculizumab treatment and outcomes in children with atypical hemolytic uremic syndrome (aHUS) are scarce and unclear. The aim of this case-series study was to evaluate the outcomes of first-line, early, and long-term eculizumab treatment in our aHUS patients.

Materials and Methods

We reviewed the data from four pediatric patients with aHUS who were treated with eculizumab. In three of them, eculizumab was used as a first-line therapy, and the follow-up period was ≥2 years in three patients.

Results

Plasma exchange could not be performed in any patient. Plasma infusions were used only in Patient 1 (a 14-month-old boy) for 8 days without any response. Therefore, eculizumab was started on day 11 after admission. Patient 2 (a 16-month-old boy), Patient 3 (an 11-year-old girl), and Patient 4 (a 32-month-old girl) were treated with eculizumab as a first-line therapy, which was started 2–4 days after admission. The dosage of eculizumab was adjusted according to body weight. The hematologic parameters (the time frames were 3–17 days) and C ₃ (the time frames were 10–17 days) returned to normal in all patients after receipt of eculizumab. Although Patient 1 developed stage III chronic kidney disease, complete renal recovery occurred in Patients 2 and 4. Patient 3 also had reflux nephropathy with bilateral grade III vesicoureteral reflux and renal scars. Her creatinine clearance returned to the baseline value after receiving eculizumab. No complications related to eculizumab were observed in any patient during the follow-up period.

Conclusion

Eculizumab can be successfully used as a first-line therapy in pediatric aHUS patients. We observed that the early initiation of eculizumab was associated with the complete recovery of renal function.

http://ift.tt/2cjK9eN

New water-soluble palladium(II) complexes of lidocaine and phenylcyanamide derivative ligands: cytotoxicity and cellular response mechanisms

Summary

Three new palladium(II) complexes of lidocaine and phenylcyanamide derivative ligands of formula K[Pd(2,6-Me₂pcyd)₂(LC)], 1, K[Pd(2,6-Et₂pcyd)₂(LC)], 2, K[Pd(2,6-Cl₂pcyd)₂(LC)], 3 (LC: lidocaine, 2,6-Me₂pcyd: 2,6-dimethyl phenylcyanamide, 2,6-Et₂pcyd: 2,6-diethyl phenylcyanamide, 2,6-Cl₂pcyd: 2,6-dichloro phenylcyanamide) have been synthesized and fully characterized. The complexes 1–3 revealed a significant in vitro antiproliferative activity against human ovarian carcinoma (A2780), colorectal adenocarcinoma (HT29), breast (MCF-7), liver hepatocellular carcinoma (HepG-2) and lung adenocarcinoma (A549) cancer cell lines. All the complexes are more active than cisplatin and follow the trend 2 > 1 > 3. Mechanistic studies showed that the trend in cytotoxicity of the Pd(II) complexes is mainly consistent with their ability to accumulate into cancer cells and to increase intracellular basal reactive oxygen species levels, which consequently results in the loss of mitochondrial membrane potential and apoptosis induction.

http://ift.tt/2daiWbo