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! # Ola via Alexandros G.Sfakianakis on Inoreader

Δευτέρα, 26 Ιουνίου 2017

Treatment of Hyperkalemia in Heart Failure

Abstract

Purpose of Review

The aim of this paper is to discuss strategies for prevention and management of hyperkalemia in patients with heart failure, including the role of novel therapies.

Recent Findings

Renin-angiotensin-aldosterone system (RAAS) antagonists, including angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), and mineralocorticoid receptor antagonists (MRA) decrease mortality and morbidity in heart failure but increase the risk of hyperkalemia, especially when used in combination. Prevention of hyperkalemia and its associated complications requires careful patient selection, counseling regarding dietary potassium intake, awareness of drug interactions, and regular laboratory surveillance. Recent data suggests that the risk of hyperkalemia may be further moderated through the use of combined angiotensin-neprilysin inhibitors, novel MRAs, and novel potassium binding agents.

Summary

Clinicians should be mindful of the risk of hyperkalemia when prescribing RAAS inhibitors to patients with heart failure. In patients at highest risk, such as those with diabetes, the elderly, and advanced chronic kidney disease, more intensive laboratory surveillance of potassium and creatinine may be required. Novel therapies hold promise for reducing the risk of hyperkalemia and enhancing the tolerability of RAAS antagonists.



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Targeting Mitochondrial Calcium Handling and Reactive Oxygen Species in Heart Failure

Abstract

Purpose of Review

In highly prevalent cardiac diseases, new therapeutic approaches are needed. Since the first description of oxidative stress in heart failure, reactive oxygen species (ROS) have been considered as attractive drug targets. Though clinical trials evaluating antioxidant vitamins as ROS-scavenging agents yielded neutral results in patients at cardiovascular risk, the knowledge of ROS as pathophysiological factors has considerably advanced in the past few years and led to novel treatment approaches. Here, we review recent new insights and current strategies in targeting mitochondrial calcium handling and ROS in heart failure.

Recent Findings

Mitochondria are an important ROS source, and more recently, drug development focused on targeting mitochondria (e.g. by SS-31 or MitoQ). Important advancement has also been made to decipher how the matching of energy supply and demand through calcium (Ca2+) handling impacts on mitochondrial ROS production and elimination. This opens novel opportunities to ameliorate mitochondrial dysfunction in heart failure by targeting cytosolic and mitochondrial ion transporters to improve this matching process. According to this approach, highly specific substances as the preclinical CGP-37157, as well as the clinically used ranolazine and empagliflozin, provide promising results on different levels of evidence. Furthermore, the understanding of redox signalling relays, resembled by catalyst-mediated protein oxidation, is about to change former paradigms of ROS signalling. Novel methods, as redox proteomics, allow to precisely analyse key regulatory thiol switches, which may induce adaptive or maladaptive signalling. Additionally, the generation of genetically encoded probes increased the spatial and temporal resolution of ROS imaging and opened a new methodological window to subtle, formerly obscured processes.

Summary

These novel insights may broaden our understanding of why previous attempts to target oxidative stress have failed, and at the same time provide us with new targets for drug development.



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Neuroendocrine Tumors of the Esophagus: State of the Art in Diagnostic and Therapeutic Management

Abstract

Introduction

Neuroendocrine tumors (NETs) are a heterogeneous group of neoplasms composed of cells containing dense-core neuroendocrine secretory granules in their cytoplasm. NETs of the esophagus are exceedingly uncommon, with a parallel absence of data published on clinical features, prognosis, and proposed treatment strategies.

Methods

As relevant classification is not well-established, knowledge acquired in NETs of lung and gastrointestinal sites usually guides esophageal NET management. Associated subtypes are divided based upon shared neuroendocrine features into small and large cell NET, typical and atypical carcinoid.

Results

Common presenting symptoms include dysphagia, abdominal discomfort, weight loss, melena, and on occasion, signs of carcinoid syndrome. Endoscopic findings describe a polypoid, nodular elevated lesion with an overlying surface depicted as mostly smooth and glistening. Disease metastasis is assessed using anatomical imaging, including computed tomography (CT), endoscopic ultrasonography (EUS), and positron emission tomography (PET)-CT. Prognosis is influenced by the extent of lymph node metastasis and potential lymphovascular invasion. Furthermore, proliferative activity, estimated using mitotic count or Ki-67 immunostaining, has been suggested as a significant prognostic parameter.

Conclusion

Therapeutic approach depends on clinical staging. Nevertheless, currently, a specific treatment algorithm for esophageal NETs has not been elucidated. Endoscopic resection has been proposed in NETs less than 1 cm in size with absence of regional lymph node metastasis, while surgical excision combined with adjuvant chemotherapy remains the treatment of choice.



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Barcelona Clinic Liver Cancer (BCLC) Staging: Does It Cover All Our Expectation



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Erratum to: Numerical Modelling of Femur Fracture and Experimental Validation Using Bone Simulant



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Electrospun PLGA Nanofiber Scaffolds Release Ibuprofen Faster and Degrade Slower After In Vivo Implantation

Abstract

While delayed delivery of non-steroidal anti-inflammatory drugs (NSAIDs) has been associated with improved tendon healing, early delivery has been associated with impaired healing. Therefore, NSAID use is appropriate only if the dose, timing, and mode of delivery relieves pain but does not impede tissue repair. Because delivery parameters can be controlled using drug-eluting nanofibrous scaffolds, our objective was to develop a scaffold for local controlled release of ibuprofen (IBP), and characterize the release profile and degradation both in vitro and in vivo. We found that when incubated in vitro in saline, scaffolds containing IBP had a linear release profile. However, when implanted subcutaneously in vivo or when incubated in vitro in serum, scaffolds showed a rapid burst release. These data demonstrate that scaffold properties are dependent on the environment in which they are placed and the importance of using serum, rather than saline, for initial in vitro evaluation of biofactor release from biodegradable scaffolds.



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Fingolimod Exerts only Temporary Antiepileptogenic Effects but Longer-Lasting Positive Effects on Behavior in the WAG/Rij Rat Absence Epilepsy Model

Abstract

One of the major challenges in the epilepsy field is identifying disease-modifying drugs in order to prevent or delay spontaneous recurrent seizure onset or to cure already established epilepsy. It has been recently reported that fingolimod, currently approved for the treatment of relapsing–remitting multiple sclerosis, has demonstrated antiepileptogenic effects in 2 different preclinical models of acquired epilepsy. However, to date, no data exist regarding the role of fingolimod against genetic epilepsy. Therefore, we have addressed this issue by studying the effects of fingolimod in Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats, a well-established genetic model of absence epilepsy, epileptogenesis, and neuropsychiatric comorbidity. Our results have demonstrated that an early long-term treatment with fingolimod (1 mg/kg/day), started before absence seizure onset, has both antiepileptogenic and antidepressant-like effects in WAG/Rij rats. However, these effects were transitory, as 5 months after treatment discontinuation, both absence seizure and depressive like-behavior returned to control levels. Furthermore, a temporary reduction of mTOR signaling pathway activity, indicated by reduced phosphorylated mammalian target of rapamycin and phosphorylated p70S6k levels, and by increased phosphorylated Akt in WAG/Rij rats of 6 months of age accompanied the transitory antiepileptogenic effects of fingolimod. Surprisingly, fingolimod has demonstrated longer-lasting positive effects on cognitive decline in this strain. This effect was accompanied by an increased acetylation of lysine 8 of histone H4 (at both 6 and 10 months of age). In conclusion, our results support the antiepileptogenic effects of fingolimod. However, the antiepileptogenic effects were transitory. Moreover, fingolimod might also have a positive impact on animal behavior and particularly in protecting the development of memory decline.



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Therapeutic Targets for Multiple Sclerosis: Current Treatment Goals and Future Directions

Abstract

Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system, and the most common cause of nontraumatic disability in young adults. Most patients have a relapsing–remitting course, and roughly half of them will eventually enter a degenerative progressive phase, marked by gradual accrual of disability over time in the absence of relapses. Early initiation of treatment has delayed the onset of disability progression. Thus, there is increased interest in treating to target in MS, particularly targeting no evidence of disease activity. This review will describe the most common treatment goals in MS: the Rio scores, disease-free survival, and no evidence of disease activity. We will also cover how well current disease-modifying therapies achieve no evidence of disease activity, and discuss future options for improving MS treatment targets.



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Development of an Electromechanical Grade to Assess Human Knee Articular Cartilage Quality

Abstract

Quantitative assessments of articular cartilage function are needed to aid clinical decision making. Our objectives were to develop a new electromechanical grade to assess quantitatively cartilage quality and test its reliability. Electromechanical properties were measured using a hand-held electromechanical probe on 200 human articular surfaces from cadaveric donors and osteoarthritic patients. These data were used to create a reference electromechanical property database and to compare with visual arthroscopic International Cartilage Repair Society (ICRS) grading of cartilage degradation. The effect of patient-specific and location-specific characteristics on electromechanical properties was investigated to construct a continuous and quantitative electromechanical grade analogous to ICRS grade. The reliability of this novel grade was assessed by comparing it with ICRS grades on 37 human articular surfaces. Electromechanical properties were not affected by patient-specific characteristics for each ICRS grade, but were significantly different across the articular surface. Electromechanical properties varied linearly with ICRS grade, leading to a simple linear transformation from one scale to the other. The electromechanical grade correlated strongly with ICRS grade (r = 0.92, p < 0.0001). Additionally, the electromechanical grade detected lesions that were not found visually. This novel grade can assist the surgeon in assessing human knee cartilage by providing a quantitative and reliable grading system.



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Moving Beyond Serendipity to Mechanism-Driven Psychiatric Therapeutics



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Clozapine as a Model for Antipsychotic Development

Abstract

Schizophrenia is a devastating illness that affects up to 1% of the population; it is characterized by a combination of positive symptoms, negative symptoms, and cognitive impairment. Currently, treatment consists of one class of medications known as antipsychotics, which include typical (first-generation) and atypical (second-generation) agents. Unfortunately, antipsychotic medications have limited efficacy, with up to a third of patients lacking a full response. Clozapine, the first atypical antipsychotic developed, is the only medication shown to be superior to all other antipsychotics. However, owing to several life-threatening side effects and required enrollment in a registry with routine blood monitoring, clozapine is greatly underutilized in the US. Developing a medication as efficacious as clozapine with limited side effects would likely become the first-line therapy for schizophrenia and related disorders. In this review, we discuss the history of clozapine, landmark studies, and its clinical advantages and disadvantages. We further discuss the hypotheses for clozapine's superior efficacy based on neuroreceptor binding, and the limitations of a receptor-based approach to antipsychotic development. We highlight some of the advances from pharmacogenetic studies on clozapine and then focus on studies of clozapine using unbiased approaches such as pharmacogenomics and gene expression profiling. Finally, we examine how these approaches could provide insights into clozapine's mechanism of action and side-effect profile, and lead to novel and improved therapeutics.



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Chronic Paroxetine Treatment Prevents the Emergence of Abnormal Electroencephalogram Oscillations in Huntington’s Disease Mice

Abstract

Disturbance of rapid eye movement (REM) sleep appears early in both patients with Huntington's disease (HD) and mouse models of HD. Selective serotonin reuptake inhibitors are widely prescribed for patients with HD, and are also known to suppress REM sleep in healthy subjects. To test whether selective serotonin reuptake inhibitors can correct abnormal REM sleep and sleep-dependent brain oscillations in HD mice, we treated wild-type and symptomatic R6/2 mice acutely with vehicle and paroxetine (5, 10, and 20 mg/kg). In addition, we treated a group of R6/2 mice chronically with vehicle or paroxetine (20 mg/kg/day) for 8 weeks, with treatment starting before the onset of overt motor symptoms. During and after treatment, we recorded electroencephalogram/electromyographm from the mice. We found that both acute and chronic paroxetine treatment normalized REM sleep in R6/2 mice. However, only chronic paroxetine treatment prevented the emergence of abnormal low-gamma (25–45 Hz) electroencephalogram oscillations in R6/2 mice, an effect that persisted for at least 2 weeks after treatment stopped. Chronic paroxetine treatment also normalized REM sleep theta rhythm in R6/2 mice, but, interestingly, this effect was restricted to the treatment period. By contrast, acute paroxetine treatment slowed REM sleep theta rhythm in WT mice but had no effect on abnormal theta or low-gamma oscillations in R6/2 mice. Our data show that paroxetine treatment, when initiated before the onset of symptoms, corrects both REM sleep disturbances and abnormal brain oscillations, suggesting a possible mechanistic link between early disruption of REM sleep and the subsequent abnormal brain activity in HD mice.



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Evidence-Based Psychotherapy: Advantages and Challenges

Abstract

Evidence-based psychotherapies have been shown to be efficacious and cost-effective for a wide range of psychiatric conditions. Psychiatric disorders are prevalent worldwide and associated with high rates of disease burden, as well as elevated rates of co-occurrence with medical disorders, which has led to an increased focus on the need for evidence-based psychotherapies. This chapter focuses on the current state of evidence-based psychotherapy. The strengths and challenges of evidence-based psychotherapy are discussed, as well as misperceptions regarding the approach that may discourage and limit its use. In addition, we review various factors associated with the optimal implementation and application of evidence-based psychotherapies. Lastly, suggestions are provided on ways to advance the evidence-based psychotherapy movement to become truly integrated into practice.



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Assessment of the Validity and Reproducibility of a Novel Standardized Test Meal for the Study of Postprandial Triacylglycerol Concentrations

Abstract

Lipotest® is a standardized fat-rich meal designed for use as a test meal during a fat tolerance test (FTT) for the study of postprandial triacylglycerol (TAG) concentrations. Herein we examined the precision and reproducibility of examination using Lipotest® on postprandial TAG levels. A total of 26 healthy consenting subjects were examined twice after 8–10 h fasting with an interval of approximately 1 week apart. Blood samples were collected at baseline and 1, 2, 3, and 4 h after consumption of the test meal for measurement of plasma total TAG levels. We examined agreement, precision, and accuracy between the two visits using the Altman plots and correlation coefficient. Reproducibility was tested using the coefficient of variation (CV) and intraclass correlation coefficient (ICC). Moreover, the area under the curve (AUC) as a summary measure of the overall postprandial TAG levels was calculated. The agreement, precision (r ≥ 0.74, p < 0.001), and accuracy (≥0.99) between the measurements in plasma TAG during Lipotest® testing in the two visits were high. In terms of reproducibility, the values of CV were 15.59–23.83% while those of ICC were ≥0.75. The values of the AUCs in the visits were not different (p = 0.87). A single measurement of plasma TAG levels at 4 h after Lipotest® consumption depicted peak postprandial TAG concentration. A FTT using Lipotest® as a standardized meal has good precision and reproducibility for the study of postprandial TAG levels in healthy individuals. A single determination of plasma TAG concentration at 4 h after Lipotest® consumption captures peak postprandial TAG response.



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Bacillus alcaliphilum sp. nov., a bacterium isolated from a soda lake

Abstract

Two novel (14BT and 7B) Gram-stain-positive, rod-shaped, motile and endospore-forming bacterial strains were isolated from Lonar soda lake, India. Based on 16S rRNA gene sequence analysis, the strains 14BT and 7B were identified as belonging to the class Firmibacteria and were most closely related to Bacillus halodurans LMG 7121T (99.7 and 99.8%, respectively), Bacillus okuhidensis LMG 22468T (99.1 and 99.2%, respectively) and other members in the genus Bacillus (<97.0%). However, the DNA–DNA relatedness studies indicated that the strains 14BT and 7B were distantly related to B. halodurans LMG 7121T (49.1 ± 0.6 and 45.7 ± 0.6, respectively) and B. okuhidensis LMG 22468T (40.9 ± 0.9 and 42.1 ± 0.5, respectively). The high 16S rRNA gene sequence similarity (99.9%) and DNA–DNA relatedness (88 ± 9) indicated that strains 14BT and 7B were members of a single species. The strains grew optimally at a pH of 9.0–9.5 with 2–5% (w/v) NaCl and temperature of 37 °C. Strains 14BT and 7B were catalase positive and oxydase negative. The cell wall of strain 14BT contained meso-diaminopimelic acid as the diagnostic diamino acid. Polar lipids include diphosphatidylglycerol (DPG), phosphatidylglycerol (PG), phosphatidylethanolamine (PE), an unknown aminophospholipid (APL1) and three unknown lipids (L1–3). The predominant isoprenoid quinone is MK-7. anteiso-C15:0 (30.8%) was the predominant fatty acid, and significant proportions of iso-C15:0 (24.9%), iso-C16:0 (17.9%) and anteiso-C17:0 (12.3%) were also detected in strains 14BT and 7B. The DNA G+C content of strains 14BT and 7B was 41.6 and 41.3 mol%, respectively. The results of molecular, physiological and biochemical tests allowed a clear differentiation of strains 14BT and 7B from all other members of the genus Bacillus, for which the name Bacillus alcaliphilum sp. nov. is proposed. The type strain is 14BT (=KCTC 33777T = CGMCC 1.15474T).



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Identification of Elevated ST Segment and Deep Q Type MI Variant Using Cross Wavelet Transform and Hierarchical Classification From ECG Signals

Abstract

Coronary artery disease being one of the leading causes of mortality in the world requires prompt attention and for which technological intervention is helpful. The present manuscript proposes a cross wavelet transform based method for classification of Type I Inferior Myocardial Infraction (ST elevated and attenuated T wave) and Type II Inferior Myocardial Infarction (elongated Q wave and inverted T wave morphology). Cross-examination of cross-correlation between two time series reveals localised similarities in time-scale where distinguishing parameters for classification are extracted from wavelet cross spectrum and wavelet coherence. When ECG pattern in the QT region differ from the normal cardiac cycle and a variation is observed in the QT region of lead III, which gives an indication of Inferior MI. The WCS and WCOH of the ECG spectrum together show substantive spectral variations in the QRS complex region (R1) and over the T wave occurrences (R2). The classification of two types of MIs and normal parameters are identified from the corresponding regions R1 and R2. This method gives an accuracy of 99.43% for normal and abnormal class and 88.5 and 87.02% for Type I and Type II Inferior MI respectively.



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First case report of a curative wedge resection in epithelial–myoepithelial carcinoma of the lung

Abstract

Epithelial–myoepithelial carcinoma is a well differentiated malignant neoplasm, which originates from the salivary glands. The primary pulmonary manifestation is rare—about 30 cases have been reported worldwide. In the literature, anatomical resection has been described as the standard surgical approach. In the presented case, a wedge resection was performed, with no evidence for tumor relapse in the follow-up reevaluation after 24 months. This is the first case report of a primary pulmonary epithelial–myoepithelial carcinoma that has been treated with a non-anatomical wedge resection and lymph node dissection as a curative approach.



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Quantitative Pneumatic Otoscopy Using a Light-Based Ranging Technique

Abstract

Otitis media is the leading cause of hearing loss in children. It is commonly associated with fluid in the ear, which can result in up to 45 dB of hearing loss for extended periods of time during a child's most important developmental years. Accurate assessment of middle ear effusions is an important part of understanding otitis media. Current technologies used to diagnose otitis media with effusion are pneumatic otoscopy, tympanometry, and acoustic reflectometry. While all of these techniques can reasonably diagnose the presence of an effusion, they provide limited information about the infection present behind the tympanic membrane.

We have developed a technique based on low-coherence interferometry—a non-invasive optical ranging technique capable of sensing depth-resolved microscopic scattering features through the eardrum—to quantify eardrum thickness and integrity, as well as detect any effusion, purulence, or biofilm behind the tympanic membrane. In this manuscript, the technique is coupled with a pneumatic otoscope to measure minute deflections of the tympanic membrane from insufflation pressure stimuli. This results in quantitative measurements of tympanic membrane mobility, which may be used to gain a better understanding of the impact of infection on the membrane dynamics. A small pilot study of 15 subjects demonstrates the ability of pneumatic low-coherence interferometry to quantitatively differentiate normal ears from ears with effusions present. Analysis of the strengths and weaknesses of the technique, as well as focus areas of future research, is also discussed.



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Patients’ Perspectives on Adverse Drug Reaction Reporting in a Developing Country: A Case Study from Ghana

Abstract

Introduction

Recent efforts to introduce direct patient reporting into pharmacovigilance systems have proved that patient reports contribute significantly to medicine safety, but there is a paucity of information relating to patients' perspectives regarding adverse drug reaction reporting in developing countries.

Objective

The objective of this study was to explore patients' knowledge, attitudes, behaviours and opinions on spontaneous adverse drug reaction reporting in Ghana.

Methods

A cross-sectional study using questionnaires administered through face-to-face interviews was carried out from 25 August, 2016 to 20 September, 2016 with 442 patients aged 18 years and above selected by convenience sampling from two community pharmacies in urban and rural Ghana. Reasons and opinions on patients' reporting on adverse drug reactions were surveyed using a 5-point Likert scale. The Pearson chi-square test was used to determine associations between background variables and responses on knowledge of adverse drug reaction reporting.

Results

Responses from 434 patients (86.7%) were included in the analysis. Among those interviewed, there was a high level of awareness regarding the existence of the National Pharmacovigilance Centre (81.6%). Approximately half of the respondents (49.5%) were aware that patients were able to report adverse drug reactions associated with medicinal products directly to the National Pharmacovigilance Centre. Of the respondents, 46.3% stated that they had an adverse drug reaction to their medicines in the past; of these, 53.2% reported to healthcare professionals and 36.9% failed to report because they stopped their medication. The three main reasons for patients' reporting were desire for extra information (92.4%), desire to share experiences with other people (91.7%) and expectation for the National Pharmacovigilance Centre to inform others about the possible adverse drug reactions (88.0%). Patients' opinions were to contribute to research/knowledge (96.5%) and improvements in drug safety (96.5%). Patients' behaviour towards adverse drug reaction reporting was affected by the likely consequences of reporting, influence of others and the ease of reporting.

Conclusion

Patients have a positive attitude and good knowledge on adverse drug reaction reporting to the National Pharmacovigilance Centre and report because they expect extra information and to contribute to drug safety. Patients' positive attitude towards adverse drug reaction reporting could be sustained by hosting periodic public awareness campaigns addressing the importance of adverse drug reaction reporting and by providing timely feedback to patients on regulatory decisions taken as a result of the reports that they submitted.



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Structural, morphological and thermal characterization of poly (2-hydroxyethyl methacrylate-co-acrylonitrile) (P (HEMA-co-AN)) Cryogels: evaluation of water sorption potential and cytotoxicity

Abstract

Cryogels are macroporous hydrogels which are synthesized through cryogelation method. In the present study cryogels of poly (2-hydroxyethyl methacrylate-co-acrylonitrile) (P (HEMA-co-AN)) were synthesized by copolymerization of 2-hydroxyethyl methacrylate (HEMA) and acrylonitrile (AN) monomers by redox polymerization using cryogelation technique. The synthesized cryogels were characterized by FTIR, SEM, XRD, DSC and TGA techniques. Different compositions of the cryogels were prepared by varying concentrations of the monomers and redox initiators in the feed mixture. These cryogels were then subjected to swelling studies and porosity determination. The swelling behavior was studied as function of concentration of the monomers, redox initiators, temperature, pH, and simulated biological fluids. The prepared cryogels were also characterized for their network parameters using water sorption data. The biocompatibility of P (HEMA-co-AN) cryogel was evaluated by in vitro cytotoxicity test. The results indicated that the P (HEMA-co-AN) cryogel had macroporous morphology and exhibited good water absorption capacity. Moreover, the cryogel was thermally stable and biocompatible in nature.



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Treatment and outcome of metastatic paraganglioma of the spine

Abstract

Background

Spinal metastatic paraganglioma (MPG) is rare and only reported in individual case reports. The low incidence makes it difficult to define appropriate therapy and prognosis. Our study illustrated the largest series to discuss the possible treatment and outcomes of patients with spinal MPG.

Methods

A retrospective study of 15 patients with spinal MPG who were surgically treated between 2005 and 2014 was performed. Three surgical modalities were applied, and radiotherapy and chemotherapy were utilized as adjuvant therapy.

Results

The mean patients age was 40.9 (range 23–58) years. The period between primary surgery and spinal metastasis averaged 8.2 (0.5–15) years. Lesions were mainly located in cervical spine (2), thoracic spine (8), lumbar spine (3), and sacrum (2). The mean follow-up period was 35.0 months. Lesion progression was detected in nine patients, whereas five patients (33.3%) passed away. For solitary spine, multiple bone and both bone and nonosseous metastasis cases, the mean progression-free survival was 41 (range 9–56), 22.5 (range 12–38) and 8.3 (range 3–18) months, respectively.

Conclusions

The cases presented in the current study highlight the crucial role of surgery. Total en bloc for solitary spinal MPG could result in a satisfying prognosis and piecemeal total resection with postoperative radiotherapy could be an alternative therapy. Radiotherapy and chemotherapy were advocated, especially for the multiple metastasis.



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Book Review



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Book Review



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Is There Detectable Long-term Depletion of Genetic Variation in Freshwater Fish Species Affected by an Oil Spill?

Abstract

Oil spills might lead to severe environmental impacts to the affected fauna, disrupting local food webs, and causing mass mortality in many species. However, little is known about long-term impacts of oil spills, or even if such impacts can be detectable after several generations. In this study, we investigate the genetic variability of three freshwater species—Mimagoniates microlepis (Characiformes: Characidae), Scleromystax barbatus (Siluriformes: Callichthyidae), and Phalloceros harpagos (Cyprinodontiformes: Poeciliidae)—in rivers that were affected by a large oil spill in the state of Paraná, southern Brazil, on February of 2001. Samples were obtained from nine different locations, such that rivers that were directly affected by the oil spill could be compared with similar rivers in the same region that were unaffected. A fragment of the cytochrome C oxidase subunit I mitochondrial gene was sequenced from each specimen, and the level of genetic variability was assessed. Based on estimates of haplotype and nucleotide diversity, no impact of the oil spill could be detected in impacted rivers. These results suggest that fish populations in the region showed resilience to the pollutant, such that immigration from other locations was able to reestablish levels of genetic variability comparable to those of unimpacted rivers.



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Advances in Robotic Transaxillary Thyroidectomy in Europe

Abstract

Purpose of review

The robotic surgical approach for minimally invasive thyroid surgery has been well described from the Korean surgeons and shows a wide spread diffusion in Asian area. This paper gives a systematic review aiming to pointed out the interest and the way of behaving of the European surgeons about the role of the robotic thyroidectomy (RT).

Recent findings

A literature search was performed using Pubmed, MEDLINE, Cochrane and ClinicalTrials.gov databases, including only papers wrote from european surgeons enrolling patients operated in Europe. Outcomes of interest included patients characteristics, patients position, surgical devices, surgical technique, surgical outcomes, and complications. Eighteen studies have been included in the analysis, published from 2011 to 2017. An overall number of 1108 patients were treated in studies included. In the 44.4% of studies (eight trials), the Kuppersmith position was chosen, whereas in the 22.2% (four trials), the Chung position was selected, with a mean length on axilla skin incision of 5.8 ± 1.5 cm. Considering the characteristics of the surgical technique, the mean total surgical time was 166.8 ± 36.6 min (including total thyroidectomy and loboisthmectomy together), divided three consecutive phases, such as mean working space was 50.7 ± 21.8 min, mean docking time 16.0 ± 11.9 min and mean console time 102.87 ± 38.8 min. Considering the complications, only 50% of studies included reported data about acute complications. In particular, the most frequent was hypocalcemia, occurring in 32 cases (2.9%). RLN palsy occurred in 29 patients (2.6%), definitive in 13.8% of these cases and transient in 86.2%. Only nine studies reported the discharge time, with a mean of 2.4 ± 1.2 days after surgery.

Summary

Despite the papers included in the study show a different way of collecting data, the transaxillary approach for robotic thyroidectomy for European patients is both feasible and safe. This procedure has to be carried out by surgeons expert in thyroid surgery with knowledge in robotic procedure. In the future, the incoming of dedicated instruments could improve and developed this technique.



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Table of Contents



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Introduction and Welcome



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19th IUPAB congress and 11th EBSA congress



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Scientific Programme



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Abstracts



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List of participants



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Author index



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Histopathological factors predicting response to neoadjuvant therapy in gastric carcinoma

Abstract

Background

Neoadjuvant therapy (NAT) is a useful therapeutic option. However, some patients respond poorly to it and can even show tumor progression. It is important to define factors that can predict response to NAT.

Materials and methods

This is a retrospective cohort study to define histopathological factors predicting response to NAT in gastric tubular carcinoma. This study has enrolled 80 patients receiving chemotherapy for locally advanced gastric carcinoma.

Results

44.5% of the patients were men; mean age was 64.49 years. Only 5.7% of the patients showed a complete response to therapy, 10% had grade 1, 21.4% grade 2, and 62.9% grade 3 regression. On follow-up, 43.8% of the patients showed recurrence of disease (57.1% distant metastasis) and 33.8% eventually died of it. We found a statistically significant association between response and prognosis. We found a statistically significant association between regression and perineural, vascular, and lymph vessel invasion. Logistic regression model showed that only lymph vessel invasion had independent influence. Lymph vessel invasion not only indicated lack of response to therapy, but also higher incidence of lymph node involvement in the gastrectomy specimen.

Discussion

Our study indicates that the presence of vascular or perineural invasion in the endoscopic biopsies and high histopathological grade predict poor response to therapy. This seems peculiar, for undifferentiated tumors are supposed to have better response to therapy.

Conclusion

Our study indicates that undifferentiated tumors respond worse to therapy. Furthermore, studies are necessary to define lack of response, to help avoid neoadjuvant therapy in unfavorable cases.



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R1-Resektion beim Pankreaskarzinom

Zusammenfassung

Hintergrund

Die chirurgische Therapie ist das einzig potenziell kurative Therapieverfahren beim Pankreaskarzinom, eine R0-Situation wird aber nicht immer erreicht.

Fragestellung

Der Einfluss einer R1-Situation beim Pankreaskarzinom auf das Überleben und die Behandlungsmöglichkeiten (operativ/multimodal) bei nachgewiesener R1-Situation (intra-/postoperativ)

Ergebnisse

Bei intraoperativ nachgewiesener R1-Situation kann durch eine Nachresektion (Pankreasparenchym, Gallengang, Magen, venöse Gefäße) oftmals eine R0-Situation erreicht werden. Die Erweiterung der Operation mit arterieller Gefäßresektion bzw. die Resektion von Nachbarorganen ist manchmal technisch-chirurgisch durchführbar und kann im Einzelfall erwogen werden. Durch neue neoadjuvante und adjuvante Therapiekonzepte konnte sowohl die Rate an resezierbaren Pankreaskarzinomen erhöht, als auch das Überleben von Patienten mit einer R0/R1-Situation verbessert werden.

Schlussfolgerungen

Das Ziel der chirurgischen Therapie beim Pankreaskarzinom sollte die R0-Resektion sein, da die R1-Resektion mit einem verminderten Überleben einhergeht.



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Contributions of community pharmacists to patients on antidepressants—a qualitative study among key informants

Abstract

Background Patients with an antidepressant drug treatment (ADT) report unmet needs and a significant proportion stop their ADT prematurely. Community pharmacists can play a key role in supporting these patients. Objective To explore the perspectives of various leaders in health care about the current and potential contributions of community pharmacists to patients on ADT. Setting The province of Quebec (Canada). Method We conducted a qualitative descriptive exploratory study using interviews among leaders who were involved in health care services, pharmaceutical services, physician and pharmacist education, as well as patient and healthcare professional associations. Verbatim transcripts of interviews were analyzed using computer-assisted thematic analysis. Main outcome measure Perspectives about the contributions of community pharmacists to patients on ADT. Results Interviews revealed that pharmacists are perceived to be accessible drug experts whose particular strengths are their thorough knowledge of drugs, their commitment to ensure ADT safety and tolerability, as well as their commitment to inform and support patients. Leaders trained in pharmacy or representatives of pharmacy organizations had concrete expectations for pharmacists' increased involvement in monitoring ADT adherence and efficacy. They extensively discussed the regulatory and organizational changes required to enhance this role. Leaders also stated that, in addition to patients, health care teams could benefit from pharmacists' expertise and support. Conclusion Participating key informants perceived the need for enhanced pharmacist monitoring of ADT adherence and efficacy. They also expressed their openness to an increased collaboration between health care teams and pharmacists.



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A medication assessment tool to evaluate prescribers’ adherence to evidence-based guidelines in bipolar disorder

Abstract

Background The goal of evidence-based clinical practice has led to an increased interest in the development of tools to measure adherence to national guidelines in different diseases. This aids in detecting and measuring inappropriate prescribing to specific patient groups by using quality standards extracted from evidence-based guidelines, and ultimately provide the basis of consistent standardized prescribing. Objective To design and validate a medication assessment tool to assess prescribers' adherence to international guideline recommendations in the management of bipolar disorder (MATBD). Setting Outpatient psychiatry clinic at a secondary healthcare setting in Kuwait. Method International guidelines concerned with the management of bipolar disorder were reviewed in order to develop MATBD. Face and content validity of the developed tool (MATBD) was performed with a research and expert group. A 4-point Likert scale was used to assess the expert group's level of agreement to individual criterion. Content validity ratio (CVR) was calculated for each criterion (n = 54) and the content validity index (CVI) was calculated for each section (n = 5) of the MATBD. Finally, feasibility testing was performed on 19 patient records to confirm the tool's fitness for purpose. Main Outcomes Measure Perceived relevance, utility, and clarity of individual criteria, and reliability of their application to clinical settings. Results Face validity and content validity were achieved with a research and expert group (n = 14). Content validity ratio (CVR) was demonstrated for 54 criteria; criteria with a negative CVR were removed. This resulted in a draft MATBD comprising of 52 criteria (CVI: 0.814). Feasibility testing on 19 patients' records resulted in a final MATBD comprising of 49 criteria divided into 3 sections: initial assessment, acute management and monitoring. Conclusion A medication assessment tool was developed and validated to be used as a means of profiling potential opportunities for medication therapy management optimization, and improving therapeutic interventions regarding the management of bipolar disorder.



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Future enhanced clinical role of pharmacists in Emergency Departments in England: multi-site observational evaluation

Abstract

Background There are concerns about maintaining appropriate clinical staffing levels in Emergency Departments. Pharmacists may be one possible solution. Objective To determine if Emergency Department attendees could be clinically managed by pharmacists with or without advanced clinical practice training. Setting Prospective 49 site cross-sectional observational study of patients attending Emergency Departments in England. Method Pharmacist data collectors identified patient attendance at their Emergency Department, recorded anonymized details of 400 cases and categorized each into one of four possible options: cases which could be managed by a community pharmacist; could be managed by a hospital pharmacist independent prescriber; could be managed by a hospital pharmacist independent prescriber with additional clinical training; or medical team only (unsuitable for pharmacists to manage). Impact indices sensitive to both workload and proportion of pharmacist manageable cases were calculated for each clinical group. Main outcome measure Proportion of cases which could be managed by a pharmacist. Results 18,613 cases were observed from 49 sites. 726 (3.9%) of cases were judged suitable for clinical management by community pharmacists, 719 (3.9%) by pharmacist prescribers, 5202 (27.9%) by pharmacist prescribers with further training, and 11,966 (64.3%) for medical team only. Impact Indices of the most frequent clinical groupings were general medicine (13.18) and orthopaedics (9.69). Conclusion The proportion of Emergency Department cases that could potentially be managed by a pharmacist was 36%. Greatest potential for pharmacist management was in general medicine and orthopaedics (usually minor trauma). Findings support the case for extending the clinical role of pharmacists.



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Three-dimensional laser scanning under the pinhole camera with lens distortion

Abstract

This paper proposes a 3D laser scanning technology for the pinhole camera with lens distortion. On the basis of the pinhole camera mathematical model, we improve the extraction algorithm of Harris corner points, and introduce the professional 2D RAC calibration, 3D reconstruction, and 3D volume calculation. With the help of stepper motor, and the camera, we can capture a series of images and obtain the object 3D surface information. Furthermore, we use the line laser with Gaussian distribution as the measurement illuminant, and select the samples at the peak of intensity distribution. This brings both high accuracy and speed of measurement.



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Author’s reply to Paravidino et al.: Comment on: “Effect of exercise training on non-exercise physical activity: a systematic review and meta-analysis of randomized controlled trials”



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Comment on: “Effect of Exercise Training on Non-exercise Physical Activity: A Systematic Review and Meta-Analysis of Randomized Controlled Trials”



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Role of Jagged1-Notch pathway in thyroid development

Abstract

The zebrafish thyroid gland shows a unique pattern of growth. Despite the lack of a compact gland, the zebrafish thyroid tissue originates from the pharyngeal endoderm and the main genes involved in its patterning and early development are conserved between zebrafish and mammals. In recent years, the research has been focused to the search of novel candidate genes and environmental factors underlying congenital hypothyroidism. Among these, it has been demonstrated that the Notch signalling plays a central role during zebrafish thyroid development. In this review, we will provide an overview of the current knowledge of the distinct roles of the Notch signalling and of the jag1a and jag1b ligands during the different phases of thyroid organogenesis. Furthermore, we will discuss the role of JAG1 variants in congenital thyroid defects.



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Adherence of psychopharmacological prescriptions to clinical practice guidelines in patients with eating behavior disorders

Abstract

Purpose

The purpose of this study was to analyze the adherence of psychopharmacological prescriptions to clinical practice guidelines (CPGs) for patients with eating behavior disorders (EDs) and to compare the effectiveness, safety, and cost of treatment according to adherence.

Methods

This retrospective observational study included ED patients admitted to the eating disorders unit (EDU) of Ciudad Real Hospital (Spain) between January 2006 and December 2009 and followed until December 2014. Psychopharmaceuticals prescribed during EDU stay(s) were compared with guidelines published by American Psychiatric Association (APA), National Institute for Clinical Excellence (NICE), and Spanish Ministry of Health and Consumption (SMHC). Adherence was considered as the percentage of patients whose prescription followed all recommendations.

Results

The study included 113 ED patients. Adherence to APA and NICE/SMHC was 30.1% and 45.1%, respectively. Weekly weight gain during hospital stay was higher (p = 0.037) in the APA "adherence" (807.6 g) versus "non-adherence" (544.4 g) group. An association was found between CPG adherence and higher 5-year full recovery rate (p < 0.040). Adherence to NICE/SMHC was associated with lower incidence (p = 0.001) of adverse effects (33.3% in adherence vs. 66.1% in non-adherence group). CPG adherence was associated with lower medication costs (p < 0.020). The age was higher and there was a greater frequency of self-harm behavior and psychiatric comorbidities in the non-adherence than adherence group (p ≤ 0.040).

Conclusions

CPG adherence was low in EDU-admitted patients. Long-term follow-up showed that clinical outcomes were better and medication costs lower in patients with versus without CPG-adherent prescriptions, likely influenced by the apparently greater severity of illness in those with non-CPG-adherent prescriptions.



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Explaining Ethnic Variability of Transporter Substrate Pharmacokinetics in Healthy Asian and Caucasian Subjects with Allele Frequencies of OATP1B1 and BCRP: A Mechanistic Modeling Analysis

Abstract

Background

Ethnic variability in the pharmacokinetics of organic anion transporting polypeptide (OATP) 1B1 substrates has been observed, but its basis is unclear. A previous study hypothesizes that, without applying an intrinsic ethnic variability in transporter activity, allele frequencies of transporters cannot explain observed ethnic variability in pharmacokinetics. However, this hypothesis contradicts the data collected from compounds that are OATP1B1 substrates but not breast cancer resistance protein (BCRP) substrates.

Objective

The objective of this study is to evaluate a hypothesis that is physiologically reasonable and more consistent with clinical observations.

Methods

We evaluated if allele frequencies of two transporters (OATP1B1 and BCRP) are key contributors to ethnic variability. In this hypothesis, the same genotype leads to the same activity independent of ethnicity, in contrast to the previous hypothesis of intrinsic ethnic variability in OATP1B1 activity. As a validation, we perform mechanistic pharmacokinetic modeling for SLCO1B1 (encoding OATP1B1) and ABCG2 (encoding BCRP) genotyped pharmacokinetic data from 18 clinical studies with healthy Caucasian and/or Asian subjects.

Results

Simulations based on the current hypothesis reasonably describe SLCO1B1 and ABCG2 genotyped pharmacokinetic time course data for five transporter substrates (atorvastatin, pitavastatin, pravastatin, repaglinide, and rosuvastatin) in Caucasian and Asian populations.

Conclusion

This hypothesis covers the observations that can (e.g., ethnic differences in rosuvastatin pharmacokinetics) or cannot (e.g., lack of differences for pitavastatin pharmacokinetics) be explained by the previous hypothesis. It helps to characterize sources of ethnic variability and provides a foundation for predicting ethnic variability in transporter substrate pharmacokinetics.



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The role of intraoperative nerve monitoring in tracheal surgery: 20-year experience with 110 cases

Abstract

Purpose

To determine the utility of intraoperative nerve monitoring (IONM) during tracheal resection or slide tracheoplasty to prevent recurrent laryngeal nerve injury.

Methods

110 patients underwent tracheal resection or tracheoplasty between 1997 and 2016. During the first 10-year period, IONM was not used while during the second 10-year period, IONM was used. 49 patients had surgery without IONM while 61 had surgery with IONM. During the post-operative period, patients with nerve injury were compared to determine if significant difference existed between the two modalities.

Results

In patients who had surgery without IONM, 7 (14.2%) patients were found to have compromised nerve function whereas 8 (13.1%) patients in the group with IONM had nerve injury. 3 patients regained function in the first group while four regained function in the second. A Fisher's exact test was run on the entire cohort and the difference in vocal fold injury was not found to be statistically significant (p > 0.05).

Conclusion

Based on this single surgeon experience, there may be no protective benefit with the use of IONM during tracheal surgery.



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Enlargement of the infraorbital canal following Caldwell–Luc surgery

Abstract

Objectives

The infraorbital canal (IOC), which runs in the roof of the maxillary sinus, is a useful anatomical landmark for the infraorbital nerve (ION) on computed tomography (CT) images. Enlargement of the IOC on CT images is thought to be a pathological state that usually affects the ION. However, we have frequently observed enlargement of the IOC in patients with a history of radical surgery of the maxillary sinus: so-called Caldwell–Luc (CL) surgery. In this study, the size of the IOC of the maxillary sinus was compared between patients with a history of CL surgery (post-CL IOCs) and those with no history of CL surgery (control IOCs).

Methods

A total of 347 consecutive patients who underwent facial CT from January 2014 to October 2014 for various indications were evaluated. After excluding groove-type IOCs and IOCs with pathological lesions that could affect their diameters, 47 post-CL IOCs in 26 patients were finally compared with 504 control IOCs in 252 patients. To evaluate IOC size, the short-axis diameter of the IOC was measured on a reconstructed coronal image at the level of the posterior pole of the eyeball.

Results

The short-axis diameters of the post-CL IOCs and control IOCs were 3.0 ± 0.6 and 1.4 ± 0.3 mm, respectively (p < 0.005).

Conclusions

The short-axis diameters of post-CL IOCs are significantly enlarged (approximately double the diameter) compared to those of control IOCs.



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