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Τετάρτη 6 Φεβρουαρίου 2019
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from #Audiology via ola Kala on Inoreader http://bit.ly/2GfwCn4
This Feed Will Stop Updating on March 1st 2019! Please contact the owner to avoid disruption.
This Feed Will Stop Updating on March 1st 2019! Please contact the owner to avoid disruption.
This Feed Will Stop Updating on March 1st 2019! Please contact the owner to avoid disruption.
According to our new plans, Inoreader Pro is required to export RSS feeds.
If you are the owner of the feed, please consider upgrading to Pro.
http://bit.ly/2GfwCn4
Evaluation of propidium monoazide–based qPCR to detect viable oocysts of Toxoplasma gondii
Abstract
Information on the viability of Toxoplasma gondii oocysts is crucial to establish the public health significance of this environmental transmission stage that can contaminate water and foods. Interest for molecular-based methods to assess viability is growing and the aim of our study was to assess, for the first time, a propidium monoazide (PMA)–qPCR approach to determine the viability of T. gondii oocysts. Untreated and heat-killed (99 °C, 5 min) oocysts were incubated with PMA, a photoreactive DNA binding dye, and analyzed by confocal microscopy and flow cytometry to characterize oocysts' dye permeability. Different PMA concentrations (50 to 150 μM), incubation temperatures (22, 37, and 45 °C), amplicon length, selected targeted gene, and dyes (PMA, PMAxx™) were evaluated to define optimal conditions to discriminate specifically viable oocysts by PMA–qPCR. In theory, PMA binding to DNA would inhibit PCR amplification in dead but not in viable oocysts. Incubation at 22 °C with 100 μM PMA coupled to qPCR targeting a 123-bp sequence of the 529-bp repeat element allowed the distinction between viable and heated oocysts. However, the reduction of viability following heating of oocysts at high temperature was slight and, contrarily to reverse transcriptase-qPCR, the qPCR signal was not totally suppressed in heated suspensions. Therefore, PMA–qPCR is able to assess the impact of heating on T. gondii oocysts' viability but underestimates the efficacy of this treatment. The relevance of this technique to evaluate the efficacy of other inactivation processes and assess exposure of humans to this pathogen requires further investigations.
http://bit.ly/2UM1nmJ
Medical Education Texts
Objective Skills Clinical Examination: Every Day in the Field of Practice
Assessing Competence in Medicine and Other Health Professions
Diabetes abolish cardioprotective effects of remote ischemic conditioning: evidences and possible mechanisms
Abstract
Diabetes mellitus significantly hampers the development of cardioprotective response to remote pre/post/perconditioning stimuli by impairing the activation of cardioprotective signaling pathways. Among the different pathways, the impairment in O-linked β-N-acetylglucosamine (O-GlcNAc) signaling and release of cardioprotective humoral factor may contribute in attenuating remote preconditioning-induced cardioprotection. Moreover, the failure to phosphorylate extracellular signal related kinase (ERK), phosphoinositide-3-kinase (PI3K), and AKT along with up-regulation of mechanistic target of rapamycin (mTOR) and decrease in autophagy may also attenuate remote preconditioning-induced cardioprotection. Remote perconditioning stimulus also fails to phosphorylate AKT kinase in diabetic heart. In addition, diabetes may increase the oxidative stress, reactive oxygen species (ROS) production, decrease the beclin expression, and inhibit autophagy to attenuate remote perconditioning-induced cardioprotection. Moreover, diabetes-induced increase in the Rho-associated kinase (ROCK) activity, decrease in the arginase activity, and reduction in nitric oxide (NO) bioavailability may also contribute in decreasing remote perconditioning-induced cardioprotection. Diabetes may reduce the phosphorylation of adenosine 5′-monophosphate activated protein kinase (AMPKα) and increase the phosphorylation of mTOR to attenuate cardioprotection of remote postconditioning. The present review describes the role of diabetes in attenuating remote ischemic conditioning-induced cardioprotection along with the possible mechanisms.
http://bit.ly/2DX7xuF
Time-dependent analysis of electroosmotic fluid flow in a microchannel
Abstract
The present work models electroosmotic induced fluid flow in a microfluidic device. For theoretical analysis, the geometry of this device is considered as an asymmetric, narrow, wavy channel with charged surface. It is assumed that the length of the channel is finite and the characteristic wavelength is very large compared to the half width of the channel. The flow is assumed to be governed by Navier–Stokes equations augmented with electric body force. A transient two-dimensional flow analysis is presented by employing lubrication theory. Debye–Hückel linearization is adopted to obtain a general solution of Poisson–Boltzmann equation. The flow rate, velocity profile, pressure distribution, and wall shear stress are analyzed as functions of various parameters involved like zeta-potential ratio, Debye–Hückel parameter, etc. It is noted that the fluctuations in pressure and shear stress increase with the increasing zeta-potential ratio when the Helmholtz–Smoluchowski velocity is positive. The streamline pattern and the particle trajectories are analyzed to understand the trapping phenomenon and the retrograde motion. It is observed that the electroosmosis phenomenon drastically modulates the fluid flow in microchannels. Although the asymmetric nature of the wavy channel does not support active particle transport, the applied electric field enhances the particle motion favoring optimal conditions. It is observed that the extreme asymmetry of the wall motility reduces the net flow rate. Further, it is noticed that the asymmetry reduces the amplitudes of the pressure. This model can help toward designing artificial organs based on microfluidic devices which can also be applicable to analyze lumenal flow inside arteries and flow inside intrauterine system, and to implant the embryo at the best location in the uterus for human-assisted reproduction.
http://bit.ly/2Tw5wel
Spatio-temporal variation of natural regeneration in Pinus pinea and Pinus pinaster Mediterranean forests in Spain
Abstract
Recent research undertaken in Mediterranean pine forests suggests that the establishment of Pinus pinea L. and Pinus pinaster Ait. natural regeneration is determined by different spatial and temporal factors. In this context, we analyzed the establishment and success of natural regeneration in these two species and we examined the hypothesis that the spatial pattern of natural regeneration depends on adult tree presence, density or stand composition, while temporal patterns are typically driven by climatic conditions. For the purposes of the experiment we used 1936 plots of 0.02 ha established in mixed and pure forests of P. pinea and P. pinaster in the Northern Plateau of Spain. Plots were installed following regeneration fellings, and regeneration was monitored annually between 2001 and 2015. We used contingency tables and principal component analysis (PCA) to evaluate the main factors affecting the spatial distribution of the regeneration. PCA was also used to assess the temporal variation as a function of climatic variables. Finally, we checked for the existence of interspecific and intraspecific synchrony through Tau-Kendall synchrony analysis. We found that natural regeneration of P. pinea was more successful than that of P. pinaster over the whole of the studied period. Contingency tables showed that P. pinaster regeneration was associated with conspecific adult trees, while the relationship between P. pinea regeneration and adult trees varied depending on the regeneration development stage, i.e., seedling or saplings. Furthermore, we found that natural regeneration in both species could be enhanced through the presence of mixtures of adult trees. The spatial variability, analyzed through PCA, showed similar responses in both species, although temporal variability associated with climate variables differed between P. pinea and P. pinaster. Finally, we found different synchrony patterns affecting natural regeneration, depending on the species and the regeneration stages. In this context, temporal patterns seem to be species specific during the sapling stage of regeneration. These findings allow the observed regeneration patterns in Mediterranean pinewoods to be generalized at forest management scale.
http://bit.ly/2SgQ4pJ
Characterization of the plasma proteome of nonhuman primates during Ebola virus disease or melioidosis: a host response comparison
Abstract
Background
In-depth examination of the plasma proteomic response to infection with a wide variety of pathogens can assist in the development of new diagnostic paradigms, while providing insight into the interdependent pathogenic processes which encompass a host's immunological and physiological responses. Ebola virus (EBOV) causes a highly lethal infection termed Ebola virus disease (EVD) in primates and humans. The Gram negative non-spore forming bacillus Burkholderia pseudomallei (Bp) causes melioidosis in primates and humans, characterized by severe pneumonia with high mortality. We sought to examine the host response to infection with these two bio-threat pathogens using established animal models to provide information on the feasibility of pre-symptomatic diagnosis, since the induction of host molecular signaling networks can occur before clinical presentation and pathogen detection.
Methods
Herein we report the quantitative proteomic analysis of plasma collected at various times of disease progression from 10 EBOV-infected and 5 Bp-infected nonhuman primates (NHP). Our strategy employed high resolution LC–MS/MS and a peptide-tagging approach for relative protein quantitation. In each infection type, for all proteins with > 1.3 fold abundance change at any post-infection time point, a direct comparison was made with levels obtained from plasma collected daily from 5 naïve rhesus macaques, to determine the fold changes that were significant, and establish the natural variability of abundance for endogenous plasma proteins.
Results
A total of 41 plasma proteins displayed significant alterations in abundance during EBOV infection, and 28 proteins had altered levels during Bp infection, when compared to naïve NHPs. Many major acute phase proteins quantitated displayed similar fold-changes between the two infection types but exhibited different temporal dynamics. Proteins related to the clotting cascade, immune signaling and complement system exhibited significant differential abundance during infection with EBOV or Bp, indicating a specificity of the response.
Conclusions
These results advance our understanding of the global plasma proteomic response to EBOV and Bp infection in relevant primate models for human disease and provide insight into potential innate immune response differences between viral and bacterial infections.
http://bit.ly/2SeZqT2
Diagnostic value of diffusion-weighted MRI for imaging synovitis in pediatric patients with inflammatory conditions of the knee joint
Abstract
Background
Diffusion-weighted imaging (DWI) of synovitis has been suggested as a possible non-invasive alternative to contrast-enhanced T1w imaging (ce-T1w). We aimed to study DWI for diagnosing synovitis in the knee joint of pediatric patients, to quantify inter-observer agreement on DWI and ce-T1w and to calculate quantitative measures of synovial diffusivity and conspicuity.
Methods
Forty consecutive patients with known or suspected arthritis of the knee (25 girls, median age 12 years) underwent routine 1.5T MRI with ce-T1w and transverse DWI with b values 50 and 800 s/mm2. Mean apparent diffusion coefficient (ADC) values and signal intensity of inflamed synovium, joint effusion and muscle were measured with regions of interest retrospectively. Post-contrast T1w images (diagnostic standard) and diffusion-weighted images at b = 800 s/mm2 with ADC map were separately rated by three independent and blinded readers with different levels of expertise for the presence and degree of synovitis along with the level of diagnostic confidence.
Results
Thirty-one (78%) patients showed at least some synovial contrast enhancement, 17 (43%) children were diagnosed with synovitis on ce-T1w. Ratings by the 1st reader on ce-T1w and on DWI for synovitis showed very good agreement (kappa = 0.90). Inter-observer agreement on DWI ranged from moderate to substantial with kappa values between 0.68 and 0.79 (all P < 0.001). Agreement and diagnostic confidence were generally lower in patients with mild and without synovial enhancement, compared to patients with synovitis. DWI yielded higher signal of inflamed synovium vs. muscle tissue, but lower signal vs. joint effusion, compared to ce-T1w (all P < 0.001).
Conclusions
Diffusion-weighted imaging is a promising, though reader-dependent alternative to contrast-enhanced imaging in patients with arthritis of the knee, based on our preliminary findings. It holds potential for increasing patient safety and comfort.
http://bit.ly/2DqiWBZ
Aflatoxin in maize: a review of the early literature from “moldy-corn toxicosis” to the genetics of aflatoxin accumulation resistance
Abstract
Aflatoxin is a potent toxin produced by Aspergillus flavus Link:Fr, an opportunistic ear-rot pathogen of maize (Zea mays L. subsp. Mays). Prior to the discovery of aflatoxin, A. flavus was considered a minor pathogen and was not a priority for maize breeders or pathologists. Aflatoxin was discovered in England in 1961 following an epidemic in poultry. By the early 1970s, surveys of agricultural commodities in the USA found that maize produced in the Southeast was especially vulnerable to aflatoxin contamination. Aflatoxin contamination was initially treated as a post-harvest issue, but pre-harvest contamination was proven by 1975. Pre-harvest contamination meant that genetically based host-plant resistance was a possible solution. The potential magnitude of the problem became apparent in 1977 when the southeastern US maize crop suffered epidemic aflatoxin contamination. The first experiment demonstrating the heritability of host-plant resistance to aflatoxin accumulation was published in 1978. These events combined to make breeding for reduced aflatoxin contamination both a high priority and a rational breeding objective. This review surveys the early scientific literature in order to place research on the genetics of aflatoxin accumulation in maize into historical context. It tells the story of how multi-disciplinary research began with veterinary diseases of unknown etiology and resulted in host-plant resistance to a previously minor plant pathogen becoming a central public sector breeding objective.
http://bit.ly/2SxA6Xz
Independent risk factors for contralateral patent processus vaginalis undetected by pre-operative ultrasonography in boys with unilateral inguinal hernia
Abstract
Purpose
Many trials have been done to make sure probability of metachronous contralateral side hernia (MCH) and contralateral patent processus vaginalis (CPPV). But the necessity of contralateral side exploration is still on debate. The aim is to investigate the risk factors for the consideration of contralateral examination on operation.
Materials and methods
The study was designed as retrospectively. Patients with unilateral inguinal hernia from January 2010 to May 2015 were enrolled. Pre-operative ultrasonography was done in all patients. Patients with obvious contralateral side hernia on pre-operative US were excluded. The presence of CPPV was evaluated by transinguinal laparoscopy during the operation.
Results
In univariate analysis, hernial sac size only shows difference (P value: 0.001). The others, location of the hernia, age at surgery, gestational age (preterm), low birth weight and parent's age, did not show statistically significant differences. Multivariate analysis also demonstrates CPPV is more common in patients with large hernial sac (Odds ratio: 2.727, 95% confidence interval 1.495–4.974, P value: 0.001).
Conclusion
We propose that surgeons should consider contralateral evaluation during operation in case with large ipsilateral hernial sac, although CPPV was not detected by pre-operative US.
http://bit.ly/2MRhXPj
Gene and miRNA expression in giant cell arteritis—a concise systematic review of significantly modified studies
Abstract
Giant cell arteritis (GCA) is a systemic vasculitis in individuals older than 50 years, characterized by headaches, visual disturbances, painful scalp, jaw claudication, impairment of limb arteries, and systemic inflammation, among other symptoms. GCA diagnosis is confirmed by a positive temporal artery biopsy (TAB) or by imaging modalities. A prominent acute phase response with inflammation is the hallmark of the disease, predominantly targeting large- and medium-sized arteries leading to stenosis or occlusion of arterial lumen. To date, there are no reliable tissue markers specific for GCA. Scarce reports have indicated the importance of epigenetics in GCA. The current systematic review reports significantly changed candidate biomarkers in TABs of GCA patients compared to non-GCA patients using qPCR.
http://bit.ly/2HSbi8G
The impact of obesity on SLE disease activity: findings from the Southern California Lupus Registry (SCOLR)
Abstract
The role of obesity in systemic lupus erythematosus (SLE) remains controversial. Studies have linked adiposity with a heightened risk of clinical complications including neurocognitive decline, renal impairment, dampened physical activity, and depressed quality of life—but not disease activity. We aimed to reexamine whether obesity in SLE patients independently associates with higher disease activity. Adult patients with SLE were recruited from the longitudinal, multi-ethnic Southern California Lupus Registry (SCOLR). Disease status was ascertained by calculating SLE Disease Activity Index (SLEDAI), which was then statistically analyzed for association with increased body mass index (BMI) by univariable and multivariable regression analyses. One hundred and thirty-seven patients were included in the study; 37% were obese (BMI ≥ 30 kg/m2). Obesity was significantly associated with SLEDAI (P = 0.026) and current steroid use (P = 0.029). Multivariable regression analysis demonstrated that obesity remained independently associated with lupus activity (OR 2.335, P = 0.026). In a representative sample of patients with SLE, obesity independently associated with worse SLE disease activity. Obesity may therefore be an important target for improving SLE outcomes.
http://bit.ly/2GcJKcx
Detection of a novel mutation in NLRP3/CIAS1 gene in an Indian child with Neonatal-Onset Multisystem Inflammatory Disease (NOMID)
Abstract
Neonatal-Onset Multisystem Inflammatory Disease (NOMID) or Chronic Infantile Neurologic Cutaneous Articular (CINCA) syndrome is a monogenic autoinflammatory disorder characterized by urticarial skin rash, fever, chronic meningitis and joint manifestations. Here we report a case of an Indian male child who presented at the age of 9 months with fever, respiratory distress, urticarial skin rash, arthritis, and neuroregression. Suspecting NOMID/CINCA syndrome, the child's blood was sent to the Jaslok Hospital and Research Centre for mutation analysis of the CIAS1/NLRP3 gene. The DNA was screened for mutations in exon 3 of CIAS1/NLRP3 gene by automated Sanger sequencing. DNA sequencing showed a novel heterozygous c.1813A➔G, p.R605G mutation in exon 3 of CIAS1/NLRP3 gene (ref no NM_001243133.1). His parents tested negative for this mutation. We therefore identified a novel de novo mutation in this family in the CIAS1/NLRP3 gene responsible for the child's clinical features.
http://bit.ly/2I5qorM
Osteoarthritis: a call for research on central pain mechanism and personalized prevention strategies
Abstract
Osteoarthritis (OA) is one of the world's leading causes of pain, disability. Symptomatic OA should be suspected in patients with pain in the joints of the fingers, shoulders, hips, knees, or ankles, especially if those patients are older than 40 years. The socioeconomic cost of treating the condition and the burden of the expense is growing with the increasing and aging population. Joint-preserving interventions currently used to manage the condition include joint-protection technique instruction, manual therapy, adaptive equipment provision and instruction, heat modalities, orthoses, strengthening and range-of-motion exercises, adaptive technique instruction, patient education in symptom control techniques, and provision of a home exercise program. Some show potential, but at present, few have a proven ability to arrest or delay disease progression. Recent research regarding central pain mechanisms indicates treating central pain sensitization may be an effective treatment approach. Additional research is required to determine the efficacy of treatment and symptom management of OA.
http://bit.ly/2GcJFFL
Serum interleukin-37 level and interleukin-37 gene polymorphism in patients with Behçet disease
Abstract
Behçet's disease (BD) is a chronic inflammatory disease. The etiopathogenesis of BD is not well understood and several cytokines and genetic factors have been investigated. Interleukin (IL)-37, which a member of IL-1 family is an anti-inflammatory cytokine. The aim of the study was to analyze serum IL-37 level and IL-37 gene polymorphisms to assess its possible role in BD. Two hundred twenty-three patients with BD and 80 healthy controls (HC) were enrolled. Serum IL-37 level was measured using an enzyme-linked immunosorbent assay (ELISA). Deoksiribo Nucleic acids (DNA) were extracted using a genomic DNA isolation kit. Single nucleotide polymorphism (SNP) of IL-37 gene (rs3811047) was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR/RFLP) methods. Serum IL-37 level was not significantly different in BD and HC (p > 0.05). Serum IL-37 level was not associated with the disease activity (p > 0.05). However, its level was higher in mucocutaneous involvement compared with systemic involvement (p = 0.002) and HC (p = 0.005). IL-37 gene polymorphisms were similar in BD and HC (p > 0.05). IL-37 may play a role in the etiopathogenesis of BD by contributing to manifestation with more moderate clinical symptoms.
http://bit.ly/2I5qgZk
Feasibility of and patients’ perspective on nilotinib dried blood spot self-sampling
Abstract
Purpose
To obtain insight into the feasibility of, and the patients' perspective on, dried blood spot (DBS) self-sampling by patients with chronic myeloid leukemia (CML) using nilotinib.
Methods
Sixty-eight patients with CML using nilotinib participated in this multicenter observational study. Patients were asked to perform blood sampling by means of the DBS method at home just before drug intake (trough level) and to complete a questionnaire including demographics and five questions on their experience with DBS self-sampling.
Results
Sixty-one patients (57.5 ± 15.0 years, 49% female) provided 178 DBS samples of which 137 (77%) proved useful in clinical practice. Twenty percent of the samples were rejected because the spot size was too small for analysis. A further 3% were taken at the wrong time. Unsuitable DBS samples were provided by 23 patients. Their educational level was significantly lower than that of patients whose samples were all suitable (p = 0.041). Patients considered DBS self-sampling easy and not painful, and three quarters of the patients performed DBS sampling without additional assistance. Patients' belief in the reliability of DBS self-sampling was moderate to high. It was preferred over venous sampling by 37% of the patients, whereas 39% had no preference.
Conclusion
DBS self-sampling by CML patients is feasible in clinical practice provided that patients, particularly those with a lower educational level, are adequately instructed about sample collection with emphasis on timing and volume of sample collection.
http://bit.ly/2DhFQem
The evidence-based choice for antipsychotics in children and adolescents should be guaranteed
Abstract
Purpose
Drug use in the pediatric population still often features off-label prescriptions, particularly for psychotropic drugs. We reviewed the registration status, scientific evidence, and recommendations from the guidelines for antipsychotics used for psychiatric disorders in children.
Methods
Antipsychotic drugs marketed in Italy, the United Kingdom (UK) and United States (US) were identified with the ATC Classification System. The licensing status and Summary of Product Characteristics (SPC) were taken from the national formularies. We analyzed reviews and guidelines on antipsychotics use in children and adolescents in the MEDLINE, EMBASE, and PsycINFO databases.
Results
Out of 67 drugs, 19 were marketed with a pediatric license in at least one country: three in all the selected countries, and only paliperidone with the same indications. Haloperidol was the only antipsychotic authorized for autism in Italy and the UK, and as well as risperidone and aripiprazole in the US. Aripiprazole and paliperidone were licensed in all three countries for schizophrenia. Aripiprazole was licensed for bipolar disorders in all three countries. Haloperidol was licensed for Tourette syndrome in Italy and the UK, and pimozide and aripiprazole in the US.
We retrieved 21 pertinent reviews and 13 guidelines for the management of neuropsychiatric disorders in pediatrics. There was a complete overlap between the authorized therapeutic indications and the available scientific evidence for autism in the US, for conduct disorders and bipolar disorders in the UK, and for Tourette syndrome and tics in the UK and Italy.
Conclusions
These results highlight the different regulatory processes that deny to many children and adolescents the most appropriate and rational antipsychotic therapy.
http://bit.ly/2Sehcpr
GeM-Pro: a tool for genome functional mining and microbial profiling
Abstract
Gem-Pro is a new tool for gene mining and functional profiling of bacteria. It initially identifies homologous genes using BLAST and then applies three filtering steps to select orthologous gene pairs. The first one uses BLAST score values to identify trivial paralogs. The second filter uses the shared identity percentages of found trivial paralogs as internal witnesses of non-orthology to set orthology cutoff values. The third filtering step uses conditional probabilities of orthology and non-orthology to define new cutoffs and generate supportive information of orthology assignations. Additionally, a subsidiary tool, called q-GeM, was also developed to mine traits of interest using logistic regression (LR) or linear discriminant analysis (LDA) classifiers. q-GeM is more efficient in the use of computing resources than Gem-Pro but needs an initial classified set of homologous genes in order to train LR and LDA classifiers. Hence, q-GeM could be used to analyze new set of strains with available genome sequences, without the need to rerun a complete Gem-Pro analysis. Finally, Gem-Pro and q-GeM perform a synteny analysis to evaluate the integrity and genomic arrangement of specific pathways of interest to infer their presence. The tools were applied to more than 2 million homologous pairs encoded by Bacillus strains generating statistical supported predictions of trait contents. The different patterns of encoded traits of interest were successfully used to perform a descriptive bacterial profiling.
http://bit.ly/2DYxw4Z
l -Cysteine production by metabolically engineered Corynebacterium glutamicum
Abstract
l-Cysteine is a commercially important amino acid. Here, we report the construction of l-cysteine-producing Corynebacterium glutamicum using a metabolic engineering approach. l-Serine O-acetyltransferase (SAT), encoded by cysE gene, is a key enzyme of l-cysteine biosynthesis, because of its feedback inhibition by l-cysteine. Therefore, we introduced a mutation into the C. glutamicum cysE gene, which appeared to desensitize SAT against feedback inhibition by l-cysteine. We successfully produced l-cysteine by overexpressing this mutant cysE gene in C. glutamicum, while the wild-type strain scarcely produced l-cysteine. To enhance the biosynthesis of l-serine (a substrate for SAT), a mutant serA gene, encoding D-3-phosphoglycerate dehydrogenase to desensitize it against feedback inhibition by l-serine, was additionally overexpressed in the mutant cysE-overexpressing strain and its l-cysteine production was indeed improved. Moreover, we disrupted the ldh gene encoding l-lactate dehydrogenase and the aecD gene encoding cysteine desulfhydrase to prevent the formation of lactic acid as a by-product and degradation of l-cysteine produced at the stationary phase, respectively, which resulted in enhanced l-cysteine production. However, since the concentration of l-cysteine produced still decreased at the stationary phase despite the aecD disruption, NCgl2463 encoding a possible cystine importer protein was further disrupted to prevent cystine import, because the produced l-cysteine is immediately oxidized to cystine. As a result, the time before the start of the decrease in l-cysteine concentration was successfully prolonged. Approximately 200 mg/L of l-cysteine production was achieved by overexpression of mutant cysE and serA genes and disruption of aecD and NCgl2463 genes in C. glutamicum.
http://bit.ly/2WNgVbK
Psychrophilic lifestyles: mechanisms of adaptation and biotechnological tools
Abstract
Cold-adapted microorganisms inhabiting permanently low-temperature environments were initially just a biological curiosity but have emerged as rich sources of numerous valuable tools for application in a broad spectrum of innovative technologies. To overcome the multiple challenges inherent to life in their cold habitats, these microorganisms have developed a diverse array of highly sophisticated synergistic adaptations at all levels within their cells: from cell envelope and enzyme adaptation, to cryoprotectant and chaperone production, and novel metabolic capabilities. Basic research has provided valuable insights into how these microorganisms can thrive in their challenging habitat conditions and into the mechanisms of action of the various adaptive features employed, and such insights have served as a foundation for the knowledge-based development of numerous novel biotechnological tools. In this review, we describe the current knowledge of the adaptation strategies of cold-adapted microorganisms and the biotechnological perspectives and commercial tools emerging from this knowledge. Adaptive features and, where possible, applications, in relation to membrane fatty acids, membrane pigments, the cell wall peptidoglycan layer, the lipopolysaccharide component of the outer cell membrane, compatible solutes, antifreeze and ice-nucleating proteins, extracellular polymeric substances, biosurfactants, chaperones, storage materials such as polyhydroxyalkanoates and cyanophycins and metabolic adjustments are presented and discussed.
http://bit.ly/2RHi5Sk
Identification of novel epitopes targeting non-structural protein 2 of PRRSV using monoclonal antibodies
Abstract
Porcine reproductive and respiratory syndrome virus (PRRSV) is leading to huge losses in the swine industry worldwide. Its nonstructural protein 2 (Nsp2), with a cysteine protease domain (PL2), is crucial for virus replication and as a trigger to host innate immune regulation. In this study, three monoclonal antibodies (mAbs) to Nsp2, designated 4A12, 4G8, and 8H11, were generated. Subsequently, a sequence of recombinant peptides with partial overlap was utilized to determine the epitopes using these mAbs. We found three novel minimal linear Nsp2 B cell epitopes, 188ELSDDSNRPV197, 42HLKRYSPPAE51, and 54CGWHCISA61, which were identified by the antibodies 4A12, 4G8, and 8H11, respectively. Structure analysis indicates that 42HLKRYSPPAE51 and 188ELSDDSNRPV197 are located separately in hypervariable region 1 and hypervariable region 2 of Nsp2. Interestingly, 54CGWHCISA61 is located in the PL2 region, which is highly conserved in all arteriviruses, particularly at the expected conserved catalytic site at Cys54. Importantly, 54CGWHCISA61 is located in the inner region of the expected 3D structure of Nsp2, which reveals that the epitope is cryptic. These findings not only provide valuable insight for vaccine design and hold diagnostic potential for the identified epitopes, but also reveal a protective mechanism against variation under selective pressure in an important epitope.
http://bit.ly/2Gtiaac
Association of continuous positive airway pressure with F2-isoprostanes in adults with obstructive sleep apnea: a meta-analysis
Abstract
Purpose
Obstructive sleep apnea (OSA) is associated with increased F2-isoprostanes, a reliable standard biomarker of oxidative stress. Treatment with continuous positive airway pressure (CPAP) is effective for all degrees of OSA. However, it remains unknown whether treatment with CPAP will decrease F2-isoprostanes. A meta-analysis was conducted to determine the effect of CPAP treatment on F2-isoprostanes among patients with OSA.
Methods
The PubMed, Embase, Web of Science, and Cochrane library were searched before September, 2018. Eight articles assessing indices of F2-isoprostanes from various body fluids were identified. Pooled standardized mean difference (SMD) and weighted mean difference (WMD) were appropriately calculated through fixed or random effects models after assessing between-study heterogeneity.
Results
A total of 4 studies with 108 patients were pooled for exhaled breath condensate (EBC) F2-isoprostanes; 3 studies with 93 patients were pooled for serum or plasma F2-isoprostanes; and 3 studies with 102 patients were pooled for urinary F2-isoprostanes. A significant decrease of EBC F2-isoprostanes was observed after CPAP treatment (WMD = 2.652, 95% CI = 0.168 to 5.136, z = 2.09, p = 0.036), as well as serum or plasma F2-isoprostanes and urinary F2-isoprostanes (SMD = 1.072, 95% CI = 0.276 to 1.868, z = 2.64, p = 0.008 and WMD = 85.907, 95% CI = 50.443 to 121.372, z = 4.75, p = 0.000, respectively).
Conclusions
This meta-analysis suggested that CPAP therapy was associated with a significant decrease in F2-isoprostanes in patients with OSA.
http://bit.ly/2UJRhCX
Detection, genotyping, and phylogenetic analysis of Leishmania isolates collected from infected Jordanian residents and Syrian refugees who suffered from cutaneous leishmaniasis
Abstract
Leishmania is a parasitic protozoan which is transmitted to humans through the bite of an infected female Phlebotomus and Lutzomyia sand flies. Cutaneous leishmaniasis (CL), caused by Leishmania major and L. tropica, is an endemic disease in many areas of Jordan and considered as a major public health problem. The political instability in the Syrian Arab Republic has resulted in the immigration of large number of refugees into Jordan where most of them resided in camps near the Syrian borders. Therefore, the main objective of the present study was to inspect Leishmania species/genotypes which are responsible for CL infections among Syrian refugees and compare them with the recovered species/genotypes isolated from Jordanian patients. Three molecular-based assays (ITS1-PCR-RFLP, Nested ITS1-5.8S rDNA PCR, and Kinetoplast DNA PCR) followed by sequencing and phylogenetic analysis were undertaken and compared for their efficiency to confirm CL diagnosis and genotype the infecting Leishmania species. Thereafter, the evolutionary relationships among various Leishmania isolates from Syrian and Jordanian CL patients were elucidated. Results from the present study indicated that 20 and 9 out of the inspected 66 patients (39 Jordanian and 27 Syrian) were infected with L. major and L. tropica respectively. ITS1-PCR RFLP typing proved to be more sensitive in the detection of Leishmania species (positive in 44% of the isolates) compared to both ITS1-5.8S rDNA gene and Kinetoplast DNA PCR which were successful in identifying Leishmania species only in 23% and 33% of the isolates respectively. Sequencing and phylogenetic analysis of ITS1 and ITS1-5.8S rDNA genes revealed high levels of heterogeneity among the sequenced isolates. One sample typed as L. tropica from Jordanian patient showed high similarity with L. tropica sample isolated from a Syrian patient in a Lebanon refugee camp; therefore, the need for comprehensive studies to confirm if any new L. tropica strains might be introduced to Jordan by Syrian refugees is urgently indicated. These observations highlighted the need for further studies to clarify the risk status of species and strains which might be introduced from Syria to Jordan.
http://bit.ly/2SyqX13
Query answering over uncertain RDF knowledge bases: explain and obviate unsuccessful query results
Abstract
Several large uncertain knowledge bases (KBs) are available on the Web where facts are associated with a certainty degree. When querying these uncertain KBs, users seek high-quality results, i.e., results that have a certainty degree greater than a given threshold \(\alpha \) . However, as they usually have only a partial knowledge of the KB contents, their queries may be failing i.e., they return no result for the desired certainty level. To prevent this frustrating situation, instead of returning an empty set of answers, our approach explains the reasons of the failure with a set of \(\alpha \) minimal failing subqueries ( \(\alpha \) MFSs) and computes alternative relaxed queries, called \(\alpha \) maXimal succeeding subqueries ( \(\alpha \) XSSs), that are as close as possible to the initial failing query. Moreover, as the user may not always be able to provide an appropriate threshold \(\alpha \) , we propose three algorithms to compute the \(\alpha \) MFSs and \(\alpha \) XSSs for other thresholds, which also constitutes a relevant feedback for the user. Multiple experiments with the WatDiv benchmark show the relevance of our algorithms compared to a baseline method.
http://bit.ly/2GiPstF
Stabilization of vulnerable carotid plaques with proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab
Abstract
Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, a novel class of monoclonal antibodies, reduce low-density lipoprotein cholesterol levels and improve outcomes of myocardial infarction and stroke. However, the effects of PCSK9 inhibitors on carotid plaques remain unclear. We describe three patients treated with PCSK9 inhibitor alirocumab for progressive carotid stenosis despite lipid-lowering statin therapy. All three patients had vulnerable plaques on magnetic resonance (MR) plaque imaging. After alirocumab treatment initiation, no patients suffered stroke or adverse events, and the stabilization of the carotid plaques was observed on MR plaque imaging.
http://bit.ly/2SkFa2A
Evolutionary Robotics Applied to Hexapod Locomotion: a Comparative Study of Simulation Techniques
Abstract
The Evolutionary Robotics (ER) process has been applied extensively to developing control programs to achieve locomotion in legged robots, as an automated alternative to the arduous task of manually creating control programs for such robots. The evolution of such controllers is typically performed in simulation by making use of a physics engine-based robotic simulator. Making use of such physics-based simulators does, however, have certain challenges associated with it, such as these simulators' computational inefficiency, potential issues with lack of accuracy and the human effort required to construct such simulators. The current study therefore proposed and investigated an alternative method of simulation for a hexapod (six-legged) robot in the ER process, and directly compared this newly-proposed simulation method to traditional physics-based simulation. This alternative robotic simulator was built based solely on experimental data acquired directly from observing the behaviour of the robot. This data was used to construct a simulator for the robot based on Artificial Neural Networks (ANNs). To compare this novel simulation method to traditional physics simulation, the ANN-based simulators were used to evolve simple open-loop locomotion controllers for the robot in simulation. The real-world performance of these controllers was compared to that of controllers evolved in a more traditional physics-based simulator. The obtained results indicated that the use of ANN-based simulators produced controllers which could successfully perform the required locomotion task on the real-world robot. In addition, the controllers evolved using the ANN-based simulators allowed the real-world robot to move further than those evolved in the physics-based simulator and the ANN-based simulators were vastly more computationally efficient than the physics-based simulator. This study thus decisively indicated that ANN-based simulators offer a superior alternative to widely-used physics simulators in ER for the locomotion task considered.
http://bit.ly/2RKoR9K
Iterative Learning-Based Admittance Control for Autonomous Excavation
Abstract
This paper presents the development and field validation of an iterative learning-based admittance control algorithm for autonomous excavation in fragmented rock using robotic wheel loaders. An admittance control strategy is augmented with iterative learning, which automatically updates control parameters based on the error between a target bucket fill weight and the measured fill weight at the end of each excavation pass. The algorithm was validated through full-scale autonomous excavation experiments with a 14-tonne capacity load-haul-dump (LHD) machine and two different types of excavation materials: fragmented rock and gravel. In both excavation scenarios, the iterative learning algorithm is able to update the admittance control parameters for a specified target bucket fill weight, eliminating the need to manually re-tune control parameters as material characteristics change. These results have practical significance for increasing the autonomy of robotic wheel loaders used in mining and construction.
http://bit.ly/2Sv9mr0
Retrospective study of the digestive tract mucositis derived from myeloablative and non-myeloablative/reduced-intensity conditionings with busulfan in hematopoietic cell transplantation patient
Abstract
Busulfan is a major component of chemotherapy conditioning in hematopoietic cell transplantation (HCT). This alkylating agent is highly toxic at myeloablative doses, exposing HCT patients to risks of mortality. Non-myeloablative (NMA) and reduced-intensity conditioning (RIC) using busulfan have shown impaired toxicity. However, the toxicity of NMA/RIC in the digestive tract is poorly described. This study aimed to characterize the mucositis in the oral cavity (OM), oropharynx/esophagus, and gastrointestinal tract derived from conditionings with myeloablative and non-myeloablative doses of busulfan. We retrospectively retrieved clinical data of HCT patients (n = 100) who underwent myeloablative conditioning (MAC) or NMA/RIC with busulfan. Frequency and time duration of mucositis in the oral cavity and oropharynx/esophagus, diarrhea, and prescription of total parenteral nutrition (TPN) and opioids were also collected. OM severity (p = 0.009) and time duration of mucositis in oropharynx/esophagus (p = 0.022) were frequently higher in MAC than NMA/RIC. A myeloablative dose of busulfan was a risk factor for OM grade ≥ 2 (OR = 4.8, p = 0.002) and for mucositis in oropharynx/esophagus ≥ 5 days (OR = 2.64, p = 0.035). A longer duration of mucositis in the oropharynx/esophagus was also associated with an increase in the prescription of opioids (OR = 7.10, p < 0.001).Overall survival (OS) in MAC was significantly higher than that in NMA/RIC (p = 0.017). No variables related to mucositis interfere significantly in OS. In conclusion, myelosuppression in busulfan-based regimens are predisposed to a high risk for severe OM and to prolonged mucositis in the oropharynx/esophagus.
http://bit.ly/2DXNOuQ
Prevention of chemotherapy-induced nausea and vomiting after high-dose melphalan and stem cell transplantation: review of the evidence and suggestions
Abstract
Introduction
High-dose melphalan (HDMel) is the most common conditioning chemotherapy regimen for autologous stem cell transplantation (SCT) in patients affected by multiple myeloma (MM). No consensus exists for the emetogenicity or prophylaxis of chemotherapy-induced nausea and vomiting (CINV) in this regimen.
Methods
Data on the incidence and efficacy/safety of CINV prophylaxis among patients affected by MM undergoing autologous SCT with the HDMel regimen was extracted from electronic databases and analyzed.
Results
Eleven studies involving multiple CINV prophylaxis regimens were identified and included. No consensus on HDMel emetogenicity was reached, but most studies summarized the emetogenicity as moderate-high risk. An aprepitant-based three-drug regimen (aprepitant + serotonin receptor antagonist (5HT3RA) + dexamethasone) showed better efficacy than a two-drug regimen (5HT3RA + dexamethasone) for CINV prevention without increasing the frequency in adverse events.
Conclusions
The aprepitant-based three-drug regimen should be the regimen of choice for CINV prophylaxis for MM patients undergoing autologous SCT with HDMel conditioning.
http://bit.ly/2GqASPI
Correction to: The effect of routine training on the self-efficacy of informal caregivers of colorectal cancer patients
The "NCI Grant No. 5R25CA116339, Outcomes Research Branch of the National Cancer Institute, National Institutes of Health" is not included in the Funding information. The below is the correct "Funding/Support".
http://bit.ly/2MUmfFQ
Pupillary response: cognitive effort for breast cancer survivors
Abstract
Purpose
The purpose of this cross-sectional comparative pilot study was to evaluate cognitive effort, indexed by pupillary response (PR), for breast cancer survivors (BCS) with complaints of cognitive dysfunction following chemotherapy.
Study Aims
Compare the cognitive effort employed by BCS to healthy controls (HC) during neuropsychological tests (NPT) for memory, sustained attention, verbal fluency, visuospatial ability, processing speed and executive function; and Investigate the relationship between PR-indexed cognitive effort and participants' self-report of cognitive function.
Methods
Self-report of cognitive function was collected from 23 BCS and 23 HC. PR was measured during NPT. Independent two-sample t tests or Wilcoxon rank sum tests were used to compare group scores. Between-group effect size (Cohen's d) was calculated for each outcome. Correlation between mean self-report scores and PR values, as well as 95% confidence intervals, was calculated.
Results
No group differences were demonstrated for NPT performance. BCS reported more issues with cognitive function than HC (p < .0001). A group effect for BCS was seen with PR-indexed cognitive effort for components of most NPT (p < .05). PR was correlated with most self-report measures of cognitive function (r = 0.33–0.45).
Conclusions
PR sensitivity to cognitive effort across a variety of NPT and correlation with self-report of cognitive function was demonstrated. The portability, affordability, and "real-time" aspects of PR are attractive for potential use in the clinic setting to assess cognitive function. A larger study is needed to confirm these results. Prospective investigation of PR in BCS is needed to demonstrate sensitivity to cognitive function changes over time.
http://bit.ly/2DXNCvC
Breaking bad news of a breast cancer diagnosis over the telephone: an emerging trend
Abstract
Purpose
This study evaluated how breast cancer diagnoses were shared with patients.
Methods
Current members of the Dr. Susan Love Research Foundation's Army of Women cohort were sent one email with a link to a survey assessing how their breast cancer diagnosis was communicated, a description of their support system during treatment, basic demographic information, and breast cancer diagnosis details.
Results
Participants (n = 2896) were more likely to be given their diagnosis over the telephone in more recent years (OR 1.07, 95% CI 1.06–1.08). Up until about 10 years ago (1967–2006), breast cancer diagnoses were communicated in person more often than by telephone. Since 2006, more than half of participants learned about their diagnosis over the telephone. From 2015 to 2017, almost 60% of participants learned about their diagnosis over the telephone. Among those who heard the news in person, a steady 40% were alone. Characteristics of those who received the news over the telephone included having identified support members, heterosexual identity, and a diagnosis of in situ breast cancer.
Conclusions
Receiving a telephone call about breast cancer diagnosis may be the norm rather than the exception in health care today. Trends in practice, as well as current best practices based primarily on expert opinion, may not provide optimal care for women diagnosed with breast cancer. Patient outcome research to guide future practice, such as the impact of modes of delivery of bad news, is urgently needed to determine appropriate patient-centered approaches for notification of breast cancer diagnoses.
http://bit.ly/2SwoX9t
Safety and feasibility of electrical muscle stimulation in patients undergoing autologous and allogeneic stem cell transplantation or intensive chemotherapy
Abstract
Intensive chemotherapy, with or without following autologous or allogeneic stem cell transplantation (HSCT), is often the only curative treatment option for patients with hematological malignancies and leave many survivors physically and psychologically impaired. Electrical muscle stimulation (EMS) is a proven tool to improve physical performance in seniors and patients with chronic diseases. We therefore investigated the safety and feasibility of EMS in 45 patients undergoing autologous HSCT (n = 13), allogeneic HSCT (n = 11) and intensive chemotherapy (n = 21). Furthermore, physical (assessed by 6-min walking distance (6MWD) and short physical performance battery (SPPB)) and psychological performance (assessed by multidimensional fatigue inventory (MFI) and the EORTC QOL-C30 questionnaire) were measured before chemotherapy (T1) and at discharge from hospital (T2). Four patients died due to septic shock, two withdrew consent before the start of EMS training and five stopped EMS training during the study because of chemotherapy-related complications, loss of motivation or loss of ability to use EMS autonomously. Thirty-four out of 45 (76%) patients used EMS throughout the study period and participated in physical and psychological tests at time points 1 and 2. EMS-related adverse events were hematoma (n = 1) and muscle pain (n = 2). No bleeding events > 1 according to the WHO bleeding scale occurred. Decline in 6MWD from T1 to T2 was 24 m. The SPPB score stayed the same with 11 points at T1 and T2. Most MFI subscales showed stable fatigue levels and quality of life (QoL) did not decrease significantly throughout therapy. EMS is feasible and safe in patients undergoing intensive chemotherapy. Trial registration: NCT03467087
http://bit.ly/2GrB9C5
Multi-disciplinary proactive follow-up algorithm for patients with advanced NSCLC receiving afatinib
Abstract
Purpose
Afatinib is a standard first-line therapy for advanced EGFR-positive NSCLC. We implemented a pharmacist-led proactive follow-up algorithm to identify and manage early afatinib-related adverse events (AEs).
Methods
We conducted a retrospective chart review of all patients treated with afatinib after implementation of the algorithm at the Sunnybrook Odette Cancer Centre (Toronto, ON, Canada) from April 1, 2015 to July 31, 2016. Our in-house algorithm involved consultations in person and proactive pharmacist-led callbacks on days 5, 10, and 17. All AEs were graded and documented in real time and management based on toxicity grade was standardized. This study evaluated the impact of our algorithm on real-world AEs.
Results and discussion
Thirty-three patients were identified and reviewed. Median follow-up was 248 days. All patients experienced at least one drug-related AE; 18.2% were grade 3/4. The most common AEs were diarrhea 87.9%, rash 81.8%, stomatitis 57.6%, and paronychia 45.5%. Median dose of afatinib was 40 mg daily; 51.5% of patients had ≥ 1 dose reduction and 6.3% discontinued afatinib due to AEs. Proactive calls by the pharmacist identified 36.5% of all drug-related AEs, 33.3% of grade 3/4 AEs, 58.1% of first drug-related AEs and identified two patients that were non-compliant. Only 3.2% of AEs were identified by an emergency room/urgent clinic visit.
Conclusions
This proactive multi-disciplinary AE management algorithm resulted in a low rate of urgent assessments and discontinuation due to toxicity while maintaining afatinib at ideal dose, thus providing a useful tool for centers prescribing afatinib.
http://bit.ly/2DYxxpz
The new challenge for improving psychosocial cancer care: shifting to a system-based approach
Abstract
Introduction
There is a need to improve the psychosocial well-being of cancer patients. To date, intervention research has primarily focussed on improving psychosocial well-being through targeting singular aspects of care at the individual patient level. Sustainable, high-quality psychosocial care should address the issues faced by people diagnosed with cancer throughout the care pathway using a system-based approach.
Aims
To examine the number of intervention trials attempting to improve psychosocial cancer care that have implemented a system-based approach.
Method
Five journals were selected and relevant studies across all years were extracted. Four criteria, argued to be essential characteristics of system-based change, were assessed: (1) establishing a culture change within the healthcare system/organisation, through designated leaders who endorse organisational goals; (2) adopting a multidisciplinary approach to change; (3) mapping the system and identifying points of leverage; and (4) measuring the impact of change and adapting establish feedback loops.
Results
The search strategy returned 1174 citations, of which five met the inclusion criteria. Of the intervention studies identified, three met none of the four defined criteria for a systems-based intervention, one study met criterion 2 only, and one study met all four criteria, however, was not a rigorous study design.
Conclusions
This review of published psychosocial intervention trials in top-ranking psychosocial cancer care journals only found one study that met our criteria for evaluating system-based change. This is likely to be a consequence of the significant pragmatic and political barriers to conducting system-based intervention research.
http://bit.ly/2SDe0TA
Endurance and resistance training in patients with acute leukemia undergoing induction chemotherapy—a randomized pilot study
Abstract
Purpose
Acute leukemia (AL) and its initial treatment can impair physical functioning and capacity significantly. Exercise as a countermeasure has been investigated in few studies confirming its feasibility and safety during intensive induction chemotherapy, but the relative effects of diverse exercise programs have not been analyzed. Therefore, we aimed to investigate independent effects of endurance and resistance training on physical capacity and quality of life (QOL).
Methods
Twenty-nine adult AL patients were randomly allocated to an endurance (EG), resistance (RG), or control (CG) group. The intervention took place during induction chemotherapy with three exercise sessions per week for 30–45 min each. Endurance capacity at individual anaerobic threshold, maximum knee extension and flexion strength, standardized phase angle (SPA), and QOL were measured at baseline prior to induction chemotherapy and before discharge.
Results
Endurance capacity changed in neither the EG, RG, or CG (P = 0.104); descriptively, the EG (− 0.05 W/kg) and RG (− 0.04 W/kg) exhibited a smaller decrease than CG (− 0.22 W/kg). We noted a significant difference in knee extension strength (P = 0.002); RG improved their maximum strength (+ 0.14 Nm/kg), while the EG's (− 0.13 Nm/kg) and CG's (− 0.19 Nm/kg) was significantly reduced. QOL and SPA revealed no change after the intervention.
Conclusions
We conclude that resistance training is a key component when exercising during induction chemotherapy: it improved maximum strength, but also influenced endurance capacity even during intensive treatment. Considering the prognostic value of physical function, we strongly propose integrating exercise, especially resistance-based training, already during induction chemotherapy to preserve AL patients' physical capacity and functional status.
http://bit.ly/2GxGlUS
Physical activity and associations with treatment-induced adverse effects among prostate cancer patients
Abstract
Purpose
The present study aimed to determine the level of physical activity (PA) among prostate cancer (PCa) patients across treatment modalities and explore the association between PA and treatment-induced adverse effects (AEs).
Methods
The present study was based on a cross-sectional postal survey among members of the Norwegian Prostate Cancer Association. Patients were eligible for the present study if they had either (1) completed radical prostatectomy, (2) completed radiotherapy and (neo)-adjuvant androgen deprivation therapy (ADT), or (3) were undergoing lifelong ADT. Adverse effects were measured by the Expanded Prostate Cancer Index Composite for Clinical Practice.
Results
In total, 696 patients were included. There was no statistically significant difference in level of PA across treatment modalities. Bowel symptoms mainly related to radiotherapy decreased the odds of exercising ≥ 2 times per week, along with age ≥ 70 years, participation in the workforce, and BMI ≥ 25 kg/m2. Among patients who were undergoing ADT, 5 years or more since diagnosis reduced the odds of exercising ≥ 2 times per week by almost 60%.
Conclusion
The level of PA did not differ across PCa patients treated with different modalities. Increasing bowel symptoms reduced the likelihood of exercising ≥ 2 times per week. PCa patients should be educated about possible treatment-induced AEs affecting PA level, enabling them to counteract the development of physical inactivity.
http://bit.ly/2DXEaIU
Risk factors associated with chemotherapy-induced nausea and vomiting in the triplet antiemetic regimen including palonosetron or granisetron for cisplatin-based chemotherapy: analysis of a randomized, double-blind controlled trial
Abstract
Purpose
The triplet antiemetic regimen is recommended for cisplatin-based highly emetogenic chemotherapy, in the current guidelines for antiemetic prophylaxis. Although risk factors related to chemotherapy-induced nausea and vomiting (CINV) have been identified by several prior studies, there are only few studies evaluating risk factors associated with the prophylactic triplet antiemetic therapy, particularly in palonosetron use. The present study aimed to reveal the risk factors related to CINV development in patients receiving cisplatin and to compare CINV risk factors between palonosetron and granisetron use.
Methods
In total, 825 patients in a phase III trial receiving palonosetron with graniestron were evaluated. Multivariate logistic regression models were used to predict risk factors associated with CINV development. Additionally, risk factors associated with CINV development were separately evaluated in each treatment group.
Results
Multivariate analysis of the entire study group revealed that sex, age, cisplatin dose, and granisetron use were significant and independent factors affecting CINV development in the overall phase. Similarly, sex and age were risk factors for CINV in both treatment groups. Kaplan–Meier curves classified by each treatment group showed no significant difference between the groups among patients without any risk factors for CINV (P = 0.353). Conversely, complete response rates for patients with at least one risk factor were higher in patients receiving palonosetron (P = 0.049).
Conclusions
This analysis revealed the importance of previously reported CINV risk factors when using triplet antiemetics. Palonosetron might be preferred for patients with at least one risk factor.
http://bit.ly/2Gu6R1K
Real-world use of granulocyte colony-stimulating factor in ambulatory breast cancer patients: a cross-sectional study
Abstract
Purpose
To prevent febrile neutropenia (FN), European Organisation for Research and Treatment of Cancer (EORTC) guidelines recommend primary prophylaxis with granulocyte colony-stimulating factors (PPG) for patients at high risk (≥ 20%) of FN. In Belgium, the use of PPG is restricted by specific reimbursement criteria. The impact of these criteria on PPG use and adherence to guidelines is unknown.
Methods
This multicentre, cross-sectional, observational study aimed to describe PPG use by FN risk category in breast cancer patients who were scheduled to receive myelosuppressive chemotherapy in outpatient clinics in Belgium during a 2-week period between 13 October and 12 December 2014.
Results
In total, 490 patients were enrolled. Median age was 57.0 years. Based on their chemotherapy regimen, 53.9, 5.1 and 41.0% of patients were at a low, intermediate and high risk of FN, respectively. Overall, 39.8% of patients received PPG (17.0, 12.0 and 73.1% of those receiving low-, intermediate- and high-risk regimens, respectively). In the high-risk category, PPG was used in 89.9% of dose-dense and in 25.0% of classical chemotherapy regimens. PPG use was adherent to EORTC guidelines in 75.3% of patients (30.6% appropriate use, 44.7% appropriate non-use). EORTC guidelines would recommend PPG use in 46.1% of this study population (n = 226), and its use was reimbursable in Belgium in 76.1% of these patients (n = 172), but only 66.4% of them received PPG (n = 150).
Conclusions
Both Belgian reimbursement criteria and physician decision-making led to a proportion of patients for whom PPG treatment was recommended but finally not receiving it.
http://bit.ly/2DZ0t0N
Impact of adjuvant lorazepam with granisetron on chemotherapy-induced nausea and vomiting in pediatric patients with acute lymphoblastic leukemia
Abstract
Purpose
Chemotherapy-induced nausea and vomiting (CINV) affects quality of life for patients with cancer undergoing chemotherapy. We aimed to assess the effect of lorazepam with granisetron on CINV in children with acute lymphoblastic leukemia (ALL).
Methods
We reviewed the records of 71 consecutive patients with newly diagnosed ALL who received chemotherapy including vincristine, anthracycline, and systemic steroids between January 2011 and December 2016 in our hospital. The number of chemotherapy cycles reviewed was 164. All patients received granisetron as CINV prophylaxis.
Results
Nausea was observed in 51/71 patients (72%) and 93/164 cycles (57%). Vomiting was observed in 47/71 patients (66%) and 79/164 cycles (48%). Age and gender distribution were not significantly different between patients who received lorazepam at the initiation of the chemotherapy cycle (LZP group, n = 30) and those who did not receive lorazepam (non-LZP group, n = 134). There were no significant differences in the incidence of CIN and CIV between the LZP group and non-LZP group (CIN, 67% vs. 57%, P = 0.31; CIV, 53% vs. 47%, P = 0.98). In multivariate logistic regression, female gender and older age (> 5 years) were significant risk factors for CIV (female, odds ratio (OR) 2.5, 95% confidence interval (CI) 1.3–5.0, P = 0.007; older age, OR 2.5, CI 1.3–4.8, P = 0.008).
Conclusions
We found no beneficial effect of providing lorazepam as adjuvant antiemetic for prevention of CINV in children with ALL.
http://bit.ly/2GtQYbl
The feasibility of dexamethasone omission in weekly paclitaxel treatment for breast cancer patients
Abstract
Objectives
Patients with breast cancer who receive weekly paclitaxel therapy may experience deleterious effects associated with prophylactic dexamethasone use for 12 consecutive weeks. Approximately 90% of paclitaxel hypersensitivity reactions (HSRs) occur within the first 10 to 15 min of the first two infusions. We investigated the feasibility of dexamethasone withdrawal between weeks 3 and 12 (W3 and W12) in early stage breast cancer patients treated with weekly paclitaxel at the standard dose (80 mg/m2).
Methods
All patients received intravenous prophylaxis of dexamethasone 20 mg, ranitidine 50 mg, and diphenhydramine 50 mg in the first 2 weeks (W1 and W2) of treatment. Provided that no serious (G3/G4) HSRs events occurred, dexamethasone was omitted between W3 and W12, while ranitidine and diphenhydramine were continued. The primary end point was the incidence of any grade HSRs during the treatment period, and the secondary end points were quality of life and weight changes.
Results
Twenty-five patients were included in the study, and 300 infusion cycles of paclitaxel were evaluated for HSRs. The overall incidence of HSRs was 0.6% (2 events), and both of these events occurred in the first week. There were no incidents of serious HSRs or anaphylaxis and no G3 or G4 toxicities. Scores from the EORTC QLQ-C30 questionnaire did not change significantly for the global health status/quality of life scale or for the symptoms scales, although changes in scores differed significantly for the functional scales. There were no clinically relevant weight changes during the treatment period.
Conclusions
Dexamethasone withdrawal from W3 to W12 in early stage breast cancer patients treated with weekly paclitaxel is feasible. The incidence of all grades of HSRs was comparable to that reported in trials with dexamethasone for 12 consecutive weeks, and no serious events (G3/G4) occurred. Studies with larger sample sizes are needed to confirm our results which are important, especially for patients for whom corticosteroids are contraindicated.
http://bit.ly/2DX3Xk6
Sexual health in cancer: the results of a survey exploring practices, attitudes, knowledge, communication, and professional interactions in oncology healthcare providers
Abstract
Purpose
To assess, focusing on population of healthcare professionals providing oncosexology care to men with cancer, clinical practice, attitudes, knowledge, communication, and professional interaction.
Methods
We performed a descriptive cross-sectional study with an online self-administered e-questionnaire addressed to all medical, paramedical, or administrative professionals attending the 4th "Cancer, Sexuality and Fertility" Meeting in Toulouse, France. Their participation was voluntary and totally anonymous.
Results
The 165 respondents comprised 44% of physicians, 47% of paramedics, and 9% of other health professionals in oncology, from all French regions. Paramedics were significantly younger than physicians (p = .006). One third of respondents were degreed in sexology, but 75.8% were in demand of oncosexology-specific trainings, particularly paramedics (p = .029). Regarding the oncosexology network, respondents declared being linked to organ specialists (56.8%), psychologists (49.5%), oncologists (47.4%), nurses (31.5%), radiation therapists (27.4%), and general practitioners (25.3%). Compared to paramedics, physicians were more likely to be engaged in oncosexology care (p = .039) and couple counseling (p = .005), but the proportions of counseled patients or couple were identical (p = .430 and p = .252, respectively). Overall, 90% of respondents reported discussing sexuality issues with patients. Regarding the time for discussion, physicians reported communicating more at cancer announcement (p = .004) or after treatments (p = .015), while more paramedics reported discussing at another time (p = .005). Regarding the place for discussion, paramedics more frequently reported talking about sexuality in the hospital room (p = .001) or during a specific consult (p = .007).
Conclusions
Results emphasize various levels for improving existing oncosexology care, such as developing oncosexology-specific educational and practical training programs, particularly for paramedics; consolidating information, counseling, and therapeutic education with formal procedures like implementing medical and paramedical "oncosexology moments," or strengthening the community-hospital networks, from diagnosis to survivorship.
http://bit.ly/2GvgHQL
Irinotecan-induced neutropenia is reduced by oral alkalization drugs: analysis using retrospective chart reviews and the spontaneous reporting database
Abstract
Purpose
SN-38, an active metabolite of irinotecan, is reabsorbed by the intestinal tract during excretion, causing diarrhoea and neutropenia. In addition, the association between blood levels of SN-38 and neutropenia has been reported previously, and the rapid excretion of SN-38 from the intestinal tract is considered to prevent neutropenia. Oral alkalization drugs are used as prophylactic agents for suppressing SN-38 reabsorption. The relationship between oral alkalization drugs and neutropenia, however, has not been well studied. The aim of this study was to investigate the relationship between oral alkalization drugs and neutropenia in irinotecan-treated patients.
Methods and results
Patients with cervical or ovarian cancer were administered irinotecan and investigated by medical chart reviews to determine whether oral alkalization drugs were effective at ameliorating irinotecan-induced neutropenia. The drug combination in the oral alkalization drugs—ursodeoxycholic acid, magnesium oxide, and sodium hydrogen carbonate—significantly improved neutrophil counts and reduced dose intensity compared with those of non-users. In the large-scale Japanese Adverse Drug Event Report database, the reporting odds ratio of irinotecan-induced neutropenia was significantly lower when irinotecan had been given in combination with oral alkalization drugs.
Conclusions
These data indicate that oral alkalization drugs may reduce the frequency of neutropenia caused by irinotecan administration, making it possible to increase the dose safely.
http://bit.ly/2DVq9uY
Effect of biologic disease-modifying anti-rheumatic drugs for patients with rheumatoid arthritis who hope to become mothers
Abstract
Objectives
We examined the effect of biologic disease-modifying anti-rheumatic drugs on the time to pregnancy in patients with rheumatoid arthritis who hope to become mothers. Additionally, we evaluated adverse pregnancy outcomes and risk factors of these drugs.
Method
We retrospectively investigated 25 pregnancies of 19 patients who were taking disease-modifying anti-rheumatic drugs. In 15 pregnancies, patients continued biologic disease-modifying anti-rheumatic drugs until conception (group A). In 10 pregnancies, patients discontinued biologic disease-modifying anti-rheumatic drugs and conventional synthetic disease-modifying anti-rheumatic drugs at the time of planning to conceive (group B). We used tumor necrosis factor inhibitors (certolizumab pegol and etanercept) for group A patients.
Results
The mean time to pregnancy was shorter in group A than in group B (5.9 ± 3.8 vs 11.0 ± 6.5 months, P = 0.04). The mean birth weight of newborns was lighter in group B than in group A (2446.5 ± 352.4 vs 2969.4 ± 459.9 g, P = 0.007). There were no significant differences in the rates of preterm birth, light-for-date, and premature rupture of the membranes between the groups. In patients with preterm birth or light-for-date newborns, the mean dose of corticosteroids during pregnancy was significantly higher compared with that in those with full-term birth or non-light-for-date newborns (P = 0.02, P < 0.01, respectively).
Conclusions
In patients with rheumatoid arthritis who hope to conceive, continuing biologic disease-modifying anti-rheumatic drugs at the time of conception could shorten the time to pregnancy. Using biologic disease-modifying anti-rheumatic drugs before pregnancy does not affect abortion, preterm birth, light-for-date, and premature rupture of the membranes.
http://bit.ly/2RKq0y5
Physiologically Based Pharmacokinetic Modelling for First-In-Human Predictions: An Updated Model Building Strategy Illustrated with Challenging Industry Case Studies
Abstract
Physiologically based pharmacokinetic modelling is well established in the pharmaceutical industry and is accepted by regulatory agencies for the prediction of drug–drug interactions. However, physiologically based pharmacokinetic modelling is valuable to address a much wider range of pharmaceutical applications, and a new regulatory impact is expected as its full power is leveraged. As one example, physiologically based pharmacokinetic modelling is already routinely used during drug discovery for in-vitro to in-vivo translation and pharmacokinetic modelling in preclinical species, and this leads to the application of verified models for first-in-human pharmacokinetic predictions. A consistent cross-industry strategy in this application area would increase confidence in the approach and facilitate further learning. With this in mind, this article aims to enhance a previously published first-in-human physiologically based pharmacokinetic model-building strategy. Based on the experience of scientists from multiple companies participating in the GastroPlus™ User Group Steering Committee, new Absorption, Distribution, Metabolism and Excretion knowledge is integrated and decision trees proposed for each essential component of a first-in-human prediction. We have reviewed many relevant scientific publications to identify new findings and highlight gaps that need to be addressed. Finally, four industry case studies for more challenging compounds illustrate and highlight key components of the strategy.
http://bit.ly/2RJZFjY
Apnea and hypopnea characterization using esophageal pressure, respiratory inductance plethysmography, and suprasternal pressure: a comparative study
Abstract
Objectives
To determine if recording of suprasternal pressure (SSP) can classify apneas and hypopneas as reliably as respiratory inductance plethysmography (RIP) belts and to compare the two methods to classification with esophageal pressure (Pes), the reference method for assessing respiratory effort.
Methods
In addition to polysomnographic recordings that included Pes, SSP was recorded. Recordings from 32 patients (25 males, mean age 66.7 ± 15.3 years, and mean BMI 30.1 ± 4.5 kg/m2) were used to compare the classification of detected apneas and hypopneas by three methods of respiratory effort evaluation (Pes, RIP belts, and SSP). Signals were analyzed randomly and independently from each other. All recordings were analyzed according to AASM guidelines.
Results
Using Pes as a reference for apnea characterization, the Cohen kappa (κ) was 0.93 for SSP and 0.87 for the RIP. The sensitivity/specificity of SSP was 97.0%/96.9% for obstructive, 93.9%/98.3% for central, and 94.9%/97.9% for mixed apneas. The sensitivity/specificity of the RIP was 97.4%/91.9% for obstructive, 87.5%/97.9% for central, and 85.6%/96.6% for mixed apneas. For hypopnea characterization using the Pes as a reference, κ was 0.92 for SSP and 0.86 for the RIP. The sensitivity/specificity of SSP was 99.7%/97.6% for obstructive and 97.6%/99.7% for central. The sensitivity/specificity of the RIP was 99.8%/81.1% for obstructive and 81.1%/99.8% for central.
Conclusions
These results confirm the excellent agreement in the detection of respiratory effort between SSP, RIP belts, and Pes signals. Thus, we conclude that apnea and hypopnea characterization in adults with SSP is a reliable method.
http://bit.ly/2DVT5Tz
Using benzodiazepines and Z-drugs for managing primary insomnia in adults in Saudi Arabia: an e-Delphi study to aid the development of clinical guidelines
Abstract
Purpose
This study aims to obtain consensus statements required for the development of clinical guidelines for the use of benzodiazepines (BZDs) and Z-drugs for the management of primary insomnia in adults in Saudi Arabia.
Methods
Three rounds of the e-Delphi technique using a Bristol Online Survey (BOS) were conducted between May and August 2018. The Director of the Saudi Sleep Medicine Group helped recruit the country's sleep medicine experts. Snowballing was used to forward invitation emails, information sheets, and the survey to known sleep medicine experts and physicians deemed to be interested in the field. All participants' details were anonymised except to the researcher.
Results
Fifteen experts from four different regions and specialities in Saudi Arabia participated in Round 1. Twenty-one statements originated from participants' responses. In Round 2, there were 17 respondents and 16 of the statements obtained the required consensus of 70% or higher. Eleven experts participated in Round 3 and eight statements received 100% agreement, two received 91%, and six received 82%. Having obtained the required consensus of 80% or higher in Round 3, these 16 statements fulfilled the criteria to be included in future guidelines. The five statements that failed to attain the required consensus were rejected as inappropriate for inclusion in Saudi Arabian clinical guidelines.
Conclusions
The items that achieved the required consensus can be included in future guidelines for the use of BZDs and Z-drugs in the treatment of primary insomnia in adults to standardize best practices in sleep medicine in Saudi Arabia.
http://bit.ly/2GrtBPL
New Study Links Hearing Loss with Greater Risk of Cognitive Decline
A new study links hearing loss with increased risk of subjective cognitive decline, adding more key evidence to the connection between these conditions.
Researchers from Brigham and Women's Hospital and Harvard Medical School analyzed data collected over eight years on 10,107 men aged 62 years and over who were asked about their hearing status and hearing aid use. They found that those who reported having hearing loss had a higher risk of cognitive decline—30 percent higher for men with mild hearing loss than those with normal hearing and 42 percent for those with moderate hearing loss. Among study participants with severe hearing loss, those who used hearing aids had 37 percent higher risk while those who didn't wear hearing aids had 54 percent higher risk of cognitive decline.
The participants received questionnaires about diseases and health-related topics like smoking, physical activity, and medications taken, explained lead author Sharon G. Curhan, MD. "We assessed subjective cognitive function (SCF) scores based on responses to a 6-item questionnaire administered in 2008, 2012, and 2016," she noted. "SCF decline was defined as a new report of at least one SCF concern during follow-up." Questionnaires on the participants' detailed dietary information were also administered in four-year intervals.
Considering the study's large sample size and prospective study design with long-term follow-up, it's a notable addition to current investigations into the connection between hearing loss and dementia.
"The challenges were considerable in conducting a longitudinal study of this scope, in an ongoing cohort of this large size, achieving such high rates of follow-up, using detailed validated measures to assess cognition and the many demographic, medical, dietary, and lifestyle factors that were considered as covariates in our multivariable analyses," Dr. Curhan noted. "We were also able to consider age, race, occupation, body mass index, waist circumference, smoking, physical activity, hypertension, diabetes, hypercholesterolemia, detailed dietary intake, aspirin, acetaminophen and NSAID use, and depression."
The researchers also looked at how hearing aid use affected the participant's trajectory of cognitive decline.
"We found that among men with severe hearing loss, the size of the elevated risk of cognitive decline was somewhat smaller but was not statistically significantly different than the risk among men with severe hearing loss who used hearing aids," Dr. Curhan said. "However, we did not have detailed information on the many factors that can influence the effectiveness of hearing aid use." Thus, further investigations are needed to see if specific hearing-related management strategies could influence the risk of cognitive decline in this population.
"Another notable finding in our study is that in a sensitivity analysis that did not include questions potentially influenced by hearing status in the SCF score, the size of the relations was somewhat attenuated," Dr. Curhan told The Hearing Journal. "This suggests that some measures typically used in cognitive research could be sensitive to hearing ability. Therefore, hearing status could be an important methodologic consideration in studies of cognitive decline and dementia."
Published: 2/4/2019 1:39:00 PM
from #Audiology via ola Kala on Inoreader http://bit.ly/2SggPdV
The ABL kinase inhibitor imatinib causes phenotypic changes and lethality in adult Schistosoma japonicum
Abstract
Schistosomiasis caused by different species of schistosome parasites is one of the most debilitating helminthic diseases of humans worldwide. For decades, chemotherapy is the main method of controlling schistosomiasis. However, the fear of drug resistance has motivated the search for alternatives. It has been demonstrated that the ABL kinase inhibitor imatinib affected the development and survival of Schistosoma mansoni in vitro; however, there is still lack of information on whether imatinib also affects other schistosome species such as Schistosoma japonicum. In the present study, the anti-schistosomal potency of imatinib on adult S. japonicum was investigated in vitro, and the results showed that imatinib had a significant impact on various physiological processes of S. japonicum adult worms. Besides its negative effects on worm motility, pairing stability, and gonad development, imatinib caused pathological changes in the gastrodermis as well as the death of the parasite. Our findings suggest that imatinib is an intriguing candidate for further development as an option to fight S. japonicum.
http://bit.ly/2GvaGUb
Characteristics of adverse events of endocrine therapies among older patients with breast cancer
Abstract
Purpose
To clarify the profile of adverse events from endocrine therapies in older patients.
Methods
We surveyed 15 subjective symptoms including hot flashes, sweating, knuckle stiffness, knee/shoulder joint pain, limb numbness, lethargy, forgetfulness, depressive state, irritated state, genital bleeding, leukorrhea increase, vaginal dryness, bone fracture, and weight gain by a questionnaire among 2044 patients over 55 years old (total number of answered sheets, 8875) and compared the results according to age (56–69 years old vs. ≥ 70 years old) and type of therapy (aromatase inhibitors (AIs) vs. selective estrogen receptor modulators (SERMs)). Among patients 56–69 years old, 6093 and 314 responses were from patients treated with AIs (1477 patients) and SERMs (123 patients), respectively, and 2292 and 176 responses were from those ≥ 70 years old treated with AIs (581 patients) and SERMs (51 patients), respectively.
Results
In patients ≥ 70 years old, sweating, knuckle stiffness, knee/shoulder joint pain, limb numbness, and lethargy were significantly more frequent/severe with AIs than with SERMs. In those aged 56–69, knuckle stiffness and vaginal dryness were significantly more frequent with AIs than with SERMs, but the opposite occurred for hot flashes, leukorrhea increase, genital bleeding, and weight gain.
Conclusions
Among patients ≥ 70 years old, many symptoms were significantly more frequent/severe with AIs than with SERMs, compared with those aged 56–69, which suggests a difference in the profile of adverse events according to the type of endocrine therapy and the patient's age. It is important to consider the benefits and risks of each treatment to optimize endocrine therapy for older patients.
http://bit.ly/2TD0gWk
Exploring metabolic and inflammatory abnormalities in rheumatoid arthritis patients developing stroke disease: a case-control study using electronic medical record data in northern China
Abstract
Objectives
Intend to investigate the roles of serum lipids, inflammatory markers, and serological status in rheumatoid arthritis and stroke patients by using case-control study.
Materials and methods
Clinical data were retrieved from the electronic medical record of the First Affiliated Hospital of China Medical University during January 2011 to March 2018. The obtained data were categorized into case groups and three control groups, in the ratios of 1:2, respectively, with all matching age and gender. Multinomial logistic regression analysis and restricted cubic spline were conducted examining the associations between serum lipids, inflammatory markers, serological status, and the risk of stroke among RA patients.
Results
The present studies included 1057 study subjects. The elevated ESR, LDL-C levels, and much higher CRP levels ≥ 230 mg/L were independent risk factors for RA patients in developing stroke. Furthermore, we found that ESR and LDL-C levels could exhibit a linear association with the risk of comorbid stroke while CRP level had a nonlinearity association with stroke risk among RA patients.
Conclusions
A close monitoring is required for RA patients with dyslipidemia and elevated inflammatory markers, and the primary stroke preventive strategies should be directed against these risk factors.
http://bit.ly/2HXe64A
New Study Links Hearing Loss with Greater Risk of Cognitive Decline
A new study links hearing loss with increased risk of subjective cognitive decline, adding more key evidence to the connection between these conditions.
Researchers from Brigham and Women's Hospital and Harvard Medical School analyzed data collected over eight years on 10,107 men aged 62 years and over who were asked about their hearing status and hearing aid use. They found that those who reported having hearing loss had a higher risk of cognitive decline—30 percent higher for men with mild hearing loss than those with normal hearing and 42 percent for those with moderate hearing loss. Among study participants with severe hearing loss, those who used hearing aids had 37 percent higher risk while those who didn't wear hearing aids had 54 percent higher risk of cognitive decline.
The participants received questionnaires about diseases and health-related topics like smoking, physical activity, and medications taken, explained lead author Sharon G. Curhan, MD. "We assessed subjective cognitive function (SCF) scores based on responses to a 6-item questionnaire administered in 2008, 2012, and 2016," she noted. "SCF decline was defined as a new report of at least one SCF concern during follow-up." Questionnaires on the participants' detailed dietary information were also administered in four-year intervals.
Considering the study's large sample size and prospective study design with long-term follow-up, it's a notable addition to current investigations into the connection between hearing loss and dementia.
"The challenges were considerable in conducting a longitudinal study of this scope, in an ongoing cohort of this large size, achieving such high rates of follow-up, using detailed validated measures to assess cognition and the many demographic, medical, dietary, and lifestyle factors that were considered as covariates in our multivariable analyses," Dr. Curhan noted. "We were also able to consider age, race, occupation, body mass index, waist circumference, smoking, physical activity, hypertension, diabetes, hypercholesterolemia, detailed dietary intake, aspirin, acetaminophen and NSAID use, and depression."
The researchers also looked at how hearing aid use affected the participant's trajectory of cognitive decline.
"We found that among men with severe hearing loss, the size of the elevated risk of cognitive decline was somewhat smaller but was not statistically significantly different than the risk among men with severe hearing loss who used hearing aids," Dr. Curhan said. "However, we did not have detailed information on the many factors that can influence the effectiveness of hearing aid use." Thus, further investigations are needed to see if specific hearing-related management strategies could influence the risk of cognitive decline in this population.
"Another notable finding in our study is that in a sensitivity analysis that did not include questions potentially influenced by hearing status in the SCF score, the size of the relations was somewhat attenuated," Dr. Curhan told The Hearing Journal. "This suggests that some measures typically used in cognitive research could be sensitive to hearing ability. Therefore, hearing status could be an important methodologic consideration in studies of cognitive decline and dementia."
Published: 2/4/2019 1:39:00 PM
from #Audiology via ola Kala on Inoreader http://bit.ly/2SggPdV
via IFTTT
New Study Links Hearing Loss with Greater Risk of Cognitive Decline
A new study links hearing loss with increased risk of subjective cognitive decline, adding more key evidence to the connection between these conditions.
Researchers from Brigham and Women's Hospital and Harvard Medical School analyzed data collected over eight years on 10,107 men aged 62 years and over who were asked about their hearing status and hearing aid use. They found that those who reported having hearing loss had a higher risk of cognitive decline—30 percent higher for men with mild hearing loss than those with normal hearing and 42 percent for those with moderate hearing loss. Among study participants with severe hearing loss, those who used hearing aids had 37 percent higher risk while those who didn't wear hearing aids had 54 percent higher risk of cognitive decline.
The participants received questionnaires about diseases and health-related topics like smoking, physical activity, and medications taken, explained lead author Sharon G. Curhan, MD. "We assessed subjective cognitive function (SCF) scores based on responses to a 6-item questionnaire administered in 2008, 2012, and 2016," she noted. "SCF decline was defined as a new report of at least one SCF concern during follow-up." Questionnaires on the participants' detailed dietary information were also administered in four-year intervals.
Considering the study's large sample size and prospective study design with long-term follow-up, it's a notable addition to current investigations into the connection between hearing loss and dementia.
"The challenges were considerable in conducting a longitudinal study of this scope, in an ongoing cohort of this large size, achieving such high rates of follow-up, using detailed validated measures to assess cognition and the many demographic, medical, dietary, and lifestyle factors that were considered as covariates in our multivariable analyses," Dr. Curhan noted. "We were also able to consider age, race, occupation, body mass index, waist circumference, smoking, physical activity, hypertension, diabetes, hypercholesterolemia, detailed dietary intake, aspirin, acetaminophen and NSAID use, and depression."
The researchers also looked at how hearing aid use affected the participant's trajectory of cognitive decline.
"We found that among men with severe hearing loss, the size of the elevated risk of cognitive decline was somewhat smaller but was not statistically significantly different than the risk among men with severe hearing loss who used hearing aids," Dr. Curhan said. "However, we did not have detailed information on the many factors that can influence the effectiveness of hearing aid use." Thus, further investigations are needed to see if specific hearing-related management strategies could influence the risk of cognitive decline in this population.
"Another notable finding in our study is that in a sensitivity analysis that did not include questions potentially influenced by hearing status in the SCF score, the size of the relations was somewhat attenuated," Dr. Curhan told The Hearing Journal. "This suggests that some measures typically used in cognitive research could be sensitive to hearing ability. Therefore, hearing status could be an important methodologic consideration in studies of cognitive decline and dementia."
Published: 2/4/2019 1:39:00 PM
from #Audiology via ola Kala on Inoreader http://bit.ly/2SggPdV
via IFTTT
Risk factors associated with contamination of allograft valves in a tissue bank
Abstract
The contamination of the transport solution used in cardiovascular allografts can occur from different sources. Risk factors associated with positive microbiological test of transport solution have not been reported previously. This study aimed to determine the risk factor for contamination of transport solution used in the heart valve allografts stored in a Brazilian tissue bank. This retrospective study was conducted on all donors of cardiovascular allografts stored in a tissue bank from December 2008 to December 2017. Microbiological cultures for aerobic and anaerobic bacteria, fungi/yeasts were carried out in TS. Clinical variables were included. From 1001 transport solution, 52% were contaminated. A total of 770 microorganisms were identified, and Staphylococcus spp. was identified in 248 isolates (32.2%). Skin bacteria from skin microbiota were the most commonly identified microorganisms (Staphylococcus spp., Cutibacterium spp., Corynebacterium spp., and Bacillus spp.), occurring in 49.6%. The presence of a diagnosis of healthcare-associated infection was not associated with skin contamination (odds ratio [OR] 0.62 [0.41–0.94]; p = 0.014). Conditions like fever, use of antibiotics, and leukocytosis were less likely associated with contamination of transport solution. A longer warm ischemic time was associated with higher frequency of contamination. In the multivariable analysis, warm ischemic time was independently associated with contamination, and antibiotic therapy was a factor that decreased the rate of contamination (p < 0.05). Contamination of transport solution is associated with modifiable risk factors, such as warm ischemic time. Measures to minimize contamination should be employed to avoid unnecessary tissue discharges.
http://bit.ly/2SiZcdx
Comparative study of different anticoagulants and coagulants in the evaluation of clinical application of platelet-rich plasma (PRP) standardization
Abstract
To investigate the impact of different anticoagulants and coagulants with autologous platelet-rich plasma (PRP) in order to evaluate the clinical application of PRP standardization. Bone marrow stem cells (BMSCs) were seeded into autologous PRP gel scaffolds with different anticoagulants (EDTA, heparin sodium HS, and sodium citrate SC) as well as control group (the whole blood group). Quality of PRP was evaluated and flow cytometric assay was used to detect the activity of the platelet (CD62p, PAC-1). BMSCs were also seeded into PRP with different coagulants (Thrombin, Collagen-I, ADP) as well as PRP un-activated (negative group) and L-DMEM complete culture without PRP (control group). The effects of different coagulants with PRP on proliferation, osteogenic differentiation of BMSCs were analyzed by methyl thiazolyl tetrazolium assay (MTT), ALP staining, Von Kossa staining, Confocal microscopic observation, RT-PCR and Western Blot at the morphological, cellular and molecular levels. Different anticoagulants (EDTA, HS, and SC) could affect the quality of PRP. EDTA group revealed the best quality and activity (CD62p, PAC-1). With different coagulants (Thrombin, Collagen-I and ADP) in the proliferation of BMSCs, the MTT assay showed that the proliferation of BMSCs was increased in all groups with time. On the sixth day of culture, the cell number of each PRP group was significantly higher than that in the control group (P < 0.05), while the most rapidly increasing was found in Collagen-I group. The cumulative release of growth factor (TGF-β1, PDGF) at each time point in the PRP gel of the four groups was higher than that in the control group (P < 0.05). Collagen-I was considered as the best PRP coagulant. When thrombin was used as a platelet coagulant, the release of growth factor in PRP was rapid and direct, while the release of growth factor in Collagen-I-activated PRP was sustained and slow, and the total release of ADP-activated PRP growth factors was the lowest. The study demonstrated the similar outcome in osteogenic differentiation. In terms of gene expression and western bolt, the PCR results showed that the expression levels of OCN gene and RUNX2 protein in each PRP group were higher than that in the control group (P < 0.05). Different anticoagulants caused different degrees of lysis and spontaneous activation of platelets, which lead to different quality of PRP. Compared with HS and SC, EDTA could maintain the structural integrity of platelets, reduce their spontaneous activation, and increase the release of PRP growth factors for a longer period of time, thus ensuring the biomass of PRP. In addition, different coagulants also showed different results in the proliferation as well as osteogenic differentiation of BMSCs. Compared with Thrombin and ADP, Collagen-I may be a better choice.
http://bit.ly/2DptGk3
Biodegradation of polyacrylic and polyester polyurethane coatings by enriched microbial communities
Abstract
Microbial communities are more effective in degrading natural polymers and xenobiotics than pure cultures. Biodegradation of polyacrylic and polyurethane polymers by bacterial and fungal strains has been addressed, but limited information about their biodegradation by microbial communities exists. The aim of this work was to evaluate the ability of three enriched microbial communities (BP1h, BP3h, and BP7h), selected from deteriorated foam pieces collected in a landfill, to biodegrade the polyacrylic component of the 2K-PU coating Bayhydrol® A2470 and the polyester polyurethane coating NeoRez™ R-9637. Two communities were further selected to quantify extracellular esterase, protease, and urease activities, to identify their taxonomic composition, and to analyze the ability of their isolated members to grow in those polymers. The growth of the three communities was larger in polyester polyurethane than in polyacrylic and their biodegradative activities affected ester, urethane, ether, aromatic, and aliphatic groups of the compounds present in the coatings. From all the communities growing in polyacrylic or in polyester polyurethane, two and five different types of colonies were isolated, respectively. In polyacrylic, extracellular esterase and protease activities were at their maximum level at 7 days of culture, whereas in polyester polyurethane, protease and urease were greatest at 21 days. All the isolated community members were identified as xenobiotics degraders. The complete communities grew better in media with the polymers than the isolated members. This is one of the few studies reporting biodegradation of synthetic polymers by microbial communities and serves as basis for developing synthetic consortia with enhanced degradative abilities.
http://bit.ly/2DWJkVc
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