Combination of “quadratic adaptive algorithm” and “hybrid operator splitting” or uniformization algorithms for stability against acceleration in the Markov model of sodium ion channels in the ventricular cell model

Abstract

The Markovian model has generally been used for cardiac electrophysiological simulations. However, the Markovian model is so stiff that speeding up the computation of the algorithms with variable time-steps always results in simulation instability. In particular, the unstable simulations always occur at a low voltage rate or current change, while transition rates in the Markovian model are changing markedly. The uniformization (UNI) method allows for a Markovian model simulation with high stability but also a high computation cost. To save computation costs with variable time-steps, we propose a speed increasing idea that is a compromise to the trade-off between stability and acceleration by combining Chen-Chen-Luo's "quadratic adaptive algorithm" (CCL) method with "hybrid operator splitting" (HOS) into the solver (CCL + HOS solver). The computation cost of this CCL + HOS solver is approximately 24 times lower than the CCL + UNI solver, and the CCL + HOS solver can function 295 times faster in comparison to the HOS solver with a fixed time-step (DT). The suggested optimal solver should be CCL + HOS solver with a maximum time-step at 0.1 ms due to its high speed with low error. Additionally, the CCL method has much better performance and stability than the hybrid method in this single-cell model simulation.

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Photochemical removal of acetaldehyde using 172 nm vacuum ultraviolet excimer lamp in N 2 or air at atmospheric pressure

Abstract

The photochemical removal of acetaldehyde was studied in N₂ or air (O₂ 1–20%) at atmospheric pressure using side-on and head-on types of 172 nm Xe₂ excimer lamps. When CH₃CHO was decomposed in N₂ using the head-on lamp (HL), CH₄, CO, and CO₂ were observed as products in FTIR spectra. The initial removal rate of CH₃CHO in N₂ was ascertained as 0.37 min⁻¹. In air (1–20% O₂), HCHO, HCOOH, CO, and CO₂ were observed as products in FTIR spectra. The removal rate of CH₃CHO in air using the side-on lamp (SL) increased from 3.2 to 18.6 min⁻¹ with decreasing O₂ concentration from 20 to 1%. It also increased from 2.5 to 3.7 min⁻¹ with increasing CH₃CHO concentration from 150 to 1000 ppm at 20% O₂. The best energy efficiency of the CH₃CHO removal using the SL in a flow system was 2.8 g/kWh at 1% O₂. Results show that the contribution of O(₁D) and O₃ is insignificant in the initial decomposition of CH₃CHO. It was inferred that CH₃CHO is initially decomposed by the O(₃P) + CH₃CHO reaction at 5–20% O₂, whereas the contribution of direct vacuum ultraviolet (VUV) photolysis increases concomitantly with decreasing O₂ pressure at < 5% O₂. After initial decomposition of CH₃CHO, it was oxidized further by reactions of O(₃P), OH, and O₃ with various intermediates such as HCHO, HCOOH, and CO, leading to CO₂ as a final product.

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Exploring inter-species sensitivity to a model hydrocarbon, 2-Methylnaphtalene, using a process-based model

Abstract

We compared inter-species sensitivity to a model narcotic compound, 2-Methylnaphthalene, to test if taxonomical relatedness, feeding guilds, and trophic level govern species sensitivities on species distributed in different regions. We fitted a toxicokinetic-toxicodynamic model to survival patterns over time for 26 species using new and raw data from the literature. Species sensitivity distributions provided little insight into understanding patterns in inter-species sensitivity. The range of no-effect concentrations (NEC) obtained for 26 species showed little variation (mean 0.0081 mM; SD 0.009). Results suggest that the NEC alone does not explain the complexity of the species tolerances. The dominant rate constant and the derived time to observe an effect (t₀), a function of concentration, might provide the means for depicting patterns in sensitivity and better ecotoxicological testing. When comparing the t₀ functions, we observed that Arctic species have shorter time frames to start showing effects. Mollusks and second trophic level species took longer to build up a lethal body burden than the rest. Coupling our results with fate and transport models would allow forecasting narcotic compounds toxicity in time and thus improve risk assessment.

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CFTR structure, stability, function and regulation

Journal Name: Biological Chemistry
Issue: Ahead of print


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Effects of extreme temperatures on cerebrovascular mortality in Lisbon: a distributed lag non-linear model

Abstract

Cerebrovascular diseases are the leading cause of mortality in Portugal, especially when related with extreme temperatures. This study highlights the impacts of the exposure-response relationship or lagged effect of low and high temperatures on cerebrovascular mortality, which can be important to reduce the health burden from cerebrovascular diseases. The purpose of this study was to assess the effects of weather on cerebrovascular mortality, measured by ambient temperature in the District of Lisbon, Portugal. A quasi-Poisson generalized additive model combined with a distributed lag non-linear model was applied to estimate the delayed effects of temperature on cerebrovascular mortality up to 30 days. With reference to minimum mortality temperature threshold of 22 °C, there was a severe risk (RR = 2.09, 95% CI 1.74, 2.51) of mortality for a 30-day-cumulative exposure to extreme cold temperatures of 7.3 °C (1st percentile). Similarly, the cumulative effect of a 30-day exposure to an extreme hot temperature of 30 °C (99th percentile) was 52% (RR = 1.65, 95% CI 1.37, 1.98) higher than same-day exposure. Over the 13 years of study, non-linear effects of temperature on mortality were identified, and the probability of dying from cerebrovascular disease in Lisbon was 7% higher in the winter than in the summer. The findings of this study provide a baseline for future public health prevention programs on weather-related mortality.

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Site-specific hourly resolution wet bulb globe temperature reconstruction from gridded daily resolution climate variables for planning climate change adaptation measures

Abstract

Changes in the environmental heat stress need to be properly evaluated to manage the risk of heat-related illnesses, particularly in the context of climate change. The wet bulb globe temperature (WBGT) is a useful index for evaluating heat stress and anticipating conditions related to heat-related illness in the present climate, but projecting the WBGT with a sufficiently high temporal and spatial resolution remains challenging for future climate conditions. In this study, we developed a methodological framework for estimating the site-specific hourly resolution WBGT based on the output of general circulation models using only simple calculations. The method was applied to six sites in Japan and its performance was evaluated. The proposed method could reproduce the site-specific hourly resolution WBGT with a high accuracy. Based on the developed framework, we constructed future (2090s) projections under two different greenhouse gas emission pathways. These projections showed a consistent rise in the WBGT and thus the capacity to perform physically demanding activities is expected to decrease. To demonstrate the usefulness of the projected WBGT in planning adaptation measures, we identified the optimal working schedules which would minimize outdoor workers' exposure to heat at a specific site. The results show that a substantial shift in the working time is required in the future if outdoor workers are to compensate the effect of increased heat exposure only by changing their working hours. This methodological framework and the projections will provide local practitioners with useful information to manage the increased risk of heat stress under climate change.

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Utilizing d‐pπ Bond for Ultralong Organic Phosphorescence

Developing pure organic materials with ultralong lifetimes is attractive but challenging. Here we report a concise chemical approach to regulate the electronic configuration for phosphorescent enhancement. After introduction of d‐pπ bonds in phenothiazine model, up to 19 times phosphorescence lifetime enhancement was observed for DOPPMO, compared with the reference PPMO. A record phosphorescence lifetime of up to 876 ms was obtained in phenothiazine phosphors. Theoretical calculations and single crystal analysis reveal that the d‐pπ bond not only reduces the (n, π*) proportion of T1, but also frames rigid molecular environment with multiple intermolecular interactions, thus enabling long‐lived phosphorescence. This finding will take a giant step forward in prolonging phosphorescence lifetime and extending the scope of phosphorescent materials.

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Generation of biodiesel from industrial wastewater using oleaginous yeast: performance and emission characteristics of microbial biodiesel and its blends on a compression injection diesel engine

Abstract

Microbial-derived biodiesel was tested on a lab scale CI diesel engine for carrying out exhaust emission and performance characteristics. The performance, emission, and combustion characteristics of a single cylinder four stroke fixed compression ratio engine when fueled with microbial bio-diesel and its 10–30% blends with diesel (on a volume basis) were investigated and compared with conventional diesel. The bio-diesel was obtained from microbes which were grown by combining distillery spent wash with lignocellulosic hydrolysate at nutrient deprived conditions. The microbes consumed the wastes and converted the high strength waste water into lipids, which were trans-esterified to form bio-diesel. Testing of microbial bio-diesel blends with ordinary diesel at different loading pressures and the emission characteristics were compared. Results indicate that with increasing of the blends, reduction of HC and CO emissions were observed, whilst brake thermal efficiency maxed out at 20% blending. Further increase of blends showed a tendency of increasing of both emissions in the exhaust stream. The Brake Specific Fuel consumption was observed to decline with blending until 20% and then increased. The nitrogen oxide emissions, however, were found to increase with increasing blend ratios and reached a maximum at 20% blend. The escalation of HC, CO, CO₂, and NOx emissions was also observed at higher blending ratios and higher engine loads. The performance studies were able to show that out of the three blends of biodiesel, 20% biodiesel blend was able to deliver the best of reduced hydrocarbon and carbon monoxide emissions, whilst also delivering the highest Brake thermal efficiency and the lowest Brake Specific Fuel consumption.

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Snapshot of environmental condition in different tropical estuarine systems by using S. cucullata (an edible oyster) as bio-indicator

Abstract

Accumulation of toxic metals and indigenous bacteria in oyster, (Saccostrea cucullata) and their impact on antioxidant enzyme activities in the biological system was studied and used to provide snapshot of environmental condition in different tropical estuarine systems. The sedimentary Cd, Pb, and Hg concentration varied from 0.1 to 1.8, 22.0 to 98.0, and 0.03 to 0.11 mg kg⁻¹ (dry wt.) respectively. The bioaccumulated Cd, Pb, and Hg concentration in the oysters ranged from 3.6 to 9.0, 0.03 to 8.0, and 0.06 to 0.1 mg kg⁻¹ (dry wt.) respectively. In the oyster, the Cd concentration was well above the safe limit whereas the Pb and Hg concentrations were below the safe limit recommended by the European Commission (EC No. 1881/2006) for human consumption. The MPN value in the raw oyster for fecal coliforms (33–110 × 10³/100 g) exceeded the United States Food and Drug Administration (USFDA) approved limits. Increase in antioxidant enzymes (catalase, superoxide dismutase, glutathione-s-transferase, and metallothionein) activities with increasing pollutants loading was observed. The activities of antioxidant enzymes in the oyster were found to be very useful tool for evaluating environmental condition in any tropical estuarine systems.

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Combined effects of NaCl and fluoxetine on the freshwater planarian, Schmidtea mediterranea (Platyhelminthes: Dugesiidae)

Abstract

Increasing salinity levels in freshwaters due to natural and anthropogenic sources pose risk to exposed aquatic organisms. However, there is a paucity of information on how salinity may influence the effects of other chemical stressors especially psychiatric pharmaceuticals. Freshwater planarians which have been suggested as bioindicator species in aquatic habitats were used in this study to evaluate toxic effects of sodium chloride (NaCl) used here as a surrogate for increasing salinity, and its influence on the effects of the antidepressant, fluoxetine. Effects of NaCl on Schmidtea mediterranea were evaluated using survival, regeneration, locomotion, feeding, and reproduction as endpoints. Subsequently, combined effects of NaCl and fluoxetine on planarians' locomotion and reproduction were also evaluated. Result showed that exposure to increased NaCl concentrations is toxic to planarians with 48 and 96 h LC₅₀ of 9.15 and 7.55 g NaCl L⁻¹ respectively and exposure to sub-lethal concentrations led to reductions in feeding (LOEC of 0.75 g NaCl L⁻¹ or 1906 μS cm⁻¹ at 20 °C) and reproduction (LOEC 3.0 g NaCl L⁻¹ or 5530 μS cm⁻¹ at 20 °C), delayed head regeneration (LOEC of 1.5 g NaCl L⁻¹ or 3210 μS cm⁻¹ at 20 °C), and also slight decreases in locomotor activity. Moreover, some developmental malformations were observed in regenerating planarians, as well as delayed or inhibition of wound healing and degeneration after fissioning and during head regeneration. A significant interaction between fluoxetine and NaCl was observed for locomotor activity and unlike planarians exposed to fluoxetine alone, fissioned planarians and their pieces from the combined exposure treatments were also unable to regenerate missing portions. Results show that S. mediterranea can be highly sensitive to low NaCl concentrations and that this stressor can alter the effects of fluoxetine. The implication of these effects for planarian populations in the natural habitat is discussed as well as the need for more research on the effects of neuroactive pharmaceuticals under relevant exposure scenarios.

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The language profile of progressive supranuclear palsy

Publication date: Available online 22 February 2019

Source: Cortex

Author(s): E. Catricalà, V. Boschi, S. Cuoco, F. Galiano, M. Picillo, E. Gobbi, A. Miozzo, C. Chesi, V. Esposito, G. Santangelo, M.T. Pellecchia, V.M. Borsa, P. Barone, P. Garrard, S. Iannaccone, S.F. Cappa

Abstract

A progressive speech/language disorder, such as the non fluent/agrammatic variant of primary progressive aphasia and progressive apraxia of speech, can be due to neuropathologically verified Progressive Supranuclear Palsy (PSP). The prevalence of linguistic deficits and the linguistic profile in PSP patients who present primarily with a movement disorder is unknown. In the present study, we investigated speech and language performance in a sample of clinically diagnosed PSP patients using a comprehensive language battery, including, besides traditional language tests, a detailed analysis of connected speech (picture description task assessing 26 linguistic features). The aim was to identify the most affected linguistic levels in seventeen PSP with a movement disorder presentation, compared to 21 patients with Parkinson's disease and 27 healthy controls. Machine learning methods were used to detect the most relevant language tests and linguistic features characterizing the language profile of PSP patients. Our results indicate that even non-clinically aphasic PSP patients have subtle language deficits, in particular involving the lexical-semantic and discourse levels. Patients with the Richardson's syndrome showed a lower performance in the word comprehension task with respect to the other PSP phenotypes with predominant frontal presentation, parkinsonism and progressive gait freezing. The present findings support the usefulness of a detailed language assessment in all patients in the PSP spectrum.

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Recent electrochemical methods in electrochemical degradation of halogenated organics: a review

Abstract

Halogenated organics are widely used in modern industry, agriculture, and medicine, and their large-scale emissions have led to soil and water pollution. Electrochemical methods are attractive and promising techniques for wastewater treatment and have been developed for degradation of halogenated organic pollutants under mild conditions. Electrochemical techniques are classified according to main reaction pathways: (i) electrochemical reduction, in which cleavage of C-X (X = F, Cl, Br, I) bonds to release halide ions and produce non-halogenated and non-toxic organics and (ii) electrochemical oxidation, in which halogenated organics are degraded by electrogenerated oxidants. The electrode material is crucial to the degradation efficiency of an electrochemical process. Much research has therefore been devoted to developing appropriate electrode materials for practical applications. This paper reviews recent developments in electrode materials for electrochemical degradation of halogenated organics. And at the end of this paper, the characteristics of new combination methods, such as photocatalysis, nanofiltration, and the use of biochemical method, are discussed.

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Association between Family History of Cancer and Lung Cancer Risk among Japanese Men and Women.

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Association between Family History of Cancer and Lung Cancer Risk among Japanese Men and Women.

Tohoku J Exp Med. 2019;247(2):99-110

Authors: Yoshida K, Takizawa Y, Nishino Y, Takahashi S, Kanemura S, Omori J, Kurosawa H, Maemondo M, Minami Y

Abstract
Although cigarette smoking is a major risk factor for lung cancer, genetic susceptibility may also affect lung cancer risk. To explore the role of genetic risk, this case-control study investigated the association between family history of cancer at several sites and lung cancer risk. A total of 1,733 lung cancer cases and 6,643 controls were selected from patients aged 30 years and over admitted to a single hospital in Japan between 1997 and 2009. Information on family history of cancer was collected using a self-administered questionnaire and odds ratios (ORs) were estimated by unconditional logistic regression. Family history of lung cancer in first-degree relatives was associated with an increased risk of lung cancer among both sexes. According to histology and type of relatives, a parental history of lung cancer was significantly associated with an increased risk of female adenocarcinoma (OR = 1.72). Stratification by smoking status revealed that this significant positive association in women was limited to ever-smokers (OR = 4.13). In men, a history of lung cancer in siblings was significantly associated with an increased risk of small cell carcinoma (OR = 2.28) and adenocarcinoma (OR = 2.25). Otherwise, positive associations between history of breast (OR = 1.99) and total (OR = 1.71) cancers in siblings and the risk of male adenocarcinoma were observed. These results suggest that inherited genetic susceptibility may contribute to the development of lung cancer. In men, shared exposure to environmental factors among siblings may also be responsible for the increase in lung cancer risk.

PMID: 30787235 [PubMed - in process]

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Early Initiation of Post-Pyloric Feeding in Patients with Major Burns: Experience in Taiwan Formosa Water Park Dust Explosion Disaster.

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Early Initiation of Post-Pyloric Feeding in Patients with Major Burns: Experience in Taiwan Formosa Water Park Dust Explosion Disaster.

Tohoku J Exp Med. 2019;247(2):111-118

Authors: Tseng YC, Chen BC, Chen CT, Chou YC, Dai NT, Chen PJ, Huang TY, Shih YL, Chang WK, Hsieh TY, Lin JC

Abstract
Early initiation of enteral nutrition improves clinical outcomes in critical patients with serious burns. Post-pyloric tube feeding is a valuable therapeutic option for severely burned patients with poor gastric emptying. How early post-pyloric feeding can be initiated to provide more benefits to patients has not yet been examined. A fire erupted at a recreational water park in New Taipei City, Taiwan, on June 27, 2015. The results of early initiation versus delayed post-pyloric feeding in severely burned patients in this mass-casualty incident were compared. Door-to-post-pyloric feeding time ≤ 24 h was considered as early post-pyloric feeding (EPF) and that > 24 h was considered as delayed post-pyloric feeding (DPF). Thirteen patients with severe burn injuries (> 40% of the total body surface area) were assigned to undergo either EPF (five patients) or DPF (eight patients). This study is a "fortuitously controlled" study, and the authors were able to formulate and test whether EPF is better than DPF by comparing the two groups. In patients in the EPF, the intake of calories increased rapidly and was maintained throughout the study period. In addition, rapid restoration of plasma magnesium concentrations as well as pronounced recovery of platelet count in the EPF group was observed. In conclusion, our findings indicate that the time from injury to the onset of post-pyloric feeding is crucial, and EPF allows for the administration of calculated caloric needs. Therefore, EPF can be successfully initiated with beneficial outcomes of nutritional reconstruction in severely burned patients.

PMID: 30787234 [PubMed - in process]

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Identification and characterization of a highly metastatic epithelial cancer cell line from rat tongue cancer.

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Identification and characterization of a highly metastatic epithelial cancer cell line from rat tongue cancer.

Arch Oral Biol. 2018 Nov;95:58-67

Authors: Qin X, Yan M, Li R, Ye D, Zhang J, Xu Q, Feng Y, Sun Q, Jiang C, Chen W

Abstract
OBJECTIVES: Tongue squamous cell carcinoma (TSCC) is a clinically devastating disease. However, most established TSCC cell lines currently show undesirable malignant behaviours. The purpose of this study is to establish a highly metastatic TSCC cell line to serve as a useful tool for basic research.
MATERIALS AND METHODS: TSCCs were induced by 4-nitroquinoline-1-oxide (4NQO) in Sprague-Dawley rats. Tumor cells were obtained from the cancer tissues by primary culture and were then purified by an in vitro invasion assay and a limiting dilution assay. The growth rate, cell cycle distribution, apoptotic rate, tumorigenicity and distant metastatic phenotypes of the rat tongue cancer cells were fully investigated and characterized.
RESULTS: To date, the rat tongue cancer cell line, named Rca-T, has been continuously cultured in vitro for over 210 passages and exhibit a long spindle-shaped morphology, adherent growth, and a stable epithelial phenotype. The population doubling time of Rca-T cells is 23.35 h. Approximately 39.8% of these cells are in S phase, and the apoptosis rate of Rca-T cells is 7.46%. Furthermore, in immunodeficient nude mice, both the xenograft rate and the incidence of experimental lung metastasis are 100%. The in vitro assays further reveal the highly malignant and epithelial-mesenchymal transition-like properties of Rca-T cells.
CONCLUSION: In this study, the tumorigenic and highly distant metastatic TSCC cell line Rca-T was established. The malignant features of this cell line, especially its metastatic potential, will enable a wealth of functional studies on the molecular mechanisms of TSCC metastasis in the future.

PMID: 30059808 [PubMed - indexed for MEDLINE]

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Future Oncology; +41 new citations

41 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

Future Oncology

These pubmed results were generated on 2019/02/23

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

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Neural network and logistic regression diagnostic prediction models for giant cell arteritis: development and validation

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Interaction Between Transcranial Random Noise Stimulation and Observation-Execution Matching Activity Promotes Motor Cortex Excitability.

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Interaction Between Transcranial Random Noise Stimulation and Observation-Execution Matching Activity Promotes Motor Cortex Excitability.

Front Neurosci. 2019;13:69

Authors: Qi F, Nitsche MA, Zschorlich VR

Abstract
Pathways of the human mirror neuron system are activated during both, action observation and action execution, including lateralized activation of respective areas, as shown by observed right-or left-hand actions. Here, we investigated whether execution-dependent motor cortex excitability is affected by prior interaction between transcranial random noise stimulation (tRNS) and action observation. Sham or real tRNS (1 mA) was applied for 10-min over the left primary motor cortex during action observation. In the main experiments, participants received sham or real tRNS while they watched a video showing repeated tapping tasks, involving either the right-hand (Experiment 1, congruent action observation), or a mirror-reversed video showing the same performance (Experiment 2), followed by action execution of the right-hand. In control Experiments 1-3, participants received real tRNS while observing a perceptual sequence, watching a landscape picture, or observing the left-hand performing the action (the sequence was identical to Experiment 1), followed by action execution of the right-hand. In control Experiment 4, participants received real tRNS during congruent action observation, and then took 6-min rest. Motor-evoked potentials (MEP) were recorded before action observation, a perceptual sequence or a landscape picture, immediately after, and after action execution, or an interval of 6-min, dependent on the respective experimental condition. MEPs in the right first dorsal interosseous muscle increased significantly after real tRNS combined with congruent action observation, and after action execution compared to the sham session in Experiment 1 and control experiments. We conclude that prior interaction between real tRNS and action observation of mirror-matched movements modulates subsequent execution-dependent motor cortex excitability.

PMID: 30792626 [PubMed]

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MR-Guided Focused Ultrasound Versus Radiofrequency Capsulotomy for Treatment-Refractory Obsessive-Compulsive Disorder: A Cost-Effectiveness Threshold Analysis.

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MR-Guided Focused Ultrasound Versus Radiofrequency Capsulotomy for Treatment-Refractory Obsessive-Compulsive Disorder: A Cost-Effectiveness Threshold Analysis.

Front Neurosci. 2019;13:66

Authors: Kumar KK, Bhati MT, Ravikumar VK, Ghanouni P, Stein SC, Halpern CH

Abstract
Meta-analytic techniques support neuroablation as a promising therapy for treatment-refractory obsessive-compulsive disorder (OCD). This technique appears to offer a more favorable complication rate and higher utility than deep brain stimulation. Moreover, these pooled findings suggest that bilateral radiofrequency (RF) capsulotomy has marginally greater efficacy than stereotactic radiosurgery or cingulotomy. MR-guided focused ultrasound (MRgFUS) capsulotomy is an emerging approach with a potentially more favorable profile than RF ablation and radiosurgery, with preliminary data suggesting safety and efficacy. As a clinical trial is being developed, our study examined the cost and clinical parameters necessary for MRgFUS capsulotomy to be a more cost-effective alternative to RF capsulotomy. A decision analytical model of MRgFUS with RF capsulotomy for OCD was performed using outcome parameters of percent surgical improvement in Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score, complications, and side effects. The analysis compared measured societal costs, derived from Medicare reimbursement rates, and effectiveness, based on published RF data. Effectiveness was defined as the degree to which MRgFUS lowered Y-BOCS score. Given that MRgFUS is a new therapy for OCD with scant published data, theoretical risks of MRgFUS capsulotomy were derived from published essential tremor outcomes. Sensitivity analysis yielded cost, effectiveness, and complication rates as critical MRgFUS parameters defining the cost-effectiveness threshold. Literature search identified eight publications (162 subjects). The average reduction of preoperative Y-BOCS score was 56.6% after RF capsulotomy with a 22.6% improvement in utility, a measure of quality of life. Complications occurred in 16.2% of RF cases. In 1.42% of cases, complications were considered acute-perioperative and incurred additional hospitalization cost. The adverse events, including neurological and neurobehavioral changes, in the other 14.8% of cases did not incur further costs, although they impacted utility. Rollback analysis of RF capsulotomy yielded an expected effectiveness of 0.212 quality-adjusted life years/year at an average cost of $24,099. Compared to RF capsulotomy, MRgFUS was more cost-effective under a range of possible cost and complication rates. While further study will be required, MRgFUS lacks many of the inherent risks associated with more invasive modalities and has potential as a safe and cost-effective treatment for OCD.

PMID: 30792625 [PubMed]

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Mechanisms Underlying Neuroprotection by the NSAID Mefenamic Acid in an Experimental Model of Stroke.

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Mechanisms Underlying Neuroprotection by the NSAID Mefenamic Acid in an Experimental Model of Stroke.

Front Neurosci. 2019;13:64

Authors: Khansari PS, Halliwell RF

Abstract
Stroke is a devastating neurological event with limited treatment opportunities. Recent advances in understanding the underlying pathogenesis of cerebral ischemia support the involvement of multiple biochemical pathways in the development of the ischemic damage. Fenamates are classical non-steroidal anti-inflammatory drugs but they are also highly subunit-selective modulators of GABAA receptors, activators of IKS potassium channels and antagonists of non-selective cation channels and the NLRP3 inflammosome. In the present study we investigated the effect of mefenamic acid (MFA) in a rodent model of ischemic stroke and then addressed the underlying pharmacological mechanisms in vitro for its actions in vivo. The efficacy of MFA in reducing ischemic damage was evaluated in adult male Wistar rats subjected to a 2-h middle cerebral artery occlusion. Intracerebroventricular (ICV) infusion of MFA (0.5 or 1 mg/kg) for 24 h, significantly reduced the infarct volume and the total ischemic brain damage. In vitro, the fenamates, MFA, meclofenamic acid, niflumic acid, and flufenamic acid each reduced glutamate-evoked excitotoxicity in cultured embryonic rat hippocampal neurons supporting the idea that this is a drug class action. In contrast the non-fenamate NSAIDs, ibuprofen and indomethacin did not reduce excitotoxicity in vitro indicating that neuroprotection by MFA was not dependent upon anti-inflammatory actions. Co-application of MFA (100 μM) with either of the GABAA antagonists picrotoxin (100 μM) or bicuculline (10 μM) or the potassium channel blocker tetraethylammonium (30 mM) did not prevent neuroprotection with MFA, suggesting that the actions of MFA also do not depend on GABAA receptor modulation or potassium channel activation. These new findings indicate that fenamates may be valuable in the adjunctive treatment of ischemic stroke.

PMID: 30792624 [PubMed]

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Local Diffusion Homogeneity Provides Supplementary Information in T2DM-Related WM Microstructural Abnormality Detection.

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Local Diffusion Homogeneity Provides Supplementary Information in T2DM-Related WM Microstructural Abnormality Detection.

Front Neurosci. 2019;13:63

Authors: Liang Y, Zhang H, Tan X, Liu J, Qin C, Zeng H, Zheng Y, Liu Y, Chen J, Leng X, Qiu S, Shen D

Abstract
Objectives: We aimed to investigate whether an inter-voxel diffusivity metric (local diffusion homogeneity, LDH), can provide supplementary information to traditional intra-voxel metrics (i.e., fractional anisotropy, FA) in white matter (WM) abnormality detection for type 2 diabetes mellitus (T2DM). Methods: Diffusion tensor imaging was acquired from 34 T2DM patients and 32 healthy controls. Voxel-based group-difference comparisons based on LDH and FA, as well as the association between the diffusion metrics and T2DM risk factors [i.e., body mass index (BMI) and systolic blood pressure (SBP)], were conducted, with age, gender and education level controlled. Results: Compared to the controls, T2DM patients had higher LDH in the pons and left temporal pole, as well as lower FA in the left superior corona radiation (p < 0.05, corrected). In T2DM, there were several overlapping WM areas associated with BMI as revealed by both LDH and FA, including right temporal lobe and left inferior parietal lobe; but the unique areas revealed only by using LDH included left inferior temporal lobe, right supramarginal gyrus, left pre- and post-central gyrus (at the semiovale center), and right superior radiation. Overlapping WM areas that associated with SBP were found with both LDH and FA, including right temporal pole, bilateral orbitofrontal area (rectus gyrus), the media cingulum bundle, and the right cerebellum crus I. However, the unique areas revealed only by LDH included right inferior temporal lobe, right inferior occipital lobe, and splenium of corpus callosum. Conclusion: Inter- and intra-voxel diffusivity metrics may have different sensitivity in the detection of T2DM-related WM abnormality. We suggested that LDH could provide supplementary information and reveal additional underlying brain changes due to diabetes.

PMID: 30792623 [PubMed]

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Influence of Quadrato Motor Training on Salivary proNGF and proBDNF.

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Influence of Quadrato Motor Training on Salivary proNGF and proBDNF.

Front Neurosci. 2019;13:58

Authors: Caserta M, Ben-Soussan TD, Vetriani V, Venditti S, Verdone L

Abstract
Previous studies demonstrated exercise-induced modulation of neurotrophins, such as Nerve Growth Factor (NGF) and Brain-Derived Neurotrophic Factor (BDNF). Yet, no study that we are aware of has examined their change as a function of different training paradigms. In addition, the understanding of the possible training-induced relationship between NGF and BDNF change is still lacking. Consequently, in the current study we examined the effect of a Walking Training (WT) and of Quadrato Motor Training (QMT) on NGF and BDNF precursors (proNGF and proBDNF). QMT is a specifically structured sensorimotor training that involves sequences of movements based on verbal commands, that was previously reported to improve spatial cognition, reflectivity, creativity as well as emotion regulation and general self-efficacy. In addition, QMT was reported to induce electrophysiological and morphological changes, suggesting stimulation of neuroplasticity processes. In two previous independent studies we reported QMT-induced changes in the salivary proNGF and proBDNF levels. Our present results demonstrate that following 12 weeks of daily QMT practice, proNGF level increases while proBDNF showed no significant change. More importantly, while no correlation between the two neurotrophins prior to training was detectable, there was a significant correlation between change in proNGF and proBDNF levels. Taken together the current results suggest that the two neurotrophins undergo a complex modulation, likely related to the different pathways by which they are produced and regulated. Since variations of these neurotrophins have been previously linked to depression, stress and anxiety, the current study may have practical implications and aid in understanding the possible physiological mechanisms that mediate improved well-being, and the dynamic change of neurotrophins as a result of training.

PMID: 30792622 [PubMed]

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Increased Peripheral Interleukin 10 Relate to White Matter Integrity in Schizophrenia.

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Increased Peripheral Interleukin 10 Relate to White Matter Integrity in Schizophrenia.

Front Neurosci. 2019;13:52

Authors: Fu G, Zhang W, Dai J, Liu J, Li F, Wu D, Xiao Y, Shah C, Sweeney JA, Wu M, Lui S

Abstract
Background: Schizophrenia is characterized by the disruption of microstructural white matter (WM) integrity, while the pathogenesis remains unclear. Inflammation has been associated with the WM pathology in schizophrenia. Interleukin 10 (IL-10) has been proven to be related to schizophrenia in both animal and human models. The aim of this study was to explore whether peripheral IL-10 was associated with microstructural WM integrity in schizophrenia. Methods: A total of 47 patients with schizophrenia (SZ) and 49 healthy controls (HC) underwent diffusion tensor imaging and venous blood sampling. Tract-based spatial statistics was conducted to explore the differences in fractional anisotropy (FA), radial diffusivity (RD), mean diffusivity (MD), and axial diffusivity (AD) between patients and controls. A quantitative chemiluminescence assay was performed to measure peripheral IL-10 levels. General linear regression analysis using a stepwise method was applied to examine the relationship between peripheral IL-10 and diffusion measures. Results: Compared with the HC, peripheral IL-10 levels were higher and a significant reduction of FA and AD, and increase of RD and MD were observed in SZ (corrected p < 0.05). A regression analysis revealed that peripheral IL-10 was negatively correlated with FA in the right posterior thalamic radiation and left inferior fronto-occipital fasciculus, in SZ (β = -0.51, p = 0.01; β = -0.47, p = 0.02, respectively) but not in HC (β = -0.01, p = 0.95; β = -0.003, p = 0.98, respectively), and the differences in regression curves were significant (z = 2.50, p = 0.01; z = 2.37, p = 0.02, respectively). IL-10 was negatively connected with MD in the right parietal arcuate fasciculus (β = -0.40, p = 0.048) and body of the corpus callosum (β = -0.43, p = 0.03) in SZ, while not in HC. The magnitude of correlation in the patient and control group was different (z = 2.48, p = 0.01 and z = 2.61, p < 0.01, respectively). In addition, IL-10 was positively correlated with RD in the right parietal arcuate fasciculus in patients (β = 0.45, p = 0.04) but not in HC (β = 0.26, p = 0.94), but the correlation coefficients were not significant (z = 0.98, p = 0.32). Conclusion: Our findings demonstrated that elevated peripheral IL-10 levels were associated with the disruption of microstructural WM integrity in schizophrenia, supporting the notion that inflammation plays a regulatory role in the pathology of microstructural WM and is associated with schizophrenia.

PMID: 30792621 [PubMed]

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Behavioral Paradigms to Probe Individual Mouse Differences in Value-Based Decision Making.

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Behavioral Paradigms to Probe Individual Mouse Differences in Value-Based Decision Making.

Front Neurosci. 2019;13:50

Authors: Alabi OO, Fortunato MP, Fuccillo MV

Abstract
Value-based decision making relies on distributed neural systems that weigh the benefits of actions against the cost required to obtain a given outcome. Perturbations of these systems are thought to underlie abnormalities in action selection seen across many neuropsychiatric disorders. Genetic tools in mice provide a promising opportunity to explore the cellular components of these systems and their molecular foundations. However, few tasks have been designed that robustly characterize how individual mice integrate differential reward benefits and cost in their selection of actions. Here we present a forced-choice, two-alternative task in which each option is associated with a specific reward outcome, and unique operant contingency. We employed global and individual trial measures to assess the choice patterns and behavioral flexibility of mice in response to differing "choice benefits" (modeled as varying reward magnitude ratios) and different modalities of "choice cost" (modeled as either increasing repetitive motor output to obtain reward or increased delay to reward delivery). We demonstrate that (1) mouse choice is highly sensitive to the relative benefit of outcomes; (2) choice costs are heavily discounted in environments with large discrepancies in relative reward; (3) divergent cost modalities are differentially integrated into action selection; (4) individual mouse sensitivity to reward benefit is correlated with sensitivity to reward costs. These paradigms reveal stable individual animal differences in value-based action selection, thereby providing a foundation for interrogating the neural circuit and molecular pathophysiology of goal-directed dysfunction.

PMID: 30792620 [PubMed]

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Integrin αVβ3 Function Influences Citalopram Immobility Behavior in the Tail Suspension Test.

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Integrin αVβ3 Function Influences Citalopram Immobility Behavior in the Tail Suspension Test.

Front Neurosci. 2019;13:70

Authors: Pan H, Dohn MR, Kingston R, Carneiro AMD

Abstract
Human studies first identified genetic and expression interactions between integrin β3 and serotonin (5-HT) transporter (SERT) genes. This association has been further strengthened by our discovery that integrin β3-containing receptors (αvβ3) physically interact with, and thereby define, a subpopulation of SERTs that may represent the main target of selective serotonin reuptake inhibitors (SSRIs). In this study, we examine how integrin αvβ3 function influences the behavioral response to the highly SSRI citalopram in the tail suspension test. Mice bearing a conditional deletion of the integrin β3 gene in neurons, or those expressing a constitutively active αvβ3 receptor, have decreased sensitivity to citalopram, when compared to wild-type littermates. To identify potential signaling pathways downstream of integrin αvβ3 that could be altered in these mouse lines, and consequently influence citalopram response in vivo, we performed antibody array analyses of midbrain synaptosomes isolated from mice bearing genetically altered integrin β3. We then pharmacologically targeted focal adhesion (FAK) and extracellular-signal-regulated (ERK) kinases and determined that FAK and ERK activity are critical for the actions of citalopram. Taken together, our studies have revealed a complex relationship between integrin αvβ3 function, SERT-dependent 5-HT uptake, and the effective dose of citalopram in the TST, thus implicating a role for integrin signaling pathways in the behavioral response to SSRIs.

PMID: 30787865 [PubMed]

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Oxytocin Facilitates Social Learning by Promoting Conformity to Trusted Individuals.

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Oxytocin Facilitates Social Learning by Promoting Conformity to Trusted Individuals.

Front Neurosci. 2019;13:56

Authors: Xu L, Becker B, Kendrick KM

Abstract
There is considerable interest in the role of the neuropeptide oxytocin in promoting social cohesion both in terms of promoting specific social bonds and also more generally for increasing our willingness to trust others and/or to conform to their opinions. These latter findings may also be important in the context of a modulatory role for oxytocin in improving the efficacy of behavioral therapy in psychiatric disorders. However, the original landmark studies claiming an important role for oxytocin in enhancing trust in others, primarily using economic game strategies, have been questioned by subsequent meta-analytic approaches or failure to reproduce findings in different contexts. On the other hand, a growing number of studies have consistently reported that oxytocin promotes conformity to the views of groups of in-group individuals. Most recently we have found that oxytocin can increase acceptance of social advice given by individual experts without influencing their perceived trustworthiness per se, but that increased conformity in this context is associated with how much an expert is initially trusted and liked. Oxytocin can also enhance the impact of information given by experts by facilitating expectancy and placebo effects. Here we therefore propose that a key role for oxytocin is not in facilitating social trust per se but in conforming to, and learning from, trusted individuals who are either in-group members and/or perceived experts. The implications of this for social learning and use of oxytocin as an adjunct to behavioral therapy in psychiatric disorders are discussed. Interpersonal trust within social groups is of key importance for social interactions, bonds, cooperation and learning and trust between different groups can also help ensure a stable and peaceful co-existence as well as mutually beneficial co-operation and trade. Trust is generally considered to be critical for co-operation and reciprocity in social and economic interactions but importantly trust also involves risk of potential injury if misplaced or broken and we have a natural aversion to taking such risks (Hardin, 2002; Ostrom and Walker, 2003). Indeed, an important factor influencing our trust behavior is that we are strongly motivated to avoid others betraying our trust (Bohnet and Zeckhauser, 2004; Bohnet et al., 2008). Trust can potentially be influenced by our assessment of the level of risk that trusting others might have and also by increased sensitivity to physical and/or other cues for detecting trustworthiness. It is therefore of great importance to identify both behavioral and physiological factors which can act to enhance trust, particularly in situations where individuals have impaired trust and therefore find it hard to interact socially with others and learn from them and/or to benefit optimally from cognitive and behavioral therapeutic strategies.

PMID: 30787864 [PubMed]

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Brain Activation Time-Locked to Sleep Spindles Associated With Human Cognitive Abilities.

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Brain Activation Time-Locked to Sleep Spindles Associated With Human Cognitive Abilities.

Front Neurosci. 2019;13:46

Authors: Fang Z, Ray LB, Owen AM, Fogel SM

Abstract
Simultaneous electroencephalography and functional magnetic resonance imaging (EEG-fMRI) studies have revealed brain activations time-locked to spindles. Yet, the functional significance of these spindle-related brain activations is not understood. EEG studies have shown that inter-individual differences in the electrophysiological characteristics of spindles (e.g., density, amplitude, duration) are highly correlated with "Reasoning" abilities (i.e., "fluid intelligence"; problem solving skills, the ability to employ logic, identify complex patterns), but not short-term memory (STM) or verbal abilities. Spindle-dependent reactivation of brain areas recruited during new learning suggests night-to-night variations reflect offline memory processing. However, the functional significance of stable, trait-like inter-individual differences in brain activations recruited during spindle events is unknown. Using EEG-fMRI sleep recordings, we found that a subset of brain activations time-locked to spindles were specifically related to Reasoning abilities but were unrelated to STM or verbal abilities. Thus, suggesting that individuals with higher fluid intelligence have greater activation of brain regions recruited during spontaneous spindle events. This may serve as a first step to further understand the function of sleep spindles and the brain activity which supports the capacity for Reasoning.

PMID: 30787863 [PubMed]

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Modular Functional-Metabolic Coupling Alterations of Frontoparietal Network in Schizophrenia Patients.

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Modular Functional-Metabolic Coupling Alterations of Frontoparietal Network in Schizophrenia Patients.

Front Neurosci. 2019;13:40

Authors: Xiang Q, Xu J, Wang Y, Chen T, Wang J, Zhuo K, Guo X, Zeljic K, Li W, Sun Y, Wang Z, Li Y, Liu D

Abstract
Background: Brain functional dysconnectivity, as well as altered network organization, have been demonstrated to occur in schizophrenia. Brain networks are increasingly understood to exhibit modular community structures, which provides advantages in robustness and functional adaptivity. The frontoparietal network (FPN) serves as an important functional module, and metabolic and functional alterations in the FPN are associated with the pathophysiology of schizophrenia. However, how intra-modular biochemical disruptions lead to inter-modular dysfunction of the FPN, remains unclear. In this study, we aim to investigate alterations in the modular functional-metabolic coupling of the FPN, in patients with schizophrenia. Methods: We combined resting-state functional magnetic resonance imaging (rs-fMRI) and magnetic resonance spectroscopy (MRS) technology and acquired multimodal neuroimaging data in 20 patients with schizophrenia and 26 healthy controls. For the MRS, the dorsolateral prefrontal cortex (DLPFC) region within the FPN was explored. Metabolites including gamma aminobutyric acid (GABA), N-aspart-acetyl (NAA) and glutamate + glutamine (Glx) were quantified, using LCModel software. A graph theoretical approach was applied for functional modular parcellation. The relationship between inter/intra-modular connectivity and metabolic concentration was examined using the Pearson correlation analysis. Moreover, correlations with schizophrenia symptomatology were investigated by the Spearman correlation analysis. Results: The functional topological network consisted of six modules in both subject groups, namely, the default mode, frontoparietal, central, hippocampus, occipital, and subcortical modules. Inter-modular connectivity between the frontoparietal and central modules, and the frontoparietal and the hippocampus modules was decreased in the patient group compared to the healthy controls, while the connectivity within the frontoparietal modular increased in the patient group. Moreover, a positive correlation between the frontoparietal and central module functional connectivity and the NAA in the DLPFC was found in the healthy control group (r = 0.614, p = 0.001), but not in the patient group. Significant functional dysconnectivity between the frontoparietal and limbic modules was correlated with the clinical symptoms of patients. Conclusions: This study examined the links between functional connectivity and the neuronal metabolic level in the DLPFC of SCZ. Impaired functional connectivity of the frontoparietal areas in SCZ, may be partially explained by a neurochemical-functional connectivity decoupling effect. This disconnection pattern can further provide useful insights in the cognitive and perceptual impairments of schizophrenia in future studies.

PMID: 30787862 [PubMed]

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epilepsy treatment; +33 new citations

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Trends and projections of cancer mortality in Osaka, Japan from 1977 to 2032.

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Trends and projections of cancer mortality in Osaka, Japan from 1977 to 2032.

Jpn J Clin Oncol. 2019 Feb 22;:

Authors: Fukui K, Ito Y, Nakayama T

Abstract
Projecting cancer mortality is fundamental to the process of planning cancer control. Although the prefecture is one of the main units for the implementation and evaluation of cancer control in Japan, a long-term detailed future projection of cancer mortality has not been conducted by prefecture. The main objective of this paper is to estimate the future number of cancer deaths in Osaka prefecture. Projections were made using the Nordpred model to estimate future trends in cancer mortality. The projected age-standardized mortality rate decreased by 24.5% in males and 16.8% in females from 2012-16 to 2032-36. However, the number of deaths showed a small decrease in males (1.3%) and an increase in females (13.1%). The largest contributor to the increasing number of cancer deaths is the aging population. In Japan, cancer control programmes are implemented by prefecture; our report can therefore be used for prefecture-level cancer control planning.

PMID: 30793210 [PubMed - as supplied by publisher]

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Biomarker discordance between primary breast cancer and bone or bone marrow metastases.

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Biomarker discordance between primary breast cancer and bone or bone marrow metastases.

Jpn J Clin Oncol. 2019 Feb 22;:

Authors: Yuda S, Shimizu C, Yoshida M, Shiino S, Kinoshita T, Maeshima AM, Tamura K

Abstract
BACKGROUND: Discordance in biomarker expression between primary and metastatic tumor sites has been reported in several studies; yet, few have examined this feature in bone lesions.
METHODS: We retrospectively enrolled patients with breast cancer metastasis to the bone or bone marrow, excluding cases where samples from both the primary and metastatic lesions were not available. Expression patterns of the estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2) and Ki67 were compared in primary tumors and bone or bone marrow lesions.
RESULTS: Forty-six patients with a median age of 52 years (range, 34-72 years) were included in the study. Discordant rates of ER, PgR and HER2 were 20%, 46% and 0%, respectively. Physicians usually determined treatment options considering the results of biomarker re-evaluation. It is unlikely that biomarker discordance was related to prior treatment.
CONCLUSIONS: Biomarker discordance in bone or bone marrow lesions is common in patients with breast cancer. An accurate and thorough analysis of biomarkers and metastatic tumor properties is important for clinical decision-making.

PMID: 30793198 [PubMed - as supplied by publisher]

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Chemoradiotherapy for locally advanced lung cancer patients with interstitial lung abnormalities.

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Chemoradiotherapy for locally advanced lung cancer patients with interstitial lung abnormalities.

Jpn J Clin Oncol. 2019 Feb 22;:

Authors: Higo H, Kubo T, Makimoto S, Makimoto G, Ihara H, Masaoka Y, Ninomiya T, Ichihara E, Ohashi K, Sato A, Hotta K, Tabata M, Takigawa N, Maeda Y, Kiura K

Abstract
INTRODUCTION: Although chemoradiotherapy for locally advanced lung cancer has the potential for cure, treatment is avoided in patients with interstitial lung disease because of the risk for severe radiation pneumonitis. Interstitial lung abnormalities (ILA) can be evaluated using high-resolution computed tomography (HRCT) to assess interstitial changes. In this study, we retrospectively examined the feasibility and efficacy of chemoradiotherapy for locally advanced lung cancer patients with ILA.
METHODS: Patients who underwent chemoradiotherapy for locally advanced lung cancer at Okayama University Hospital between 2012 and 2015 were reviewed retrospectively. HRCT prior to treatment was evaluated by one pulmonologist and two radiologists using a sequential reading method.
RESULTS: Of the 77 patients enrolled in this study, ILA was present in 25 (32.5%) and indeterminate ILA in 24 patients; 28 patients did not have ILA. Desaturation at rest (SpO2 < 95%) and honeycombing on HRCT were not observed in ILA patients. Only one patient with ILA had a low vital capacity (%VC < 80%). Severe radiation pneumonitis (≥Grade 2) occurred in 36.0% of the patients with ILA, but it was controllable; Grade 4 or 5 was not observed. Multivariate analysis showed that >25% of the lung volume receiving >20 Gy was risk factors of severe radiation pneumonitis, but ILA was not. The 2-year survival rates of patients with and without ILA were 56.8% and 74.1%, respectively, but the difference was not significant (P = 0.33).
CONCLUSIONS: Chemoradiotherapy was feasible and effective in some patient population with ILA without desaturation, low VC and honeycombing on HRCT.

PMID: 30793176 [PubMed - as supplied by publisher]

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What influences the willingness of cancer patients to receive hospice palliative care at end of life?

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What influences the willingness of cancer patients to receive hospice palliative care at end of life?

Jpn J Clin Oncol. 2019 Feb 22;:

Authors: Chen TR, Hu WY, Two SN, Chiu TY

Abstract
BACKGROUND: The benefits of hospice palliative care (HPC) for end-of-life (EoL) patients have been widely acknowledged in recent years. There is still limited knowledge about cancer patients' willingness toward HPC. This study aimed to investigate the willingness of cancer patients to receive HPC and the influencing factors.
METHODS: A cross-sectional study was conducted with cancer patients enrolled from teaching hospitals in Taiwan. The questionnaire included demographic characteristics, EoL care preferences, and scales for measuring the willingness to receive HPC, HPC knowledge, and attitude towards HPC. Data were collected by senior nurses and they were analyzed using descriptive and a regression analysis.
RESULTS: A total of 148 valid questionnaires were collected. The participants indicated that they 'willing to receive' HPC (mean3.8 on a 5-point scale). The predictors for their willingness to receive HPC were knowledge about HPC (P = 0.001), positive attitude towards HPC (P = 0.008), preference for hospital death (P = 0.022), and preference for quality of life (P = 0.047) as the goal of EoL care. These factors explained 32.7% of the total variance in the willingness to receive HPC.
CONCLUSIONS: Cancer patients were generally willing to receive HPC. Clinician should discuss EoL care with them earlier. Develop appropriate educational strategies that can provide cancer patients with sufficient and tailored HPC information to develop their knowledge and to create a positive attitude about HPC is necessary, thereby to allow for early HPC intervention and to fulfill the patients' need for HPC.

PMID: 30793175 [PubMed - as supplied by publisher]

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Impact of tumor size on patient survival after radical nephrectomy for pathological T3a renal cell carcinoma.

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Impact of tumor size on patient survival after radical nephrectomy for pathological T3a renal cell carcinoma.

Jpn J Clin Oncol. 2019 Feb 22;:

Authors: Sugiyama Y, Yatsuda J, Murakami Y, Ito N, Yamasaki T, Mikami Y, Ogawa O, Kamba T

Abstract
PURPOSE: We recently reported the results from a multi-institutional retrospective outcome study involving 814 patients with renal cell carcinomas (RCCs) who had undergone radical surgery and whose diagnoses were confirmed via a central pathological review. This study aimed to clarify the impact of tumor size on survival outcomes in patients with pT3aN0M0 RCC after radical nephrectomy using this cohort.
METHODS: Using the Kaplan-Meier method, overall survival (OS), cancer-specific survival (CSS) and relapse-free survival (RFS) were estimated for 103 pT3aN0M0 patients. The differences in the OS, CSS and RFS according to tumor size were evaluated using the log-rank test. To identify independent prognostic factors that affected each survival outcome, clinicopathological factors were examined using univariate and multivariate analyses, and the Cox proportional hazards model.
RESULTS: The OS, CSS and RFS rates for 26 patients with pT3a RCCs ≤4 cm were significantly better than those for 77 patients with pT3a RCCs that were 4-7 cm or >7 cm (P = 0.0064, 0.0169 and 0.0001, respectively). Tumor size and venous invasion were independent prognosticators for OS, CSS and RFS. The OS and CSS for patients with pT3a tumors ≤4 cm were comparable with those for patients with pT1 RCCs, and the RFS for patients with pT3a RCCs ≤4 cm was similar to that for patients with pT1b RCCs.
CONCLUSIONS: Tumor size significantly influenced the prognosis for patients with pT3aN0M0 RCC. This study's results suggest that the postoperative management of pT3a RCCs could be individualized according to tumor size.

PMID: 30793163 [PubMed - as supplied by publisher]

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Attitude of Japanese palliative care specialists towards adjuvant analgesics cancer-related neuropathic pain refractory to opioid therapy: a nationwide cross-sectional survey.

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Attitude of Japanese palliative care specialists towards adjuvant analgesics cancer-related neuropathic pain refractory to opioid therapy: a nationwide cross-sectional survey.

Jpn J Clin Oncol. 2019 Feb 22;:

Authors: Matsuoka H, Tagami K, Ariyoshi K, Oyamada S, Kizawa Y, Inoue A, Koyama A

Abstract
Cancer-related neuropathic pain (CNP) requires therapy involving multiple pharmaceuticals, including anticonvulsants and antidepressants; however, strong evidence to support this practice is limited. This study is a cross-sectional questionnaire-based survey. As the standard dose of adjuvant analgesics for CNP refractory to opioid therapy is not clear, the purpose of this study is to clarify the opinions of specialists about the usage of duloxetine and pregabalin for patients with CNP refractory to opioid therapy. Two hundred and eight certified palliative care specialists were surveyed and a total of 87 (42%) responses were analyzed. Twenty-five percent of specialists had considered increasing duloxetine doses up to 60 mg/day and 58% had considered increasing pregabalin doses up to 300 mg/day for CNP refractory to opioid therapy. However, 23% of the specialists succeeded in increasing duloxetine doses up to 60 mg/day and 17% in increasing pregabalin doses up to 300 mg/day, respectively.

PMID: 30793161 [PubMed - as supplied by publisher]

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Smartphone problem-solving therapy to reduce fear of cancer recurrence among breast cancer survivors: an open single-arm pilot study.

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Smartphone problem-solving therapy to reduce fear of cancer recurrence among breast cancer survivors: an open single-arm pilot study.

Jpn J Clin Oncol. 2019 Feb 22;:

Authors: Imai F, Momino K, Katsuki F, Horikoshi M, Furukawa TA, Kondo N, Toyama T, Yamaguchi T, Akechi T

Abstract
OBJECTIVES: The purpose of this study was to investigate a newly developed smartphone problem-solving therapy (PST) application's feasibility and preliminary effectiveness for reducing fear of cancer recurrence (FCR) among breast cancer survivors.
METHODS: Female disease-free breast cancer survivors aged 20-49 years who were more than 6 months post-breast surgery participated in the study. The patients received the smartphone PST using an iPhone or iPad for 8 weeks. The feasibility of the intervention program was evaluated using the overall participation rate, the percentage of survivors who expressed interest in the intervention, and the percentage of completion of the study. Patients were also asked to complete the Concern About Recurrence Scale (CARS) as a primary outcome at baseline, 4 weeks and 8 weeks.
RESULTS: A total of 38 patients participated in this study. The overall participation and completion rates in the study were 47.1% and 97.4%, respectively. The overall fear assessed by CARS was significantly reduced at 8 weeks compared with baseline. A pairwise comparison showed a significant decrease from 4 weeks to 8 weeks and from baseline to 8 weeks.
CONCLUSIONS: Smartphone PST, a novel brief intervention to reduce FCR, was well accepted by breast cancer survivors and yielded a favorable effect on FCR. The efficacy of this newly developed smartphone PST needs to be confirmed in a future well-designed randomized controlled trial.

PMID: 30793156 [PubMed - as supplied by publisher]

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Kidney cancer incidence rates in the world from the Cancer Incidence in Five Continents XI.

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Kidney cancer incidence rates in the world from the Cancer Incidence in Five Continents XI.

Jpn J Clin Oncol. 2019 Feb 21;:

Authors: Hori M, Matsuoka J

PMID: 30789667 [PubMed - as supplied by publisher]

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Hepatocellular carcinoma (HCC) versus non-HCC: accuracy and reliability of Liver Imaging Reporting and Data System v2018

Abstract

Purpose

The Liver Imaging Reporting and Data System (LI-RADS) was created to standardize the diagnostic criteria for hepatocellular carcinoma (HCC) and has undergone multiple revisions including a recent update in 2018 (v2018). The primary aim of this study was to determine the diagnostic performance and interrater reliability (IRR) of LI-RADS v2018 for distinguishing HCC from non-HCC primary hepatic malignancy in patients 'at-risk' for HCC. A secondary aim was to assess the impact of changes introduced in the v2018 diagnostic algorithm.

Methods

This retrospective study combined a 10-year experience of pathologically proven primary liver malignancies from two large liver transplant centers. Two blinded readers independently evaluated each lesion and assigned a LI-RADS diagnostic category, additionally scoring all relevant imaging features. Changes in category based on the reader-provided features and the new v2018 criteria were assessed by a study coordinator.

Results

The final study cohort comprised 105 HCCs and 73 non-HCC primarily liver malignancies. LI-RADS had a high specificity for distinguishing HCC from non-HCC (89% and 90% for reader 1 and reader 2, respectively), and IRR was moderate to substantial for final LI-RADS category and most features. Revision of the LI-RADS v2018 diagnostic algorithm resulted in very few changes [5 (2.8%) and 3 (1.7%) for reader 1 and reader 2, respectively] in overall lesion classification.

Conclusion

LI-RADS diagnostic categories and features had moderate to substantial IRR and high specificity for distinguishing HCC from non-HCC primary liver malignancy. Revision of LI-RADS v2018 diagnostic algorithm resulted in reclassification of very few lesions.

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Effect of labelling plane angulation and position on labelling efficiency and cerebral blood flow quantification in pseudo-continuous arterial spin labelling

Publication date: Available online 22 February 2019

Source: Magnetic Resonance Imaging

Author(s): Magdalena Sokolska, Alan Bainbridge, Alvaro R. Villabona, Xavier Golay, David Thomas

Abstract

Pseudo-continuous arterial spin labelling (pCASL) is the MRI method of choice for non-invasive perfusion measurement in research and clinical practice. Knowledge of the labelling efficiency, α, is essential for accurate quantification of cerebral blood flow (CBF). Typically, a theoretical α value is used, based on an idealistic model and an assumption of spins flowing perpendicularly to the labelling plane. The aim of this work was to investigate the effect of violating this assumption, and to characterize the influence of labelling plane angulation with respect to the vessel direction on labelling efficiency and measured CBF.

The effect of labelling plane angulation on labelling efficiency was demonstrated using a numerical simulation of spins at different velocities. Acquisitions from healthy volunteers were used to test the effect of a range of angulation offsets. Additional sub-optimal positions of the labelling plane with respect to the vertebral arteries, at locations where the direction of flow changes significantly from the head-foot direction, were also considered.

No significant change in the measured CBF was seen when the labelling plane was angled up to 60° to the labelled vessel or when it was placed in sub-optimal positions. This study shows that in adult subjects, the efficiency of pCASL is robust to the angulation and positioning of the labelling plane beyond the range of potential operator error.

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High throughput bar adsorptive microextraction: A novel cost-effective tool for monitoring benzodiazepines in large number of biological samples

Publication date: 1 July 2019

Source: Talanta, Volume 199

Author(s): S.M. Ahmad, J.M.F. Nogueira

Abstract

In this work, we propose an innovative high throughput (HT) apparatus using the bar adsorptive microextraction (BAμE) technique, which enables the simultaneous enrichment of up to 100 samples. This novel configuration was combined with microliquid desorption and high-performance liquid chromatography-diode array detection to monitor trace levels of eight benzodiazepines (diazepam, prazepam, bromazepam, oxazepam, lorazepam, alprazolam, temazepam and loflazepate) in biological samples. The proposed methodology was fully developed, optimized and validated, resulting in suitable intraday and interday precision (RSD ≤ 15%), with recovery yields ranging from 33.0% to 104.5%. The lower limits of quantification were between 20.0 and 100.0 µg L⁻¹, using 1.0 mL of urine and 0.5 mL of plasma or serum samples. The application of the proposed methodology to real matrices resulted in average sample preparation time of around 2 min per sample, demonstrating that it is user-friendly, cost-effective and a rapid decision-making tool, whenever large number of samples are involved.

Graphical abstract

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High Expression of HLA-G in Ovarian Carcinomatosis: The Role of Interleukin-1β

Publication date: March 2019

Source: Neoplasia, Volume 21, Issue 3

Author(s): Matti Ullah, Dallel Azazzen, Rachid Kaci, Nadia Benabbou, Eric Pujade Lauraine, Marc Pocard, Massoud Mirshahi

Abstract

The present study focuses on the influence of the tumor microenvironment on the expression of HLA-G in ovarian cancer and its impact on immune cells. We used carcinomatosis fluids (n = 16) collected from patients diagnosed with epithelial ovarian cancer, detected by an increase in CA125 levels. Our results indicate that HLA-G is expressed by 1) ascitic cell clusters, 2) stromal cells (hospicells) extracted from cancer cell clusters, and 3) cancer cell lines and tumor cells. The origin of HLA-G was linked to inflammatory cytokines present in the cancer microenvironment. In parallel, the ascitic fluid of patients with ovarian cancer contains soluble HLA-G (sHLA-G). The mesothelial cell layer and submesothelial tissues, as well as the immune cell infiltrate, do not secrete HLA-G. In contrast, sHLA-G is absorbed by peritoneal tissues along with mesothelial layers as well as immune cell infiltrates. We demonstrated that interleukin-1β along with TGF-β can be a major HLA-G–inducing factor that upregulates HLA-G expression through the NF-κB pathway. The level of HLA-G in ascites correlated positively with the expression of T regulatory (T-regs) cells, while it negatively correlated with the expression of natural killer and memory cells in tumor-infiltrating immune cells. In conclusion, the production of HLA-G is associated with the presence of inflammatory cytokines and is strongly correlated with microenvironment tolerant cells such as T-regs and diminution of NK and memory T cells.

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Wnt Signaling Mediates the Aging-Induced Differentiation Impairment of Intestinal Stem Cells.

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Wnt Signaling Mediates the Aging-Induced Differentiation Impairment of Intestinal Stem Cells.

Stem Cell Rev. 2019 Feb 21;:

Authors: Cui H, Tang D, Garside GB, Zeng T, Wang Y, Tao Z, Zhang L, Tao S

Abstract
Stem cell aging underlies aging-associated disorders, such as steeply increased incidences of tumors and impaired regeneration capacity upon stress. However, whether and how the intestinal stem cells age remains largely unknown. Here we show that intestinal stem cells derived from 24-month-old mice hardly form typical organoids with crypt-villus structures, but rather mainly form big, rounded cysts devoid of differentiated cell types, which mimics the culturing of heterozygous APC-deficient cells from the APCmin mouse line. Further analysis showed that cultured crypts derived from aged mice exhibited reduced expression levels of differentiation genes and higher expression of Wnt target genes. Lowering the concentration of R-spondin-1 in the culture system significantly reduced formation of rounded cysts, accompanied by an increased formation of organoids from crypts derived from old mice. We are the first to uncover that intestinal stem cells derived from old mice harbor significant deficiency in differentiation that can be partially rescued through a reduction in R-spondin-1 exposure. This could be highly relevant to intestinal tumor development and the reduced regeneration potential observed in the aged population. Our study provides the first experimental evidence that an over-responsiveness to Wnt/beta-catenin signaling of aged intestinal stem cells mediates the aging-induced deficiency in differentiation, and could serve as a potential target to ameliorate aging-associated intestinal pathologies.

PMID: 30790135 [PubMed - as supplied by publisher]

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Bevacizumab Combined With Oxaliplatin/Capecitabine in Patient With Refractory and Recurrent Mucinous Adenocarcinoma of the Appendix: A Case Report.

Bevacizumab Combined With Oxaliplatin/Capecitabine in Patient With Refractory and Recurrent Mucinous Adenocarcinoma of the Appendix: A Case Report.

Front Oncol. 2019;9:55

Authors: Liu W, Liu L, Wang R, Gong G, Ding X, Yang B, Bao Y, Wang Z, Zhang B, Zhao D, Wu F, Ding Y

Abstract
Primary appendiceal adenocarcinoma with peritoneal pseudomyxoma (PPM) has a high recurrence rate and refractory to medical interventions such as repetitive debulking surgery and systemic chemotherapy. Genome-based targeted therapy for such cases has not been well-documented. Here we present a 63-years-old women, who was diagnosed with recurrent mucinous adenocarcinoma of the appendix with local invasions and peritoneal carcinomatosis, was refractory to systemic chemotherapy after surgery. We used a regime developed using whole exome sequencing. Somatic mutations in the genes encoding VEGFR2, FGFR1, FGFR2, FGFR3, and KRAS were identified in the patient's tumor tissue. The patient was then treated with bevacizumab plus oxaliplatin. After 4 months of treatment, pelvic CT showed dramatic reduction of pseudomyoma and a decline of CA199 level from 5436.7 to 1121.4 U/ml. Continual treatment with bevacizumab-capecitabine remained effective and the patient's CA199 level further decreased to 401.26 U/ml according to the follow-up examination on Aug 15th, 2018. Results from this study show the evidence of gene mutations involving VEGF signal activation in the recurrence of appendiceal adenocarcinoma. Our results also suggest the association of these mutations with the effectiveness of anti-VEGF treatment using bevacizumab. Therefore, the screening of gene mutations involved in VEGF signaling and targeted therapy with anti-VEGF drugs may provide a new option to manage refractory/recurrent advanced-stage appendiceal adenocarcinoma.

PMID: 30792968 [PubMed]

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On the Other Side: Manipulating the Immune Checkpoint Landscape of Dendritic Cells to Enhance Cancer Immunotherapy.

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On the Other Side: Manipulating the Immune Checkpoint Landscape of Dendritic Cells to Enhance Cancer Immunotherapy.

Front Oncol. 2019;9:50

Authors: Kong BY, Bolton H, Kim JW, Silveira PA, Fromm PD, Clark GJ

Abstract
Monoclonal antibodies targeting co-inhibitory immune checkpoint molecules have been successful in clinical trials of both solid and hematological malignancies as acknowledged by the 2018 Nobel Prize in Medicine, however improving clinical response rates is now key to expanding their efficacy in areas of unmet medical need. Antibodies to checkpoint inhibitors target molecules on either T cells or tumor cells to stimulate T cells or remove tumor mediated immunosuppression, respectively. However, many of the well-characterized T cell immune checkpoint receptors have their ligands on antigen presenting cells or exert direct effects on those cells. Dendritic cells are the most powerful antigen presenting cells; they possess the ability to elicit antigen-specific responses and have important roles in regulation of immune tolerance. Despite their theoretical benefits in cancer immunotherapy, the translation of DC therapies into the clinic is yet to be fully realized and combining DC-based immunotherapy with immune checkpoint inhibitors is an attractive strategy. This combination takes advantage of the antigen presenting capability of DC to maximize specific immune responses to tumor antigens whilst removing tumor-associated immune inhibitory mechanisms with immune checkpoint inhibition. Here we review the expression and functional effects of immune checkpoint molecules on DC and identify rational combinations for DC vaccination to enhance antigen-specific T cell responses, cytokine production, and promotion of long-lasting immunological memory.

PMID: 30788290 [PubMed]

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Adjunctive Use of Circulating Tumor DNA Testing in Detecting Pancreas Cancer Recurrence.

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Adjunctive Use of Circulating Tumor DNA Testing in Detecting Pancreas Cancer Recurrence.

Front Oncol. 2019;9:46

Authors: Soyano AE, Baldeo C, Kasi PM

Abstract
Liquid biopsies (circulating tumor DNA-ctDNA testing) are increasingly being utilized in clinical trials as well as practice for the detection of cancer, monitoring of tumor genomic abnormalities, response to treatment and early detection of relapse/recurrence. Here, we present a challenging case where liquid biopsy was used to confirm an early recurrence of pancreatic cancer where acquisition of tissue was not safe or feasible on more than one occasion.

PMID: 30788289 [PubMed]

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ACE Insertion/Deletion Polymorphism (rs4646994) Is Associated With the Increased Risk of Multiple Myeloma.

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ACE Insertion/Deletion Polymorphism (rs4646994) Is Associated With the Increased Risk of Multiple Myeloma.

Front Oncol. 2019;9:44

Authors: Zmorzynski S, Szudy-Szczyrek A, Popek-Marciniec S, Korszen-Pilecka I, Wojcierowska-Litwin M, Luterek M, Chocholska S, Styk W, Swiderska-Kołacz G, Januszewska J, Mielnik M, Hus M, Filip AA

Abstract
Introduction: The insertion (I allele) deletion (D allele) polymorphism of ACE gene (rs4646994) may influence the etiopathogenesis of multiple myeloma (MM). ACE gene is expressed in bone marrow cells and encodes angiotensin converting enzyme (ACE). It converts angiotensin I to active peptide angiotensin II, which stimulates proliferation of hematopoietic stem cells. This suggests possible association of ACE I/D gene polymorphism with MM. The aim of our study was to check possible impact of this polymorphism on risk of development and outcome of MM, as well as, sensitivity to bortezomib in cell cultures derived from MM patients. Objects and Methods: Genomic DNA from 98 newly diagnosed MM patients and 100 healthy blood donors were analyzed by PCR method. Chromosomal aberrations were detected by use of cIg-FISH. In a subgroup of 40 MM patients nucleated bone marrow cells were treated with bortezomib in vitro. Results: The Hardy-Weinberg equilibrium test showed that genotypic frequencies diverged significantly from the equilibrium. The differences between I and D allele frequencies in control and study population were significant (p = 0.046). We observed the association between DD genotype and more than 2-fold risk of MM - OR = 2.69; p < 0.0001. We did not detect any significant differences among studied genotypes regarding clinical and laboratory parameters. Moreover, we did not observe the association between survival of MM patients and I/D genotypes. Bortezomib increased number of apoptotic and necrotic cells, but the only statistically significant differences were observed in the number of viable cells at 1 nM between ID and DD genotypes (p = 0.026). Conclusion: Presented results confirmed the significant relationship between ACE (I/D) polymorphism and risk of MM development. We did not observe the association of ACE I/D polymorphism with disease outcome and bortezomib in vitro sensitivity.

PMID: 30788288 [PubMed]

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Differential Oxygenation in Tumor Microenvironment Modulates Macrophage and Cancer Cell Crosstalk: Novel Experimental Setting and Proof of Concept.

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Differential Oxygenation in Tumor Microenvironment Modulates Macrophage and Cancer Cell Crosstalk: Novel Experimental Setting and Proof of Concept.

Front Oncol. 2019;9:43

Authors: Campillo N, Falcones B, Otero J, Colina R, Gozal D, Navajas D, Farré R, Almendros I

Abstract
Hypoxia is a common characteristic of many solid tumors that has been associated with tumor aggressiveness. Limited diffusion of oxygen generates a gradient of oxygen availability from the blood vessel to the interstitial space and may underlie the recruitment of macrophages fostering cancer progression. However, the available data based on the recruitment of circulating cells to the tumor microenvironment has been so far carried out by conventional co-culture systems which ignore the hypoxic gradient between the vessel to the tumor interstitium. Here, we have designed a novel easy-to-build cell culture device that enables evaluation of cellular cross-talk and cell migration while they are being simultaneously exposed to different oxygenation environments. As a proof-of-concept of the potential role of differential oxygenation among interacting cells we have evaluated the activation and recruitment of macrophages in response to hypoxic melanoma, breast, and kidney cancer cells. We found that hypoxic melanoma and breast cancer cells co-cultured with normoxic macrophages enhanced their directional migration. By contrast, hypoxic kidney cells were not able to increase their recruitment. We also identified well-described hypoxia-induced pathways which could contribute in the immune cell recruitment (VEGFA and PTGS2 genes). Moreover, melanoma and breast cancer increased their proliferation. However, oxygenation levels affected neither kidney cancer cell proliferation nor gene expression, which in turn resulted in no significant changes in macrophage migration and polarization. Therefore, the cell culture device presented here provides an excellent opportunity for researchers to reproduce the in vivo hypoxic gradients in solid tumors and to study their role in recruiting circulating cells to the tumor in specific types of cancer.

PMID: 30788287 [PubMed]

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The CXCL8-CXCR1/2 Axis as a Therapeutic Target in Breast Cancer Stem-Like Cells.

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The CXCL8-CXCR1/2 Axis as a Therapeutic Target in Breast Cancer Stem-Like Cells.

Front Oncol. 2019;9:40

Authors: Ruffini PA

Abstract
Cancer stem-like cells (CSC) have been targeted by different strategies over the last decade. This mini review focuses on preclinical and clinical results obtained by interfering with chemokine receptors CXCR1 and CXCR2 in breast cancer. This strategy is currently being tested in a randomized, double blind phase 2 clinical trial.

PMID: 30788286 [PubMed]

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Prognostic Value of CD44 and Its Isoforms in Advanced Cancer: A Systematic Meta-Analysis With Trial Sequential Analysis.

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Prognostic Value of CD44 and Its Isoforms in Advanced Cancer: A Systematic Meta-Analysis With Trial Sequential Analysis.

Front Oncol. 2019;9:39

Authors: Han S, Huang T, Li W, Wang X, Wu X, Liu S, Yang W, Shi Q, Li H, Hou F

Abstract
Objective: Cancer stem cell marker CD44 and its variant isoforms (CD44v) may be correlated with tumor growth, metastasis, and chemo-radiotherapy resistance. However, the prognostic power of CD44 and CD44v in advanced cancer remains controversial. Therefore, the purpose of our study was to generalize the prognostic significance of these cancer stem cell markers in advanced cancer patients. Methods: Hazard ratios (HRs) with 95% confidence intervals (95% CIs) were calculated from multivariable analysis to assess the associations among CD44, CD44v6, and CD44v9 positivity and overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), cancer-specific survival (CSS), and recurrence-free survival (RFS). Trial sequential analysis (TSA) was also conducted. Results: We included 15 articles that reported on 1,201 patients with advanced cancer (CD44: nine studies with 796 cases, CD44v6: three studies with 143 cases, and CD44v9: three studies with 262 cases). CD44 expression was slightly linked to worse OS (HR = 2.03, P = 0.027), but there was no correlation between CD44 expression and DFS, RFS, or PFS. Stratified analysis showed that CD44 expression was not correlated with OS at ≥5 years or OS in patients receiving adjuvant therapy. CD44v6 expression was not associated with OS. CD44v9 expression was closely associated with poor 5-years CSS in patients treated with chemo/radiotherapy (HR = 3.62, P < 0.001). However, TSA suggested that additional trials were needed to confirm these conclusions. Conclusions: CD44 or CD44v9 might be novel therapeutic targets for improving the treatment of advanced cancer patients. Additional prospective clinical trials are strongly needed across different cancer types.

PMID: 30788285 [PubMed]

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Case 267.

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Case 267.

Radiology. 2019 Mar;290(3):839-842

Authors: Cz Arniecki M, Barrett T, Thiruchelvam N, Wiseman O

Abstract
History A 28-year-old man presented with lifelong anejaculation, which had become an issue because of family planning. The patient had a history of normal erections and experienced the sensation of orgasm without ever ejaculating. On physical examination, both testes were present in the scrotum, with normal dimensions and a normal epididymis bilaterally. The patient had a slightly tender left testicle, and digital rectal examination findings were normal. The patient underwent further investigation for the possibility of retrograde ejaculation with urine cytology, the results of which were negative. Genetic testing was performed to exclude Y chromosome microdeletions. Serum-luteinizing and follicle-stimulating hormone levels were normal, with a borderline low level of testosterone (7.6 nmol/L; normal range, 8.0-29.0 nmol/L). All other pertinent laboratory results were noncontributory. Pelvic MRI was requested to exclude an anatomic cause of anejaculation. MRI was performed in accordance with the standard clinical prostate protocol, with a dynamic contrast material-enhanced study ( Figs 1 - 3 ). CT of the upper abdomen was also performed ( Fig 4 ). The patient subsequently underwent cystoscopy, which revealed an intravesicular fluid-filled mass near the left ureteric orifice ( Fig 5 ). Figure 1a: (a) Coronal and (b, c) axial fast spin-echo T2-weighted MR images of the pelvis, with b being superior to c. Figure 1b: (a) Coronal and (b, c) axial fast spin-echo T2-weighted MR images of the pelvis, with b being superior to c. Figure 1c: (a) Coronal and (b, c) axial fast spin-echo T2-weighted MR images of the pelvis, with b being superior to c. Figure 2a: (a) Coronal T2-weighted (repetition time msec/echo time msec, 4574/86.5) MR image of the pelvis. (b) Axial T2-weighted (3000/85.4) MR image of the pelvis. Figure 2b: (a) Coronal T2-weighted (repetition time msec/echo time msec, 4574/86.5) MR image of the pelvis. (b) Axial T2-weighted (3000/85.4) MR image of the pelvis. Figure 3: Unenhanced axial fat-saturated T1-weighted (6.2/3.1) MR images. Figure 4: Coronal CT urogram. Figure 5: Image obtained at cystoscopy.

PMID: 30789814 [PubMed - in process]

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Trainee Research Prizes from the 2018 RSNA Scientific Assembly and Annual Meeting.

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Trainee Research Prizes from the 2018 RSNA Scientific Assembly and Annual Meeting.

Radiology. 2019 Mar;290(3):585-588

Authors:

PMID: 30789813 [PubMed - in process]

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2019 RSNA Leadership.

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2019 RSNA Leadership.

Radiology. 2019 Mar;290(3):583

Authors:

PMID: 30789812 [PubMed - in process]

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Case 263: Malaysian Charm Needles (Susuk).

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Case 263: Malaysian Charm Needles (Susuk).

Radiology. 2019 Mar;290(3):843-847

Authors: Martin JL, Vlachou PA

Abstract
History A 58-year-old woman was seen in the rheumatology clinic for bilateral wrist and knee pain that was unresponsive to physiotherapy and intra-articular steroid injections. Remote fracture of the left tibia from a motor vehicle collision was reported and was previously treated with conservative management. Serologic work-up for inflammatory disease was negative. The patient reported no prior surgical or medical history. Social history revealed remote immigration from Malaysia. Radiographs of the hands and knees were obtained.

PMID: 30789811 [PubMed - in process]

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Diagnostic Utility of Gut α-Synuclein in Parkinson’s Disease: A Systematic Review and Meta-Analysis

Publication date: Available online 22 February 2019

Source: Behavioural Brain Research

Author(s): Jin Bu, Jinsong Liu, Kun Liu, Zhaohui Wang

Abstract

Background

The accumulation of misfolded α-synuclein in the brain is associated with Parkinson's disease. However, the association between gut α-synuclein and PD and diagnostic value of α-synuclein in the gut still remain controversial.

Methods

A literature search from inception to June 2018 was conducted, yielding 21 studies eligible for a systematic review and meta-analysis. We included studies that reported data on gut α-synuclein or phosphorylated α-synuclein in patients with PD and controls. The odds ratio(OR) was pooled using random-effect models, and heterogeneity was reported as I². Studies were assessed for quality using the Newcastle-Ottawa Scale. Sensitivity and specificity analyses were performed using the summary receiver operating characteristics curve approach.

Results

The database search yielded 395 results, of which 21 studies were deemed relevant. The PD group had a pooled OR of 10.01 (95% CI: 3.15-31.82, I² = 72%) for gut α-synuclein compared with the control group. Sensitivity and specificity for distinguishing PD from controls were 0.568 and 0.819, respectively, for the colon, and 0.579 and 0.822, respectively, for phosphorylated α-synuclein.

Conclusion

Heterogeneity was high in most of the studies. This systematic review and meta-analysis confirmed a high degree of association between gut α-synuclein and PD, which suggested that gut α-synuclein is a potential therapeutic intervention. The measurement of gut α-synuclein alone could lead to the underdiagnosis of PD. Future research combining gut α-synuclein with other biochemical markers could improve the standardization of current assays.

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