Machine learning for automatic prediction of the quality of electrophysiological recordings

The quality of electrophysiological recordings varies a lot due to technical and biological variability and neuroscientists inevitably have to select “good” recordings for further analyses. This procedure is time-consuming and prone to selection biases. Here, we investigate replacing human decisions by a machine learning approach. We define 16 features, such as spike height and width, select the most informative ones using a wrapper method and train a classifier to reproduce the judgement of one of our expert electrophysiologists. Generalisation performance is then assessed on unseen data, classified by the same or by another expert. We observe that the learning machine can be equally, if not more, consistent in its judgements as individual experts amongst each other. Best performance is achieved for a limited number of informative features; the optimal feature set being different from one data set to another. With 80–90% of correct judgements, the performance of the system is very promising within the data sets of each expert but judgments are less reliable when it is used across sets of recordings from different experts. We conclude that the proposed approach is relevant to the selection of electrophysiological recordings, provided parameters are adjusted to different types of experiments and to individual experimenters

Modeling the heart

Quantitative prediction over multiple space and time scales using computer models of the electrical activity in the mammalian heart, based on membrane and intracellular ion transport and binding dynamics, digital histology, and three-dimensional cardiac anatomy and architecture

Antisense-Mediated Knockdown of NaV1.8, but Not NaV1.9, Generates Inhibitory Effects on Complete Freund's Adjuvant-Induced Inflammatory Pain in Rat

Tetrodotoxin-resistant (TTX-R) sodium channels NaV1.8 and NaV1.9 in sensory neurons were known as key pain modulators. Comparing with the widely reported NaV1.8, roles of NaV1.9 on inflammatory pain are poorly studied by antisense-induced specific gene knockdown. Here, we used molecular, electrophysiological and behavioral methods to examine the effects of antisense oligodeoxynucleotide (AS ODN) targeting NaV1.8 and NaV1.9 on inflammatory pain. Following complete Freund's adjuvant (CFA) inflammation treatment, NaV1.8 and NaV1.9 in rat dorsal root ganglion (DRG) up-regulated mRNA and protein expressions and increased sodium current densities. Immunohistochemical data demonstrated that NaV1.8 mainly localized in medium and small-sized DRG neurons, whereas NaV1.9 only expressed in small-sized DRG neurons. Intrathecal (i.t.) delivery of AS ODN was used to down-regulate NaV1.8 or NaV1.9 expressions confirmed by immunohistochemistry and western blot. Unexpectedly, behavioral tests showed that only NaV1.8 AS ODN, but not NaV1.9 AS ODN could reverse CFA-induced heat and mechanical hypersensitivity. Our data indicated that TTX-R sodium channels NaV1.8 and NaV1.9 in primary sensory neurons played distinct roles in CFA-induced inflammatory pain and suggested that antisense oligodeoxynucleotide-mediated blocking of key pain modulator might point toward a potential treatment strategy against certain types of inflammatory pain

Internet Gaming Disorder Behaviors in emergent adulthood: a pilot study examining the interplay between anxiety and family cohesion

Understanding risk and protective factors associated with Internet Gaming Disorder (IGD) has been highlighted as a research priority by the American Psychiatric Association, (2013). The present study focused on the potential IGD risk effect of anxiety and the buffering role of family cohesion on this association. A sample of emerging adults all of whom were massively multiplayer online (MMO) gamers (18–29 years) residing in Australia were assessed longitudinally (face-to-face: N = 61, Mage = 23.02 years, SD = 3.43) and cross-sectionally (online: N = 64, Mage = 23.34 years, SD = 3.39). IGD symptoms were assessed using the nine-item Internet Gaming Disorder Scale-Short Form (IGDS-SF9; Pontes & Griffiths Computers in Human Behavior, 45, 137–143. https://doi.org/10.1016/j.chb.2014.12.006, 2015). The Beck Anxiety Inventory (BAI; Beck and Steer, 1990) and the balanced family cohesion scale (BFC; Olson Journal of Marital & Family Therapy, 3(1) 64–80. https://doi.org/10.1111/j.1752-0606.2009.00175.x, 2011) were applied to assess anxiety and BFC levels, respectively. Linear regressions and moderation analyses confirmed that anxiety increased IGD risk and that BFC weakened the anxiety-related IGD risk

Painful and painless mutations of SCN9A and SCN11A voltage-gated sodium channels

Chronic pain is a global problem affecting up to 20% of the world’s population and has a significant economic, social and personal cost to society. Sensory neurons of the dorsal root ganglia (DRG) detect noxious stimuli and transmit this sensory information to regions of the central nervous system (CNS) where activity is perceived as pain. DRG neurons express multiple voltage-gated sodium channels that underlie their excitability. Research over the last 20 years has provided valuable insights into the critical roles that two channels, NaV1.7 and NaV1.9, play in pain signalling in man. Gain of function mutations in NaV1.7 cause painful conditions while loss of function mutations cause complete insensitivity to pain. Only gain of function mutations have been reported for NaV1.9. However, while most NaV1.9 mutations lead to painful conditions, a few are reported to cause insensitivity to pain. The critical roles these channels play in pain along with their low expression in the CNS and heart muscle suggest they are valid targets for novel analgesic drugs

Systematic Review of Potential Health Risks Posed by Pharmaceutical, Occupational and Consumer Exposures to Metallic and Nanoscale Aluminum, Aluminum Oxides, Aluminum Hydroxide and Its Soluble Salts

Aluminum (Al) is a ubiquitous substance encountered both naturally (as the third most abundant element) and intentionally (used in water, foods, pharmaceuticals, and vaccines); it is also present in ambient and occupational airborne particulates. Existing data underscore the importance of Al physical and chemical forms in relation to its uptake, accumulation, and systemic bioavailability. The present review represents a systematic examination of the peer-reviewed literature on the adverse health effects of Al materials published since a previous critical evaluation compiled by Krewski et al. (2007). Challenges encountered in carrying out the present review reflected the experimental use of different physical and chemical Al forms, different routes of administration, and different target organs in relation to the magnitude, frequency, and duration of exposure. Wide variations in diet can result in Al intakes that are often higher than the World Health Organization provisional tolerable weekly intake (PTWI), which is based on studies with Al citrate. Comparing daily dietary Al exposures on the basis of “total Al”assumes that gastrointestinal bioavailability for all dietary Al forms is equivalent to that for Al citrate, an approach that requires validation. Current occupational exposure limits (OELs) for identical Al substances vary as much as 15-fold. The toxicity of different Al forms depends in large measure on their physical behavior and relative solubility in water. The toxicity of soluble Al forms depends upon the delivered dose of Al+ 3 to target tissues. Trivalent Al reacts with water to produce bidentate superoxide coordination spheres [Al(O2)(H2O4)+ 2 and Al(H2O)6 + 3] that after complexation with O2•−, generate Al superoxides [Al(O2•)](H2O5)]+ 2. Semireduced AlO2• radicals deplete mitochondrial Fe and promote generation of H2O2, O2 • − and OH•. Thus, it is the Al+ 3-induced formation of oxygen radicals that accounts for the oxidative damage that leads to intrinsic apoptosis. In contrast, the toxicity of the insoluble Al oxides depends primarily on their behavior as particulates. Aluminum has been held responsible for human morbidity and mortality, but there is no consistent and convincing evidence to associate the Al found in food and drinking water at the doses and chemical forms presently consumed by people living in North America and Western Europe with increased risk for Alzheimer\u27s disease (AD). Neither is there clear evidence to show use of Al-containing underarm antiperspirants or cosmetics increases the risk of AD or breast cancer. Metallic Al, its oxides, and common Al salts have not been shown to be either genotoxic or carcinogenic. Aluminum exposures during neonatal and pediatric parenteral nutrition (PN) can impair bone mineralization and delay neurological development. Adverse effects to vaccines with Al adjuvants have occurred; however, recent controlled trials found that the immunologic response to certain vaccines with Al adjuvants was no greater, and in some cases less than, that after identical vaccination without Al adjuvants. The scientific literature on the adverse health effects of Al is extensive. Health risk assessments for Al must take into account individual co-factors (e.g., age, renal function, diet, gastric pH). Conclusions from the current review point to the need for refinement of the PTWI, reduction of Al contamination in PN solutions, justification for routine addition of Al to vaccines, and harmonization of OELs for Al substances