Effects of transcranial direct current stimulation and transcranial random noise stimulation on working memory and task-related EEG in major depressive disorder.

OBJECTIVE: To compare effects of transcranial direct current stimulation (tDCS) and transcranial random noise stimulation with a direct-current offset (tRNS + DC-offset) on working memory (WM) performance and task-related electroencephalography (EEG) in individuals with Major Depressive Disorder (MDD). METHODS: Using a sham-controlled, parallel-groups design, 49 participants with MDD received either anodal tDCS (N = 16), high-frequency tRNS + DC-offset (N = 16), or sham stimulation (N = 17) to the left dorsolateral prefrontal cortex (DLPFC) for 20-minutes. The Sternberg WM task was completed with concurrent EEG recording before and at 5- and 25-minutes post-stimulation. Event-related synchronisation/desynchronisation (ERS/ERD) was calculated for theta, upper alpha, and gamma oscillations during WM encoding and maintenance. RESULTS: tDCS significantly increased parieto-occipital upper alpha ERS/ERD during WM maintenance, observed on EEG recorded 5- and 25-minutes post-stimulation. tRNS + DC-offset did not significantly alter WM-related oscillatory activity when compared to sham stimulation. Neither tDCS nor tRNS + DC-offset improved WM performance to a significantly greater degree than sham stimulation. CONCLUSIONS: Although tDCS induced persistent effects on WM-related oscillatory activity, neither tDCS nor tRNS + DC-offset enhanced WM performance in MDD. SIGNIFICANCE: This reflects the first sham-controlled comparison of tDCS and tRNS + DC-offset in MDD. These findings directly contrast with evidence of tRNS-induced enhancements in WM in healthy individuals.

Introducing RELAX: An automated pre-processing pipeline for cleaning EEG data - Part 1: Algorithm and application to oscillations.

OBJECTIVE: Electroencephalographic (EEG) data are often contaminated with non-neural artifacts which can confound experimental results. Current artifact cleaning approaches often require costly manual input. Our aim was to provide a fully automated EEG cleaning pipeline that addresses all artifact types and improves measurement of EEG outcomes METHODS: We developed RELAX (the Reduction of Electroencephalographic Artifacts). RELAX cleans continuous data using Multi-channel Wiener filtering [MWF] and/or wavelet enhanced independent component analysis [wICA] applied to artifacts identified by ICLabel [wICA_ICLabel]). Several versions of RELAX were compared using three datasets (N = 213, 60 and 23 respectively) against six commonly used pipelines across a range of artifact cleaning metrics, including measures of remaining blink and muscle activity, and the variance explained by experimental manipulations after cleaning. RESULTS: RELAX with MWF and wICA_ICLabel showed amongst the best performance at cleaning blink and muscle artifacts while preserving neural signal. RELAX with wICA_ICLabel only may perform better at differentiating alpha oscillations between working memory conditions. CONCLUSIONS: RELAX provides automated, objective and high-performing EEG cleaning, is easy to use, and freely available on GitHub. SIGNIFICANCE: We recommend RELAX for data cleaning across EEG studies to reduce artifact confounds, improve outcome measurement and improve inter-study consistency.

RELAX part 2: A fully automated EEG data cleaning algorithm that is applicable to Event-Related-Potentials.

OBJECTIVE: Electroencephalography (EEG) is often used to examine neural activity time-locked to stimuli presentation, referred to as Event-Related Potentials (ERP). However, EEG is influenced by non-neural artifacts, which can confound ERP comparisons. Artifact cleaning reduces artifacts, but often requires time-consuming manual decisions. Most automated methods filter frequencies <1 Hz out of the data, so are not recommended for ERPs (which contain frequencies <1 Hz). Our aim was to test the RELAX (Reduction of Electroencephalographic Artifacts) pre-processing pipeline for use on ERP data. METHODS: The cleaning performance of multiple versions of RELAX were compared to four commonly used EEG cleaning pipelines across both artifact cleaning metrics and the amount of variance in ERPs explained by different conditions in a Go-Nogo task. Results RELAX with Multi-channel Wiener Filtering (MWF) and wavelet-enhanced independent component analysis applied to artifacts identified with ICLabel (wICA_ICLabel) cleaned data most effectively and produced amongst the most dependable ERP estimates. RELAX with wICA_ICLabel only or MWF_only may detect effects better for some ERPs. CONCLUSIONS: RELAX shows high artifact cleaning performance even when data is high-pass filtered at 0.25 Hz (applicable to ERP analyses). SIGNIFICANCE: RELAX is easy to implement via EEGLAB in MATLAB and freely available on GitHub. Given its performance and objectivity we recommend RELAX to improve artifact cleaning and consistency across ERP research.

Sodium accumulation in breast cancer predicts malignancy and treatment response.

BACKGROUND: Breast cancer remains a leading cause of death in women and novel imaging biomarkers are urgently required. Here, we demonstrate the diagnostic and treatment-monitoring potential of non-invasive sodium (23Na) MRI in preclinical models of breast cancer. METHODS: Female Rag2-/- Il2rg-/- and Balb/c mice bearing orthotopic breast tumours (MDA-MB-231, EMT6 and 4T1) underwent MRI as part of a randomised, controlled, interventional study. Tumour biology was probed using ex vivo fluorescence microscopy and electrophysiology. RESULTS: 23Na MRI revealed elevated sodium concentration ([Na+]) in tumours vs non-tumour regions. Complementary proton-based diffusion-weighted imaging (DWI) linked elevated tumour [Na+] to increased cellularity. Combining 23Na MRI and DWI measurements enabled superior classification accuracy of tumour vs non-tumour regions compared with either parameter alone. Ex vivo assessment of isolated tumour slices confirmed elevated intracellular [Na+] ([Na+]i); extracellular [Na+] ([Na+]e) remained unchanged. Treatment with specific inward Na+ conductance inhibitors (cariporide, eslicarbazepine acetate) did not affect tumour [Na+]. Nonetheless, effective treatment with docetaxel reduced tumour [Na+], whereas DWI measures were unchanged. CONCLUSIONS: Orthotopic breast cancer models exhibit elevated tumour [Na+] that is driven by aberrantly elevated [Na+]i. Moreover, 23Na MRI enhances the diagnostic capability of DWI and represents a novel, non-invasive biomarker of treatment response with superior sensitivity compared to DWI alone.

Assessment of the adequacy of counselling regarding reproductive-related issues in women of childbearing age on anti-epileptic drugs.

BACKGROUND: The use of anti-epileptic drugs (AEDs) in women of childbearing age (WCBA) necessitates careful counselling regarding reproductive-related issues. AIM: (i) To compare documentation of appropriate counselling regarding reproductive-related issues in WCBA prescribed AEDs for non-epilepsy vs. epilepsy indications, and (ii) to examine whether the frequency of counselling improved after introduction of 'standardized typed advice'. DESIGN: Retrospective audit and quality assessment and improvement programme. METHODS: We analysed medical records of all WCBA prescribed gabapentin, pregabalin, topiramate, valproate or carbamazepine by a general neurology clinical service before (Study period A) and after (Study period B) introduction of standardized typed passages regarding potential teratogenicity ± interactions with hormonal contraception at a university teaching hospital. The χ2 test or the Fisher's exact test was employed, as appropriate. RESULTS: In WCBA prescribed AEDs for non-epilepsy indications, documentation of appropriate counselling regarding potential teratogenicity improved from 49% (17/35 patients) in Period A to 79% (27/34 patients) in Period B (P = 0.008). The frequency of counselling regarding teratogenicity was higher in patients prescribed AEDs for epilepsy compared with non-epilepsy indications in Study period A (100% vs. 49%, P = 0.002), but was no longer significantly different in Study period B (86% vs. 79%, P = 0.64). Documentation of counselling regarding potential interaction of enzyme-inducing AEDs with hormonal contraception did not significantly change between study periods. CONCLUSION: Significant improvements in documentation regarding potential teratogenicity of AEDs prescribed for non-epilepsy indications can be achieved by introducing standardized, typed passages copied to patients. Such a practice change is practical and widely applicable to neurological and non-neurological practice worldwide.

Transcranial random noise stimulation is more effective than transcranial direct current stimulation for enhancing working memory in healthy individuals: Behavioural and electrophysiological evidence.

BACKGROUND: Transcranial direct current stimulation (tDCS) has been shown to improve working memory (WM) performance in healthy individuals, however effects tend to be modest and variable. Transcranial random noise stimulation (tRNS) can be delivered with a direct-current offset (DC-offset) to induce equal or even greater effects on cortical excitability than tDCS. To-date, no research has directly compared the effects of these techniques on WM performance or underlying neurophysiological activity. OBJECTIVE: To compare the effects of anodal tDCS, tRNS + DC-offset, or sham stimulation over the left dorsolateral prefrontal cortex (DLPFC) on WM performance and task-related EEG oscillatory activity in healthy adults. METHODS: Using a between-subjects design, 49 participants were allocated to receive either anodal tDCS (N = 16), high-frequency tRNS + DC-offset (N = 16), or sham stimulation (N = 17) to the left DLPFC. Changes in WM performance were assessed using the Sternberg WM task completed before and 5- and 25-min post-stimulation. Event-related synchronisation/desynchronisation (ERS/ERD) of oscillatory activity was analysed from EEG recorded during WM encoding and maintenance. RESULTS: tRNS induced more pronounced and consistent enhancements in WM accuracy when compared to both tDCS and sham stimulation. Improvements in WM performance following tRNS were accompanied by increased theta ERS and diminished gamma ERD during WM encoding, which were significantly greater than those observed following anodal tDCS or sham stimulation. CONCLUSIONS: These findings demonstrate the potential of tRNS + DC-offset to modulate cognitive and electrophysiological measures of WM and raise the possibility that tRNS + DC-offset may be more effective and reliable than tDCS for enhancing WM performance in healthy individuals.

Impact of improved observed hand hygiene on bloodstream infection rates in Ireland. A prospective segmented regression analysis, 2009-2016.

Participation in European surveillance for bloodstream infection (BSI) commenced in Ireland in 1999 with all laboratories (n = 39) participating by 2014. Observational hand hygiene auditing (OHHA) was implemented in 2011. The aim of this study was to evaluate the impact of OHHA on hand hygiene compliance, alcohol hand rub (AHR) procurement and the incidence of sensitive and resistant Staphylococcus aureus and Enterococcus faecium and faecalis BSI. A prospective segmented regression analysis was performed to determine the temporal association between OHHA and outcomes. Observed hand hygiene improved from 74.7% (73.7-75.6) in 2011 to 90.8% (90.1-91.3) in 2016. AHR procurement increased from 20.1 l/1000 bed days used (BDU) in 2009 to 33.2 l/1000 BDU in 2016. A pre-intervention reduction of 2% per quarter in the ratio of methicillin sensitive Staphylococcus aureus BSI/BDU stabilized in the time period after the intervention (P < 0.01). The ratio of Methicillin resistant Staphylococcus aureus (MRSA) BSI/BDU was decreasing by 5% per quarter pre-intervention, this slowed to 2% per quarter post intervention, (P < 0.01). There was no significant change in the ratio of vancomycin sensitive (P = 0.49) or vancomycin resistant (P = 0.90) Enterococcus sp. BSI/BDU post intervention. This study shows national OHHA increased observed hand hygiene compliance and AHR procurement, however there was no associated reduction in BSI.

Individuals with depression display abnormal modulation of neural oscillatory activity during working memory encoding and maintenance.

PURPOSE: To investigate neural oscillatory activity supporting working memory (WM) processing in depressed individuals and healthy controls. METHODS: Forty-six participants with Major Depressive Disorder (MDD) and 41 healthy controls balanced on age, gender, and WM ability completed a Sternberg verbal WM task with concurrent electroencephalography recording. Oscillatory activity was calculated for upper alpha, theta, and gamma frequency bands during WM encoding and maintenance. RESULTS: WM performance did not differ between groups. When compared to healthy controls, depressed individuals displayed reduced frontal-midline theta power and increased occipital upper alpha power during WM encoding, and reductions in frontal-midline theta power and occipital gamma and upper alpha power during WM maintenance. Higher depression severity was associated with greater reductions upper alpha and gamma power during WM maintenance. CONCLUSIONS: Depressed individuals displayed prominent alterations in oscillatory activity during WM encoding and maintenance, indicating that the neural processes which support WM processing are altered in MDD even when no cognitive impairments are observed.

Low prevalence of epilepsy and onchocerciasis after more than 20 years of ivermectin treatment in the Imo River Basin in Nigeria.

BACKGROUND: High epilepsy prevalence and incidence have been reported in areas with high onchocerciasis transmission. Recent findings suggest that proper community-directed treatment with ivermectin (CDTI) is potentially able to prevent onchocerciasis-associated epilepsy (OAE). We assessed the epilepsy prevalence and onchocerciasis transmission in two Nigerian villages following more than 20 years of CDTI. METHODS: A cross-sectional door-to-door survey was performed in two villages in the Imo River Basin reported to be mesoendomic for onchocerciasis (Umuoparaodu and Umuezeala). Individuals were screened for epilepsy using a validated 5-item questionnaire. Persons suspected to have epilepsy were examined by a neurologist or a physician with training in epilepsy for confirmation. Onchocerciasis was investigated via skin snip microscopy and rapid diagnostic tests for Ov16 antibodies. Results were compared with previous findings from the Imo river basin. RESULTS: A total of 843 individuals from 257 households in the two villages were encountered. We detected four persons with epilepsy (PWE) giving a crude epilepsy prevalence of 0.5%. This finding differs from observations reported 14 years ago which showed an epilepsy prevalence of 2.8% in the neighbouring village of Umulolo (P = 0.0001), and 1.2% from 13 villages in the Imo river basin (P = 0.07). The seroprevalence of Ov16 antibodies was found to be 0%. Only 4.6% of skin snips were positive compared to 26.8% in previous surveys (P < 0.0001). Ivermectin mass distribution coverage in the study sites in 2017 was 79.7%. CONCLUSIONS: A low epilepsy and onchocerciasis prevalence was observed following more than 20 years of CDTI in the Imo River Basin. Absence of Ov16 antibodies indicates minimal transmission of onchocerciasis. These results contrast with observations from areas of high onchocerciasis transmission, where epilepsy prevalence and incidence remain high. Findings from this study suggest that sustained efforts could eventually achieve elimination of onchocerciasis in these villages.

Piscirickettsia salmonis infection in cultured lumpfish (Cyclopterus lumpus L.).

A Piscirickettsia salmonis infection was diagnosed in lumpfish (Cyclopterus lumpus L.) juveniles held in a marine research facility on the west coast of Ireland. The main clinical signs and pathology included marked ascites, severe multifocal liver necrosis and severe diffuse inflammation and necrosis of the exocrine pancreas and peri-pancreatic adipose tissue. Numerous Piscirickettsia-like organisms were observed by histopathology in the affected organs, and the bacterial species was characterized by molecular analysis. Sequencing of the partial 16S rDNA gene and internal transcribed spacer region showed the lumpfish sequences to be closely related to previously identified Atlantic salmon (Salmo salar L.) sequences from Ireland. To the authors' knowledge, this is the first detection of P. salmonis in lumpfish worldwide. The infection is considered potentially significant in terms of lumpfish health and biosecurity.

First record of Tetramicra brevifilum in lumpfish (Cyclopterus lumpus, L.).

A microsporidian species with 98.3-98.4% nucleotide identity to Tetramicra brevifilum (Journal of Fish Diseases, 3, 1980, 495) was diagnosed in lumpfish (Cyclopterus lumpus, L.) broodstock held at a breeding and rearing facility in western Ireland. The fish were wild-caught from the west coast of Ireland, and the first case was diagnosed one year after capture. Clinical signs included severe bloating, lethargy, exophthalmos, anorexia, white patches on the cornea and externally visible parasitic cysts on skin and fins. Necropsy revealed severe ascites, white nodules and vacuoles in all the internal organs and partial liquefaction of the skeletal muscle. On histological examination, microsporidian xenomas were observed in all internal organs, the skin, skeletal muscle, gills and the eyes. The microsporidian species was identified by molecular analysis and transmission electron microscopy. This is the first record of T. brevifilum infecting lumpfish, and the disease is considered to be of potential significance to the rising aquaculture industry of this species.

Demographic trends in suicide in the UK and Ireland 1980-2010.

BACKGROUND: Ireland has the 17th highest suicide rate in the EU and the 4th highest among 15-24-year-old males (WHO 2012). Suicide is the leading cause of death in this age group; death by hanging accounted for 69 % of suicides in 2010. METHODS: This study examines youth suicide rates from 1980 to 2010 in Ireland and compares them to the rates in Northern Ireland, Scotland, England and Wales. Irish data were obtained from the Central Statistics Office and their annual reports on Vital Statistics. Northern Irish data were obtained from the Northern Ireland Statistics and Research Agency website; Scottish data were from the General Register Office for Scotland and English/Welsh data from the Office for National Statistics website. RESULTS: There has been a threefold increase in young male suicide in Ireland over the past three decades (8.9-29.7 per 100,000). In contrast, there has been approximately a threefold reduction in deaths by road traffic accidents in young men in the same period (42.7-16.2 per 100,000). Suicide rates in young men are similar in Scotland and Northern Ireland for the same period but are 50 % lower in England and Wales. Despite the rates of hanging as a method of suicide increasing in all jurisdictions, the overall rate in England and Wales has continued to decline. CONCLUSION: The suicide rate in Ireland remains very high and strategies to address this are urgently required. Our study indicates that national suicide prevention strategies can be effective.

The use of digital media by women using the maternity services in a developed country.

The provision of high quality healthcare information about pregnancy is important to women and to healthcare professionals and it is 1 driven, in part, by a desire to improve clinical outcomes,. The objective of this study was to examine the use of digital media by women' to access pregnancy information. A questionnaire was distributed to women attending a large maternity hospital. Of the 522 respondents, the mean age was 31.8 years, 45% (235/522) were nulliparous, 62% (324/522) lived in the capital city and 29% (150/522) attended the hospital as private patients. Overall 95% (498/522) used the internet for pregnancy information, 76% (399/522) had a smartphone and 59% (235/399) of smartphone owners had used a pregnancy smartapp. The nature of internet usage for pregnancy information included discussion forums (70%), social networks (67%), video media (48%), e-books (15%), blogs (13%), microblogs (9%) and podcasts (4%). Even women who were socially disadvantaged reported high levels of digital media usage. In contemporary maternity care women use digital media extensively for pregnancy information. All maternity services should have a digital media strategy.

Testing for urinary tract colonization before high-dose corticosteroid treatment in acute multiple sclerosis relapses: prospective algorithm validation.

BACKGROUND AND PURPOSE: To evaluate a dipstick algorithm for urinary tract colonization, prior to high-dose corticosteroid treatment in acute relapses of multiple sclerosis (MS). METHODS: Prospective cohort study of 267 consecutive patients with MS relapses requiring corticosteroid treatment in a hospital-based, ambulatory, acute MS relapse clinic. A total of 18 participants met the exclusion criteria, leaving 249 for analysis. Main outcome measures were urinary dipstick sensitivity, specificity, positive predictive value, negative predictive value and safety of antibiotic co-treatment with high-dose corticosteroids. RESULTS: Significant bacteriuria (≥10(5) colonies ml) rate in this population was 11% (95% CI, 7.1-14.9). Specificity and sensitivity of positive leucocyte esterase or nitrite were 78% and 65%. Negative predictive value of urine dipstick was 96%. No clinical adverse events occurred in the 3% (95% CI, 0.9-5.1) of patients with a false-negative dipstick. Eighteen per cent of patients were unnecessarily treated with antibiotics for 48 h. CONCLUSION: Urinary dipstick testing allows for rapid and safe management of patients suffering from an acute MS relapse. The algorithm is conservative, and future work is needed to reduce the false-positive rate.

Venous thromboembolism risk and prophylaxis in the acute hospital care setting: the Irish results of the ENDORSE study.

ENDORSE (Epidemiologic International Day for the Evaluation of Patients at Risk for Venous Thromboembolism in the Acute Hospital Care Setting), is a multinational, cross-sectional survey of venous thromboembolism (VTE) risk prevalence and effective prophylaxis in the acute hospital care setting. Three Irish hospitals enrolled in the study. The American College of Chest Physicians (ACCP) guidelines were employed to evaluate VTE risk and prophylaxis. Of 552 patients, 297 (53.8%) and 255 (46.2%) were categorised as surgical or medical, respectively, with 175 (59%) surgical and 109 (43%) medical patients deemed to be at risk for VTE. Of these, only 112 (64%) and 51 (47%) received recommended VTE prophylaxis, respectively. The results are consistent with those observed in other countries and demonstrate a high prevalence of risk for VTE and a low rate of prophylaxis use, particularly in medical patients. Awareness of VTE guidelines should be an integral component of health policy.

Impact of the European Antimicrobial Resistance Surveillance System on the development of a national programme to monitor resistance in Staphylococcus aureus and Streptococcus pneumoniae in Ireland, 1999-2003.

Presented here is the 5-year impact of a national antimicrobial resistance surveillance system in Ireland, which was introduced in accordance with the European Antimicrobial Resistance Surveillance System (EARSS). Participation in EARSS began in Ireland in 1999. Initially, 12 laboratories serving a mix of general and tertiary hospitals participated, but by 2003, participation had increased to 28 laboratories with a population coverage of 89%. During 1999-2003, 4,146 episodes of Staphylococcus aureus bacteraemia were reported, and methicillin resistance was detected in 1,709 (41.2%) of these isolates. Over the same period, 1,245 invasive (blood or cerebrospinal fluid) episodes of Streptococcus pneumoniae infection were reported, and 160 (12.9%) isolates were found to be non-susceptible to penicillin, with 23 (1.8%) demonstrating high-level penicillin resistance. By 2003, most Irish hospitals were participating in EARSS, which has been a catalyst for the development of a national antimicrobial resistance surveillance programme.

Hydrogen exchange reveals a stable and expandable core within the aspartate receptor cytoplasmic domain.

Intensive study of bacterial chemoreceptors has not yet revealed how receptor methylation and ligand binding alter the interactions between the receptor cytoplasmic domain and the CheA kinase to control kinase activity. Both monomeric and dimeric forms of an Asp receptor cytoplasmic fragment have been shown to be highly dynamic, with a small core of slowly exchanging amide hydrogens (Seeley, S. K., Weis, R. M., and Thompson, L. K. (1996) Biochemistry 35, 5199-5206). Hydrogen exchange studies of the wild-type cytoplasmic fragment and an S461L mutant thought to mimic the kinase-inactivating state are used to investigate the relationship between the stable core and dimer dissociation. Our results establish that (i) decreasing pH stabilizes the dimeric state, (ii) the stable core is present also in the transition state for dissociation, and (iii) this core is expanded significantly by small changes in electrostatic and hydrophobic interactions. These kinase-inactivating changes stabilize both the monomeric and the dimeric states of the protein, which has interesting implications for the mechanism of kinase activation. We conclude that the cytoplasmic domain is a flexible region poised for stabilization by small changes in electrostatic and hydrophobic interactions such as those caused by methylation of glutamate residues and by ligand-induced conformational changes during signaling.

Prediction of uphill time-trial bicycling performance in humans with a scaling-derived protocol.

The present study sought to create a scaling-derived cycle ergometer protocol (SDP) that was derived theoretically and would correlate highly with actual uphill time-trial (TT) cycling performance. Local competitive cyclists each completed the SDP (an incremental test to exhaustion) using their own bicycle mounted on a stationary trainer, together with either a short (6.2 km, 2.9% grade; n = 8 men and 5 women) or long-course (12.5 km, 2.7% grade; n = 8 men) uphill TT. Maximal power output (Wmax) and power at the ventilatory threshold (WVT) were determined from the SDP results, as well as maximal oxygen uptake (VO2max), using standard indirect calorimetry procedures. Actual TT speed correlated very highly with both SDP completion time (r = 0.97-0.98) and relative Wmax (watts per kilogram; r = 0.92-0.97) for both uphill TT races. Correlations between TT speed and more demanding measurements (VO2max, WVT) (VO2max, WVT) were generally lower and more variable (r = 0.54-0.97). These results would indicate that two non-laboratory dependent measurements (SDP completion time and relative Wmax) derived from the SDP are valid markers for predicting actual uphill TT performance. This protocol may be useful to cycling coaches and athletes in identifying talented cyclists or for tracking changes in cycling performance outside of the sports science laboratory environment.