Wnt and Notch signaling govern self-renewal and differentiation in a subset of human glioblastoma stem cells.

Developmental signal transduction pathways act diversely, with context-dependent roles across systems and disease types. Glioblastomas (GBMs), which are the poorest prognosis primary brain cancers, strongly resemble developmental systems, but these growth processes have not been exploited therapeutically, likely in part due to the extreme cellular and genetic heterogeneity observed in these tumors. The role of Wnt/ßcatenin signaling in GBM stem cell (GSC) renewal and fate decisions remains controversial. Here, we report context-specific actions of Wnt/ßcatenin signaling in directing cellular fate specification and renewal. A subset of primary GBM-derived stem cells requires Wnt proteins for self-renewal, and this subset specifically relies on Wnt/ßcatenin signaling for enhanced tumor burden in xenograft models. In an orthotopic Wnt reporter model, Wnthi GBM cells (which exhibit high levels of ßcatenin signaling) are a faster-cycling, highly self-renewing stem cell pool. In contrast, Wntlo cells (with low levels of signaling) are slower cycling and have decreased self-renewing potential. Dual inhibition of Wnt/ßcatenin and Notch signaling in GSCs that express high levels of the proneural transcription factor ASCL1 leads to robust neuronal differentiation and inhibits clonogenic potential. Our work identifies new contexts for Wnt modulation for targeting stem cell differentiation and self-renewal in GBM heterogeneity, which deserve further exploration therapeutically.

Enhancing learning outcomes through multisensory integration: A fMRI study of audio-visual training in virtual reality.

The integration of information from different sensory modalities is a fundamental process that enhances perception and performance in real and virtual environments (VR). Understanding these mechanisms, especially during learning tasks that exploit novel multisensory cue combinations provides opportunities for the development of new rehabilitative interventions. This study aimed to investigate how functional brain changes support behavioural performance improvements during an audio-visual (AV) learning task. Twenty healthy participants underwent a 30 min daily VR training for four weeks. The task was an AV adaptation of a 'scanning training' paradigm that is commonly used in hemianopia rehabilitation. Functional magnetic resonance imaging (fMRI) and performance data were collected at baseline, after two and four weeks of training, and four weeks post-training. We show that behavioural performance, operationalised as mean reaction time reduction in VR, significantly improves. In separate tests in a controlled laboratory environment, we showed that the behavioural performance gains in the VR training environment transferred to a significant mean RT reduction for the trained AV voluntary task on a computer screen. Enhancements were observed in both the visual-only and AV conditions, with the latter demonstrating a faster response time supported by the presence of audio cues. The behavioural learning effect also transfers to two additional tasks that were tested: a visual search task and an involuntary visual task. Our fMRI results reveal an increase in functional activation (BOLD signal) in multisensory brain regions involved in early-stage AV processing: the thalamus, the caudal inferior parietal lobe and cerebellum. These functional changes were only observed for the trained, multisensory, task and not for unimodal visual stimulation. Functional activation changes in the thalamus were significantly correlated to behavioural performance improvements. This study demonstrates that incorporating spatial auditory cues to voluntary visual training in VR leads to augmented brain activation changes in multisensory integration, resulting in measurable performance gains across tasks. The findings highlight the potential of VR-based multisensory training as an effective method for enhancing cognitive function and as a potentially valuable tool in rehabilitative programmes.

Education and employment outcomes in pediatric chronic kidney disease.

As outcomes and survival for children with chronic kidney disease (CKD) have improved over the last 30 years, there is an emerging need to characterize and understand later educational and employment outcomes across the spectrum of pediatric CKD severity-ranging from mild CKD to requirement for dialysis and kidney transplantation. Although large-scale research on the topic of long-term educational and employment outcomes in the pediatric CKD population is relatively scarce, the existing literature does support that children across the spectrum of CKD severity are at risk for education-related difficulties including chronic school absenteeism. These education-related difficulties are compounded by well-described neurocognitive deficits-particularly in the domain of executive functioning-that may potentially perpetuate the risk for academic underachievement. This is particularly concerning given that data from the general pediatric population suggest that childhood academic underachievement is associated with higher likelihood of un-/underemployment in adulthood. This review highlights what is known about educational and employment outcomes among persons with a history of childhood CKD, as well as suggestions for interventions to improve educational outcomes for this population.

Harm reduction behaviours and harm experiences of people who use 3,4-methylenedioxymethamphetamine (MDMA) in Aotearoa New Zealand.

BACKGROUND: 3,4-Methylenedioxymethamphetamine (MDMA) is drug of high prevalence in Aotearoa New Zealand and is the primary drug analysed by legal drug checking services. We aimed to address the gap in literature pertaining to MDMA-related harm reduction behaviour and harm experiences within the country. METHODS: An online survey was used to assess the harm reduction behaviours (e.g., limiting consumption, planning use, seeking information) of people who use MDMA, in addition to their use of reagent testing and the major national drug checking and harm reduction service, KnowYourStuffNZ. RESULTS: In total, 915 people completed the survey (60.7% females, aged 18-65, median = 24, IQR = 20-28). Frequency of various MDMA-related harm reduction behaviours differed, although these were carried out relatively frequently by most participants. Those who reported experiencing harm (physical, psychological, spiritual, social) from MDMA, or another drug presumed to be MDMA, reported less frequent harm reduction behaviours than non-harmed consumers. Reagent testing of MDMA had been conducted by 42.3% of the sample. Approximately 27% of the sample had used KnowYourStuffNZ services. Of KnowYourStuffNZ clients, 95.9% reported learning about harm reduction, and 53.3% reported changing their behaviour because of the service. Reasons for not using the KnowYourStuffNZ service were primarily lack of availability in local area (32.8%) or at relevant events (51.8%), and lack of concern with substance quality (29.8%). MDMA harm was reported by 14.4% of the sample, whilst reported harm was more common from consumption of presumably non-MDMA substances, self-reported as being mistaken for MDMA. Harm was primarily physical or psychological. Potential MDMA dependence was apparent in 6.9% of the sample. CONCLUSIONS: The findings highlight potential targets for harm reduction education and interventions and emphasize the need for greater availability of readily accessible drug checking services in Aotearoa New Zealand.

A thematic analysis of MDMA-related harm and harm reduction experiences and knowledge in Aotearoa New Zealand.

BACKGROUND: Methylenedioxymethamphetamine (MDMA) is a popular drug worldwide and use is prevalent in Aotearoa New Zealand. Although associated with some significant harms, including fatalities, MDMA is ultimately less harmful than other commonly consumed drugs. We aimed to expand the understanding of MDMA harm and harm reduction strategies from a consumer perspective so that national harm reduction efforts can be better informed. METHODS: We conducted 14 semi-structured focus group discussions including 60 people (aged 18-67, median = 21) who use MDMA in the Southern region of Aotearoa New Zealand to explore their thoughts and experiences regarding MDMA associated harm and harm reduction. Reflexive thematic analysis was conducted from a critical realist perspective. RESULTS: Five themes were generated; (1) Mindset and setting matters; (2) Looking after your body and mind, not overdoing it; (3) Other substances increase risk and harm; (4) Trusted friends and peers are protective; and (5) Valid information is key for healthy self-determination; and one subtheme 5.1) Drug checking is essential harm reduction. CONCLUSIONS: We discuss the implications for MDMA consumers and aim to inform national drug policy and the harm reduction practices of consumers and organisations, for the ultimate purpose of reducing MDMA-related harm in Aotearoa New Zealand.

Impact of Prostate Urethral Lift Device on Prostate Magnetic Resonance Image Quality.

PURPOSE: Prostatic urethral lift with UroLift is a minimally invasive approach to treat symptomatic benign prostatic hypertrophy. This device causes artifacts on prostate magnetic resonance images. Our aim was to evaluate the impact of artifact on prostate magnetic resonance image quality. MATERIALS AND METHODS: This was a single-center retrospective review of patients with UroLift who subsequently had prostate magnetic resonance imaging. Two readers graded UroLift artifact on each pulse sequence using a 5-point scale (1-nondiagnostic; 5-no artifact). Prostate Imaging Quality scores were assigned for the whole data set. The volume of gland obscured by artifact was measured. Linear and logistic regression models were used to identify predictors of poor image quality. RESULTS: Thirty-seven patients were included. Poor image quality occurs more in the transition zone than the peripheral zone (15% vs 3%), at base/mid regions vs the apex (13%, 9%, and 5%, respectively) and on diffusion-weighted images vs T2-weighted and dynamic contrast-enhanced sequences (27%, 0.3%, 0%, respectively; P < .001). Suboptimal image quality (ie, Prostate Imaging Quality score <2) was found in 16%-24% of exams. The percentage of gland obscured by the UroLift artifact was higher on diffusion-weighted images and dynamic contrast-enhanced sequences than T2-weighted (32%, 9%, and 6%, respectively; P < .001). CONCLUSIONS: UroLift artifact negatively affects prostate magnetic resonance image quality with greater impact in the mid-basal transition zone, obscuring a third of the gland on diffusion-weighted images. Patients considering this procedure should be counseled on the impact of this device on image quality and its potential implications for any image-guided prostate cancer workup.

Methane Emissions from Dairy Operations in California's San Joaquin Valley Evaluated Using Airborne Flux Measurements.

State inventories indicate that dairy operations account for nearly half of California's methane budget. Recent analyses suggest, however, that these emissions may be underestimated, complicating efforts to develop emission reduction strategies. Here, we report estimates of dairy methane emissions in the southern San Joaquin Valley (SJV) of California in June 2021 using airborne flux measurements. We find average dairy methane fluxes of 512 ± 178 mg m-2 h-1 from a region of 300+ dairies near Visalia, CA using a combination of eddy covariance and mass balance-based techniques, corresponding to 118 ± 41 kg dairy-1 h-1. These values estimated during our June campaign are 39 ± 48% larger than annual average estimates from the recently developed VISTA-CA inventory. We observed notable increases in emissions with temperature. Our estimates align well with inventory predictions when parametrizations for the temperature dependence of emissions are applied. Our measurements further demonstrate that the VISTA-CA emission inventory is considerably more accurate than the EPA GHG-I inventory in this region. Source apportionment analyses confirm that dairy operations produce the majority of methane emissions in the southern SJV (∼65%). Fugitive oil and gas (O&G) sources account for the remaining ∼35%. Our results support the accuracy of the process-based models used to develop dairy emission inventories and highlight the need for additional investigation of the meteorological dependence of these emissions.

Perianal Fistulas Are Associated with Persistently Higher Direct Health Care Costs in Crohn's Disease: A Population-Based Study.

BACKGROUND: The economic impact of perianal fistulas in Crohn's disease (CD) has not been formally assessed in population-based studies in the biologic era. AIM: To compare direct health care costs in persons with and without perianal fistulas. METHODS: We performed a longitudinal population-based study using administrative data from Ontario, Canada. Adults (> 17 years) with CD were identified between 2007 and 2013 using validated algorithms. Perianal fistula positive "cases" were matched to up to 4 "controls" with CD without perianal fistulas based on age, sex, geographic region, year of CD diagnosis and duration of follow-up. Direct health care costs, excluding drug costs from private payers, were estimated annually beginning 5 years before (lookback) and up to 9 years after perianal fistula diagnosis (study completion) for cases and a standardized date for matched controls. RESULTS: A total of 581 cases were matched to 1902 controls. The annual per capita direct cost for cases was similar at lookback compared to controls ($2458 ± 6770 vs $2502 ± 10,752; p = 0.952), maximally greater in the first year after perianal fistulas diagnosis ($16,032 ± 21,101 vs $6646 ± 13,021; p < 0.001) and remained greater at study completion ($11,358 ± 17,151 vs $5178 ± 9792; p < 0.001). At perianal fistula diagnosis, the cost difference was driven primarily by home care cost (tenfold greater), publicly-covered prescription drugs (threefold greater) and hospitalizations (twofold greater), whereas at study completion, prescription drugs were the dominant driver (threefold greater). CONCLUSION: In our population-based cohort, perianal fistulas were associated with significantly higher direct healthcare costs at the time of perianal fistulas diagnosis and sustained long-term.

Hydroxyapatite cement cranioplasty for reconstruction of translabyrinthine approach: aesthetic results, long-term satisfaction, quality of life, and complications.

BACKGROUND: Translabyrinthine approaches (TLAs) for resection of skull base neoplasms are complex with variable reconstruction techniques. Fat grafts in conjunction with hydroxyapatite bone cement techniques have seldom been described in terms of possible superiority to other skull base reconstruction techniques. We sought to determine the impact of this skull base reconstruction technique on clinical outcomes and patient's satisfaction. METHOD: We performed a retrospective analysis of all patients who underwent translabyrinthine approaches for resection of CPA lesions over a 5-year period. Both post-op objective and subjective markers of reconstruction, as well as postoperative complications, were collected and analyzed. RESULTS: Sixty-nine patients were included, 34 underwent reconstruction with hydroxyapatite and fat (rHAC) and 35 with fat alone (rF). rHAC was associated with fewer cranial wound superficial infection/dehiscence (0% vs 14.3%; p = 0.029) and shorter length of stay (mean ± standard deviation) (6.9 ± 7.4 vs 4.4 ± 3.7 days, p = 0.008). Postoperative subjective characterization of rHAC demonstrated improved satisfaction scores (1.38 ± 0.5 vs 1.83 ± 1; p = 0.049) and fewer reports of post-operative irregularities (11.5% vs 37.5%; p = 0.017). CONCLUSION: The use of hydroxyapatite for cranial reconstruction after translabyrinthine approaches has improved patient satisfaction and decreased cranial defects in our small series. Postoperative complications are consistent with other described methods, but with shorter hospital stay, decreased risk of superficial wound dehiscence/infection, and a perceived superiority in preventing percutaneous post-op CSF leaks.

Inhibition of Isoleucyl-tRNA Synthetase by the Hybrid Antibiotic Thiomarinol.

Hybrid antibiotics are an emerging antimicrobial strategy to overcome antibiotic resistance. The natural product thiomarinol A is a hybrid of two antibiotics: holothin, a dithiolopyrrolone (DTP), and marinolic acid, a close analogue of the drug mupirocin that is used to treat methicillin-resistant Staphylococcus aureus (MRSA). DTPs disrupt metal homeostasis by chelating metal ions in cells, whereas mupirocin targets the essential enzyme isoleucyl-tRNA synthetase (IleRS). Thiomarinol A is over 100-fold more potent than mupirocin against mupirocin-sensitive MRSA; however, its mode of action has been unknown. We show that thiomarinol A targets IleRS. A knockdown of the IleRS-encoding gene, ileS, exhibited sensitivity to a synthetic analogue of thiomarinol A in a chemical genomics screen. Thiomarinol A inhibits MRSA IleRS with a picomolar Ki and binds to IleRS with low femtomolar affinity, 1600 times more tightly than mupirocin. We find that thiomarinol A remains effective against high-level mupirocin-resistant MRSA and provide evidence to support a dual mode of action for thiomarinol A that may include both IleRS inhibition and metal chelation. We demonstrate that MRSA develops resistance to thiomarinol A to a substantially lesser degree than mupirocin and the potent activity of thiomarinol A requires hybridity between DTP and mupirocin. Our findings identify a mode of action of a natural hybrid antibiotic and demonstrate the potential of hybrid antibiotics to combat antibiotic resistance.

Assessing the Influence of COVID-19 on the Shortwave Radiative Fluxes Over the East Asian Marginal Seas.

The Coronavirus Disease 2019 (COVID-19) pandemic led to a widespread reduction in aerosol emissions. Using satellite observations and climate model simulations, we study the underlying mechanisms of the large decreases in solar clear-sky reflection (3.8 W m-2 or 7%) and aerosol optical depth (0.16 W m-2 or 32%) observed over the East Asian Marginal Seas in March 2020. By separating the impacts from meteorology and emissions in the model simulations, we find that about one-third of the clear-sky anomalies can be attributed to pandemic-related emission reductions, and the rest to weather variability and long-term emission trends. The model is skillful at reproducing the observed interannual variations in solar all-sky reflection, but no COVID-19 signal is discerned. The current observational and modeling capabilities will be critical for monitoring, understanding, and predicting the radiative forcing and climate impacts of the ongoing crisis.

Infiltrative Renal Malignancies: Imaging Features, Prognostic Implications, and Mimics.

Infiltrative renal malignancies are a subset of renal masses that are morphologically characterized by a poorly defined interface with the renal parenchyma. Infiltrative renal malignancies are less common but more aggressive than more typical renal malignancies and carry an overall worse prognosis. Although an infiltrative renal process often represents a malignant neoplasm, infiltrative masses include a wide spectrum of diseases including primary renal cortical, medullary, and pelvic tumors; lymphoproliferative processes; metastases; and various infectious, inflammatory, immune-mediated, and vascular mimics. The imaging features of these masses are often nonspecific, but with the appropriate history, laboratory results, and clinical context, the radiologist can help narrow the diagnosis and guide further treatment. An invited commentary by Lee is available online.Online supplemental material is available for this article. ©RSNA, 2021.

FluNet: An AI-Enabled Influenza-Like Warning System.

Influenza is an acute viral respiratory disease that is currently causing severe financial and resource strains worldwide. With the COVID-19 pandemic exceeding 153 million cases worldwide, there is a need for a low-cost and contactless surveillance system to detect symptomatic individuals. The objective of this study was to develop FluNet, a novel, proof-of-concept, low-cost and contactless device for the detection of high-risk individuals. The system conducts face detection in the LWIR with a precision rating of 0.98, a recall of 0.91, an F-score of 0.96, and a mean intersection over union of 0.74 while sequentially taking the temperature trend of faces with a thermal accuracy of ± 1 K. In parallel, determining if someone is coughing by using a custom lightweight deep convolutional neural network with a precision rating of 0.95, a recall of 0.92, an F-score of 0.94 and an AUC of 0.98. We concluded this study by testing the accuracy of the direction of arrival estimation for the cough detection revealing an error of ± 4.78°. If a subject is symptomatic, a photo is taken with a specified region of interest using a visible light camera. Two datasets have been constructed, one for face detection in the LWIR consisting of 250 images of 20 participants' faces at various rotations and coverings, including face masks. The other for the real-time detection of coughs comprised of 40,482 cough / not cough sounds. These findings could be helpful for future low-cost edge computing applications for influenza-like monitoring.

2017 AUA Renal Mass and Localized Renal Cancer Guidelines: Imaging Implications.

Renal cell carcinoma (RCC) is a common cancer that is increasing in incidence because of the increased prevalence of risk factors, including tobacco use, hypertension, and obesity, and the improved detection of these tumors due to increased use of imaging. Localized renal cancer now accounts for more than 60%-70% of new RCC cases. Renal masses suggestive of cancer include enhancing solid renal lesions and Bosniak III and IV complex cystic lesions. Most of these tumors are detected incidentally, and many are slow growing with little propensity to metastasize. Radiologists have a vital role in evaluation of these tumors and subsequent patient counseling. Options for managing RCC include radical nephrectomy (RN), partial nephrectomy (PN), thermal ablation, and active surveillance. However, historically, the use of these strategies has varied among practices. Improved understanding of the biologic features of these tumors and data indicating the heterogeneous clinical course of many clinically localized renal tumors led to the development of the American Urological Association (AUA) Localized Renal Cancer Panel Guidelines in 2009, and these guidelines were updated in 2017. The format of the updated guidelines has moved from management recommendations based on index patients to individualized decision making, taking into account patient age and comorbidities, tumor characteristics, and important renal function considerations. A distinct role for RN is defined for cases of tumors with increased oncologic potential in patients with a normal contralateral kidney. Beyond this, nephron-sparing options, particularly PN, should be a priority. The updated guidelines also recommend increased use of renal mass biopsy, thermal ablation, and active surveillance in appropriately selected patients. The 2017 AUA guidelines are reviewed, with emphasis on the implications for practicing radiologists. ©RSNA, 2018.

Computerized Tomography Based Diagnosis of Visceral Obesity and Hepatic Steatosis is Associated with Low Urine pH.

PURPOSE: Uric acid nephrolithiasis is associated with an elevated visceral fat area in kidney stone formers. Hepatic steatosis has also been linked to visceral obesity and nephrolithiasis. We evaluated the association of noncontrast computerized tomography based diagnosis of visceral obesity and hepatic steatosis with 24-hour urine parameters and stone composition in kidney stone formers. MATERIALS AND METHODS: A total of 98 kidney stone formers were included in study who had computerized tomography imaging and 24-hour urine studies available. For each patient a single computerized tomography axial area measurement was obtained of the visceral fat area. Hepatic steatosis was diagnosed by comparing the HU of regions from the liver and spleen. Univariate analysis was performed to compare patients with or without an elevated visceral fat area and hepatic steatosis. Multivariate linear and logistic regression was done to assess for variables associated with 24-hour urine parameters and stone composition. RESULTS: An elevated visceral fat area was associated with higher 24-hour urine sodium (175 vs 157 mg per day, p <0.036) and lower 24-hour urine pH (5.724 vs 6.478, <0.0001). Urine pH less than 6 (OR 2.52) was associated with hepatic steatosis. Low urine pH less than 6 (OR 11.1, p = 0.004) and stone volume greater than 65 mm3 (OR 5.12, p = 0.023) were associated with an elevated visceral fat area. Low urine pH less than 6 (OR 5.87) and visceral fat area greater than 48% (OR 5.33) were associated with uric acid stones. Linear regression demonstrated that the percent of visceral fat area was associated with lower 24-hour urine pH (ß-coefficient -0.438, p <0.0001). CONCLUSIONS: Noncontrast computerized tomography based diagnosis of visceral obesity is associated with low urine pH, high urinary sodium and uric acid stone formation. Hepatic steatosis is associated with low urine pH.

Dynamic Contrast Enhanced Magnetic Resonance Imaging Improves Classification of Prostate Lesions: A Study of Pathological Outcomes on Targeted Prostate Biopsy.

PURPOSE: PI-RADS™, version 2 stipulates that dynamic contrast enhanced imaging should be used to classify diffusion-weighted imaging score 3 peripheral zone lesions as PI-RADS score 3 (dynamic contrast enhanced imaging negative or nonenhancing) or 4 (dynamic contrast enhanced imaging positive or enhancing). However, to our knowledge it is unknown whether dynamic contrast enhanced imaging separates lesions into clinically meaningful pathological groups. We examined whether dynamic contrast enhanced imaging would improve the detection of clinically significant cancer. MATERIALS AND METHODS: We identified patients without a prior diagnosis of prostate cancer who underwent multiparametric magnetic resonance imaging-transrectal ultrasound fusion targeted biopsy of peripheral zone lesions with a diffusion-weighted imaging score of 3 or 4. Each lesion was grouped into 1 of 3 classifications, including group 1-diffusion-weighted imaging score 3/nonenhancing/PI-RADS score 3, group 2-diffusion-weighted imaging score 3/enhancing/PI-RADS score 4 or group 3-diffusion-weighted imaging score 4/PI-RADS score 4. We measured the rate of grade group 2 or greater pathology detected for each lesion group with subgroup analyses in patients with vs without prior negative systematic biopsy. RESULTS: We identified a total of 389 peripheral zone diffusion-weighted imaging score 3 or 4 lesions in 290 patients. The rate of grade group 2 or greater cancer on biopsy for group 1, 2 and 3 lesions was 8.9%, 21% and 36.5%, respectively (p <0.03). The rate of grade group 2 or greater pathology was higher in group 2 than group 1 lesions in patients with prior negative systematic prostate biopsy (28% vs 5.0%, p <0.001) but not in those without such a biopsy (16% vs 12%, p = 0.5). Group 3 lesions had a higher rate of grade group 2 or greater cancer than group 2 lesions in the biopsy naïve subgroup (46% vs 16%, p = 0.001). However, the rates were similar in patients with prior negative systematic prostate biopsy (27% vs 28%, p = 0.9). CONCLUSIONS: Diffusion-weighted imaging score 3 peripheral zone lesions were more likely to be clinically significant cancer (grade group 2 or greater) if they were dynamic contrast enhanced T1-weighted imaging positive. That was most apparent in patients with a prior negative systematic prostate biopsy. In such patients including a dynamic contrast enhanced sequence in multiparametric magnetic resonance imaging allowed for optimal lesion risk stratification.

Maternal immune activation alters sensitivity to action-outcome contingency in adult rat offspring.

Epidemiological studies have provided convincing evidence for a role of maternal immune activation in the pathogenesis of neurodevelopmental disorders such as autism and schizophrenia. In recent years, several research groups have capitalised on this discovery and developed animal models such as the maternal immune activation (MIA) model that emulates many phenotypes characteristic of disorders such as schizophrenia. In the present series of experiments we used the MIA model to examine motivation, a core component of the negative symptomatology in schizophrenia. Contrary to what we expected, in the progressive ratio task, which assesses an animals' willingness to work for a reward under increasing effort requirements, we found that MIA rats appeared more motivated than controls. Subsequent tests showed that this seemingly enhanced motivation was not due to an overall increase in responding, nor due to enhanced attribution of incentive salience to reward associated responses. Instead, we found that the increased willingness to work exhibited by MIA animals was due to an inability to detect changes in the contingency between their behaviour and the resulting rewarding outcome. With regard to motivation, the experiments reported here are the first to subject the MIA model to a rigorous experimental analysis of behaviour by parsing underlying processes that give rise to the overt symptoms in psychiatric disease.

The effect of acute taurine ingestion on 4-km time trial performance in trained cyclists.

Taurine (TAU) has been shown to improve exercise time to exhaustion and 3-km running performance; however, no studies have considered the effect of acute TAU ingestion on short duration cycling time trial (TT) performance. The aim of this study was to determine the effects of a single oral acute dose of 1000 mg of TAU on a laboratory simulated 4-km cycling TT. Eleven trained male cyclists performed three, 4-km TTs. The first of the trials was a familiarisation, followed by two subsequent trials which were performed two hours after the consumption of either 1000 mg of TAU or placebo (P), using a double-blind randomised crossover design. Capillary blood samples were obtained prior to the start and immediately after each TT for the measurement of lactate, pH and HCO3-. There was no effect of TAU (p = 0.731, d = 0.151) on performance (390 ± 27 and 388 ± 21 s for TAU and P, respectively), nor were there any condition main effects for VO2, lactate, pH, or HCO3- (p > 0.05) despite post TT changes in lactate (7.3 ± 2.5 mmol l-1, p < 0.001, d = 2.86, 7.6 ± 2.0 mmol l-1 p < 0.001, d = 3.75); pH (-0.255 ± 0.1, p < 0.001, d = 2.62, -0.258 ± 0.09, p < 0.001, d = 2.87); HCO3- (-13.58 ± 2.7 mmol l-1, p < 0.001, d = 5.04 vs. -13.36 ± 2.3, p < 0.001, d = 5.72 for TAU and P, respectively). The findings of this study suggest that a pre-exercise dose of 1000 mg TAU offers no performance advantage during 4-km TT nor does it alter the blood buffering responses in trained cyclists.

Rolling through TikTok: An analysis of 3,4-methylenedioxymethamphetamine-related content.

INTRODUCTION: TikTok has quickly gained popularity through its platforming of large amounts of short video content. Given its widespread popularity, unrestricted access and poor content monitoring may allow 3,4-methylenedioxymethamphetamine (MDMA)-related content to influence perception of MDMA use. We aimed to investigate how MDMA-related videos are portrayed on TikTok and explore MDMA-related harm reduction content. METHODS: MDMA-related hashtags and sounds were utilised to collect data from TikTok (n = 498). Video views, likes, comments and shares were recorded and quantified, and videos were coded for depiction/sentiment towards MDMA and thematic content. RESULTS: The total sample view count was 82,413,781. Videos had a median view count of 28,900 (SD = ±561,645), median like count of 2269 (SD = ±102,904), median comment count of 52 (SD = ±755), and median share count of 34 (SD = ±3292). Most videos depicted MDMA neutrally (40.6%), while 34.9% were positive. MDMA intoxication was presumed in 40.2% of videos. The analysis produced seven themes, of which humour was the most common (80.5%). Harm reduction content was present in nine videos, viewed 999,700 times, and consisted of mixed subject matter. DISCUSSION AND CONCLUSIONS: Similar themes and issues surrounding drug-related content on TikTok are relevant to MDMA, and intoxication was present in a significant portion of the sample. Better monitoring or regulation of content could potentially offset harm that may arise from consumption of such content. Promotion of harm reduction content could also be trialled to minimise harm.