Enhanced Cd2+ removal from aqueous solution using olivine and magnesite combination: New insights into the mechanochemical synergistic effect.

In this study, an efficient stabilizer material for cadmium (Cd2+) treatment was successfully prepared by simply co-milling olivine with magnesite. Several analytical methods including XRD, TEM, SEM and FTIR, combined with theoretical calculations (DFT), were used to investigate mechanochemical interfacial reaction between two minerals, and the reaction mechanism of Cd removal, with ion exchange between Cd2+ and Mg2+ as the main pathway. A fixation capacity of Cd2+ as high as 270.61 mg/g, much higher than that of the pristine minerals and even the individual/physical mixture of milled olivine and magnesite, has been obtained at optimized conditions, with a neutral pH value of the solution after treatment to allow its direct discharge. The as-proposed Mg-based stabilizer with various advantages such as cost benefits, green feature etc., will boosts the utilization efficiency of natural minerals over the elaborately prepared adsorbents.

Immediate and long-term brain activation of acupuncture on ischemic stroke patients: an ALE meta-analysis of fMRI studies.

Background: Acupuncture, as an alternative and complementary therapy recommended by the World Health Organization for stroke treatment, holds potential in ameliorating neurofunctional deficits induced by ischemic stroke (IS). Understanding the immediate and long-term effects of acupuncture and their interrelation would contribute to a better comprehension of the mechanisms underlying acupuncture efficacy. Methods: Activation likelihood estimation (ALE) meta-analysis was used to analyze the brain activation patterns reported in 21 relevant functional neuroimaging studies. Among these studies, 12 focused on the immediate brain activation and 9 on the long-term activation. Single dataset analysis were employed to identify both immediate and long-term brain activation of acupuncture treatment in IS patients, while contrast and conjunction analysis were utilized to explore distinctions and connections between the two. Results: According to the ALE analysis, immediately after acupuncture treatment, IS patients exhibited an enhanced cluster centered around the right precuneus (PCUN) and a reduced cluster centered on the left middle frontal gyrus (MFG). After long-term acupuncture treatment, IS patients showed an enhanced cluster in the left PCUN, along with two reduced clusters in the right insula (INS) and hippocampus (HIP), respectively. Additionally, in comparison to long-term acupuncture treatment, the right angular gyrus (ANG) demonstrated higher ALE scores immediately after acupuncture, whereas long-term acupuncture resulted in higher scores in the left superior parietal gyrus (SPG). The intersecting cluster activated by both of them was located in the left cuneus (CUN). Conclusion: The findings provide initial insights into both the immediate and long-term brain activation patterns of acupuncture treatment for IS, as well as the intricate interplay between them. Both immediate and long-term acupuncture treatments showed distinct patterns of brain activation, with the left CUN emerging as a crucial regulatory region in their association. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, CRD42023480834.

T-cell specific in vivo gene delivery with DART-AAVs targeted to CD8.

One of the biggest challenges for in vivo gene therapy are vectors mediating highly selective gene transfer into a defined population of therapy-relevant cells. Here we present DARPin-targeted AAVs (DART-AAVs) displaying DARPins specific for human and murine CD8. Insertion of DARPins into the GH2/GH3 loop of the capsid protein 1 (VP1) of AAV2 and AAV6 resulted in high selectivity for CD8-positive T cells with unimpaired gene delivery activity. Remarkably, the capsid core structure was unaltered with protruding DARPins detectable. In complex primary cell mixtures, including donor blood or systemic injections into mice, the CD8-targeted AAVs were by far superior to unmodified AAV2 and AAV6 in terms of selectivity, target cell viability and gene transfer rates. In vivo, up to 80% of activated CD8+ T cells were hit upon a single vector injection into conditioned humanized or immunocompetent mice. While gene transfer rates decreased significantly under non-activated conditions, genomic modification selectively in CD8+ T cells was still detectable upon Cre delivery into indicator mice. In both mouse models, selectivity for CD8+ T cells was close to absolute with exceptional detargeting from liver. The CD8-AAVs described here expand strategies for immunological research and in vivo gene therapy options.

[Side effects of Immune Checkpoint Inhibitors : Diagnostics and Management-an Update]. / Nebenwirkungen von Immuncheckpoint-Inhibitoren : Diagnostik und Management ­ ein Update.

Immune checkpoint inhibitors (ICI) represent a breakthrough in cancer therapy. They are effective in various tumor entities and can be used in more and more treatment settings. This leads to an increase in the number and complexity of cases with immune-related adverse events (irAE). The most common irAE are cutaneous, gastrointestinal and endocrine side effects, whereas less common irAE include pneumonitis, nephritis, myocarditis or neurological reactions. IrAE can usually be successfully treated, mainly with corticosteroids or other immunosuppressants, but they can also result in long-term sequelae or death. The optimal management of patients with steroid-refractory or steroid-dependent side effects still remains unclear. Broad awareness of these irAE across specialties is therefore of crucial importance to ensure early diagnosis and to improve irAE management.

MEG Microstates: An Investigation of Underlying Brain Sources and Potential Neurophysiological Processes.

Microstates are transient scalp configurations of brain activity measured by electroencephalography (EEG). The application of microstate analysis in magnetoencephalography (MEG) data remains challenging. In one MEG dataset (N = 113), we aimed to identify MEG microstates at rest, explore their brain sources, and relate them to changes in brain activity during open-eyes (ROE) or closed-eyes resting state (RCE) and an auditory Mismatch Negativity (MMN) task. In another dataset of simultaneously recorded EEG-MEG data (N = 21), we investigated the association between MEG and EEG microstates. Six MEG microstates (mMS) provided the best clustering of resting-state activity, each linked to different brain sources: mMS 1-2: left/right occipito-parietal; mMS 3: fronto-temporal; mMS 4: centro-medial; mMS 5-6: left/right fronto-parietal. Increases in occipital alpha power in RCE relative to ROE correlated with greater mMS 1-2 time coverage (τbs < 0.20, ps > .002), while the lateralization of deviance detection in MMN was associated with mMS 5-6 time coverage (τbs < 0.16, ps > .012). No temporal correlation was found between EEG and MEG microstates (ps > .05), despite some overlap in brain sources and global explained variance between mMS 2-3 and EEG microstates B-C (rs > 0.60, ps < .002). Hence, the MEG signal can be decomposed into microstates, but mMS brain activity clustering captures phenomena different from EEG microstates. Source reconstruction and task-related modulations link mMS to large-scale networks and localized activities. Thus, mMSs offer insights into brain dynamics and task-specific processes, complementing EEG microstates in studying physiological and dysfunctional brain activity.

Patient-centered care in diabetes care-concepts, relationships and practice.

We still do not have comprehensive knowledge of which framework of patient-centered care (PCC) is appropriate for diabetes care, which elements of PCC are evidence-based, and the mechanism by which PCC elements are associated with outcomes through mediators. In this review, we elaborate on these issues. We found that for diabetes care, PCC elements such as autonomy support (patient individuality), cooperation and collaboration (system-level approach), com-munication and education (behavior change techniques), emotional support (biopsychosocial approach), and family/other involvement and support are critically important. All of these factors are directly associated with different patient outcomes and indirectly associated with outcomes through patient activation. We present the practical implications of these PCC elements.

Quadriceps Activation After Anterior Cruciate Ligament Reconstruction: The Early Bird Gets the Worm!

Arthrogenic Muscle Inhibition (AMI) is a phenomenon observed in individuals with joint injury or pathology, characterized by a reflexive inhibition of surrounding musculature, altered neuromuscular control, and compromised functional performance. After anterior cruciate ligament reconstruction (ACLR) one of the most obvious consequences of AMI is the lack of quadriceps activation and strength. Understanding the underlying mechanisms of AMI is crucial for developing effective therapeutic interventions. The surgical procedure needed to reconstruct the ACL has biochemical et physiological consequences such as inflammation, pain, and altered proprioception. These alterations contribute to the development of AMI. Therapeutic interventions aimed at addressing AMI encompass a multidimensional approach targeting pain reduction, inflammation management, proprioceptive training, and quadriceps activation. Early management focusing on pain modulation through modalities like ice, compression, and pharmacological agents help mitigate the inflammatory response and alleviate pain, thereby reducing the reflexive inhibition of quadriceps. Quadriceps activation techniques such as neuromuscular electrical stimulation (NMES) and biofeedback training aid in overcoming muscle inhibition and restoring muscle strength. NMES elicits muscle contractions through electrical stimulation, bypassing the inhibitory mechanisms associated with AMI, thus facilitating muscle activation and strength gains. Comprehensive rehabilitation programs tailored to individual needs and stage of recovery are essential for optimizing outcomes in AMI. The objective of this clinical viewpoint is to delineate the significance of adopting a multimodal approach for the effective management of AMI, emphasizing the integration of pain modulation, proprioceptive training, muscle activation techniques, and manual therapy interventions. Highlighting the critical role of early intervention and targeted rehabilitation programs, this article aims to underscore their importance in restoring optimal function and mitigating long-term complications associated with AMI.

Transcriptional noise, gene activation, and roles of SAGA and Mediator Tail measured using nucleotide recoding single-cell RNA-seq.

We describe a time-resolved nascent single-cell RNA sequencing (RNA-seq) approach that measures gene-specific transcriptional noise and the fraction of active genes in S. cerevisiae. Most genes are expressed with near-constitutive behavior, while a subset of genes show high mRNA variance suggestive of transcription bursting. Transcriptional noise is highest in the cofactor/coactivator-redundant (CR) gene class (dependent on both SAGA and TFIID) and strongest in TATA-containing CR genes. Using this approach, we also find that histone gene transcription switches from a low-level, low-noise constitutive mode during M and M/G1 to an activated state in S phase that shows both an increase in the fraction of active promoters and a switch to a noisy and bursty transcription mode. Rapid depletion of cofactors SAGA and MED Tail indicates that both factors play an important role in stimulating the fraction of active promoters at CR genes, with a more modest role in transcriptional noise.

Superoxide radicals mediated by high-spin Fe catalysis for organic wastewater treatment.

Water resources are indispensable basic resources and important environmental carriers; the presence of organic contaminants in wastewater poses considerable risks to the health of both humans and ecosystems. Although the Fenton-like reactions using H2O2 as the oxidant to destroy organic pollutants are attractive, there are still challenges in improving reaction activity under neutral or even alkaline conditions. Herein, we designed a H2O2 activation pathway with O2•- as the main active species and elucidated that the spin interaction between Fe sites and coordinated O atoms effectively promotes the generation of the key intermediate Fe-*OOH. Furthermore, we successfully captured and analyzed the Fe-*OOH intermediate by in situ Raman spectroscopy. When applying FBOB to a continuous-flow reactor, CIP removal efficiency remained at around 90% within 600 min of continuous operation, achieving excellent efficiency, stability, and pH tolerance in removing pollutants.

Calciprotein particle counts associate with vascular remodelling in chronic kidney disease.

AIMS: Calciprotein particles (CPPs) are circulating calcium and phosphate nanoparticles associated with development of vascular calcification (VC) in chronic kidney disease (CKD). Although recent studies have been focusing on associations of CPPs with presence of VC in CKD, insights in the underlying processes and mechanisms by which CPPs might aggravate VC and vascular dysfunction in vivo are currently lacking. Here, we assessed overall burden of abdominal VC in healthy kidney donors and CKD patients, and subsequently performed transcriptome profiling in vascular tissue obtained from these subjects, linking outcome to CPP counts and calcification propensity. METHODS AND RESULTS: Calcification scores were quantified in renal arteries, iliac arteries and abdominal aorta, using computed tomography (CT) scans of kidney donors and CKD patients. Vascular tissue was collected from kidney donors (renal artery) and CKD patients (iliac artery), after which bulk RNA sequencing and gene set enrichment analysis (GSEA) was performed on a subset of patients. Calcification propensity (crystallization time, T50) was measured using nephelometry, and CPP counts with microparticle flow cytometric analysis. Increased calcification scores (based on CT) were found in CKD patients compared to kidney donors. Transcriptome profiling revealed enrichment for processes related to endothelial activation, inflammation, extracellular matrix (ECM) remodelling and ossification in CKD vascular biopsies compared to kidney donors. Calcification propensity was increased in CKD, as well as CPP counts, of which the latter significantly associated with markers of vascular remodelling. CONCLUSIONS: Our findings reveal that CKD is characterized by systemic VC with increased calcification propensity and CPP counts. Transcriptome profiling showed altered vascular gene expression with enrichment for endothelial activation, inflammation, ECM remodelling and ossification. Moreover, we demonstrate for the first time that vascular remodelling processes are associated with increased circulating CPP counts. Interventions targeting CPPs are promising avenues for alleviating vascular remodelling and VC in CKD.

Luteolin-7-diglucuronide, a novel PTP1B inhibitor, ameliorates hepatic stellate cell activation and liver fibrosis in mice.

Liver fibrosis, one of the leading causes of morbidity and mortality worldwide, lacks effective therapy. The activation of hepatic stellate cells (HSCs) is the dominant event in hepatic fibrogenesis. Luteolin-7-diglucuronide (L7DG) is the major flavonoid extracted from Perilla frutescens and Verbena officinalis. Their beneficial effects in the treatment of liver diseases were well documented. In this study we investigated the anti-fibrotic activities of L7DG and the potential mechanisms. We established TGF-ß1-activated mouse primary hepatic stellate cells (pHSCs) and human HSC line LX-2 as in vitro liver fibrosis models. Co-treatment with L7DG (5, 20, 50 µM) dose-dependently decreased TGF-ß1-induced expression of fibrotic markers collagen 1, α-SMA and fibronectin. In liver fibrosis mouse models induced by CCl4 challenge alone or in combination with HFHC diet, administration of L7DG (40, 150 mg·kg-1·d-1, i.g., for 4 or 8 weeks) dose-dependently attenuated hepatic histopathological injury and collagen accumulation, decreased expression of fibrogenic genes. By conducting target prediction, molecular docking and enzyme activity detection, we identified L7DG as a potent inhibitor of protein tyrosine phosphatase 1B (PTP1B) with an IC50 value of 2.10 µM. Further studies revealed that L7DG inhibited PTP1B activity, up-regulated AMPK phosphorylation and subsequently inhibited HSC activation. This study demonstrates that the phytochemical L7DG may be a potential therapeutic candidate for the treatment of liver fibrosis.

The relationship between distress tolerance and behavioral activation on anxiety and depression symptomatology in autistic youth: Leveraging self and caregiver perspectives.

Anxiety and depression are prevalent among autistic adolescents and may be difficult to accurately diagnose and treat given various factors (e.g., diagnostic overshadowing, heterogeneity). Therefore, efforts to examine transdiagnostic factors (i.e., distress tolerance, behavioral activation) may afford more parsimonious means for assessment and treatment. To our knowledge, there has been little research on distress tolerance, behavioral activation, and depressive and anxiety symptoms in autistic adolescents to guide diagnostic practices and treatment planning. In the current study, we examined the interrelationships between these transdiagnostic factors and depressive and anxiety symptoms using ratings from 100 verbally fluent autistic adolescents without intellectual disability (Mage = 13.70, SDage = 2.23, Range: 11:00-17:11 years) and 100 of their caregivers. Many adolescents reported male sex assigned at birth (61%), cisgender (87%), not Hispanic/Latinx (90%), and White (80%) identities. A series of correlational analyses were employed to examine associations between these constructs from youth and caregiver perspectives, and multiple linear regression analyses were conducted to explore the mediating roles of distress tolerance and behavioral activation. Preliminary results show that low distress tolerance and behavioral activation were associated with more severe internalizing symptoms per self- and caregiver-report. Some differences by rater emerged, which highlight the importance of multi-informant ratings in autism. Results from mediation analyses may show that behavioral activation may be more salient to assessments and treatment planning for depression than distress tolerance, while distress tolerance may be important for both anxiety and depression; however, findings are preliminary given the cross-sectional nature of the data. Findings suggest that these transdiagnostic concepts may be important to individualizing treatment approaches, including the timing of certain approaches, for anxiety and/or depression in autistic adolescents.

Hydrogenolysis of haloboranes: from synthesis of hydroboranes to formal hydroboration reactions.

Hydroboranes are versatile reagents in synthetic chemistry, but their synthesis relies on energy-intensive processes. Herein, we report a new method for the preparation of hydroboranes from hydrogen and the corresponding haloboranes. Triethylamine (NEt3) form with dialkylchloroboranes a Frustrated Lewis Pair (FLP) able to split H2 and afford the desired hydroborane with ammonium salts. Unreactive haloboranes were unlocked using a catalytic amount of Cy2BCl, enabling the synthesis of commonly used hydroboranes such as pinacolborane or catecholborane. The mechanisms of these reactions have been examined by DFT studies, highlighting the importance of the base selection. Finally, the system's robustness has been evaluated in one-pot B-Cl hydrogenolysis/hydroboration reactions of C=C unsaturated bonds.

TLR2 immunotherapy suppresses neuroinflammation, tau spread, and memory loss in rTg4510 mice.

In Alzheimer's disease, chronic neuroinflammation is accompanied by amyloid and tau pathologies. Especially, aberrant microglial activation is known to precede the regional tau pathology development, but the mechanisms how microglia affect tau spread remain largely unknown. Here, we found that toll-like receptor 2 (TLR2) in microglia recognizes oligomeric tau as a pathogenic ligand and induces inflammatory responses. Knockout of TLR2 reduced tau pathology and microglial activation in rTg4510 tau transgenic mice. Treatment of oligomeric tau induced TLR2 activation and increased inflammatory responses in microglial cells. TLR2 further mediated the tau-induced microglial activation and promoted tau uptake into neurons in neuron-microglia co-culture system and in mouse hippocampus after intracranial tau injection. Importantly, treatment with anti-TLR2 monoclonal antibody Tomaralimab blocked TLR2 activation and inflammatory responses in a dose-dependent manner, and significantly reduced tau spread and memory loss in rTg4510 mice. These results suggest that TLR2 plays a crucial role in tau spread by causing aberrant microglial activation in response to pathological tau, and blocking TLR2 with immunotherapy may ameliorate tau pathogenesis in Alzheimer's disease.

Metformin enhances endogenous neural stem cells proliferation, neuronal differentiation, and inhibits ferroptosis through activating AMPK pathway after spinal cord injury.

BACKGROUND: Inadequate nerve regeneration and an inhibitory local microenvironment are major obstacles to the repair of spinal cord injury (SCI). The activation and differentiation fate regulation of endogenous neural stem cells (NSCs) represent one of the most promising repair approaches. Metformin has been extensively studied for its antioxidative, anti-inflammatory, anti-aging, and autophagy-regulating properties in central nervous system diseases. However, the effects of metformin on endogenous NSCs remains to be elucidated. METHODS: The proliferation and differentiation abilities of NSCs were evaluated using CCK-8 assay, EdU/Ki67 staining and immunofluorescence staining. Changes in the expression of key proteins related to ferroptosis in NSCs were detected using Western Blot and immunofluorescence staining. The levels of reactive oxygen species, glutathione and tissue iron were measured using corresponding assay kits. Changes in mitochondrial morphology and membrane potential were observed using transmission electron microscopy and JC-1 fluorescence probe. Locomotor function recovery after SCI in rats was assessed through BBB score, LSS score, CatWalk gait analysis, and electrophysiological testing. The expression of the AMPK pathway was examined using Western Blot. RESULTS: Metformin promoted the proliferation and neuronal differentiation of NSCs both in vitro and in vivo. Furthermore, a ferroptosis model of NSCs using erastin treatment was established in vitro, and metformin treatment could reverse the changes in the expression of key ferroptosis-related proteins, increase glutathione synthesis, reduce reactive oxygen species production and improve mitochondrial membrane potential and morphology. Moreover, metformin administration improved locomotor function recovery and histological outcomes following SCI in rats. Notably, all the above beneficial effects of metformin were completely abolished upon addition of compound C, a specific inhibitor of AMP-activated protein kinase (AMPK). CONCLUSION: Metformin, driven by canonical AMPK-dependent regulation, promotes proliferation and neuronal differentiation of endogenous NSCs while inhibiting ferroptosis, thereby facilitating recovery of locomotor function following SCI. Our study further elucidates the protective mechanism of metformin in SCI, providing new mechanistic insights for its candidacy as a therapeutic agent for SCI.

Timing of emergency medical services activations for falls.

Objective: Falls are a major challenge to public health, particularly among older adults. Understanding factors that influence fall risk is pivotal in the prevention of falls and fall-related injuries. This study evaluated the timing of emergency medical service (EMS) activations for falls and transport patterns for adults age ≥65. Methods: A patient care report system at a single fire-based emergency medical service agency in a suburban, Midwest city was retrospectively reviewed. Type of call (lift assist/fall), time of injury (time, day, and month), and demographics (sex, age) were collected for residents age ≥65 who activated 9-1-1 for a lift assist or fall. Results: 1169 calls met inclusion criteria. Mornings and afternoons were the time of day associated with falls (33 % and 36 % of EMS activations, respectively, vs. 21 % and 10 % for evenings and nights, respectively; p = 0.002) while day of the week and month were not associated with falls or lift assists. More males requested lift assists than females (256 vs. 238) and more females called for falls than males (408 vs. 267; p < 0.001). Falls were more likely to be associated with transport to the hospital than lift assists (78% vs. 7 %). Female sex was associated with increased risk for transport to the hospital (60 % of females vs. 40 % of males; p < 0.001). Conclusions: Mornings and afternoons were associated with increased risk for falls and sex (female) with increased risk for transport to the hospital.

Self-regulation training generalizability using the regulation of craving task. An fMRI study.

Individual differences in reward salience may relate to the difficulty in regulating the effects of multiple substances (e.g., nicotine and food). Increased brain activation in reward and self-regulation (SR) regions has been evidenced while adults view appetitive cues (e.g., food pictures) to test substance use disorder treatment response. Enhancing SR with behavioral interventions may increase brain activation in SR regions and reduce responses in reward regions. Our primary analysis demonstrated increased brain activation in SR regions to smoking cues among individuals who practiced SR by delaying their first cigarette of the day for 2 weeks. However, little is known about the generalizability of SR between appetitive cues. This secondary analysis explored the influence of adherence to a SR behavioral intervention by examining the impact of practicing smoking SR on brain activation to food cues among adults who smoke. Participants (N = 65) were randomly assigned to practice SR by delaying their first daily cigarette or smoking as usual for 2-weeks. Functional magnetic resonance imaging data were collected while people were told to think of "negative" or "positive" associations with the cue. The results indicated that practicing smoking SR was linked with increased activation in the dorsolateral prefrontal cortex (dlPFC) when viewing food cues. There was no correlation between delaying smoking adherence and brain activation in the dlPFC. Exploratory analyses suggested higher dlPFC activation when people thought about "positive" associations with the food cues instead of "negative" ones. We concluded that practicing smoking SR is related to increased brain activation to food cues, suggesting potential generalizability of SR practice from smoking cues to food cues.

Analysis of the temperature-dependent plastic deformation of single crystals of quinary, quaternary and ternary equiatomic high- and medium-entropy alloys of the Cr-Mn-Fe-Co-Ni system.

Temperature-dependent plastic deformation behaviors of single crystals of quaternary and ternary equiatomic medium-entropy alloys (MEAs) belonging to the Cr-Mn-Fe-Co-Ni system were investigated in compression at temperatures in the range 9 K to 1373 K. Their critical resolved shear stresses (CRSSs) increase with decreasing temperature below room temperature. There is also a dulling of the temperature dependence of CRSS below 77 K due to dislocation inertial effects that we attribute to a decrease in the phonon drag coefficient. These behaviors were compared with those of previously investigated single crystals of the equiatomic Cr-Co-Ni and Cr-Fe-Co-Ni MEAs, and the equiatomic Cr-Mn-Fe-Co-Ni high-entropy alloy (HEA). The temperature dependence of CRSS and the apparent activation volumes below room temperature can be well described by conventional thermal activation theories of face-centered cubic (FCC) alloys. Above 673 K, there is a small increase in CRSS, which we believe is due to elastic interactions between solutes and mobile dislocations, the so-called Portevin-Le Chatelier (PL) effect. The CRSS at 0 K was obtained by extrapolation of fitted CRSS vs. temperature curves and compared with predictions from solid solution strengthening models of HEA and MEAs.

The novelty of our work entitled 'Analysis of the temperature-dependent plastic deformation of single crystals of quinary, quaternary and ternary equiatomic high- and medium-entropy alloys of the Cr-Mn-Fe-Co-Ni system' can be summarized as follows: The temperature dependences of CRSS were experimentally deduced from bulk single crystals of the six MEAs for the first time, so that fair comparison among the FCC HEA/MEAs is made.

Nicotinamide riboside first alleviates symptoms but later downregulates dopamine metabolism in proteasome inhibition mouse model of Parkinson's disease.

Parkinson's disease (PD) is associated with a reduction in 26/20S proteasome and mitochondrial function and depletion of dopamine. Activation of mitochondrial function with the NAD+ precursor nicotinamide riboside (NR) is a potential therapeutic for PD. However, despite recently started clinical trials, analysis of NR in mammalian animal PD models is lacking and data in simpler PD models is limited. We analyzed the effect of NR in C. elegans and in mouse 26/20S proteasome inhibition models of PD. In C. elegans, NR rescued α-synuclein overexpression induced phenotypes likely by activating the mitochondrial unfolded protein response. However, in a proteasome inhibitor-induced mouse model of PD, NR first partially rescued behavioural dysfunction, but later resulted in decrease in dopamine and its related gene expression in the substantia nigra. Our results suggest that reduction in 26/20S function with long term NR treatment may increase risk for developing reduced nigrostriatal DA function.

Assessing Stroke Awareness and Behavioural Response Following the National 'Act Fast' Stroke Awareness Campaign - Insights from a Cross-Sectional Survey in Qatar.

Evaluating stroke campaigns and associated behavioural changes is crucial to assess intervention effectiveness and inform future strategies. We aimed to evaluate patient's and bystanders' foreknowledge of stroke signs and symptoms and their response at stroke onset. We interviewed stroke patients using a validated questionnaire or their bystanders if the stroke patient had disabling stroke. The questionnaire was administered to 165 participants, 142 (86.1%) stroke patients and 23 (13.9%) bystanders. The mean age was 52.6 (SD = 11.7), and male-female ratio was 7:1. Among the participants, 33 (20.1%) had foreknowledge of stroke signs, and of these, 27 (16.5%) were aware of the stroke campaign in Qatar. The behavioural responses at stroke onset included; activating Emergency Medical Services (EMS) (n = 55, 33.3%), calling friends/relatives (n = 69, 41.8%), driving to hospital (n = 33, 20%), waiting for improvement in condition (n = 21, 12.7%). There was no association of ethnicity, marital status, or campaign awareness with EMS activation. Despite limited community awareness of stroke signs and campaign, help-seeking behaviour through EMS activation was generally high, underscoring the need for focused educational efforts and public health interventions.