Prescribing errors (PEs) can lead to patient harm. Prediction tools are available to detect patients at risk but are not ideal. We investigated whether doctors can identify hospitalized patients at risk of medication-related harm by assessing the prevalence of PEs. This matched case-control study was carried out on three clinical wards (Internal Medicine, Upper GI Surgery, and Otolaryngology & Oncology) in an academic hospital in the Netherlands. A total of 387 patients with 5191 prescriptions were included. A multidisciplinary in-hospital pharmacotherapeutic stewardship team detected 799 PEs affecting 279 patients (72.1%). Most (58.8%) PEs occurred during hospitalization. Doctors identified 40 patients (cases) as needing a clinical medication review (CMR). These patients were matched by age (10 years) and the number of prescriptions at the time of CMR (1), 1:1 with patients not selected for CMRs (controls). There were no significant differences in age, number of prescriptions, sex, renal function, or documented allergies or intolerances between the matched cases and controls or between controls and other patients who did not received a CMR. The incidence of PEs was higher among cases than controls, and more cases than controls had one or more PEs (97.5% versus 72.5% (OR=14.8, 95% CI [1.8 – 121.1], p=0.002)). The rate of PEs was three times higher in cases than in controls (IRR=3.0, 95% [2.3 – 4.0], p<0.001). In conclusion, clinical ward doctors can effectively identify patients with PEs thus at risk of medication-related harm. This may be a new and interesting selecting strategy for targeted PE-mitigating interventions.

This article explores the intricate journey of neural progenitor cells from the ventricular zones of the embryonic brain, focusing on their pivotal role in the formation of rich club networks, which are integral to the brain's functional architecture. Initially, the ventricular zones, particularly the cerebral ventricular zone, serve as the primary sites for the proliferation and

Based on the eventual destruction of the solar system and the critical need for human continuation, as well as humans cannot travel to the nearest habitable exoplanet within a lifetime, this article suggests sending synthetic biology- and AI-created plant-like astronauts to the closest habitable exoplanet. These astronauts have green skin, blue blood, and the ability to perform photosynthesis. They can withstand cosmic radiation and extremely low temperatures in space, while generating energy through photosynthesis. This interdisciplinary approach may offer a solution for the survival challenges faced by humanity during its eternal interstellar exploration. As long as these plant-like astronauts possess human consciousness, it is irrelevant whether they are hybrids of carbon- and silicon-based life forms. They will continue their lineage of humanity on exoplanets. Humanity has two survival options. The first option is the Martian migration program led by Elon Reeve Musk, which is both visible and realistic. It could provide an immediate option for human continuation and expansion, although it may not help us escape the future burning of the Sun during its red giant. The second option involves directly sending plant-like astronauts beyond the solar system. This kind of audacious adventure may be worth it: escaping its destruction entirely and preserving our species. Instead of struggling on Mars for thousands of years to reach today’s technological level on Earth and then initiate an “escape from Mars”, it may be more feasible to begin the “escape from Earth” to Teegarden’s Star b now. Should we consider both options simultaneously, much like how humans use their two legs to walk? We must strive with all our might; otherwise, humanity will forever be trapped within the solar system, awaiting the inevitable helium flash to come…

Efficacy and safety of a 7-week immunotherapy protocol with aluminium hydroxide absorbed hymenoptera venomTo the Editor,Hymenoptera venom allergy can cause life threatening anaphylaxis in patients sensitised to wasp and bee venom. Venom immunotherapy is effective in 77%‐84% of patients treated with honeybee venom and in 91%‐96% of patients receiving vespid venom1. Adverse events are usually rare and mild, and symptoms occur in only 4.3%‐11.4% of patients during the updosing1.A variety of therapy regimes exist for the updosing phase, from conventional, rush, ultrarush or clustered modalities1,2. Current conventional protocols are time‐consuming for patients, and some patients decline the potentially life-saving treatment due to the time commitment required for immunotherapy. Adverse events appear to be less frequent in conventional protocols during the updosing phase compared to rush and ultrarush protocols1,2; however, patients may remain unprotected for weeks as it takes considerable time to reach the maintenance dose.The only licensed venom immunotherapy product in the UK is Alutard SQ® (ALK Abelló) for Vespula and Apidae venom. The SPC recommends updosing with a 7-week clustered protocol or 15- or 25-week conventional protocol.To enhance the acceptance of treatment and increase compliance, we reduced the length of the SPC protocol. Another significant factor was the COVID-19 pandemic, which significantly reduced outpatient capacity to comply with social distancing.Based on previous data using the same product3, we introduced a shorter updosing protocol with 8 injections in 7 weeks and monitored its efficacy and safety. We used this in a wider age range of patients, including one patient with indolent mastocytosis and more patients with severe sting reactions.Seventy‐four patients aged 17 to 85 years with a history of a systemic sting reaction to vespid and apidae stings grade 2-4 were included (Table 1). Further information about patient selection and the updosing protocol is in supplementary file S1.We managed to retain all the patients during updosing and maintenance, and no dose reduction was needed.During updosing, there were no objective systemic adverse reactions recorded. Only one objective systemic adverse reaction was documented during maintenance, which was mild and limited to the skin. There were 6 incidences of mild and subjective systemic reactions during updosing and maintenance, which included symptoms of feeling hot, dizzy and itchy. The symptoms were treated with additional antihistamines with no change in regime required. We had a lower incidence of systemic reactions at 1.4% compared to Schrautzer et al3, who reported objective systemic reactions in 3.9% of patients during just the updosing phase.9.5% of our patient cohort reported large localised reactions throughout both the updosing and maintenance phase, which generally only occurred once or twice during the full treatment course.The prevalence of cardiovascular disease and treatment with beta-blockers were not related to the occurrence of side effects.Reactions to field stings were monitored to assess efficacy as sting challenges are not performed in the UK. 20 patients had field stings and all reported localised reactions. Some patients were stung by multiple insects (such as one patient who was stung by 19 insects at one time) and this was more common in beekeepers.We have extended the work of Schrautzer et al3 and demonstrated the efficacy and safety of their 7-week protocol in a large group of patients in a real-world setting. We have also demonstrated safety and efficacy of the 7-week protocol for Alutard SQ® apidae immunotherapy. Our data includes a larger group of patients with more severe reactions. Interestingly, our data also shows a lower number of reactions to immunotherapy treatment.The quicker updosing protocol improved patients’ acceptance of treatment and increased the efficiency of our immunotherapy clinic in terms of time and cost for patients, and medical staff.

A document by Cevdet Akyel . Click on the document to view its contents.

This paper compares the transborder wonen on the Sino-DPRK and the US-Mexico border. By focusing on the transborder work and living conditions and the impact of repatriation, it documents that the actual functions of the two boundaries are opposite to the metaphors represented by their physical buildings. The Sino-DPRK border bridges represent the friendship between China and North Korea and the close economic cooperation, the Mexico-US border wall represents the attitude of the US government towards illegal immigrants and the corresponding management measures. However, the wall does not become a taboo for Mexican border crossers, and the bridges cannot play a role in promoting exchanges between China and NK. Mexican trans-border women convert the wall to a bridge through their cross-border activities and close ties with the societies on both sides of the border. Women from NK are subject to strict labor management models, indoctrinated beliefs and a fear of heavy punishment, and thus resist all contact with both the host society and the home country, turning the bridge into a wall in imagery. These two groups, as representatives of the two extremes, indicate the irrelevance between the boundary entity representing the national will and people's trans-border practices.

Objective: Clinical psychology, a pivotal aspect of psychology, combines research and practice. This study aims to assess the recent decade’s clinical psychology research, particularly post-COVID-19 paradigm shifts. Method: Analyzing 69,295 clinical psychology publications from 2010 to 2022 in the Web of Science database, we used advanced bibliometrics tools (CiteSpace and Mapequation) to scrutinize authorship networks, publishing trends, and research focus in the US, the field’s rigin. Results: We found a significant upswing in clinical psychology research prompted by the advent of the pandemic, particularly in the study of psychological trauma caused by issues such as family conflict, elder abuse, collective trauma, and so on. Clinical psychology research has been profoundly formed with a dynamic group of scholars and institutions, surrounding mainly higher education systems. Research participants are widely diverse, with a progressive focus transition to the populations on gender and race minorities, maternal, and adolescents. Mental disorder, such as PTSD, anxiety, and suicidal behaviors have caught more attention especially during the pandemic. Therapeutic approaches have long been another focus in clinical psychology, interventions such as mindfulness-based practice and AI-assisted technologies have started to gain prominence. Conclusions: This paper serves as the first large-scale bibliometrics analysis in clinical psychology, which offers an interdisciplinary collaboration potential with information science besides the originality of documenting publication trends in psychology. The integration of open data initiatives, machine learning, augmented reality, and virtual reality technologies shows promise in assessing mental health and fostering well-being, indicating an evolving landscape in clinical psychology research.

We are considered with the following nonlinear Schrödinger equation −∆ u+( λa( x)+1) u= f( u) ,x∈ V, on a locally finite graph G=( V,E), where V denotes the vertex set, E denotes the edge set, λ>1 is a parameter, f( s) is asymptotically linear with respect to s at infinity, and the potential a: V→[0 ,+∞) has a nonempty well Ω. By using variational methods we prove that the above problem has a ground state solution u λ for any λ>1. Moreover, we show that as λ→∞, the ground state solution u λ converges to a ground state solution of a Dirichlet problem defined on the potential well Ω.

The production of vaccines for diseases depends entirely on its analysis. However, to test every disease extensively is costly as it would involve the investigation of every known gene related to a disease. This issue is further elevated when different variations of diseases are considered. As such the use of different computational methods are considered to tackle this issue. This research makes use of different machine learning algorithms in the identification and prediction of Single Nucleotide Polymorphism. This research presents that Gradient Boosting algorithm performs better in comparison to other algorithms in genic variation predictions with an accuracy of 70%.

Microbially mediated plant-soil feedbacks drive patterns of plant growth, competitive ability, succession, and community composition. Although rare plant species maintain unique functional traits that often facilitate negative feedbacks, there is not a consensus on the belowground drivers nor the effects of phylogenetic origin of previously plant-conditioned soil on aboveground traits associated with rare species. Using a common garden, we connect belowground fungal colonization to aboveground traits in species varying in rarity, and soil conditions varying in the phylogenetic relatedness of conditioning plant species, to demonstrate the mechanistic relationship between belowground ectomycorrhizal fungal (ECM) colonization and aboveground total plant biomass in 14 Eucalyptus species varying in their rarity status. Specifically, we found that while the rarest species displayed 88% less total biomass than common species, the rarest species also maintained 62% greater ECM colonization than common counterparts. Further, negative feedbacks resulted in reduced biomass coupled with positive feedbacks that resulted in increased ECM colonization that varied on the basis of phylogenetic relatedness. The rarest species decreased by 71% - 94% in total biomass but increased by 96% - 114% in ECM colonization in phylogenetically similar and distant soil compared to conspecific soil conditions. The effect size of ECM colonization directly affected the effect size of total biomass in phylogenetically distant conditions with a significant negative correlation (r^2 = -0.83) to show that biomass may be a function of ECM colonization acting differently among species varying in rarity. Consequently, rare plant species may utilize stronger associations with belowground mycorrhizal mutualists than common plant species, to facilitate geographic, competitive, and functional persistence, even while maintaining lower biomass.

Biogenic amines (BAs) are naturally present in various foods, and high levels of them have a negative impact on human health. Pichia kudriavzevii MZ5 exhibits excellent potential in degrading biogenic amines. Among the tested addition of the culture medium components, Mg2+ is the most effective factor of enhancing the ability of P. kudriavzevii MZ5 to degrade biogenic amines. After 72 h of cultivation, the total biogenic amines degradation rate increased from 14.2 % to 43.39 % when Mg2+presented in the medium. The biomass of P. kudriavzevii MZ5 decreased, but there was no correlation between the yeast biomass and the biogenic amines degradation rate in this experiment. The addition of Mg2+ in the medium increased the GSH of P. kudriavzevii MZ5 from 0.34 mg/mg prot to 0.82 mg/mg prot, GST from 2.76 U/mg prot to 3.30 U/mg prot, and Ca2+- Mg2+- ATPase activity from the original 5.36 U/mg prot to 17.36 U/mg prot. These results indicate that Mg2+ significate influenced the degradation ability of P. kudriavzevii MZ5 towards biogenic amines, which suggest that Mg2+ may have a great potential as a promoter for microbial degradation of biogenic amines.

During plant-pathogen interaction, plant exhibits a strong defense system utilizing diverse groups of proteins to suppress the infection and subsequent establishment of the pathogen. However, in response, pathogens trigger an anti-silencing mechanism to overcome the host defense machinery. Among plant viruses, geminiviruses are the second largest virus family with a worldwide distribution and continue to be production constraints to food, feed, and fiber crops. These viruses are spread by a diverse group of insects, predominantly by whiteflies, and are characterized by a single-stranded DNA (ssDNA) genome coding for four to eight proteins that facilitate viral infection. The most effective means to managing these viruses is through an integrated disease management strategy that includes virus-resistant cultivars, vector management, and cultural practices. Dynamic changes in this virus family enable the species to manipulate their genome organization to respond to external changes in the environment. Therefore, the evolutionary nature of geminiviruses leads to new and novel approaches for developing virus-resistant cultivars and it is essential to study molecular ecology and evolution of geminiviruses. This review summarizes the multifunctionality of each geminivirus-encoded protein. These protein-based interactions trigger the abrupt changes in the host methyl cycle and signaling pathways that turn over protein normal production and impair the plant antiviral defense system. Studying these geminivirus interactions localized at cytoplasm-nucleus could reveal a more clear picture of host-pathogen relation. Data collected from this antagonistic relationship among geminivirus, vector, and its host, will provide extensive knowledge on their virulence mode and diversity with climate change

A fifteen-year-old warmblood gelding was presented with recurrence of a histologically confirmed osteosarcoma of the left second and third metacarpal bones three years after initial diagnosis and treatment. Initially, surgical excision was performed, followed by local injection of carboplatin 11 weeks later. The horse was sound after surgery and was used for low level dressage and jumping. Three years later, the horse developed acute onset of lameness in the left forelimb and a painful soft tissue swelling at the proximomedial metacarpal region. Radiographs showed a spiculated periosteal reaction on the medial aspect of the third metacarpal bone, indicating re-activation of the lesion. Stereotactic radiation therapy was performed with a protocol consisting of three fractions under general anaesthesia (Mo-We-Fr schedule), and a total dose of 30 Gy. The technique used was volumetric modulated arc therapy guided by cone beam computed tomography for daily positioning. Following the radiation therapy, the horse became sound at walk and one month later, it became sound at trot. Follow-up by veterinary examination eighteen months after final treatment revealed no lameness at walk and trot, and a stable radiographic appearance.

Purpose: The current study aimed to evaluate the drug utilization pattern in pediatric outpatients suffering from Upper Respiratory Tract Infection (URTI) in a tertiary care center. Materials and methods: A cross-sectional study was carried out in a tertiary care hospital for period of six months (December-May) on pediatric patients (age≤12years) diagnosed with URTI. Data like demographic details, diagnosis, World Health organization (WHO) prescribing indicators, different class of drugs prescribed, antibiotic treatment, and different dosage forms etc. were gathered from pediatric outpatient’s department (OPD). Results: A total of 153 prescriptions were evaluated, of these 84(54.9%) were males and rest 69(45.1%) were females. Mainly school children 89(58.17%) of age group between 6-12 years visited outpatient’s pediatric department. Fever and cough were the commonly recorded clinical symptoms in the prescription analyzed, accounting for 81% and 66.7% respectively. The average number of drugs prescribed were 2.38 per prescription; most commonly prescribed medication for the management of URTI was antipyretics 111(72.5%), antihistamines 94(61.3%) followed by antibiotics 55(35.9%). Amoxiclav {amoxicillin + clavulanic acid} (31.66%) and cefixime (30%) were the common antibacterial prescribed. Majority of medications (85%) were from WHO model list of essential medicines, and 36.43% were prescribed by their generic name. Moreover, it was observed that more than 90% of the antibiotics were prescribed without investigations for bacterial infections. The most preferred route for administration of drugs were oral (86.3%) followed by parenteral and nasal. Conclusion: Symptomatic treatment was offered in most of the prescriptions audited and antibiotics were prescribed with no definite evidence of bacterial infection. Initiation of Antimicrobial Stewardship programs and National Action Plan on Antimicrobial Resistance (NAP-AMR) guidelines in health care institutes can help prescribers to follow rational drug therapy.

Lung cancer is one of the most fatal malignancies, with the highest death rates (~19%), of which NSCLC type, contributes to ~85%. In the search for new treatments, antimicrobial peptides have received much attention due to their propensity for selective destruction of cancer cells. In the current study, we evaluated the efficacy of metastasis-specific tumour-homing-TMTP1peptide against lung cancer using inhalable hybrid-nano-assemblies of PEG–PLGA-copolymer as a carrier for pulmonary delivery which was assessed for aerodynamic and physicochemical properties, along with peptide-release profile, physical stability, cellular uptake & biocompatibility, generation of reactive-oxygen-species, cell migration, autophagic flux, and apoptotic cell death in A549 lung cancer cells. Optimization of inhaled dose, lung retention, and efficacy studies was conducted to evaluate the formulation in NNK (Nicotine-derived nitrosamine ketone) induced tumour-bearing lung cancer, murine model. After inhalation, the formulation with nano-scale physiognomies showed good lung deposition, retention, and metabolic stability. The inhalable-nano-assemblies have shown enhanced generation of reactive-oxygen-species with increased autophagy-flux and apoptotic-cell death. Pre-clinical animal trials show substantial tumour regression by inhalable-TMTP1-based-nano-formulation with limited side effects. Our results on metastasis targeting and tumour-homing peptide TMTP1 exhibit effective tumour targeting and tumour-killing efficacy and provide a reference for the development of new therapeutics for NSCLC.

Flood risk assessment is primarily performed by a single flood driver at a specific location. A significant flaw in this approach is the oversight of the nonlinear interactions between various flood drivers (e.g., river flooding, tides, storm surges, and fluvial regimes), potentially resulting in compound flooding. This oversight can lead to underestimating the socioeconomic consequences of compound floods, which often surpass the risks posed by individual drivers acting alone. This study employs a deep learning model, mainly Long Short-Term Memory to predict water levels in tidal rivers under the influence of various flood drivers. The model is used to predict water levels at specific locations, using upstream river discharge, downstream water levels, and initial water levels as input variables. To account for coincidence/concurrence of drivers, we use Copula functions as a probabilistic approach to model the correlation between peak river discharge and coastal water levels as input features for the DL Model. The application of the proposed method is illustrated by applying it to a case study in the Buffalo Bayou area near Houston, TX. The results show that, for a 50-year flood, considering prior water level conditions represented by the 10th and 90th percentile baseflow scenarios, the projected flood inundation area can vary significantly, ranging from 30% to 70% for the same return period. The proposed methodology advances flood hazard assessment in coastal regions by capturing the complex interplay of different flood drivers and offering a robust yet practical flood inundation mapping approach.

A document by Arkadeep Roy. Click on the document to view its contents.

TITLEPatient With Spondyloarthropathy Presenting with Subglottic Stenosis: A Case Report

In this study, self-doped porous activated biochar derived from Venice lagoon’s Sargassum brown macroalgae (ABS) has been successfully prepared through thermochemical carbonization (pyrolysis) followed by CO2 physical activation and used as electrodes for supercapacitor (SC) applications. The ABS exhibits a remarkable specific surface area of 821 m2 g-1 and heteroatoms (N, O, and S) doping, both key features to attain high-performance carbon-based SC electrodes. The electrochemical performances of ABS-based SCs were assessed in three different electrolytes. Two are aqueous (i.e., 1 M H2SO4 and 8 M NaNO3), while the third one is the prototypical organic, namely 1 M TEABF4 in acetonitrile. In these three electrolytes, the ABS-based electrodes exhibited specific capacitance values (Cg) of 109.5, 79.0, and 64.3 F g-1, respectively, at a current density of 0.1 A g-1. The capacitive performance resulted in SC energy densities of 3.45 Whkg-1 at 22.5 Wkg-1, 6.35 Whkg-1 at 36.1Wkg-1, and 12.4 Whkg-1 at 57.4 Wkg-1 and maximum power densities of 147, 222, and 378 kWkg-1 in the acidic, quasi-neutral aqueous electrolyte and organic electrolyte, respectively. The ABS electrodes were used to realize a flexible solid-state SC based on the sulfonated polyether ether ketone (SPEEK):functionalized niobium disulfide flakes (f-NbS2) composite membrane. The flexible solid-state SC displayed a remarkable 97% Cg retention even under various mechanical stresses, including bending up to 1000 times and folding angles up to 180º, while keeping a Coulombic efficiency above 98%. This study reveals algae-derived ABS as a promising sustainable source of active materials for

Marriage and divorce are pivotal aspects of societal dynamics, influencing family structures and individual well-being. This research introduces an advanced mathematical model to comprehend the intricate dynamics of marital relationships. Unlike conventional models, which often overlook the unpredictability inherent in human interactions, our model integrates stochastic elements and real-world factors such as mental distress and family issues. Mathematical modeling unveils the dynamics of marriage and divorce, guiding interventions to foster relationship stability and societal cohesion amidst multifaceted influences. However, the deterministic approach is limited due to the randomness of virus behavior. To address this issue, a more realistic stochastic model for computer viruses is considered, which can better capture the unpredictability of virus spread and establish effective preventive measures. The positivity and uniqueness of the model are checked, and the extinction and persistence theorems are proved using Ito's method. Numerical simulation shows that when the value of increases the divorces increases in the population while by increasing the value of the broken individuals recovered from their conflict and came back to its married lifestyle.

A document by Mostafa Jelveh. Click on the document to view its contents.

As society transitions away from fossil fuels towards renewable energy sources, finding alternatives that are reliable becomes imperative. Waste-to-energy bioprocesses are promising options due to their ability to operate independently of weather conditions or time of day, making them sustainable and potentially lucrative solutions. This paper proposes an updated bioeconomic model, based on previous research [12, 13], to analyze investment in waste-to-energy technology and its associated valorization of waste treatment. This conceptual model represents a generic framework for studying waste-to-energy processes. By taking technological constraints into account, the updated model aims to optimize energy production processes and establish a sustainable business model. Indeed, using dynamic modeling, investment and valorization strategies will be evaluated through a maximization criterion over a finite time horizon, which is stated as an optimal control problem. The effective control strategies are then determined using the Pontryagin’s Maximum Principle. Furthermore, direct optimization methods are applied to derive and validate the effectiveness of the obtained optimal strategy. This approach allows for a thorough evaluation of the economic and environmental impacts in waste-to-energy technologies, identifying optimal investment and valorization strategies to promote sustainable waste management practices. In addition, a sensitivity analysis is conducted to evaluate the robustness of the studied model, and provide insights into biotechnological limitations. Finally, an extensive numerical exploration of the turnpike-like features that characterize the optimal long-term behavior of the investment problem is widely discussed.

Nowadays, the destruction of watersheds has increased under the influence of various human and natural factors, and the performance of watersheds and the provision of hydrological services have become a problem. Therefore, carrying out management measures, including watershed engineering and biological measures, is a human approach to deal with these threats and increase the expected hydrological services. Therefore, in this research, an attempt has been made to evaluate the impact of watershed management engineering and biological measures on the health of the Efin watershed in South Khorasan, Iran, with the conceptual approach of pressure-state-response (PSR). To do this, after determining the effective variables on the health and security of Efin watershed and removing the variables with co-linearity using Principal Component Analysis (PCA), the PSR indices were quantified and standardized and was used based on the behavioral data for determining the health and security of the watershed. In order to determine the role of watershed management operations on health and safety indicators, the variables related to watershed management measures including Normalized Difference Vegetation Index (NDVI), concentration time and Curve Number (CN) under three management scenarios of 50, 75 and 100% of the area of the measures Efin watershed was re-determined and the health index was calculated after implementing watershed measures and compared with the conditions before the operation. The results showed that the PSR indices were variable in the ranges of 0.35 to 0.73, 0.35 to 0.60 and 0.19 to 0.59, respectively. The health and security index of sub-watersheds also changed between 0.37 to 0.50 and 0.22 to 0.69, respectively. The research results showed that due to the non-change of the pressure variables, this index has not changed under the management scenarios. But on average, the status index in the first, second and third scenarios has increased by 7.38, 4.92 and 6.41%, respectively. This response index has increased in all three scenarios by 26.37, 18.95 and 14.65% respectively. In the first, second and third management scenarios, the health index has experienced an increase of 10.31, 7.32 and 6.50%, respectively. Finally, under the influence of the first, second and third management scenarios. The security index shows an increase of 35.32, 24.92 and 21.88%, respectively. As the results of the research show, the implementation of engineering and biological measures alone cannot increase the health of Efin watershed and ensure their security. Therefore, it is suggested to use comprehensive management approaches of watersheds in the direction of better and principled management of watersheds and help to improve their performance.

Numerous challenges hinder the development of neuroprotective treatments for Parkinson’s disease, with a regularly identified issue being the lack of clinically relevant animal models. Viral vector overexpression of α-synuclein is widely considered the most relevant model, however this has been limited by high variability and inconsistency. One potential method of optimisation is pairing it with a secondary insult such as FN075, a synthetic molecule demonstrated to accelerate α-synucleinopathy. Thus, the aim of this study was to investigate if sequential infusion of AAV-α-synuclein and FN075 into the rat brain can replicate α-synucleinopathy, nigrostriatal pathology and motor dysfunction associated with Parkinson’s disease. Rats received a unilateral injection of AAV-α-synuclein (or AAV-GFP) into two sites in the substantia nigra, followed 4 weeks later by unilateral injection of FN075 (or vehicle) into the striatum. Animals underwent behavioural testing every 4 weeks until sacrifice at 20 weeks, followed by immunohistochemistry assessment post-mortem. As anticipated, AAV-α-synuclein led to extensive overexpression of human α-synuclein throughout the nigrostriatal pathway, as well as elevated levels of pathological and aggregated forms of the protein. However, the sequential administration of FN075 into the striatum did not exacerbate any of the α-synuclein pathology. Furthermore, despite the extensive α-synuclein pathology, neither administration of AAV-α-synuclein nor FN075, alone or in combination, was sufficient to induce dopaminergic degeneration or motor deficits. In conclusion, this approach did not replicate the key characteristics of Parkinson’s disease, and further studies are required to create more representational models for testing of novel compounds and treatments for Parkinson’s disease.