Interventions to improve patient admission and discharge practices in adult intensive care units: A systematic review.

OBJECTIVES: To identify and synthesise interventions and implementation strategies to optimise patient flow, addressing admission delays, discharge delays, and after-hours discharges in adult intensive care units. METHODS: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines. Five electronic databases, including CINAHL, PubMed, Emcare, Scopus, and the Cochrane Library, were searched from 2007 to 2023 to identify articles describing interventions to enhance patient flow practices in adult intensive care units. The Critical Appraisal Skills Program (CASP) tool assessed the methodological quality of the included studies. All data was synthesised using a narrative approach. SETTING: Adult intensive care units. RESULTS: Eight studies met the inclusion criteria, mainly comprising quality improvement projects (n = 3) or before-and-after studies (n = 4). Intervention types included changing workflow processes, introducing decision support tools, publishing quality indicator data, utilising outreach nursing services, and promoting multidisciplinary communication. Various implementation strategies were used, including one-on-one training, in-person knowledge transfer, digital communication, and digital data synthesis and display. Most studies (n = 6) reported a significant improvement in at least one intensive care process-related outcome, although fewer studies specifically reported improvements in admission delays (0/0), discharge delays (1/2), and after-hours discharge (2/4). Two out of six studies reported significant improvements in patient-related outcomes after implementing the intervention. CONCLUSION: Organisational-level strategies, such as protocols and alert systems, were frequently employed to improve patient flow within ICUs, while healthcare professional-level strategies to enhance communication were less commonly used. While most studies improved ICU processes, only half succeeded in significantly reducing discharge delays and/or after-hours discharges, and only a third reported improved patient outcomes, highlighting the need for more effective interventions. IMPLICATIONS FOR CLINICAL PRACTICE: The findings of this review can guide the development of evidence-based, targeted, and tailored interventions aimed at improving patient and organisational outcomes.

Stereodynamic Strategies to Induce and Enrich Chirality of Atropisomers at a Late Stage.

Enantiomers, where chirality arises from restricted rotation around a single bond, are atropisomers. Due to the unique nature of the origins of their chirality, synthetic strategies to access these compounds in an enantioselective manner differ from those used to prepare enantioenriched compounds containing point chirality arising from an unsymmetrically substituted carbon center. In particular stereodynamic transformations, such as dynamic kinetic resolutions, thermodynamic dynamic resolutions, and deracemizations, which rely on the ability to racemize or interconvert enantiomers, are a promising set of transformations to prepare optically pure compounds in the late stage of a synthetic sequence. Translation of these synthetic approaches from compounds with point chirality to atropisomers requires an expanded toolbox for epimerization/racemization and provides an opportunity to develop a new conceptual framework for the enantioselective synthesis of these compounds.

Establishing critical care nursing research priorities for three Australian regional public hospitals: A mixed method priority setting study.

OBJECTIVE: To determine key priorities for critical care nursing research in three Australian regional public hospitals, representing the shared priorities of healthcare professionals and patient representatives. METHODS: A three phase priority setting study, including consensus methods (nominal group), survey, qualitative interviews and focus groups were conducted between May 2021 and March 2022. Healthcare professionals and patient representatives from critical care units in regional public hospitals in Australia participated. A patient representative contributed to research design and co-authored this paper. RESULTS: In phase one, 29 research topics were generated. In phase two, during a nominal group ranking process, the top 5 priority areas for each site were identified. In the final phase, three themes from focus groups and interviews included patient flow through intensive care, patient care through intensive care journey and intensive care patient recovery. CONCLUSION: Identifying context specific research priorities through a priority setting exercise provides insight into the topics that are important to healthcare professionals and to patients in critical care. The top research priorities for nursing research in critical care in regional Australian hospitals include patient flow, patient recovery, and evidence based patient care through the intensive care journey, such as delirium management, pain and sedation, and mobilisation. These shared priorities will be used to guide future nursing research in critical care over the next 3-5 years. IMPLICATIONS FOR CLINICAL PRACTICE: The method we used in identifying the research priorities can be used by other researchers and clinicians; close collaboration among researchers and clinicians will be beneficial for practice improvement; and how we can be reassured that our practice is evidence based is worthy of attention.

Job satisfaction and symptoms of depression, anxiety, stress, and burnout: A survey of Australian and New Zealand intensive care research coordinators.

INTRODUCTION: Intensive care unit clinical research is often implemented by specialised research coordinators (RCs). Clinical research activity within Australian and New Zealand intensive care units has escalated, particularly during the COVID-19 pandemic. Growth of the intensive care RC workforce to match research demand is poorly understood. AIM: The aim of this study was to repeat an Intensive Care Research Coordinator Interest Group workforce survey conducted in 2004 and 2009 to describe the current workforce and role satisfaction and also to determine reported symptoms of depression, anxiety, stress, and burnout in Australian and New Zealand intensive care RCs. METHODS: In April 2021, an online anonymised survey was distributed to intensive care RCs to complete demographic and workforce questions, the McCloskey/Mueller Satisfaction Scale, the Depression Anxiety Stress Scales-21, and the Maslach Burnout Inventory-Human Services Survey for Medical Personnel. RESULTS: Of 128 Intensive Care Research Coordinator Interest Group eligible members, 98 (77%) completed the survey. Respondents were mainly women (91%), the median age was 47 years, 37% have a postgraduate qualification, and a third have over 10 years of RCC experience (31%). Half do not have permanent employment (52%). The mean Depression Anxiety Stress Scales-21 scores were within the normal range, and respondents reported symptoms of depression (21 [21%]), anxiety (23 [23%]), and stress (26 [27%]). Nearly half of the respondents (44%) exhibited an early symptom of burnout by reporting problematic experiences of work. The overall role satisfaction score was 3.5/5 (neutral; neither satisfied nor dissatisfied). CONCLUSIONS: Intensive care RCs are an experienced group of professionals with limited satisfaction in the role. One-fifth of the ICU RCs experienced depression, anxiety, or stress symptoms, with close to half reporting signs of burnout. These results highlight the need to address areas of concern to ensure retention of this specialised intensive care workforce.

Stress response during early sedation with dexmedetomidine compared with usual-care in ventilated critically ill patients.

BACKGROUND: Sedative agents may variably impact the stress response. Dexmedetomidine is a sympatholytic alpha2-adrenergic agonist mainly used as a second-line sedative agent in mechanically ventilated patients. We hypothesised that early sedation with dexmedetomidine as the primary agent would result in a reduced stress response compared to usual sedatives in critically ill ventilated adults. METHODS: This was a prospective sub-study nested within a multi-centre randomised controlled trial of early sedation with dexmedetomidine versus usual care. The primary outcome was the mean group differences in plasma levels of stress response biomarkers measured over 5 days following randomisation. Other hormonal, biological and physiological parameters were collected. Subgroup analyses were planned for patients with proven or suspected sepsis. RESULTS: One hundred and three patients were included in the final analysis. Baseline illness severity (APACHE II score), the proportion of patients receiving propofol and the median dose of propofol received were comparable between groups. More of the usual-care patients received midazolam (57.7% vs 33.3%; p = 0.01) and at higher dose (median (95% interquartile range) 0.46 [0.20-0.93] vs 0.14 [0.08-0.38] mg/kg/day; p < 0.01). The geometric mean (95% CI) plasma level of the stress hormones, adrenaline (0.32 [0.26-0.4] vs 0.38 [0.31-0.48]), noradrenaline (4.27 [3.12-5.85] vs 6.2 [4.6-8.5]), adrenocorticotropic hormone (17.1 [15.1-19.5] vs 18.1 [15.9-20.5]) and cortisol (515 [409-648] vs 618 [491-776)] did not differ between dexmedetomidine and usual-care groups, respectively. There were no significant differences in any other assayed biomarkers or physiological parameters Sensitivity analyses showed no effect of age or sepsis. CONCLUSIONS: Early sedation with dexmedetomidine as the primary sedative agent in mechanically ventilated critically ill adults resulted in comparable changes in physiological and blood-borne parameters associated with the stress-response as with usual-care sedation.

Structural Basis of Stereospecific Vanadium-Dependent Haloperoxidase Family Enzymes in Napyradiomycin Biosynthesis.

Vanadium-dependent haloperoxidases (VHPOs) from Streptomyces bacteria differ from their counterparts in fungi, macroalgae, and other bacteria by catalyzing organohalogenating reactions with strict regiochemical and stereochemical control. While this group of enzymes collectively uses hydrogen peroxide to oxidize halides for incorporation into electron-rich organic molecules, the mechanism for the controlled transfer of highly reactive chloronium ions in the biosynthesis of napyradiomycin and merochlorin antibiotics sets the Streptomyces vanadium-dependent chloroperoxidases apart. Here we report high-resolution crystal structures of two homologous VHPO family members associated with napyradiomycin biosynthesis, NapH1 and NapH3, that catalyze distinctive chemical reactions in the construction of meroterpenoid natural products. The structures, combined with site-directed mutagenesis and intact protein mass spectrometry studies, afforded a mechanistic model for the asymmetric alkene and arene chlorination reactions catalyzed by NapH1 and the isomerase activity catalyzed by NapH3. A key lysine residue in NapH1 situated between the coordinated vanadate and the putative substrate binding pocket was shown to be essential for catalysis. This observation suggested the involvement of the ε-NH2, possibly through formation of a transient chloramine, as the chlorinating species much as proposed in structurally distinct flavin-dependent halogenases. Unexpectedly, NapH3 is modified post-translationally by phosphorylation of an active site His (τ-pHis) consistent with its repurposed halogenation-independent, α-hydroxyketone isomerase activity. These structural studies deepen our understanding of the mechanistic underpinnings of VHPO enzymes and their evolution as enantioselective biocatalysts.

Prevalence and factors associated with polypharmacy: a systematic review and Meta-analysis.

INTRODUCTION: Polypharmacy is commonly associated with adverse health outcomes. There are currently no meta-analyses of the prevalence of polypharmacy or factors associated with polypharmacy. We aimed to estimate the pooled prevalence of polypharmacy and factors associated with polypharmacy in a systematic review and meta-analysis. METHODS: MEDLINE, EMBASE, and Cochrane databases were searched for studies with no restrictions on date. We included observational studies that reported on the prevalence of polypharmacy among individuals over age 19. Two reviewers extracted study characteristics including polypharmacy definitions, study design, setting, geography, and participant demographics. The risk of bias was assessed using the Newcastle-Ottawa Scales. The main outcome was the prevalence of polypharmacy and factors associated with polypharmacy prevalence. The pooled prevalence estimates of polypharmacy with 95% confidence intervals were determined using random effects meta-analysis. Subgroup analyses were undertaken to evaluate factors associated with polypharmacy such as polypharmacy definitions, study setting, study design and geography. Meta-regression was conducted to assess the associations between polypharmacy prevalence and study year. RESULTS: 106 full-text articles were identified. The pooled estimated prevalence of polypharmacy in the 54 studies reporting on polypharmacy in all medication classes was 37% (95% CI: 31-43%). Differences in polypharmacy prevalence were reported for studies using different numerical thresholds, study setting, and publication year. Sex, study geography, study design and geographical location were not associated with differences in polypharmacy prevalence. DISCUSSION: Our review highlights that polypharmacy is common particularly among older adults and those in inpatient settings. Clinicians should be aware of populations who have an increased likelihood of experiencing polypharmacy and efforts should be made to review the appropriateness of prescribed medications and occurrence of adverse effects potentially associated with polypharmacy. CONCLUSIONS AND IMPLICATIONS: Clinicians should be aware of the common occurrence of polypharmacy and undertake efforts to minimize inappropriate polypharmacy whenever possible.

Image statistics determine the integration of visual cues to motion-in-depth.

Motion-in-depth perception is critical in enabling animals to avoid hazards and respond to potential threats. For humans, important visual cues for motion-in-depth include changing disparity (CD) and changing image size (CS). The interpretation and integration of these cues depends upon multiple scene parameters, such as distance moved, object size and viewing distance, posing a significant computational challenge. We show that motion-in-depth cue integration depends upon sensitivity to the joint probabilities of the scene parameters determining these signals, and on the probability of CD and CS signals co-occurring. Models that took these factors into account predicted human performance in speed-in-depth and cue conflict discrimination tasks, where standard linear integration models could not. These results suggest that cue integration is affected by both the uncertainty of sensory signals and the mapping of those signals to real-world properties. Evidence of a role for such mappings demonstrates the importance of scene and image statistics to the processes underpinning cue integration and the perception of motion-in-depth.

Biocatalytic oxidative cross-coupling reactions for biaryl bond formation.

Biaryl compounds, with two connected aromatic rings, are found across medicine, materials science and asymmetric catalysis1,2. The necessity of joining arene building blocks to access these valuable compounds has inspired several approaches for biaryl bond formation and challenged chemists to develop increasingly concise and robust methods for this task3. Oxidative coupling of two C-H bonds offers an efficient strategy for the formation of a biaryl C-C bond; however, fundamental challenges remain in controlling the reactivity and selectivity for uniting a given pair of substrates4,5. Biocatalytic oxidative cross-coupling reactions have the potential to overcome limitations inherent to numerous small-molecule-mediated methods by providing a paradigm with catalyst-controlled selectivity6. Here we disclose a strategy for biocatalytic cross-coupling through oxidative C-C bond formation using cytochrome P450 enzymes. We demonstrate the ability to catalyse cross-coupling reactions on a panel of phenolic substrates using natural P450 catalysts. Moreover, we engineer a P450 to possess the desired reactivity, site selectivity and atroposelectivity by transforming a low-yielding, unselective reaction into a highly efficient and selective process. This streamlined method for constructing sterically hindered biaryl bonds provides a programmable platform for assembling molecules with catalyst-controlled reactivity and selectivity.

Biomimetic synthesis of the non-canonical PPAP natural products yezo'otogirin C and hypermogin D, and studies towards the synthesis of norascyronone A.

Oxidative degradation and rearrangement of polycyclic polyprenylated acylphloroglucinols (PPAPs) has created diverse families of unique natural products that are attractive targets for biomimetic synthesis. Herein, we report a racemic synthesis of hyperibrin A and its oxidative radical cyclization to give yezo'otogirin C, followed by epoxidation and House-Meinwald rearrangement to give hypermogin D. We also investigated the biomimetic synthesis of norascyronone A via a similar radical cyclization pathway, with unexpected results that give insight into its biosynthesis.

A Diazo-Hooker Reaction, Inspired by the Biosynthesis of Azamerone.

Motivated by the biosynthesis of azamerone, we report the first example of a diazo-Hooker reaction, which involves the formation of a phthalazine ring system by the oxidative rearrangement of a diazoketone. Computational studies indicate that the diazo-Hooker reaction proceeds via an 8π-electrocyclization followed by ring contraction and aromatization. The biosynthetic origin of the diazoketone functional group was also chemically mimicked using a related natural product, naphterpin, as a model system.

COVID-19 Outbreak in A Forward-Deployed Expeditionary Military Command: A Retrospective Review on Preventative Measures and Outbreak Characteristics.

BACKGROUND: An outbreak of coronavirus disease 2019 (COVID-19) occured within a land based 2,000-member cohort stationed on a remote air base in the Middle East from June to August 2020. We retrospectively reviewed base characteristics and mitigation measures instituted during the outbreak. We also reviewed documentation on the individuals that were either quarantined or placed in isolation and provide data on demographics, real-time reverse transcriptase polymerase chain reaction (rRT-PCR) results, occupation, and workdays lost. RESULTS: During the reporting period, 46 individuals or 3.84% of the population had a positive COVID-19 rRT-PCR test. Aviation personnel represented 50% of the COVID-19 positive tests. Sixteen percent of health care personnel were tested positive. Overall, 10% of personnel were placed in isolation or quarantine, resulting in the loss of 1,552 workdays. CONCLUSIONS: The data show a disproportionate impact on healthcare workers and personnel involved in aviation operations. The purpose of this study is 2-fold: to describe the characteristics of the outbreak and to highlight the effectiveness of mitigation measures implemented to control it during military operations. This study may serve to inform medical professionals and military leaders in the management of a similar outbreak in a congregate living setting.

Sodium chloride or Plasmalyte-148 evaluation in severe diabetic ketoacidosis (SCOPE-DKA): a cluster, crossover, randomized, controlled trial.

PURPOSE: To determine whether treatment with Plasmalyte-148 (PL) compared to sodium chloride 0.9% (SC) results in faster resolution of diabetic ketoacidosis (DKA) and whether the acetate in PL potentiates ketosis. METHODS: We conducted a cluster, crossover, open-label, randomized, controlled Phase 2 trial at seven hospitals in adults admitted to intensive care unit (ICU) with severe DKA with hospital randomised to PL or SC as fluid therapy. The primary outcome, DKA resolution, was defined as a change in base excess to ≥ - 3 mEq/L at 48 h. RESULTS: Ninety-three patients were enrolled with 90 patients included in the modified-intention-to-treat population (PL n = 48, SC n = 42). At 48 h, mean fluid administration was 6798 ± 4850 ml vs 6574 ± 3123 ml, median anion gap 6 mEq/L (IQR 5-7) vs 7 mEq/L (IQR 5-7) and median blood ketones 0.3 mmol/L (IQR 0.1-0.5) vs 0.3 (IQR 0.1-0.5) in the PL and SC groups. DKA resolution at 48 h occurred in 96% (PL) and 86% (SC) of patients; odds ratio 3.93 (95% CI 0.73-21.16, p = 0.111). At 24 h, DKA resolution occurred in 69% (PL) and 36% (SC) of patients; odds ratio 4.24 (95% CI 1.68-10.72, p = 0.002). The median ICU and hospital lengths of stay were 49 h (IQR 23-72) vs 55 h (IQR 41-80) and 81 h (IQR 58-137) vs 98 h (IQR 65-195) in the PL and SC groups. CONCLUSION: Plasmalyte-148, compared to sodium chloride 0.9%, may lead to faster resolution of metabolic acidosis in patients with DKA without an increase in ketosis. These findings need confirmation in a large, Phase 3 trial.

Intensive care doctors and nurses personal preferences for Intensive Care, as compared to the general population: a discrete choice experiment.

BACKGROUND: To test the hypothesis that Intensive Care Unit (ICU) doctors and nurses differ in their personal preferences for treatment from the general population, and whether doctors and nurses make different choices when thinking about themselves, as compared to when they are treating a patient. METHODS: Cross sectional, observational study conducted in 13 ICUs in Australia in 2017 using a discrete choice experiment survey. Respondents completed a series of choice sets, based on hypothetical situations which varied in the severity or likelihood of: death, cognitive impairment, need for prolonged treatment, need for assistance with care or requiring residential care. RESULTS: A total of 980 ICU staff (233 doctors and 747 nurses) participated in the study. ICU staff place the highest value on avoiding ending up in a dependent state. The ICU staff were more likely to choose to discontinue therapy when the prognosis was worse, compared with the general population. There was consensus between ICU staff personal views and the treatment pathway likely to be followed in 69% of the choices considered by nurses and 70% of those faced by doctors. In 27% (1614/5945 responses) of the nurses and 23% of the doctors (435/1870 responses), they felt that aggressive treatment would be continued for the hypothetical patient but they would not want that for themselves. CONCLUSION: The likelihood of returning to independence (or not requiring care assistance) was reported as the most important factor for ICU staff (and the general population) in deciding whether to receive ongoing treatments. Goals of care discussions should focus on this, over likelihood of survival.

Meroterpenoid natural products from Streptomyces bacteria - the evolution of chemoenzymatic syntheses.

Covering: Up to January 2020Meroterpenoids derived from the polyketide 1,3,6,8-tetrahydroxynaphthalene (THN) are complex natural products produced exclusively by Streptomyces bacteria. These antibacterial compounds include the napyradiomycins, merochlorins, marinones, and furaquinocins and have inspired many attempts at their chemical synthesis. In this review, we highlight the role played by biosynthetic studies in the stimulation of biomimetic and, ultimately, chemoenzymatic total syntheses of these natural products. In particular, the application of genome mining techniques to marine Streptomyces bacteria led to the discovery of unique prenyltransferase and vanadium-dependent haloperoxidase enzymes that can be used as highly selective biocatalysts in fully enzymatic total syntheses, thus overcoming the limitations of purely chemical reagents.

Total Synthesis of Naphterpin and Marinone Natural Products.

A concise and divergent strategy for the synthesis of the naphterpin and marinone meroterpenoid families has been developed. The approach features a succession of pericyclic reactions-an aromatic Claisen rearrangement, a retro-6π-electrocyclization, and two Diels-Alder reactions-which facilitated the first total synthesis of naphterpin itself in five steps from 2,5-dimethoxyphenol, alongside similar syntheses of 7-demethylnaphterpin and debromomarinone. Late-stage oxidation and bromination reactions were also investigated, leading to the first total syntheses of naphterpins B and C and isomarinone.

The role of one-carbon metabolism and homocysteine in Parkinson's disease onset, pathology and mechanisms.

Parkinson's disease (PD) is the second most common neurodegenerative disorder. It is characterised by the progressive degeneration of dopaminergic (DA) neurons. The cause of degeneration is not well understood; however, both genetics and environmental factors, such as nutrition, have been implicated in the disease process. Deficiencies in one-carbon metabolism in particular have been associated with increased risk for PD onset and progression, though the precise relationship is unclear. The aim of the present review is to determine the role of one-carbon metabolism and elevated levels of homocysteine in PD onset and pathology and to identify potential mechanisms involved. A search of PubMed, Google Scholar and Web of Science was undertaken to identify relevant human and animal studies. Case-control, prospective cohort studies, meta-analyses and non-randomised trials were included in the present review. The results from human studies indicate that polymorphisms in one-carbon metabolism may increase risk for PD development. There is an unclear role for dietary B-vitamin intake on PD onset and progression. However, dietary supplementation with B-vitamins may be beneficial for PD-affected individuals, particularly those on l-DOPA (levodopa or l-3,4-dihydroxyphenylalanine) treatment. Additionally, one-carbon metabolism generates methyl groups, and methylation capacity in PD-affected individuals is reduced. This reduced capacity has an impact on expression of disease-specific genes that may be involved in PD progression. During B-vitamin deficiency, animal studies report increased vulnerability of DA cells through increased oxidative stress and altered methylation. Nutrition, especially folates and related B-vitamins, may contribute to the onset and progression of PD by making the brain more vulnerable to damage; however, further investigation is required.

Actions and processes that patients, family members, and physicians associate with patient- and family-centered care.

BACKGROUND: Patient- and family-centered care (PFCC) is increasingly linked to improved communication, care quality, and patient decision making. However, in order to consistently implement and study PFCC, health care systems and researchers need a solid evidentiary base. Most current definitions and models of PFCC are broad and conceptual, and difficult to translate into measurable behaviors and actions. This paper provides a brief overview of all actions that focus group respondents associated with PFCC in ambulatory (outpatient) care settings and then explores actions associated with the concept of "dignity and respect" in greater detail. METHODS: We conducted nine focus groups with patients, family members, and physicians in three metropolitan regions across the United States. Group discussions were transcribed and analyzed using a thematic analysis approach. RESULTS: We identified 14 domains and 47 specific actions that patients, family members, and physicians associate with PFCC. In addition to providing a detailed matrix of these domains and actions, this paper details the actions associated with the "dignity and respect" concept. Key domains identified under "dignity and respect" include: 1) building relationships, 2) providing individualized care, and 3) respecting patients' time. Within these domains we identified specific actions that break down these abstract ideas into explicit and measurable units such as taking time, listening, including family, and minimizing wait times. We identified 9, 6, and 3 specific actions associated, respectively, with building relationships, providing individualized care, and respecting patients' time. CONCLUSIONS: Our work fills a critical gap in our ability to understand and measure PFCC in ambulatory care settings by breaking down abstract concepts about PFCC into specific measurable actions. Our findings can be used to support research on how PFCC affects clinical outcomes and develop innovative tools and policies to support PFCC.

Paraquat Exposure Increases Oxidative Stress Within the Dorsal Striatum of Male Mice With a Genetic Deficiency in One-carbon Metabolism.

Paraquat is an herbicide that is commonly used worldwide. Exposure to paraquat results in Parkinson's disease (PD)-like symptoms including dopaminergic cell loss. Nutrition has also been linked in the pathogenesis of PD, such as reduced levels of folic acid, a B-vitamin, and component of one-carbon metabolism. Within one-carbon metabolism, methylenetetrahydrofolate reductase (MTHFR) catalyzes the irreversible conversion of 5, 10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. A polymorphism in MTHFR (677 C&→T) has been reported in 5%-15% of North American and European human populations. The MTHFR polymorphism is also prevalent in PD patients. The goal of this study was to investigate the impact of paraquat-induced PD-like pathology in the context of reduced levels of MTHFR. Three-month-old male Mthfr+/- mice, which model the MTHFR polymorphism observed in humans, were administered intraperitoneal injections of paraquat (10 mg/kg) or saline 6 times over 3 weeks. At the end of paraquat treatment, motor and memory function were assessed followed by collection of brain tissue for biochemical analysis. Mthfr+/- mice treated with paraquat showed impaired motor function. There was increased microglial activation within the substantia nigra (SN) of Mthfr+/- mice treated with paraquat. Additionally, all Mthfr+/- mice that were treated with paraquat showed increased oxidative stress within the dorsal striatum, but not the SN. The present results show that paraquat exposure increases PD-like pathology in mice deficient in one-carbon metabolism.