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Superconducting magnets based on Rare Earth Barium Copper Oxides (REBCO) offer transformative capabilities in the fields of fusion energy, high energy physics, and space exploration. A challenge shared by these applications is the limited lifetime of REBCO due to radiation damage sustained during operation. Here we present a new ion-beam facility that enables simultaneous cryogenic irradiation and in situ characterization of commercial REBCO tapes. The ion source provides spatially uniform fluxes up to 1018 protons/m2s with kinetic energies up to 3.4 MeV, in addition to helium and higher-Z species. Using this facility, we can induce uniform damage profiles in the first 10-20 µm of REBCO tapes with less than 0.25 appm of hydrogen implanted in REBCO after a dose of 1020 protons/m2. The tape can be held between 20 and 300 K with an accuracy of ±0.1 K and is connected to a four-point probe measuring the critical current, Ic, and critical temperature, Tc, before, during, and after irradiation with transport current ranging from 100 nA to 100 A, and a typical voltage noise less than 0.1 µV. These capabilities are presently used to study the effect of irradiation temperature on REBCO performance change during and after proton bombardment, to assess the possibility of Ic and Tc recovery after irradiation through thermal annealing, and to explore the instantaneous and recoverable suppression of Ic and Tc observed during irradiation.
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BACKGROUND: Negative-pressure-wound-therapy (NPWT) has become a widely used tool for the coverage and active treatment of complex wounds, including burns. This study aimed to evaluate the effectiveness of NPWT in acute burns of upper and lower extremities and to compare results to the standard-of-care (SOC) at our institution. METHODS: Patients that were admitted to our institution between May 2019 and November 2021 with burns on extremities between 0.5 % and 10 % of the total body surface area (%TBSA) were included and randomized to either NPWT or SOC (polyhexanide gel, fatty gauze, and cotton wool). Treatment was performed until complete wound healing. Patients that required skin grafts, received additional NPWT after grafting independent on the initial group allocation. RESULTS: Sixty-five patients suffering from burn injury between May 2019 and November 2021 were randomized into treatment with NPWT (n = 33) or SOC (n = 32); of these, 33 patients (NPWT) and 28 patients (SOC) had complete data sets and were included in the analysis. Both groups were similar regarding age (39.8 ± 13.7 vs. 44.8 ± 16.2 years,p = 0.192), total burn size (3.1 ± 2.3 vs. 3.4 ± 2.8 %TBSA,p = 0.721) and treated wound size (1.9 ± 1.2 vs. 1.5 ± 0.8 %TBSA,p = 0.138). We found no differences regarding healing time (11.0 ± 4.9 vs. 8.6 ± 3.8,p = 0.074, and significant differences in a number of dressing changes throughout the study (2.4 ± 1.5 vs 4.2 ± 1.9,p < 0.001). The Kaplan-Meier time-to-event analysis exhibited no statistically significant difference in the time to healing or skin grafting (p = 0.085) in NPWT group compared with SOC group. The median time to healing or skin grafting was 10(8-11) days for NPWT and 9(7-11) days for SOC. The hazard ratio for healing or skin graft was HR= 0.64(0.38-1.08). The results of the time-to-event analysis as well as the Kaplan-Meier curve on the PPS confirmed this result. We found no differences in secondary surgical operations 15.2 vs 21.4 % pain or functional outcomes. CONCLUSIONS: In this study, we found no significant difference between the two groups in terms of time to detect wound healing. We also found no difference regarding further operations for wound closure, pain and/or scarring. However, dressing changes were significantly less frequent for patients that were treated with NPWT, which may be a psychological and logistical advantage.
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INTRODUCTION: Lewy body disease (LBD) is a common primary or co-pathology in neurodegenerative syndromes. An alpha-synuclein seed amplification assay (αSyn-SAA) is clinically available, but clinical performance, especially lower sensitivity in amygdala-predominant cases, is not well understood. METHODS: Antemortem CSF from neuropathology-confirmed LBD cases was tested with αSyn-SAA (N = 56). Diagnostic performance and clinicopathological correlations were examined. RESULTS: Similar to prior reports, sensitivity was 100% for diffuse and transitional LBD (9/9), and overall specificity was 96.3% (26/27). Sensitivity was lower in amygdala-predominant (6/14, 42.8%) and brainstem-predominant LBD (1/6, 16.7%), but early spread outside these regions (without meeting criteria for higher stage) was more common in αSyn-SAA-positive cases (6/7, 85.7%) than negative (2/13, 15.4%). DISCUSSION: In this behavioral neurology cohort, αSyn-SAA had excellent diagnostic performance for cortical LBD. In amygdala- and brainstem-predominant cases, sensitivity was lower, but positivity was associated with anatomical spread, suggesting αSyn-SAA detects early LBD progression in these cohorts. HIGHLIGHTS: A cerebrospinal fluid alpha-synuclein assay detects cortical LBD with high sensitivity/specificity. Positivity in prodromal stages of LBD was associated with early cortical spread. The assay provides precision diagnosis of LBD that could support clinical trials. The assay can also identify LBD co-pathology, which may impact treatment responses.
Subject(s)
Autopsy , Lewy Body Disease , Sensitivity and Specificity , alpha-Synuclein , Humans , alpha-Synuclein/cerebrospinal fluid , Lewy Body Disease/cerebrospinal fluid , Lewy Body Disease/pathology , Female , Male , Aged , Cohort Studies , Amygdala/pathology , Aged, 80 and over , Biomarkers/cerebrospinal fluid , Middle AgedABSTRACT
Paint used to coat surfaces in aquatic environments often contain biocides to prevent biofouling, and as these coatings degrade, antifouling paint particles (APPs) end up in aquatic, and especially marine, sediments. However, it is currently unclear what further influence APPs in the sediment have on biotic communities or processes. This study investigates how a variety of commercially-available APPs effect the marine microbial community by spiking different laboratory-manufactured APPs to sediment. Following exposure for 30 and 60 days, APPs caused a clear and consistent effect on the bacterial community composition as determined by 16S metabarcoding. This effect was strongest between 0 and 30 days, but continues to a lesser extent between 30 and 60 days. APPs appear to inhibit the highly diverse, but in general rarer, fraction of the community and/or select for specific community members to become more dominant. 71 antifouling-presence and 454 antifouling-absence indicator taxa were identified by indicator analysis. The difference in the level of classification in these two indicator groups was highly significant, with the antifouling-presence indicators having much higher percentage sequence identity to cultured taxa, while the antifouling-absence indicators appear to be made up of undescribed taxa, which may indicate that APPs act as a proxy for general anthropogenic influence or that APP contamination selects for taxa capable of being cultured. Given the clear and consistent effect APPs have on the surrounding sediment microbial community, further research into how APPs affect sediment functional processes and how such effects scale with concentration is recommended to better assess the wider consequences of these pollutants for marine biogeochemical cycles in the future. SYNOPSIS: Microplastic-paint particles are commonly found in marine sediment but little is known about how these, especially antifouling, paint particles affect sediment microbial communities. This study demonstrates that antifouling paint particles fundamentally alter sediment microbial communities.
Subject(s)
Biofouling , Microbiota , Water Pollutants, Chemical , Biofouling/prevention & control , Microplastics , Plastics , Paint/analysis , Water Pollutants, Chemical/analysis , Geologic Sediments/chemistryABSTRACT
BACKGROUND: This study evaluates the implementation of postcardiac-arrest-sedation (PCAS) and -care (PRC) by prehospital emergency physicians in Germany. MATERIALS AND METHODS: Analysis of a web-based survey from October to November 2022. Questions were asked about implementation, medications used, complications, motivation for implementing or not implementing PCAS, and measures and target parameters of PRC. RESULTS: A total of 500 emergency physicians participated in the survey. In all, 73.4% stated that they regularly performed PCAS (hypnotics: 84.7%; analgesics: 71.1%; relaxants: 29.7%). Indications were pressing against the respirator (88.3%), analgesia (74.1%), synchronization to respirator (59.5%), and change of airway device (52.6%). Reasons for not performing PCAS (26.6%) included unconscious patients (73.7%); concern about hypotension (31.6%), re-arrest (26.3%), and worsening neurological assessment (22.5%). Complications of PCAS were observed by 19.3% of participants (acute hypotension [74.6%]); (re-arrest [32.4%]). In addition to baseline monitoring, PRC included 12-lead-electrocardiogram (96.6%); capnography (91.6%); catecholamine therapy (77.6%); focused echocardiography (20.6%), lung ultrasound (12.0%) and abdominal ultrasound (5.6%); induction of hypothermia (13.6%) and blood gas analysis (7.4%). An etCO2 of 35-45â¯mmâ¯Hg was targeted by 40.6%, while 9.0% of participants targeted an SpO2 of 94-98% and 19.2% of participants targeted a systolic blood pressure of ≥â¯100â¯mmâ¯Hg. CONCLUSIONS: Prehospital PRC in Germany is heterogeneous and deviations from its target parameters are frequent. PCAS is frequent and associated with relevant complications. The development of preclinical care algorithms for PCAS and PRC within preclinical care seems urgently needed.
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Recognizing multiple neuropathological entities in people with dementia improves understanding of diagnosis, prognosis, and expected outcomes from therapies. Care for the individual with dementia includes the evaluation and management of diseases associated with the aged brain, most commonly neurodegeneration and vascular brain injury (VBI). Terminology has evolved to keep pace with diagnostic, prognostic, and therapeutic advances, and autopsy studies have shown that multiple comorbid neuropathological entities are the rule, not the exception, especially in older individuals. With the advent of disease-modifying therapies, delivering dementia care requires an encompassing framework that allows clinicians to consider all of an individual's underlying diseases and their contributions to symptom burden. A diagnostic approach, common co-occurring pathologies, and implications for current and future clinical care are reviewed.
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Parkinson's disease (PD) is heterogenous in its presentation, progression and response to therapies. Genetic polymorphisms may account for some of this variability. Several single nucleotide polymorphisms (SNPs) in the brain-derived neurotrophic factor gene BDNF have been associated with differing clinical outcomes from different dopaminergic replacement strategies, and one of these, the rs6265 SNP, has been associated with a milder clinical phenotype in the unmedicated, early-stage of PD. We examined if other BDNF SNPs with potential pharmacogenetic effects also are associated with different rates of disease progression. The Deprenyl And Tocopherol Antioxidative Therapy Of Parkinsonism (DATATOP) study was analyzed retrospectively. DNA samples (n = 217) were genotyped for the BDNF rs908867, rs11030094, rs10501087, rs1157659, and rs1491850 SNPs, and the primary endpoint was time to initiate symptomatic pharmacotherapy. Genotypes were compared using the Cox proportional hazard ratio (HR) with baseline age, sex, site, time since PD diagnosis and rs6265 genotype as covariates. The primary endpoint was associated with a delay with three SNPs: rs10501087 [HR (95% Confidence Interval) = 28.3 (3.6-223.1, p = 0.002) and 7.6 (1.9-29.8, p = 0.004) for T/T and T/C subjects, respectively, vs. C/C subjects], rs1491850 [HR = 3.3 (1.3-8.4, p = 0.04) and 2.8 (1.3-6.4, p = 0.03) for T/T and T/C subjects, respectively, vs. C/C subjects] and rs11030094 [HR = 2.5 (1.1-5.6, p = 0.03) and 2.0 (1.3-6.4, p = 0.03) for A/A and A/G subjects, respectively, vs. G/G subjects]. From the primary endpoint, specific rs10501087, rs1491850, and rs11030094 SNP genotypes are associated with a slower rate of PD progression in the unmedicated state. A prospective clinical trial examining many BDNF SNPs is warranted.
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Superconducting windings will be necessary in future fusion reactors to generate the strong magnetic fields needed to confine the plasma, and these superconducting materials will inevitably be exposed to neutron damage. It is known that this exposure results in the creation of isolated damage cascades, but the presence of these defects alone is not sufficient to explain the degradation of macroscopic superconducting properties and a quantitative method is needed to assess the subtle lattice damage in between the clusters. We have studied REBCO-coated conductors irradiated with neutrons to a cumulative dose of 3.3 × 1022 n/m2 that show a degradation of both Tc and Jc values, and use HRTEM analysis to show that this irradiation introduces â¼10 nm amorphous collision cascades. In addition, we introduce a new method for the analysis of these images to quantify the degree of lattice disorder in the apparently perfect matrix between these cascades. This method utilises Fast Fourier and Discrete Cosine Transformations of a statistically relevant number of HRTEM images of pristine, neutron-irradiated and amorphous samples and extracts the degree of randomness in terms of entropy values. Our results show that these entropy values in both mid-frequency band FFT and DCT domains correlate with the expected level of lattice damage, with the pristine samples having the lowest and the fully amorphous regions the highest entropy values. Our methodology allows us to quantify 'invisible' lattice damage to and correlate these values to the degradation of superconducting properties, and also has relevance for a wider range of applications in the field of electron microscopy where small changes in lattice perfection need to be measured.
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OBJECTIVES: Treating chronic pain patients with multimodal pain therapy (MMPT) alters perception, awareness, and processing of pain at multiple therapeutic levels. Several clinical observations suggest that the effects of therapy may go beyond the possible sum of each level of therapy and may be due to a central descending inhibitory effect measurable by conditioned pain modulation (CPM). Thus, we investigated whether CPM is able to identify a group of patients that benefit particularly from MMPT. METHODS: This was an observational prospective cohort study. Patients were hospitalized on a special pain medicine ward with specially trained staff for 10 days. The patients were questioned and had investigations before and shortly after MMPT and were followed-up on 3 months post discharge. Before and after treatment, subjects were investigated via CPM and quantitative sensory testing (QST) as well as completing questionnaires. The study was registered in the German Clinical Trials Register (DRKS00006850). RESULTS: During the study period of 24 months, 224 chronic pain patients were recruited. 51 percent of patients completed the study period. There was an improvement in overall groups regarding all domains assessed, lasting beyond the end of the intervention. Patients with a sufficient CPM effect, defined as a reduction in pain during the conditioning stimulus, at baseline did show a more pronounced reduction in mean pain ratings than those without. This was not the case 3 months after therapy. Furthermore, sufficient CPM was identified as a predictor for pain reduction using a linear regression model. CONCLUSION: In conclusion, this study shows that while a heterogeneous group of patients with chronic pain disorders does sustainably benefit from MMPT in general, patients with a sufficient CPM effect do show a more pronounced decrease in pain ratings directly after therapy in comparison to those without.
Pain at one body site can be reduced, when another painful stimulus occurs at the same time. This mechanism is referred to as conditioned pain modulation (CPM).Some patients with chronic pain are treated using different methods such as medication, physiotherapy, and patient education in an in-patient setting, referred to as multimodal pain therapy (MMST). To improve pain therapy, it is vital to identify whether patients who respond especially well to a certain treatment show specific characteristics (i.e. mechanism-based therapy). We investigated whether the prospect of success of MMST is related to how well CPM works in patients. We assessed the CPM effect and sensory function of 224 patients with chronic pain before and after therapy to answer this question. Additionally, patients completed questionnaires about their pain, mood, quality of life, and sleep directly after therapy and three months later. All patients showed improvement after therapy, but in those in which CPM worked well, pain was reduced stronger than in those in which CPM did not. Three months after treatment, the difference disappeared.
Subject(s)
Chronic Pain , Aftercare , Chronic Pain/drug therapy , Humans , Pain Threshold , Patient Discharge , Prospective StudiesABSTRACT
OBJECTIVE: Enzymatic debridement of burn eschar became an accepted and widely used technique for burn wound treatment over the last years. However, this practice is not exempt from failure and recent experimental studies indicate that it may not be as efficient in scalds as in flame burns. METHODS: Patients that were admitted to the burn intensive care unit between June 2017 and February 2021 and received enzymatic debridement within the first 72 h after scald and flame burn were included. Patients with scald burns were matched regarding age, sex and per cent total body surface area (%TBSA) burned in a 1:2 ratio with patients presenting with flame burns. RESULTS: Eighteen patients with scald burns were matched with 36 with flame burns. After matching, both groups were similar in terms of age (flame burns 44.5 ± 21.1 years vs. scald 41.8 ± 22.6 years, p = 0.666), and %TBSA burned (11.0 ± 8.2% vs. 10.6 ± 9.6%, p = 0.851). Patients with scald burns significantly more often underwent further surgical eschar excision compared to controls (scald 16 (88.9%) vs. flame 19 (52.8%), p = 0.016). Length of stay per %TBSA was significantly longer in scald burns (scald 7.8 ± 9.2 days vs. flame 3.7 ± 3.8, p = 0.013). CONCLUSION: This study indicates that enzymatic debridement may not be as effective in scalds as in flame burns. It was shown that patients with scalds and subsequent enzymatic debridement more frequently underwent additional surgical intervention and that the size of the transplanted area was larger compared to control. Moreover, those patients had a longer length of stay at the hospital per %TBSA burned.
Subject(s)
Burns , Adult , Aged , Burns/surgery , Debridement/methods , Hospitalization , Humans , Length of Stay , Middle Aged , Retrospective Studies , Skin Transplantation/methods , Young AdultABSTRACT
The superposition of two partially correlated waves is shown to produce fields with drastically altered coherence properties. It is demonstrated, both theoretically and experimentally, that two strongly correlated sources may generate a field with practically zero correlation between certain pairs of points. This anomalous change in coherence is a general phenomenon that takes place in all cases of wave superposition, including Mie scattering, as is shown. Our results are particularly relevant to applications in which it is assumed that highly coherent radiation maintains its spatial coherence on propagation, such as optical systems design and the imaging of extended sources.
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We study experimentally the dynamical behavior of few large tracer particles placed in a quasi-2D granular "gas" made of many small beads in a low-gravity environment. Multiple inelastic collisions transfer momentum from the uniaxially driven gas to the tracers whose velocity distributions are studied through particle tracking. Analyzing these distributions for an increasing system density reveals that translational energy equipartition is reached at the onset of the gas-liquid granular transition corresponding to the emergence of local clusters. The dynamics of a few tracer particles thus appears as a simple and accurate tool to detect this transition. A model is proposed for describing accurately the formation of local heterogeneities.
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BACKGROUND: This study aimed to evaluate the impact of semi-absorbable mesh on donor-site morbidity and patient-reported outcomes in deep inferior epigastric perforator (DIEP) flap breast reconstruction. METHODS: We conducted a retrospective cohort study of all patients who had DIEP flap breast reconstruction in our department from July 2007 to March 2019. Patients were invited to a comparative follow-up visit and grouped according to donor-site closure: primary fascial closure (the no-mesh group) and fascial reinforcement with semi-absorbable mesh in a subfascial position (the mesh group). The primary outcome of interest was donor-site morbidity, including bulging, hernia formation and rectus abdominis muscle strength. We also surveyed, surgical site complications and patient-reported outcomes using Patient and Observer Scar Assessment Scale v2.0 and BREAST-Q© version 2.0. RESULTS: A total of 191 patients had received DIEP flap breast reconstruction. Eighty-five patients (44.5%) with 108 DIEP flaps (53 patients in the mesh group and 32 patients in the no-mesh group) were included in the study. The mean BMI of the patients was significantly higher in the mesh group (mesh group, 26.9 vs. no-mesh group, 25.0, with p = 0.03). The incidence of hernia was significantly reduced in the mesh group (mesh group, 2.8% vs. no-mesh group, 13.5%, with p = 0.03). The incidence of bulging and the extent of rectus abdominis muscle strength were similar for both groups. Operative surgical site complications were reduced in the mesh group (mesh group, 7.5% vs. no-mesh group, 18.8%). There was no difference in patients' physical well-being and satisfaction with the donor site between groups. Patient-reported scar outcome was significantly better in the no-mesh group (p < 0.001). CONCLUSION: Our novel method of donor-site closure with semi-absorbable mesh in a subfascial position for reinforcement of the anterior rectus fascia on the DIEP donor site is safe. It has no negative impact on surgical site complications and patient-reported outcomes, while reducing the incidence of hernias on the donor-site in DIEP flap breast reconstruction. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
Subject(s)
Mammaplasty , Perforator Flap , Epigastric Arteries/surgery , Humans , Mammaplasty/adverse effects , Morbidity , Patient Reported Outcome Measures , Postoperative Complications/epidemiology , Postoperative Complications/prevention & control , Rectus Abdominis/transplantation , Retrospective Studies , Surgical MeshABSTRACT
Chirality causes symmetry breaks in a large variety of natural phenomena ranging from particle physics to biochemistry. We investigate one of the simplest conceivable chiral systems, a laser-excited, oriented, effective one-electron Li target. Prepared in a polarized p state with |m|=1 in an optical trap, the atoms are exposed to co- and counterrotating circularly polarized femtosecond laser pulses. For a field frequency near the excitation energy of the oriented initial state, a strong circular dichroism is observed and the photoelectron energies are significantly affected by the helicity-dependent Autler-Townes splitting. Besides its fundamental relevance, this system is suited to create spin-polarized electron pulses with a reversible switch on a femtosecond timescale at an energy resolution of a few meV.
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We report on the implementation of a far-off-resonant, optical dipole force trap in a reaction microscope combined with a magneto-optical trap. Kinematically complete multi-photon ionization experiments were performed on optically trapped 6Li atoms and photo-associated 6Li2 molecules in their highest vibrational state. The apparatus allows us to distinguish different ionization mechanisms related to the presence of the IR field of the optical dipole trap that can occur during ionization of 6Li and 6Li2 in strong fields. In a series of proof-of-principle experiments, we detect weakly bound dimers via three-photon ionization with femtosecond pulses (τ = 30 fs) at a central wavelength of 780 nm and measure directly the momenta of the photoelectrons in coincidence with recoil ions.
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Medical ultrasound images are inherently noised with speckle noise, which may interfere with Computer Aided Diagnostics (CAD) tasks, such as automatic segmentation. A compression and speckle de-noising method is proposed and tested on real clinical breast and fetal ultrasound images. The proposed algorithm is based on the optimization of quantization coefficients when applying Wavelet representation on the image, where the optimization is held such that a pre-defined mathematical fidelity criterion with respect to a desired de-speckled image is obtained. The proposed algorithm yields effective speckle reduction whilst preserving the edges in the images, with a reduced computational burden compared to other existing state-of-the-art methods, such as Optimal Bayesian Non-Local Means (OBNLM). In addition, the images are simultaneously compressed to a target bit-rate. The proposed algorithm is evaluated using both objective mathematical fidelity criteria (such as Structural Similarity and Edge Preserve) as well as subjective radiologists tests. The experimental results demonstrate the ability of the proposed method to achieve de-speckled images with compression ratios of approximately 30:1, whilst obtaining competitive subjective as well as objective fidelity measures with respect to the desired de-speckled images.
Subject(s)
Algorithms , Data Compression/methods , Image Enhancement/methods , Ultrasonography, Mammary , Ultrasonography, Prenatal , Female , HumansABSTRACT
The microbiome research field is rapidly evolving, but the required biobanking infrastructure is currently fragmented and not prepared for the biobanking of microbiomes. The rapid advancement of technologies requires an urgent assessment of how biobanks can underpin research by preserving microbiome samples and their functional potential.
Subject(s)
Biological Specimen Banks/standards , Microbiota , Animals , Bacteria/classification , Bacteria/genetics , Bacteria/isolation & purification , Biological Specimen Banks/trends , Biomedical Research , Humans , Mammals/microbiology , Plants/microbiology , Preservation, BiologicalABSTRACT
Brain multivoxel MR spectroscopic imaging was performed in 3 consecutive patients with coronavirus disease 2019 (COVID-19). These included 1 patient with COVID-19-associated necrotizing leukoencephalopathy, another patient who had a recent pulseless electrical activity cardiac arrest with subtle white matter changes, and a patient without frank encephalopathy or a recent severe hypoxic episode. The MR spectroscopic imaging findings were compared with those of 2 patients with white matter pathology not related to Severe Acute Respiratory Syndrome coronavirus 2 infection and a healthy control subject. The NAA reduction, choline elevation, and glutamate/glutamine elevation found in the patient with COVID-19-associated necrotizing leukoencephalopathy and, to a lesser degree, the patient with COVID-19 postcardiac arrest, follow a similar pattern as seen with the patient with delayed posthypoxic leukoencephalopathy. Lactate elevation was most pronounced in the patient with COVID-19 necrotizing leukoencephalopathy.
Subject(s)
COVID-19/diagnostic imaging , Aged , Humans , Leukoencephalopathies/diagnostic imaging , Magnetic Resonance Imaging , Magnetic Resonance Spectroscopy , Male , SARS-CoV-2 , White MatterABSTRACT
Prevalent in approximately 20% of the worldwide human population, the rs6265 (also called 'Val66Met') single nucleotide polymorphism (SNP) in the gene for brain-derived neurotrophic factor (BDNF) is a common genetic variant that can alter therapeutic responses in individuals with Parkinson's disease (PD). Possession of the variant Met allele results in decreased activity-dependent release of BDNF. Given the resurgent worldwide interest in neural transplantation for PD and the biological relevance of BDNF, the current studies examined the effects of the rs6265 SNP on therapeutic efficacy and side-effect development following primary dopamine (DA) neuron transplantation. Considering the significant reduction in BDNF release associated with rs6265, we hypothesized that rs6265-mediated dysfunctional BDNF signaling contributes to the limited clinical benefit observed in a subpopulation of PD patients despite robust survival of grafted DA neurons, and further, that this mutation contributes to the development of aberrant graft-induced dyskinesias (GID). To this end, we generated a CRISPR knock-in rat model of the rs6265 BDNF SNP to examine for the first time the influence of a common genetic polymorphism on graft survival, functional efficacy, and side-effect liability, comparing these parameters between wild-type (Val/Val) rats and those homozygous for the variant Met allele (Met/Met). Counter to our hypothesis, the current research indicates that Met/Met rats show enhanced graft-associated therapeutic efficacy and a paradoxical enhancement of graft-derived neurite outgrowth compared to wild-type rats. However, consistent with our hypothesis, we demonstrate that the rs6265 genotype in the host rat is strongly linked to development of GID, and that this behavioral phenotype is significantly correlated with neurochemical signatures of atypical glutamatergic neurotransmission by grafted DA neurons.