Clonal Deletion of Tumor-Specific T Cells by Interferon-γ Confers Therapeutic Resistance to Combination Immune Checkpoint Blockade.

Resistance to checkpoint-blockade treatments is a challenge in the clinic. We found that although treatment with combined anti-CTLA-4 and anti-PD-1 improved control of established tumors, this combination compromised anti-tumor immunity in the low tumor burden (LTB) state in pre-clinical models as well as in melanoma patients. Activated tumor-specific T cells expressed higher amounts of interferon-γ (IFN-γ) receptor and were more susceptible to apoptosis than naive T cells. Combination treatment induced deletion of tumor-specific T cells and altered the T cell repertoire landscape, skewing the distribution of T cells toward lower-frequency clonotypes. Additionally, combination therapy induced higher IFN-γ production in the LTB state than in the high tumor burden (HTB) state on a per-cell basis, reflecting a less exhausted immune status in the LTB state. Thus, elevated IFN-γ secretion in the LTB state contributes to the development of an immune-intrinsic mechanism of resistance to combination checkpoint blockade, highlighting the importance of achieving the optimal magnitude of immune stimulation for successful combination immunotherapy strategies.

Microplastics' Shape and Morphology Analysis in the Presence of Natural Organic Matter Using Flow Imaging Microscopy.

Ubiquitous microplastics in urban waters have raised substantial public concern due to their high chemical persistence, accumulative effects, and potential adverse effects on human health. Reliable and standardized methods are urgently needed for the identification and quantification of these emerging environmental pollutants in wastewater treatment plants (WWTPs). In this study, we introduce an innovative rapid approach that employs flow imaging microscopy (FlowCam) to simultaneously identify and quantify microplastics by capturing high-resolution digital images. Real-time image acquisition is followed by semi-automated classification using customized libraries for distinct polyethylene (PE) and polystyrene (PS) microplastics. Subsequently, these images are subjected to further analysis to extract precise morphological details of microplastics, providing insights into their behavior during transport and retention within WWTPs. Of particular significance, a systematic investigation was conducted to explore how the presence of natural organic matter (NOM) in WWTPs affects the accuracy of the FlowCam's measurement outputs for microplastics. It was observed that varying concentrations of NOM induced a more curled shape in microplastics, indicating the necessity of employing pre-treatment procedures to ensure accurate microplastic identification when utilizing the FlowCam. These observations offer valuable new perspectives and potential solutions for designing appropriate treatment technologies for removing microplastics within WWTPs.

Removal of fluoride in membrane-based water and wastewater treatment technologies: Performance review.

The presence of excess fluoride in aqueous media above local environmental standards (e.g., the U.S. Environmental Protection Agency (EPA) standard of 4 mg/L) affects the health of aquatic life. Excess fluoride in drinking water above the maximum contaminant level (e.g., the World Health Organization (WHO) standard of 1.5 mg/L) also affects the skeletal and nervous systems of humans. Fluoride removal from aqueous solutions is difficult using conventional electrochemical, precipitation, and adsorption methods owing to its ionic size and reactivity. Thus, new technologies have been introduced to reduce the fluoride concentration in industrial wastewater effluents and various drinking water sources. Membrane technology is one of the newer technologies found to be very effective in significantly reducing fluoride to desired standards levels; however, it has received less attention than other technologies because it is perceived as a costly process. This study critically reviewed the performance of various membrane process and compared it with effluent and zero liquid discharge (ZLD) standards. The performance review has been conducted with the consideration of the theoretical background, rejection mechanisms, technical viability, and parameters affecting flux and rejection performance. This review includes membrane systems investigated for the defluoridation process but operated under pressure (i.e., reverse osmosis [RO] and nanofiltration [NF]), temperature gradients (i.e., membrane distillation [MD]), electrical potential gradients (i.e., electrodialysis [ED] and Donnan dialysis [DD]), and concentration differences (i.e., forward osmosis [FO]). Moreover, the study also addressed the advantages, limitations, & applicable conditions of each membrane based defluoridation process.

Invasive breast cancer reprograms early myeloid differentiation in the bone marrow to generate immunosuppressive neutrophils.

Expansion of myeloid cells associated with solid tumor development is a key contributor to neoplastic progression. Despite their clinical relevance, the mechanisms controlling myeloid cell production and activity in cancer remains poorly understood. Using a multistage mouse model of breast cancer, we show that production of atypical T cell-suppressive neutrophils occurs during early tumor progression, at the onset of malignant conversion, and that these cells preferentially accumulate in peripheral tissues but not in the primary tumor. Production of these cells results from activation of a myeloid differentiation program in bone marrow (BM) by a novel mechanism in which tumor-derived granulocyte-colony stimulating factor (G-CSF) directs expansion and differentiation of hematopoietic stem cells to skew hematopoiesis toward the myeloid lineage. Chronic skewing of myeloid production occurred in parallel to a decrease in erythropoiesis in BM in mice with progressive disease. Significantly, we reveal that prolonged G-CSF stimulation is both necessary and sufficient for the distinguishing characteristics of tumor-induced immunosuppressive neutrophils. These results demonstrate that prolonged G-CSF may be responsible for both the development and activity of immunosuppressive neutrophils in cancer.

Genetic Relationship of Productive Life, Production and Type Traits of Korean Holsteins at Early Lactations.

The present study was performed to study the genetic relationship of productive life with production and type traits of Korean Holsteins at first three lactations. The data for the analysis from 56,054, 28,997, and 11,816 animals of first, second and third parity cows which were born from 2006 to 2011 were collected by Dairy Cattle Improvement Center, National Agricultural Co-operative Federation. Milk, protein and fat yields adjusted for 305 days and average somatic cell score considered as production traits and analyzed type traits were stature, strength, body depth, dairy form, rump angle, rump width, rear leg side view, foot angle, front attachment placement, rear attachment height, rear attachment width, udder cleft, udder depth, front teat placement and front teat length. A multi trait genetic analysis was performed using Wombat program with restricted maximum likelihood animal model composed of fixed effect of birth year, farm and the random effect of animal and random residual effect according to the traits. Heritability estimates of productive life were between 0.06 and 0.13. Genetic and phenotypic correlations between production and productive life traits ranged from 0.35 to 0.04 for milk, 0.16 to 0.05 for protein and 0.18 to 0.02 f 15-0034 (2nd) 150520 or fat. Somatic cells score showed a negative genetic and phenotypic correlation with productive life and also udder type traits, indicating that the selection for higher udder traits will likely to improve resistance to mastitis and persistence in the herd. Among all dairy form type traits, udder characters such as udder cleft showed a significant relationship with productive life. However, a specific change of heritabilities or correlations were not observed with the change of parity. Moreover, further studies are needed to further confirm the significance of the above traits and the effect of parity on above relationships in order to minimize both voluntary and involuntary culling rates while improving herd health and maintaining high yielding dairy cows.

Removal of trivalent chromium ions in model contaminated groundwater using hexagonal boron nitride as an adsorbent.

The feasibility of using hexagonal boron nitride (h-BN) to treat heavy metal Cr(III) from model contaminated groundwater was evaluated in this study by adsorption experiments and characterizations. To the best of our knowledge, this study is the first attempt to conduct the adsorption of Cr(III) by h-BN under various experimental conditions such as exposure time, ratio of adsorbates and adsorbents, solution pH, background ions with different ionic strength, and the presence of humic acids (HA) in model contaminated groundwater. The optimized h-BN showed excellent maximum adsorption capacity (i.e., 177 mg ∙ g-1) when the concentrations of Cr(III) and h-BN were 10 and 10 mg ∙ L-1, respectively. Subsequently, we confirmed there was a negligible change in the adsorption performance of Cr(III) by h-BN in the presence of co-ions (i.e., K and Mg) in concentrations in a range from 50 to 1000 mg ∙ L-1. Furthermore, the adsorption performance of Cr(III) gradually improved with HA concentrations from 2.5 to 25 mg ∙ L-1. Interestingly, the maximum adsorption performance of Cr(III) by both HA and h-BN increased until 500 mg ∙ g-1 in the presence of 25 mg ∙ L-1 HA. The adsorption mechanism was clarified by Fourier-transform infrared spectroscopy and X-ray photoelectron spectroscopy. Additionally, we successfully confirmed that h-BN could be reused until five cycles. On the basis of the adsorption performance results and characterizations, h-BN can be utilized as an efficient and practical adsorbent to treat Cr(III) in groundwater treatment.

Adsorption of uranyl ion on hexagonal boron nitride for remediation of real U-contaminated soil and its interpretation using random forest.

Acid leaching has been widely applied to treat contaminated soil, however, it contains several inorganic pollutants. The decommissioning of nuclear power plants introduces radioactive and soluble U(VI), a substance posing chemical toxicity to humans. Our investigation sought to ascertain the efficacy of hexagonal boron nitride (h-BN), an highly efficient adsorbent, in treating U(VI) in wastewater. The adsorption equilibrium of U(VI) by h-BN reached saturation within a mere 2 h. The adsorption of U(VI) by h-BN appears to be facilitated through electrostatic attraction, as evidenced by the observed impact of pH variations, acidic agents (i.e., HCl or H2SO4), and the presence of background ions on the adsorption performance. A reusability test demonstrated the successful completion of five cycles of adsorption/desorption, relying on the surface characteristics of h-BN as influenced by solution pH. Based on the experimental variables of initial U(VI) concentration, exposure time, temperature, pH, and the presence of background ions/organic matter, a feature importance analysis using random forest (RF) was carried out to evaluate the correlation between performances and conditions. To the best of our knowledge, this study is the first attempt to conduct the adsorption of U(VI) generated from real contaminated soil by h-BN, followed by interpretation of the correlation between performance and conditions using RF. Lastly, a. plausible adsorption mechanism between U(VI) and h-BN was explained based on the experimental results, characterizations, and a. comparison with previous adsorption studies on the removal of heavy metals by h-BN.

Enhancing Genomic Prediction Accuracy for Body Conformation Traits in Korean Holstein Cattle.

The Holstein breed is the mainstay of dairy production in Korea. In this study, we evaluated the genomic prediction accuracy for body conformation traits in Korean Holstein cattle, using a range of π levels (0.75, 0.90, 0.99, and 0.995) in Bayesian methods (BayesB and BayesC). Focusing on 24 traits, we analyzed the impact of different π levels on prediction accuracy. We observed a general increase in accuracy at higher levels for specific traits, with variations depending on the Bayesian method applied. Notably, the highest accuracy was achieved for rear teat angle when using deregressed estimated breeding values including parent average as a response variable. We further demonstrated that incorporating parent average into deregressed estimated breeding values enhances genomic prediction accuracy, showcasing the effectiveness of the model in integrating both offspring and parental genetic information. Additionally, we identified 18 significant window regions through genome-wide association studies, which are crucial for future fine mapping and discovery of causal mutations. These findings provide valuable insights into the efficiency of genomic selection for body conformation traits in Korean Holstein cattle and highlight the potential for advancements in the prediction accuracy using larger datasets and more sophisticated genomic models.

Responses of earthworms exposed to low-density polyethylene microplastic fragments.

The interest in the effect of microplastics (MPs) on the terrestrial environment has been increasing recently. Different species of earthworms have been used to study the effects of MPs on different aspects of earthworm health. However, there is still a need for more studies because different studies report different effects on earthworms depending on the properties (e.g., types, shapes, sizes) of MPs in the environment and exposure conditions (e.g., exposure period). This study used Eisenia fetida as a test earthworm species to investigate the effect of different concentrations of low-density polyethylene (LDPE) MPs (≤125 µm) in soil on the growth and reproduction of earthworms. The exposure of the earthworms to the different concentrations of LDPE MPs (0-3% w/w) for 14 d and 28 d neither caused death of the earthworms nor showed significant effects on the earthworm weights in this study. The number of cocoons produced by the exposed earthworms were also similar to that of the controls (i.e., no exposure to MPs). Some previous studies reported similar results to what have been observed in this study, while some studies reported different results. On the other hand, the number of ingested MPs by the earthworms increased with increasing MPs concentrations in soil, suggesting a potential for damage to digestive tract. Also, the earthworm skin surface was damaged after exposure to MPs. The ingested MPs and the skin surface damage suggest that there is a potential for adverse effects on the earthworm growth after a longer-term exposure. Overall, the results of this study show that the effects of MPs on earthworms need to be studied using various endpoints including growth, reproduction, ingestion, and skin damage and such effects can be different depending on the exposure conditions such as MPs concentration and exposure period.

CDDO-Methyl Ester Inhibits BRAF Inhibitor Resistance and Remodels the Myeloid Compartment in BRAF-mutant Melanoma.

Approximately 50% of advanced melanomas harbor activating BRAF V600E mutations that are sensitive to BRAF inhibition. However, the duration of the response to BRAF inhibitors (BRAFi) has been limited due to the development of acquired resistance, which is preceded by recruitment of immunosuppressive myeloid cells and regulatory T cells (T regs ). While the addition of MAPK/ERK kinase 1 inhibitors (MEKi) prolongs therapeutic response to BRAF inhibition, most patients still develop resistance. Using a Braf V600E/+ /Pten -/- graft mouse model of melanoma, we now show that the addition of the methyl ester of the synthetic triterpenoid 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (C-Me) to the BRAFi vemurafenib analog PLX4720 at resistance significantly reduces tumor burden. Dual treatment remodels the BRAFi resistant-tumor microenvironment (TME), reducing infiltration of T regs and tumor associated macrophages (TAMs), and attenuates immunosuppressive cytokine production. For the first time, we characterize myeloid populations using scRNA-seq in BRAFi-resistant tumors and demonstrate that restoration of therapeutic response is associated with significant changes in immune-activated myeloid subset representation. Collectively, these studies suggest that C-Me inhibits acquired resistance to BRAFi. Use of C-Me in combination with other therapies may both inhibit melanoma growth and enhance therapeutic responsiveness more broadly.

Engineered Approaches to Facile Identification of Tiny Microplastics in Polymeric and Ceramic Membrane Filtrations for Wastewater Treatment.

Wastewater treatment plants (WWTPs) contribute to the release of significant quantities of microplastics into the aquatic environment. The facile identification of microplastics and an understanding of their occurrence and transport through WWTPs are essential for improving microplastic retention. Potential microplastic treatment technologies for both polymeric and ceramic membrane filtrations were systematically investigated to inform decisions on the optimal choice of membrane for effective microplastic retention. A blocking filtration model, based on a simple linear regression fitting, was used in experiments on the filtration of microplastic suspensions to determine the relative importance of individual fouling mechanisms. Unlike the commonly applied spectroscopic techniques, the facile identification approaches, that are closely related to the amounts of particles within wastewater samples, attempted to identify tiny microplastics (<1.0 µm) by comparing them against silica particles for reference. A larger decline in the normalized permeate flux was observed for 0.1 µm polystyrene microplastics, while standard pore blocking appeared to be the dominant fouling mechanism for all membranes. More microplastics based on turbidity and total solids were removed using the ceramic membrane than the other polymeric membranes. However, fewer microplastics, based on the particle size distribution analysis, were removed using the ceramic membrane as the pore size measurements gave a relatively large pore size for the ceramic membrane, compared with other polymeric membranes; even though a nominal pore size of 0.1 µm for all membranes were provided by the suppliers. The contribution of microplastic-containing synthetic wastewaters to overall flux decline was significantly greater than those of identical microplastic suspensions because of the aggregation of larger microplastics with dissolved organic matter in synthetic wastewater, leading to the formation of a cake layer on the membrane surface. Despite the challenges associated with the facile identification approaches, our findings provided deeper insights and understanding of how microplastics behave in membrane filtration, which could enable the application of potential microplastic treatment technologies.

Investigating the potential of ammonium retention by graphene oxide ceramic nanofiltration membranes for the treatment of semiconductor wastewater.

Ceramic membranes with high chemical and fouling resistance can play a critical role in treating industrial wastewater. In the present study, we demonstrate the fabrication of graphene oxide (GO) assembled ceramic nanofiltration (NF) membranes that provide effective ammonium retention and excellent fouling resistance for treating semiconductor wastewater. The GO-ceramic NF membranes were prepared via a layer-by-layer (LbL) assembly of GO and polyethyleneimine (PEI) on a ceramic ultrafiltration (UF) substrate. The successful fabrication of the GO-ceramic NF membranes was verified through surface characterization and pore size evaluation. We also investigated the performance of GO-ceramic NF membranes assembled with different numbers of bilayers for the rejection of ammonium ions. GO-ceramic NF membranes with three GO-PEI bilayers exhibited 8.4- and 3.2-times higher ammonium removal with simulated and real semiconductor wastewater, respectively, compared to the pristine ceramic UF substrate. We also assessed flux recovery after filtration using real semiconductor wastewater samples to validate the lower fouling potential of the GO-ceramic NF membranes. Results indicate that flux recovery increases from 39.1 % in the pristine UF substrate to 71.0 % and 90.8 % for the three- and ten-bilayers GO-ceramic NF membranes, respectively. The low-fouling GO-ceramic NF membranes developed in this study are effective and promising options for the removal of ammonium ions from semiconductor wastewater.

Transport of emerging organic ultraviolet (UV) filters in ceramic membranes: Role of polyethylene (PE) microplastics.

Microplastics can be considered potential carriers of emerging organic ultraviolet (UV) filters due to their considerable adsorption capacity in wastewater treatment. The adsorption behavior of organic UV filters, which are commonly contained in personal care products to preserve the skin against UV radiation, onto polyethylene (PE) microplastics were systematically studied to investigate their combined effects. Kinetics and isotherm analyses revealed that the adsorption of four organic UV filters onto PE microplastic surfaces followed a multi-rate and a heterogeneous multi-layer pattern. Several factors including salinity, microplastic size, and dosage also influenced the adsorption efficiency due to hydrophobic interactions. A bench-scale cross-flow ceramic membrane filtration experiment was investigated to evaluate the role of PE microplastics on the retention performance of organic UV filters. The retentions for organic UV filters were 34.2%-37.8% in the non-existence of PE microplastics. Conversely, organic UV filter retentions were significantly increased up to 82.2%-97.9% when they were adsorbed onto the PE microplastics, which were almost completely retained by the ceramic membrane. Therefore, organic UV filters can likely migrate and eventually be carried by PE microplastics, thus increasing the retention of both emerging organic UV filters and microplastics prior to discharge from wastewater treatment facilities.

Effect of the Peptization Process and Thermal Treatment on the Sol-Gel Preparation of Mesoporous α-Alumina Membranes.

Compared to traditional membrane materials, alumina membranes are particularly beneficial for industrial wastewater treatment. However, the development of mesoporous α-alumina membranes for ultrafiltration applications is still a challenge due to uncontrolled pore size. In this study, we optimized the sol-gel method for the fabrication of a high-performance mesoporous α-alumina membrane. The peptization conditions (pH and peptization time) and phase transformation of boehmite were investigated to achieve better properties of the α-alumina membrane. The surface properties of the membrane were observed to be improved by reducing the system pH to 3.5 and increasing the peptization time to 24 h. The effect of sintering temperature on the phase transformation behavior, microstructures and performance of the membranes was also elucidated. An α-alumina ultrafiltration membrane with an average thickness of 2 µm was obtained after sintering at 1100 °C. The molecular weight cut-off of the α-alumina membrane, as obtained by the filtration of aqueous PEG solution, was approximately 163 kDa (12.5 nm). This is the smallest pore size ever reported for pure α-alumina membranes.

T Cells and CDDO-Me Attenuate Immunosuppressive Activation of Human Melanoma-Conditioned Macrophages.

Melanoma tumors are highly immunogenic, making them an attractive target for immunotherapy. However, many patients do not mount robust clinical responses to targeted therapies, which is attributable, at least in part, to suppression of immune responses by tumor-associated macrophages (TAMs) in the tumor microenvironment (TME). Using a human in vitro tri-culture system of macrophages with activated autologous T cells and BRAFV600E mutant melanoma cells, we now show that activated T cells and the synthetic triterpenoid the methyl ester of 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO-Me) attenuate immune suppression. Surface expression of CD206, CD16 and CD163 on melanoma-conditioned macrophages was inhibited by the addition of T cells, suggesting relief of immuno-suppressive macrophage activation. We also demonstrated that addition of CDDO-Me to tri-cultures enhanced T cell-mediated reductions in CCL2, VEGF and IL-6 production in a contact-independent manner. Because these results suggest CDDO-Me alters melanoma-conditioned macrophage activation, we interrogated CDDO-Me-mediated changes in macrophage signaling pathway activation. Our results indicated that CDDO-Me inhibited phosphorylation of STAT3, a known inducer of TAM activation. Collectively, our studies suggest that activated T cells and CDDO-Me synergistically relieve immune suppression in melanoma cultures and implicate the potential utility of CDDO-Me in the treatment of melanoma.

Chia seed-assisted separation and detection of polyvinyl chloride microplastics in water via gas chromatography mass spectrometry.

Chia seeds were used to significantly improve the separation efficiency of polyvinyl chloride (PVC) microplastics from water samples via centrifugation. Upon hydration, the mucilage of chia seeds were able to capture PVC microplastics with sizes ranging from tens to hundreds of micrometers. Since PVC microplastics contained di-2-etylhexyl phthalate (DEHP) as a plasticizer (verified via Fourier transform infrared spectrometry), DEHP was used as an indicator in the subsequent quantification via gas chromatography - mass spectrometry (GC-MS) analysis. Specifically after verifying the DEHP peak in the GC spectrum using DEHP reference standard as a positive control, the GC spectral area of that peak was used to quantify the amount of DEHP in the sample. Using nominal operation settings at 10 min and 1000 rpm with 100 mg of chia seeds, the separation efficiency could be improved by 5 times (500%) as compared to the absence of chia seeds. Furthermore, chia seeds were also compatible with simulated synthetic wastewater samples. Most importantly, the use of chia seeds did not interfere with GC-MS quantification protocol and accuracy. The result suggested the proposed method can be used as a simple screening tool of microplastics entering wastewater treatment plant, even though a series of follow-up studies are needed in future.

Structural Characteristic of the Arcuate Fasciculus in Patients with Fluent Aphasia Following Intracranial Hemorrhage: A Diffusion Tensor Tractography Study.

This study investigated the relationship between the structural characteristics of the left arcuate fasciculus (AF) reconstructed using diffusion tensor image (DTI) and the type of fluent aphasia according to hemorrhage lesions in patients with fluent aphasia following intracranial hemorrhage (ICH). Five patients with fluent aphasia following ICH (three males, two females; mean age 55.0 years; range 47 to 60 years) and with sixteen age-matched heathy control subjects were involved in this study. The ICHs of patients 1 and 2 were located in the left parietal lobe and the left basal ganglia. ICHs were located in the left anterior temporal of patient 3, the left temporal lobe of patient 4, and the left frontal lobe of patient 5. We assessed patients' language function using K-WAB (the Korean version of the Western Aphasia Battery) and reconstructed the AF using DTI. We measured DTI parameters including the fractional anisotropy (FA), tract volume (TV), fiber number (FN), and mean diffusivity (MD). All patients showed neural tract injury (the decrement of FA, TV, and FN and increment of MD). The left AFs in patients 1 and 2 were shifted from Broca's and Wernicke's territories. The destruction of Wernicke's territory resulted in conduction or transcortical sensory aphasia in patients 3 and 4. The structural difference of the AF in patients following ICH in the left hemisphere was associated with various types of fluent aphasia.

Relationship between Visual Perception and Microstructural Change of the Superior Longitudinal Fasciculus in Patients with Brain Injury in the Right Hemisphere: A Preliminary Diffusion Tensor Tractography Study.

Right hemisphere brain damage often results in visual-spatial deficits. Because various microstructural changes of the superior longitudinal fasciculus (SLF) after a stroke in the right hemisphere affect visual perception, including neglect, the present study investigates the relationship between both microstructural change and lateralization of SLF and visual perception, using diffusion tensor imaging (DTI) in patients with lesions in the right hemisphere. Eight patients with strokes (five patients with intracranial hemorrhage, and three patients with infarction; mean age of 52.5 years) and 16 mean-age-matched healthy control subjects were involved in this study. The visual perception of all eight patients was assessed with the motor-free visual perception test (MVPT), and their SLFs were reconstructed using DTI. The results showed that there was a significant difference between the DTI parameters of the patients and the control subjects. Moreover, patients with microstructural damage to the right SLF showed impairment of visual perception. In patients with damage to both the dorsal and ventral pathways of the right SLF, spatial neglect was present. However, although a leftward SLF asymmetry was revealed in our patients, this lateralization did not show a relationship with visual perception. In conclusion, the microstructural changes of the right SLF play an important role in visual perception, and both pathways contribute to spatial neglect, but leftward lateralization of the right SFL activity after a stroke does not contribute to general visual perception.

Diffusion-Tensor-Tractography-Based Diagnosis for Injury of Corticospinal Tract in a Patient with Hemiplegia Following Traumatic Brain Injury.

This paper reports a mechanism for corticospinal tract injury in a patient with hemiplegia following traumatic brain injury (TBI) based on diffusion tensor tractography (DTT) finding. A 73-year-old male with TBI resulting from a fall, without medical history, was diagnosed as having left convexity epidural hematoma (EDH). He underwent craniotomy and suffered motor weakness on the right side of the body. Two weeks after onset, he was transferred to a rehabilitation department with an alerted level of consciousness. Four weeks after onset, his motor functions were grade 1 by the Medical Research Council's (MRC) standards in the right-side limbs and grade 4 in the left-side limbs. The result of DTT using the different regions of interest (ROIs) showed that most of the right corticospinal tract (CST) did not reach the cerebral cortex around where the EDH was located, and when the ROI was placed on upper pons, a disconnection of the CST was shown and a connection of the CST in ROI with the middle pons appeared. However, the right CST was connected to the cerebral cortex below the pons regardless of ROI. This study is the first report to use DTT to detect that the discontinuation of the left CST in the cerebral cortex and injury lesions below the lower pons and between the upper and lower pons are responsible for motor weakness in a patient.