Comprehensive CT Imaging Analysis of Primary Colorectal Squamous Cell Carcinoma: A Retrospective Study.

The aim of this study was to evaluate the findings of CT scans in patients with pathologically confirmed primary colorectal squamous-cell carcinoma (SCC). The clinical presentation and CT findings in eight patients with pathologically confirmed primary colorectal squamous-cell carcinoma were retrospectively reviewed by two gastrointestinal radiologists. Hematochezia was the most common symptom (n = 5). The tumors were located in the rectum (n = 7) and sigmoid colon (n = 1). The tumors showed circumferential wall thickening (n = 4), bulky mass (n = 3), or eccentric wall thickening (n = 1). The mean maximal wall thickness of the involved segment was 29.1 mm ± 13.4 mm. The degree of tumoral enhancement observed via CT was well enhanced (n = 4) or moderately enhanced (n = 4). Necrosis within the tumor was found in five patients. The mean total number of metastatic lymph nodes was 3.1 ± 3.3, and the mean short diameter of the largest metastatic lymph node was 16.6 ± 5.7 mm. Necrosis within the metastatic node was observed in six patients. Invasions to adjacent organs were identified in five patients (62.5%). Distant metastasis was detected in only one patient. In summary, primary SCCs that arise from the colorectum commonly present as marked invasive wall thickening or a bulky mass with heterogeneous well-defined enhancement, internal necrosis, and large metastatic lymphadenopathies.

Use of functional magnetic resonance imaging to identify cortical loci for lower limb movements and their efficacy for individuals after stroke.

BACKGROUND: Identification of cortical loci for lower limb movements for stroke rehabilitation is crucial for better rehabilitation outcomes via noninvasive brain stimulation by targeting the fine-grained cortical loci of the movements. However, identification of the cortical loci for lower limb movements using functional MRI (fMRI) is challenging due to head motion and difficulty in isolating different types of movement. Therefore, we developed a custom-made MR-compatible footplate and leg cushion to identify the cortical loci for lower limb movements and conducted multivariate analysis on the fMRI data. We evaluated the validity of the identified loci using both fMRI and behavioral data, obtained from healthy participants as well as individuals after stroke. METHODS: We recruited 33 healthy participants who performed four different lower limb movements (ankle dorsiflexion, ankle rotation, knee extension, and toe flexion) using our custom-built equipment while fMRI data were acquired. A subgroup of these participants (Dataset 1; n = 21) was used to identify the cortical loci associated with each lower limb movement in the paracentral lobule (PCL) using multivoxel pattern analysis and representational similarity analysis. The identified cortical loci were then evaluated using the remaining healthy participants (Dataset 2; n = 11), for whom the laterality index (LI) was calculated for each lower limb movement using the cortical loci identified for the left and right lower limbs. In addition, we acquired a dataset from 15 individuals with chronic stroke for regression analysis using the LI and the Fugl-Meyer Assessment (FMA) scale. RESULTS: The cortical loci associated with the lower limb movements were hierarchically organized in the medial wall of the PCL following the cortical homunculus. The LI was clearer using the identified cortical loci than using the PCL. The healthy participants (mean ± standard deviation: 0.12 ± 0.30; range: - 0.63 to 0.91) exhibited a higher contralateral LI than the individuals after stroke (0.07 ± 0.47; - 0.83 to 0.97). The corresponding LI scores for individuals after stroke showed a significant positive correlation with the FMA scale for paretic side movement in ankle dorsiflexion (R2 = 0.33, p = 0.025) and toe flexion (R2 = 0.37, p = 0.016). CONCLUSIONS: The cortical loci associated with lower limb movements in the PCL identified in healthy participants were validated using independent groups of healthy participants and individuals after stroke. Our findings suggest that these cortical loci may be beneficial for the neurorehabilitation of lower limb movement in individuals after stroke, such as in developing effective rehabilitation interventions guided by the LI scores obtained for neuronal activations calculated from the identified cortical loci across the paretic and non-paretic sides of the brain.

Successful pregnancy outcome via in-vitro fertilization and laparoscopic resection of non-communicating rudimentary horn pregnancy containing early pregnancy: a case report.

BACKGROUND: Non-communicating rudimentary horn pregnancy (NCRHP) lead to life-threatening condition for both mother and fetus. Early diagnosis of NCRHP and laparoscopic resection is important to prevent catastrophic conditions. However, delayed diagnosis until the second or third trimester makes it difficult to accurately diagnose between NCRHP and bicornuate uterine pregnancy, as both conditions present uterine rupture and massive hemoperitoneum. Furthermore, these rare cases are challenging in pregnancy trials and associated with adverse outcomes in subsequent pregnancies. CASE PRESENTATION: A 31-year-old gravida 1 para 0 Korean woman visited our infertility center with a confirmed positive urine pregnancy test after timed intercourse. Before she was scheduled to have timed intercourse, a unicornuate uterus with a non-communicating right uterine horn was suspected based on an ultrasound scan and hysterosalpingography during the initial infertility workup. A gestational sac was observed in the right non-communicating rudimentary horn at 5 weeks of gestation. Serum beta-human chorionic gonadotropin (b-hCG) level was 2052.0mIU/mL. An elective laparoscopic resection of the right rudimentary horn containing a gestational sac, along with ipsilateral salpingectomy, was performed with no adverse event. After 3-month of recovery period and three cycles of conceptional trials involving timed intercourse and intrauterine insemination, in-vitro fertilization (IVF) was performed using the antagonist protocol, and successful pregnancy was confirmed. The patient had been hospitalized from 21 + 6 weeks to 35 + 6 weeks of gestation, underwent cerclage placement and tocolytics with corticosteroid treatment. She delivered an early-term male baby by cesarean section. CONCLUSION: In this rare case, the successful pregnancy achieved through IVF following the appropriate management of NCRHP under laparoscopy underscores the critical importance of early diagnosis and intervention in cases of NCRHP. Timely identification and management of NCRHP are vital to prevent the occurrence of catastrophic conditions and to enhance the prognosis of a successful pregnancy through assisted reproductive technology (ART). Therefore, a high index of suspicion for NCRHP is important and employs a range of diagnostic modalities.

Effects of a Combination of Polynucleotide and Hyaluronic Acid for Treating Osteoarthritis.

Knee osteoarthritis (OA), an age-related degenerative disease characterized by severe pain and disability, is treated using polynucleotides (PNs) and hyaluronic acid (HA). The intra-articular (IA) injection of HA has been studied extensively in both animal models and in humans; however, the efficacy and mechanisms of action remain unclear. In addition, there has been a paucity of research regarding the use of PN alone or in combination with HA in OA. To investigate the effect of the combined injection of PN and HA in vivo, pathological and behavioral changes were assessed in an OA model. Anterior cruciate ligament transection and medial meniscectomy were performed in Sprague-Dawley rats to create the OA animal model. The locomotor activity improved following PNHA injection, while the OARSI grade improved in the medial tibia and femur. In mild OA, TNFα levels decreased histologically in the PN, HA, and PNHA groups but only the PNHA group showed behavioral improvement in terms of distance. In conclusion, PNHA exhibited anti-inflammatory effects during OA progression and improved locomotor activity regardless of the OARSI grade.

Topiramate dosage optimization for effective antiseizure management via population pharmacokinetic modeling.

OBJECTIVE: Despite the suggested topiramate serum level of 5-20 mg/L, numerous institutions have observed substantial drug response at lower levels. We aim to investigate the correlation between topiramate serum levels, drug responsiveness, and adverse events to establish a more accurate and tailored therapeutic range. METHODS: We retrospectively analyzed clinical data collected between January 2017 and January 2022 at Seoul National University Hospital. Drug responses to topiramate were categorized as "insufficient" or "sufficient" by reduction in seizure frequency ≥ 50%. A population pharmacokinetic model estimated serum levels from spot measurements. ROC curve analysis determined the optimal cutoff values. RESULTS: A total of 389 epilepsy patients were reviewed having a mean dose of 178.4 ± 117.9 mg/day and the serum level, 3.9 ± 2.8 mg/L. Only 5.6% samples exhibited insufficient response, with a mean serum level of 3.6 ± 2.5 mg/L while 94.4% demonstrated sufficient response, with a mean 4.0 ± 2.8 mg/L, having no statistical significance. Among the 69 reported adverse events, logistic regression analysis identified a significant association between ataxia and serum concentration (p = 0.04), with an optimal cutoff value of 6.5 mg/L. INTERPRETATION: This study proposed an optimal therapeutic concentration for topiramate based on patients' responsiveness to the drug and the incidence of adverse effects. We recommended serum levels below 6.5 mg/L to mitigate the risk of ataxia-related side effects while dose elevation was found unnecessary for suboptimal responders, as the drug's effectiveness plateaus at minimal doses.

Feasibility of Magnetic Resonance-Based Conductivity Imaging as a Tool to Estimate the Severity of Hypoxic-Ischemic Brain Injury in the First Hours After Cardiac Arrest.

BACKGROUND: Early identification of the severity of hypoxic-ischemic brain injury (HIBI) after cardiac arrest can be used to help plan appropriate subsequent therapy. We evaluated whether conductivity of cerebral tissue measured using magnetic resonance-based conductivity imaging (MRCI), which provides contrast derived from the concentration and mobility of ions within the imaged tissue, can reflect the severity of HIBI in the early hours after cardiac arrest. METHODS: Fourteen minipigs were resuscitated after 5 min or 12 min of untreated cardiac arrest. MRCI was performed at baseline and at 1 h and 3.5 h after return of spontaneous circulation (ROSC). RESULTS: In both groups, the conductivity of cerebral tissue significantly increased at 1 h after ROSC compared with that at baseline (P = 0.031 and 0.016 in the 5-min and 12-min groups, respectively). The increase was greater in the 12-min group, resulting in significantly higher conductivity values in the 12-min group (P = 0.030). At 3.5 h after ROSC, the conductivity of cerebral tissue in the 12-min group remained increased (P = 0.022), whereas that in the 5-min group returned to its baseline level. CONCLUSIONS: The conductivity of cerebral tissue was increased in the first hours after ROSC, and the increase was more prominent and lasted longer in the 12-min group than in the 5-min group. Our findings suggest the promising potential of MRCI as a tool to estimate the severity of HIBI in the early hours after cardiac arrest.

Evaluation of advective solute infiltration into porous media by pulsed focused ultrasound-induced acoustic streaming effects.

PURPOSE: Acoustic streaming induced by applying transcranial focused ultrasound (FUS) promotes localized advective solute transport in the brain and has recently garnered research interest for drug delivery and enhancement of brain waste clearance. The acoustic streaming behavior in brain tissue is difficult to model numerically and thus warrants an in vitro examination of the effects of using different sonication parameters, in terms of frequency, intensity, and pulse duration (PD). METHODS: Melamine and polyvinyl alcohol (PVA) foams were used to mimic the porous brain tissue, which contains leptomeningeal fenestrations and perivascular space, while agar hydrogel was used to emulate denser neuropil. FUS was delivered to these media, which were immersed in a phosphate-buffered saline containing toluidine blue O dye, across various frequencies (400, 500, and 600 kHz; applicable to transcranial delivery) in a pulsed mode at two different spatialpeak pulse-average intensities (3 and 4 W/cm2). RESULTS: Image analysis showed that the use of 400 kHz yielded the greatest dye infiltration in melamine foam, while sonication had no impact on infiltration in the agar hydrogel due to the dominance of diffusional transport. Using a fixed spatial-peak temporal-average intensity of 0.4 W/cm2 at 400 kHz, a PD of 75 ms resulted in the greatest infiltration depth in both melamine and PVA foams among the tested range (50-150 ms). CONCLUSION: These findings suggest the existence of a specific frequency and PD that induce greater enhancement of solute/fluid movement, which may contribute to eventual in vivo applications in promoting waste clearance from the brain.

Effects of food and ethnicity on the pharmacokinetics of venadaparib, a next-generation PARP inhibitor, in healthy Korean, Caucasian, and Chinese male subjects.

AIM: Venadaparib is a next-generation poly(ADP-ribose) polymerase inhibitor under development for treating gastric cancer. This study aimed to evaluate the effects of food and ethnicity on the pharmacokinetics (PKs) and safety of venadaparib after a single oral administration in healthy Korean, Caucasian, and Chinese male subjects. METHODS: In this randomized, open-label, single-dose, two-sequence, two-period, and crossover study, Korean and Caucasian subjects received venadaparib 80 mg in each period (fasted or fed state) with a seven-day washout. In an open-label, single-dose study, Chinese subjects received venadaparib 80 mg only in the fasted state. Serial blood samples were collected up to 72 h post-dosing. RESULTS: Twelve subjects from each ethnic group completed the study. The geometric mean ratios (90% confidence intervals) of the maximum plasma concentration (Cmax) and area under the plasma concentration-time curve from time zero to the last measurable time point (AUClast) of venadaparib for the fed to fasted state were 0.82 (0.7457-0.9094) and 1.02 (0.9088-1.1339) in Koreans, and 0.77 (0.6871-0.8609) and 0.96 (0.9017-1.0186) in Caucasians, respectively. No statistically significant differences were observed in Cmax (P-value = 0.45) or AUClast (P-value = 0.30) among the three ethnic groups. A single venadaparib dose was well-tolerated. CONCLUSION: The overall systemic exposure of venadaparib was not affected by the high-fat meal, despite delayed absorption with a decreased Cmax in the fed state. The PK profiles were comparable among the Korean, Caucasian, and Chinese subjects. A single venadaparib 80 mg dose was safe and well-tolerated in both fasted and fed states.

Thermal Injury to the Subhepatic Appendix Following Percutaneous Ultrasound-Guided Radiofrequency Ablation for Hepatocellular Carcinoma: A Case Report.

We present the first documented case of a fistula between the treated zone and the appendix after RFA in a patient with HCC. Contrast-enhanced CT and MRI revealed a subcapsular hepatic nodule with image findings of HCC located adjacent to the ascending colon and cecum. An ultrasound-guided core needle biopsy was subsequently performed to distinguish between hepatic metastasis and HCC. Post-RFA imaging identified a low-attenuating ablated area adjacent to an air-filled appendix. The patient later experienced complications, including increased liver enzymes and an abscess at the ablation site. Imaging revealed a fistulous tract between the RFA zone and the appendix. Over the following months, the patient underwent conservative treatment involving intravenous antibiotics and repeated percutaneous drainage, exhibiting eventual symptom relief and an absence of the fistulous tract upon subsequent imaging. This case highlights the rare complications that can arise during RFA due to peculiar anatomical variations, such as a subhepatic appendix, resulting from midgut malrotation and previous surgery. It is imperative for operators to be cognizant of potential anatomical variations when considering RFA treatment, ensuring comprehensive pre-procedural imaging and post-procedure monitoring. This case also emphasizes the potential viability of nonoperative management in complex scenarios in which surgical interventions pose significant risks.

Non-thermal Acoustic Enhancement of Chemotherapeutic Effects of Cisplatin on Xenografted Cervical Cancer in Mice.

BACKGROUND/AIM: We examined the effect of low-intensity focused ultrasound (FUS) on unbinding cisplatin from plasma proteins and enhancing its chemotherapeutic efficacy using a mouse model of xenograft human cervical cancer. MATERIALS AND METHODS: FUS, operating in a pulsed mode, was applied to a dialysis cassette immersed in a normal saline bath containing both bovine serum albumin (BSA) and cisplatin, and the unbound level of cisplatin diffused into the cassette was measured. To assess the in vivo efficacy of the technique, athymic nu/nu mice were inoculated with human cervical cancer cells under four different combinatory conditions, with and without the administration of cisplatin and FUS. FUS was delivered to the tumor mass for 1 h across four separate sessions spanning a period of 10 days, following the intraperitoneal injection of cisplatin. RESULTS: In vitro equilibrium dialysis revealed that non-thermal application of FUS increased the concentration of unbound cisplatin compared to cassettes that were not exposed to sonication, suggesting successful unbinding. Assessment of tumor growth in vivo showed that FUS following cisplatin administration resulted in a significant reduction in tumor growth, whereas the administration of cisplatin alone exhibited plateau growth. Without administration of cisplatin, equivalent rates of aggressive tumor growth were observed regardless of the application of FUS. CONCLUSION: Pulsed application of FUS can unbind cisplatin from albumin and enhance its tumoricidal effects in cervical cancer. Further assessment of intratumoral/systemic cisplatin concentration is required to quantify its selective delivery to the tumor.

Disease-microenvironment modulation by bare- or engineered-exosome for rheumatoid arthritis treatment.

BACKGROUND: Exosomes are extracellular vesicles secreted by eukaryotic cells and have been extensively studied for their surface markers and internal cargo with unique functions. A deeper understanding of exosomes has allowed their application in various research areas, particularly in diagnostics and therapy. MAIN BODY: Exosomes have great potential as biomarkers and delivery vehicles for encapsulating therapeutic cargo. However, the limitations of bare exosomes, such as rapid phagocytic clearance and non-specific biodistribution after injection, pose significant challenges to their application as drug delivery systems. This review focuses on exosome-based drug delivery for treating rheumatoid arthritis, emphasizing pre/post-engineering approaches to overcome these challenges. CONCLUSION: This review will serve as an essential resource for future studies to develop novel exosome-based therapeutic approaches for rheumatoid arthritis. Overall, the review highlights the potential of exosomes as a promising therapeutic approach for rheumatoid arthritis treatment.

Non-invasive enhancement of intracortical solute clearance using transcranial focused ultrasound.

Transport of interstitial fluid and solutes plays a critical role in clearing metabolic waste from the brain. Transcranial application of focused ultrasound (FUS) has been shown to promote localized cerebrospinal fluid solute uptake into the brain parenchyma; however, its effects on the transport and clearance of interstitial solutes remain unknown. We demonstrate that pulsed application of low-intensity FUS to the rat brain enhances the transport of intracortically injected fluorescent tracers (ovalbumin and high molecular-weight dextran), yielding greater parenchymal tracer volume distribution compared to the unsonicated control group (ovalbumin by 40.1% and dextran by 34.6%). Furthermore, FUS promoted the drainage of injected interstitial ovalbumin to both superficial and deep cervical lymph nodes (cLNs) ipsilateral to sonication, with 78.3% higher drainage observed in the superficial cLNs compared to the non-sonicated hemisphere. The application of FUS increased the level of solute transport visible from the dorsal brain surface, with ~ 43% greater area and ~ 19% higher fluorescence intensity than the unsonicated group, especially in the pial surface ipsilateral to sonication. The sonication did not elicit tissue-level neuronal excitation, measured by an electroencephalogram, nor did it alter the molecular weight of the tracers. These findings suggest that nonthermal transcranial FUS can enhance advective transport of interstitial solutes and their subsequent removal in a completely non-invasive fashion, offering its potential non-pharmacological utility in facilitating clearance of waste from the brain.

Transcranial focused ultrasound stimulation of cortical and thalamic somatosensory areas in human.

The effects of transcranial focused ultrasound (FUS) stimulation of the primary somatosensory cortex and its thalamic projection (i.e., ventral posterolateral nucleus) on the generation of electroencephalographic (EEG) responses were evaluated in healthy human volunteers. Stimulation of the unilateral somatosensory circuits corresponding to the non-dominant hand generated EEG evoked potentials across all participants; however, not all perceived stimulation-mediated tactile sensations of the hand. These FUS-evoked EEG potentials (FEP) were observed from both brain hemispheres and shared similarities with somatosensory evoked potentials (SSEP) from median nerve stimulation. Use of a 0.5 ms pulse duration (PD) sonication given at 70% duty cycle, compared to the use of 1 and 2 ms PD, elicited more distinctive FEP peak features from the hemisphere ipsilateral to sonication. Although several participants reported hearing tones associated with FUS stimulation, the observed FEP were not likely to be confounded by the auditory sensation based on a separate measurement of auditory evoked potentials (AEP) to tonal stimulation (mimicking the same repetition frequency as the FUS stimulation). Off-line changes in resting-state functional connectivity (FC) associated with thalamic stimulation revealed that the FUS stimulation enhanced connectivity in a network of sensorimotor and sensory integration areas, which lasted for at least more than an hour. Clinical neurological evaluations, EEG, and neuroanatomical MRI did not reveal any adverse or unintended effects of sonication, attesting its safety. These results suggest that FUS stimulation may induce long-term neuroplasticity in humans, indicating its neurotherapeutic potential for various neurological and neuropsychiatric conditions.

A preliminary study about the potential risks of the UV-weathered microplastic: The proteome-level changes in the brain in response to polystyrene derived weathered microplastics.

The growing use of plastic materials has resulted in a constant increase in the risk associated with microplastics (MPs). Ultra-violet (UV) light and wind break down modify MPs in the environment into smaller particles known as weathered MPs (WMPs) and these processes increase the risk of MP toxicity. The neurotoxicity of weathered polystyrene-MPs remains unclear. Therefore, it is important to understand the risks posed by WMPs. We evaluated the chemical changes of WMPs generated under laboratory-synchronized environmentally mimetic conditions and compared them with virgin MPs (VMPs). We found that WMP had a rough surface, slight yellow color, reduced molecular weight, and structural alteration compared with those of VMP. Next, 2 µg of ∼100 µm in size of WMP and VMP were orally administered once a day for one week to C57BL/6 male mice. Proteomic analysis revealed that the WMP group had significantly increased activation of immune and neurodegeneration-related pathways compared with that of the VMP group. Consistently, in in vitro experiments, the human brain-derived microglial cell line (HMC-3) also exhibited a more severe inflammatory response to WMP than to VMP. These results show that WMP is a more profound inflammatory factor than VMP. In summary, our findings demonstrate the toxicity of WMPs and provide theoretical insights into their potential risks to biological systems and even humans in the ecosystem.

A Comparison of the Pharmacokinetics and Safety of Dapagliflozin Formate, an Ester Prodrug of Dapagliflozin, to Dapagliflozin Propanediol Monohydrate in Healthy Subjects.

Background: Dapagliflozin formate (DAP-FOR, DA-2811), an ester prodrug of dapagliflozin, was developed to improve the stability and pharmaceutical manufacturing process of dapagliflozin, a sodium-glucose cotransporter-2 inhibitor. Purpose: This study aimed to evaluate the pharmacokinetics (PKs) and safety of dapagliflozin for DAP-FOR compared to those for dapagliflozin propanediol monohydrate (DAP-PDH, Forxiga) in healthy subjects. Methods: This was an open-label, randomized, single-dose, two-period, two-sequence crossover study. The subjects received a single dose of DAP-FOR or DAP-PDH 10 mg in each period, with a 7-day washout. Serial blood samples for PK analysis were collected up to 48 hours after a single administration to determine plasma concentrations of DAP-FOR and dapagliflozin. PK parameters were calculated using a non-compartmental method and compared between the two drugs. Results: In total, 28 subjects completed the study. DAP-FOR plasma concentrations were not detected in all of the blood sampling time points except for one time point in one subject, and the corresponding DAP-FOR plasma concentration in the subject was close to the lower limit of quantification. The mean plasma concentration-time profiles of dapagliflozin were comparable between the two drugs. The geometric mean ratios and its 90% confidence intervals of the maximum plasma concentration and area under the plasma concentration-time curve of dapagliflozin for DAP-FOR to DAP-PDH were within the conventional bioequivalence range of 0.80-1.25. Both drugs were well-tolerated, with a similar incidence of adverse drug reactions. Conclusion: The rapid conversion of DAP-FOR into dapagliflozin led to the extremely low exposure of DAP-FOR and comparable PK profiles of dapagliflozin between DAP-FOR and DAP-PDH. The safety profiles were also similar between the two drugs. These results suggest that DAP-FOR can be used as an alternative to DAP-PDH.

Pharmacokinetics and Pharmacodynamics of Esomezol DR, a New Dual Delayed-Release Formulation of Esomeprazole 20 Mg or 40 Mg, in Healthy Subjects.

Background: Esomeprazole, a proton pump inhibitor (PPI), is widely used to treat acid-related disorders, but it has short plasma half-life which can cause insufficient gastric acid suppression, such as nocturnal acid breakthrough. A new dual delayed-release (DR) formulation of esomeprazole (Esomezol DR), was developed to extend the duration of gastric acid suppression. Purpose: This study aimed to evaluate the pharmacokinetics (PKs) and pharmacodynamics (PDs) of esomeprazole for the DR formulation compared to a conventional enteric-coated (EC) formulation (Nexium) in healthy male subjects. Methods: Two randomized, open-label, multiple-dose, two-way crossover studies with esomeprazole 20 mg and 40 mg were conducted. Subjects received the DR formulation or the EC formulation once daily for 7 days in each period with a 7-day washout. Serial blood samples were collected up to 24 hours after the 1st dose, and 24-hour intragastric pH was continuously monitored before the 1st dose as baseline and after the 1st and the 7th dose. Results: In 20 mg and 40 mg dose groups, 38 and 44 subjects completed the study, respectively. The DR formulation exhibited the dual-release pattern of esomeprazole, resulting in more sustained plasma concentration-time profiles compared to the EC formulation. The systemic exposure of esomeprazole for the DR formulation was comparable to that for the EC formulation, showing the similar area under the plasma concentration-time curve. The 24-hour gastric acid suppression was also similar between the two formulations, while the inhibition during night-time (22:00-06:00) showed a better tendency in the DR formulation. Conclusion: The sustained exposure of esomeprazole in the DR formulation led to well-maintained and higher acid inhibition compared to the EC formulation, especially during the night-time. These results suggest that the DR formulation can be an alternative formulation to the conventional EC formulation, expecting the potential of relieving nocturnal acid-related symptoms.

Transcranial focused ultrasound-mediated unbinding of phenytoin from plasma proteins for suppression of chronic temporal lobe epilepsy in a rodent model.

The efficacy of many anti-epileptic drugs, including phenytoin (PHT), is reduced by plasma protein binding (PPB) that sequesters therapeutically active drug molecules within the bloodstream. An increase in systemic dose elevates the risk of drug side effects, which demands an alternative technique to increase the unbound concentration of PHT in a region-specific manner. We present a low-intensity focused ultrasound (FUS) technique that locally enhances the efficacy of PHT by transiently disrupting its binding to albumin. We first identified the acoustic parameters that yielded the highest PHT unbinding from albumin among evaluated parameter sets using equilibrium dialysis. Then, rats with chronic mesial temporal lobe epilepsy (mTLE) received four sessions of PHT injection, each followed by 30 min of FUS delivered to the ictal region, across 2 weeks. Two additional groups of mTLE rats underwent the same procedure, but without receiving PHT or FUS. Assessment of electrographic seizure activities revealed that FUS accompanying administration of PHT effectively reduced the number and mean duration of ictal events compared to other conditions, without damaging brain tissue or the blood-brain barrier. Our results demonstrated that the FUS technique enhanced the anti-epileptic efficacy of PHT in a chronic mTLE rodent model by region-specific PPB disruption.

The effect of rapid weight loss on sports injury in elite taekwondo athletes.

OBJECTIVES: The purpose of this study was to reveal the relationship of injury patterns between normal training period and weight loss period in Korea elite taekwondo athletes. METHODS: Since 2021, data for elite taekwondo athletes have been collected prospectively by the Korean Training Institute, there were 102 male and 95 female. The data were classified by sex, weight class, injury location, injuries during the normal training and weight loss periods. The χ2 test was used to compare groups. The injury incidence rates were calculated as the number of injuries per 1,000 hours of training. RESULTS: A total of 703 injuries were recorded during normal training, and total of 149 injuries were recorded during the weight loss period. Taekwondo athletes showed a higher incidence of during the weight loss period than during the normal training period (3.66 VS 6.88; p < 0.001). The body parts affected by injury differed significantly between the normal training period and weight loss period (p = 0.033). Injury to the lower extremities or to the head and neck was relatively higher during the normal training period, while injury to the trunk and upper extremities was relatively higher during the weight loss period. Muscle, ligament, and bone injuries were common during both the normal training and weight loss periods. Level I injuries were relatively more frequent during normal training, while level II and III injuries were relatively more frequent during weight loss (p < 0.001). CONCLUSION: Rapid weight loss is related to the injury patterns in taekwondo athletes. Injury incidence rate increases during rapid weight loss periods. Moreover, the injury site and injury severity depend on during normal training and during the weight loss period.

Epidemiology of sports injuries in korean elite female fencing athletes: a prospective cohort study / Epidemiología de las lesiones deportivas en atletas coreanas de esgrima de élite: un estudio prospectivo de cohorte / Epidemiologia das lesões esportivas em atletas coreanas de esgrima de elite: um estudo prospectivo de coorte

ABSTRACT Objectives: We aimed to assess the risk of injury associated with training activities of Korean elite female fencing athletes by weapon category. Methods: We prospectively collected 2021 data on 80 elite female fencing athletes at the Korean Training Center. Injury incidence rates were expressed as Poisson rates with a 95% confidence interval. We used χ2 tests to compare injury locations and recovery times by weapon category. Results: A total of 233 injuries were recorded, averaging 3.27 (95% CI, 2.86-3.72) injuries per 1,000 training hours. The sabre had the highest injury incidence rate, followed by the epee and the foil. Injuries to fencing athletes were the most common in the lower extremities (46.35%), followed by the upper extremities (24.03%), trunk (20.17%), and head and neck area (9.44%). The weapon category did not affect the body regions (p=0.425). However, recovery time differed significantly by body region (p=0.021). Conclusions: The weapon category was found to affect the injury incidence rate. In addition, recovery time varied depending on body region. Further research is needed to clarify these results. Level of evidence II; Therapeutic studies - investigation of treatment results.

RESUMEN Objetivos: Nuestro objetivo fue evaluar el riesgo de lesión asociado a las actividades de entrenamiento según la categoría de arma en atletas coreanas de esgrima de élite. Método: A partir de 2021, recopilamos prospectivamente datos de 80 atletas de esgrima de élite en el Centro de Entrenamiento de Corea. Las tasas de incidencia de lesiones se expresaron como tasas de Poisson con un intervalo de confianza del 95%. Usamos la prueba de χ2 para comparar el local de las lesiones y los tiempos de recuperación según la categoría de arma. Resultados: Se registró un total de 233 lesiones, con un promedio de 3,27 (IC 95 %, 2,86-3,72) lesiones por cada 1000 horas de entrenamiento. El sable tuvo la tasa de incidencia de lesiones más alta, seguido por la espada y el florete. Las lesiones de los atletas de esgrima fueron más frecuentes en las extremidades inferiores (46,35%), seguidas de las extremidades superiores (24,03%), tronco (20,17%) y región de la cabeza y cuello (9,44%). La categoría de arma no afectó las regiones del cuerpo (p=0,425). Sin embargo, el tiempo de recuperación difirió significativamente según la región del cuerpo (p=0,021). Conclusión: Se constató que la categoría de arma afecta la tasa de incidencia de lesiones. Además, el tiempo de recuperación varía según la región del cuerpo. Se necesitan más investigaciones para aclarar estos resultados. Nivel de evidencia II; Estudios terapéuticos - investigación de resultados de tratamiento.

RESUMO Objetivos: Nosso objetivo foi avaliar o risco de lesão associado às atividades de treinamento de acordo com a categoria de arma de atletas coreanas de esgrima de elite. Métodos: A partir de 2021, coletamos prospectivamente dados de 80 atletas de elite de esgrima no Centro de Treinamento Coreano. As taxas de incidência de lesões foram expressas como taxas de Poisson com intervalo de confiança de 95%. Usamos o teste de χ2 para comparar os locais de lesão e os tempos de recuperação de acordo com a categoria da arma. Resultados: Um total de 233 lesões foi registrado, com média de 3,27 (IC 95%, 2,86-3,72) lesões por 1.000 horas de treinamento. O sabre teve a maior taxa de incidência de lesões, seguido pela espada e pelo florete. As lesões dos atletas de esgrima foram mais comuns nos membros inferiores (46,35%), seguidas pelos membros superiores (24,03%), tronco (20,17%) e região da cabeça e pescoço (9,44%). A categoria da arma não influenciou as regiões do corpo (p = 0,425). No entanto, o tempo de recuperação diferiu significativamente de acordo com a região do corpo (p = 0,021). Conclusão: Verificou-se que a categoria de arma afeta a taxa de incidência de lesões. Além disso, o tempo de recuperação variou de acordo com a região do corpo. São necessárias mais pesquisas para esclarecer esses resultados. Nível de evidência II; Estudos terapêuticos - investigação de resultados de tratamento.

Effects of focused ultrasound pulse duration on stimulating cortical and subcortical motor circuits in awake sheep.

Low-intensity transcranial focused ultrasound (tFUS) offers new functional neuromodulation opportunities, enabling stimulation of cortical as well as deep brain areas with high spatial resolution. Brain stimulation of awake sheep, in the absence of the confounding effects of anesthesia on brain function, provides translational insight into potential human applications with safety information supplemented by histological analyses. We examined the effects of tFUS pulsing parameters, particularly regarding pulse durations (PDs), on stimulating the cortical motor area (M1) and its thalamic projection in unanesthetized, awake sheep (n = 8). A wearable tFUS headgear, custom-made for individual sheep, enabled experiments to be conducted without using anesthesia. FUS stimuli, each 200 ms long, were delivered to the M1 and the thalamus using three different PDs (0.5, 1, and 2 ms) with the pulse repetition frequency (PRF) adjusted to maintain a 70% duty cycle at a derated in situ spatial-peak temporal-average intensity (Ispta) of 3.6 W/cm2. Efferent electromyography (EMG) responses to stimulation were quantified from both hind limbs. Group-averaged EMG responses from each of the hind limbs across the experimental conditions revealed selective responses from the hind limb contralateral to sonication. The use of 0.5 and 1 ms PDs generated higher EMG signal amplitudes compared to those obtained using a 2 ms PD. Faster efferent response was also observed from thalamic stimulation than that from stimulating the M1. Post-sonication behavioral observation and histological assessment performed 24 h and 1 month after sonication were not indicative of any abnormalities. The results suggest the presence of pulsing scheme-dependent effects of tFUS on brain stimulation and attest its safety in awake large animals.