Investigating the link between antipsychotic use and post-stroke infections in older people: multi-centre propensity score analysis.

BACKGROUND: The risk of stroke increases with age, and although previous reports have suggested that infection risk may increase with antipsychotic use, relevant studies after stroke are scarce. We aimed to investigate whether antipsychotics increase post-stroke infection risk in the acute stroke period. METHODS: This propensity score matching study included adults diagnosed with first-ever stroke between 2011 and 2020 at five university hospitals. In-hospital antipsychotic exposure was defined as any administration during hospitalisation for stroke. The primary outcome was post-stroke infection after the first 2 days of hospitalisation, and the secondary outcome was the presence of pneumonia, bacteraemia and/or bacteriuria. RESULT: Among 23,885 first-ever stroke patients, 2,773 antipsychotic users (age 71.6 ± 12.4, male 54.6%) and 2,773 non-users (age 71.2 ± 13.2, male 54.6%) were selected as matched cohorts. After adjusting for propensity score, antipsychotics were not associated with an increased risk of post-stroke infection (odds ratio 0.99, 95% confidence interval 0.87-1.14). CONCLUSION: While our study did not find conclusive evidence linking antipsychotic medication to an increased risk of post-stroke infection, prescribing these medications should still be approached with prudence. Until further research can provide more definitive insights, clinicians should carefully weigh the potential infection risks when considering antipsychotic treatment during the acute stroke care period.

Optimized trans-cranial direct current stimulation for prolonged consciousness disorder in a patient with titanium mesh cranioplasty.

BACKGROUND: Transcranial direct current stimulation (tDCS) has been used for the restoration of awareness in patients with a minimal consciousness state (MCS). Most brains of patients in MCS may structurally and electrophysiologically differ from un-damaged brains. Moreover, tDCS is currently contraindicated for patients with craniotomy or skull with metallic implants. CASE PRESENTATION: We present a case with prolonged MCS over 1 year, who had severe brain damage, ventriculoperitoneal shunt, and cranioplasty with a titanium mesh, which was treated with tDCS which optimized with the simulation of the electric field based on the patient's brain MRI. The patient was resulting in emergence from MCS. Six months later, she ate meals orally and started walking with assistance. DISCUSSION AND PERSPECTIVE: This personalized simulation based on MRI would make the treatment available even to patients with severe brain structural changes and metallic instrumentation.

Evidence of lateralised white matter plasticity: A longitudinal study of balance performance in nonexpert healthy adults.

Training-induced plasticity by practicing expert skills has been of particular interest; however, little is known about white matter plasticity for improving a fundamental element of body function, such as balance or postural control. This study explored white matter plasticity in nonexpert healthy adults, based on stepwise balance training. Seventeen participants were included and performed a home-based balance training program for 4 weeks (30 min/day, 3 days/week). Before commencing training, they underwent a baseline diffusion tensor imaging scan. A second scan was acquired at the end of the 4-week training. Lateralised balance load was applied on the right leg to contrast any lateralised effect on the white matter tracts. The balance function was assessed using the Community Balance & Mobility Scale. We examined changes in the fractional anisotropy values of the tracts of interest between pre- and post-training. After the 4-week training, the fractional anisotropy values were enhanced in the right superior cerebellar peduncle, transverse pontine fibre, body of the corpus callosum, left fornix and left uncinate fasciculus. The Community Balance & Mobility Scale score improved after 4-week training, but an association with changes in fractional anisotropy values cannot be evaluated due to the ceiling effect of the balance assessment tools. Balance training can strengthen the cerebro-cerebellar and interhemispheric structural connections and induce microstructural changes in the limbic structures, including the fornix and uncinate fasciculus. The effect of a lateralised balance load could be projected to the specific white matter tracts in a lateralised manner.

Data-driven approach to predicting the risk of pressure injury: A retrospective analysis based on changes in patient conditions.

AIMS: To determine the risk of pressure injury development in the intensive care unit based on changes in patient conditions. DESIGN: This retrospective study was based on secondary data analysis. METHODS: Patient data from electronic health records were retrospectively obtained and we included 438 and 1752 patients with and without pressure injury, respectively, among those admitted to the medical and surgical intensive care units (ICUs) from January 2017-February 2020. Changes in patient conditions were analysed based on the first and last objective data values from the day of ICU admission to the day before the onset of pressure injury and categorised as follows: improved, maintained normal, exacerbated and unchanged. Logistic regression was performed to identify the significant predictors of pressure injury development based on 11 variables. RESULTS: The 11 selected variables were age, body mass index, activity, acute physiology and chronic health evaluation II score, nursing severity level, pulse and albumin, haematocrit, C-reactive protein, total bilirubin and blood urea nitrogen levels. The risk for a pressure injury was high with exacerbation of or persistently abnormal levels of nursing severity, albumin, haematocrit, C-reactive protein, blood urea nitrogen and pulse >100 beat/min. CONCLUSION: Periodic monitoring of haematological variables is important for preventing pressure injury in the intensive care unit. REPORTING METHOD: The study followed STROBE guidelines. PATIENT OR PUBLIC CONTRIBUTION: This study contributes to the utilisation of patient data from electronic health records. RELEVANCE TO CLINICAL PRACTICE: In addition to other pressure injury risk assessment tools, ICU nurses can help prevent pressure injuries by assessing patients' blood test results, thereby promoting patient safety and enhancing the efficacy of nursing practice.

Latent profile analysis of adaptation types and stress among medical students during the COVID-19 pandemic in South Korea.

Objective: This study aimed to identify profile groups based on personality traits and coping strategies exhibited by medical students in the context of COVID-19. Methods: We conducted a cross-sectional survey and latent profile analysis to investigate differences in stressors, psychological distress, and stress levels with academic variables. We collected data online (Google survey form) in November and December 2021. The participants included a total of 260 1st and 2nd year medical students, all completed questionnaires containing the following sections: Big Five Inventory, coping strategies, COVID-19 stressors, Kessler Psychological Distress Scale, and stress level with academic variables. For analysis, a latent profile analysis, ANOVA, and χ2 were used. Results: The results reveal the three following profile groups: adaptive (lowest neuroticism, low mental disengagement), middle-adaptive (moderate neuroticism, low mental disengagement), and maladaptive (highest neuroticism and mental disengagement), respectively comprising 25.0%, 39.2%, and 35.8% of the study sample. There were no statistically significant intergroup differences regarding grade (χ2=3.345, p=0.188) or gender (χ2=1.197, p=0.550). The maladaptive group was strongly associated with perceived stress during the COVID-19 pandemic (p<0.001). Conclusion: These findings highlight the value of considering profile groups when determining whether students require additional support during pandemics.

Single Nucleotide Polymorphisms May Increase the Risk of Aspiration Pneumonia in Post-Stroke Patients with Dysphagia.

This study aimed to evaluate whether genetic polymorphism is associated with an increased risk of infection, specifically post-stroke aspiration pneumonia. Blood samples were obtained from a total of 206 post-stroke participants (males, n = 136; mean age, 63.8 years). Genotyping was performed for catechol-O-methyltransferase (rs4680, rs165599), dopamine receptors (DRD1; rs4532, DRD2; rs1800497, DRD3; rs6280), brain-derived neurotrophic factor (rs6265), apolipoprotein E (rs429358, rs7412), and the interleukin-1 receptor antagonist gene (rs4251961). The subjects were stratified into two groups, aged < 65 (young) and ≥ 65 (elderly). Functional parameters and swallowing outcomes were measured at enrollment and at 3 months post-onset. The primary outcome was the incidence of aspiration pneumonia. Analysis of the association between genetic polymorphisms and aspiration pneumonia history showed that a minor C rs429358 allele was associated with the occurrence of aspiration pneumonia in the young group, both in the additive and the dominant models (odds ratio: 4.53; 95% CI: 1.60−12.84, p = 0.004). In the multivariable analysis, the minor C rs429358 allele increased the risk of post-stroke aspiration pneumonia in young stroke patients by 5.35 (95% CI: 1.64−20.88). In contrast, no such association was observed in the elderly group. Apolipoprotein E polymorphism may affect the risk of post-stroke aspiration pneumonia.

RORα is crucial for attenuated inflammatory response to maintain intestinal homeostasis.

Retinoic acid-related orphan receptor α (RORα) functions as a transcription factor for various biological processes, including circadian rhythm, cancer, and metabolism. Here, we generate intestinal epithelial cell (IEC)-specific RORα-deficient (RORαΔIEC) mice and find that RORα is crucial for maintaining intestinal homeostasis by attenuating nuclear factor κB (NF-κB) transcriptional activity. RORαΔIEC mice exhibit excessive intestinal inflammation and highly activated inflammatory responses in the dextran sulfate sodium (DSS) mouse colitis model. Transcriptome analysis reveals that deletion of RORα leads to up-regulation of NF-κB target genes in IECs. Chromatin immunoprecipitation analysis reveals corecruitment of RORα and histone deacetylase 3 (HDAC3) on NF-κB target promoters and subsequent dismissal of CREB binding protein (CBP) and bromodomain-containing protein 4 (BRD4) for transcriptional repression. Together, we demonstrate that RORα/HDAC3-mediated attenuation of NF-κB signaling controls the balance of inflammatory responses, and therapeutic strategies targeting this epigenetic regulation could be beneficial to the treatment of chronic inflammatory diseases, including inflammatory bowel disease (IBD).

Cough Sounds Recorded via Smart Devices as Useful Non-Invasive Digital Biomarkers of Aspiration Risk: A Case Report.

Spirometer measurements can reflect cough strength but might not be routinely available for patients with severe neurological or medical conditions. A digital device that can record and help track abnormal cough sound changes serially in a noninvasive but reliable manner would be beneficial for monitoring such individuals. This report includes two cases of respiratory distress whose cough changes were monitored via assessments performed using recordings made with a digital device. The cough sounds were recorded using an iPad (Apple, Cupertino, CA, USA) through an embedded microphone. Cough sounds were recorded at the bedside, with no additional special equipment. The two patients were able to complete the recordings with no complications. The maximum root mean square values obtained from the cough sounds were significantly reduced when both cases were diagnosed with aspiration pneumonia. In contrast, higher values became apparent when the patients demonstrated a less severe status. Based on an analysis of our two cases, the patients' cough sounds recorded with a commercial digital device show promise as potential digital biomarkers that may reflect aspiration risk related to attenuated cough force. Serial monitoring aided the decision making to resume oral feeding. Future studies should further explore the clinical utility of this technique.

Heart Rate Variability-Measured Stress and Academic Achievement in Medical Students.

OBJECTIVES: Stress can affect learning and memory in students. Previous studies on stress in students were conducted mainly through surveys. We investigated how heart rate variability (HRV)-measured stress is related to academic achievement in medical students during clerkship. SUBJECTS AND METHODS: A cross-sectional study was conducted. HRV measurements were performed in 97 third-year medical students during their family medicine clerkship course. Data on written and skilled examination scores of the end of the school year were also collected. We assessed the association between HRV-measured stress and written/skilled examination scores. RESULTS: Written examination scores showed a positive correlation with standard deviation of the normal-to-normal intervals (SDNNs) (r = 0.245, p = -0.016), sympathetic nervous system/parasympathetic nervous system (SNS/PNS) balance (r = 0.218, p = 0.033), and stress index (r = 0.381, p = 0.004). Students with an unhealthy SDNN, a dominant SNS, and a high stress index had higher scores in written examinations than students with a healthy SDNN, a balanced SNS/PNS, and a normal stress index, respectively (p = 0.004, 0.018, and 0.012, respectively). Moreover, skilled examination scores were negatively correlated with BMI (r = -0.249, p = 0.014) and were higher in female students (r = 0.240, p = 0.018). Students with an abnormal autonomic balance diagram (ABD) had a higher score than students with a normal ABD (p = 0.03). CONCLUSIONS: This study shows that medical students with higher stress measured by HRV have higher academic achievement, especially in written examinations. Further studies are needed to confirm the results of this study and to assess the long-term effects of HRV-measured stress on medical students.

Cut-off Values of the Respiratory Muscle Power and Peak Cough Flow in Post-Stroke Dysphagia.

Background and objectives: This study aimed to determine the cut-off values of the following three respiratory pressure meters; the voluntary peak cough flow (PCF), maximal expiratory pressure (MEP) and maximal inspiratory pressure (MIP); associated with post-stroke dysphagia and assess which of these parameters show good diagnostic properties associated with post-stroke dysphagia. Materials and Methods: Retrospective analysis of a prospectively maintained database. Records of patients with first-ever diagnosed dysphagia attributable to cerebrovascular disease, who had performed spirometry measurements for the PCF, MIP and MEP. Results: From a total of 237 stroke patients, 163 patients were diagnosed with dysphagia. Those with dysphagia had significantly lower PCF values than those without dysphagia (116.3 ± 75.3 vs. 219.4 ± 91.8 L/min, p < 0.001). In addition, the former group also had lower MIP (30.5 ± 24.7 vs. 41.6 ± 25.7 cmH2O, p = 0.0002) and MEP (41.0 ± 27.9 vs. 62.8 ± 32.3 cmH2O, p < 0.001) values than the latter group. The receiver operating characteristic curve analysis showed that the PCF cut-off value of 151 L/min (area under the receiver operating characteristic curve [AUC] 0.81; sensitivity 72%; specificity 78.8%) was associated with post-stroke dysphagia. The optimum MEP and MIP cut-off were 38 cmH2O (AUC 0.70, sensitivity 58%; specificity 77.7%) and 20 cmH2O (AUC 0.65, sensitivity 49%; specificity 84%). PCF showed the highest AUC results. Results from the univariate analysis indicated that PCF values of ≤151 L/min increased risk of dysphagia by 9.51-fold (4.96-18.23). Multivariable analysis showed that after controlling of other clinical factor, the PCFs at this cut-off value still showed increased risk of by 4.19 (2.02-83.69) but this was not observed with the MIPs or MEPs. Conclusions: Our study has provided cut-off values that are associated with increased risk of dysphagia. Among the three parameters, PCF showed increased association with post-stroke dysphagia.

Dedifferentiated Schwann cells secrete progranulin that enhances the survival and axon growth of motor neurons.

Schwann cells (SCs), the primary glia in the peripheral nervous system (PNS), display remarkable plasticity in that fully mature SCs undergo dedifferentiation and convert to repair SCs upon nerve injury. Dedifferentiated SCs provide essential support for PNS regeneration by producing signals that enhance the survival and axon regrowth of damaged neurons, but the identities of neurotrophic factors remain incompletely understood. Here we show that SCs express and secrete progranulin (PGRN), depending on the differentiation status of SCs. PGRN expression and secretion markedly increased as primary SCs underwent dedifferentiation, while PGRN secretion was prevented by administration of cAMP, which induced SC differentiation. We also found that sciatic nerve injury, a physiological trigger of SC dedifferentiation, induced PGRN expression in SCs in vivo. These results suggest that dedifferentiated SCs express and secrete PGRN that functions as a paracrine factor to support the survival and axon growth of neighboring neurons after injury.

Degeneration of the Inferior Cerebellar Peduncle After Middle Cerebral Artery Stroke: Another Perspective on Crossed Cerebellar Diaschisis.

Background and Purpose- Deafferentation of the cortico-ponto-cerebellar pathway has been proposed as a key mechanism of crossed cerebellar diaschisis. Although the cerebellum receives afferent stimuli from both cortico-ponto-cerebellar and spinocerebellar pathways, evidence on whether spinocerebellar deafferentation contributes to a hypofunctional cerebellum is lacking. Therefore, we aimed to determine whether changes in the spinocerebellar pathway occur after middle cerebral artery stroke. Methods- Twenty-three patients admitted to our inpatient rehabilitation facility and 23 age-matched healthy controls were retrospectively enrolled. Patients' functional ambulation category was determined and the Medical Research Council muscle scale test of the lower limb muscles was performed at admission and discharge. The fractional anisotropy (FA) values of the corticospinal tract and the inferior cerebellar peduncle (ICP), as the final route of the dorsal spinocerebellar pathway, were compared between the groups. The FA laterality indices of the ICP and corticospinal tract were calculated as follows: (FAaffected-FAunaffected)/(FAaffected+FAunaffected). Pearson correlation analysis and multivariate linear regression models were used to determine the associations between the FA laterality indices and ambulatory function. Results- The FAs of the corticospinal tract and ICP were lower in the patient group than in the control group. The FA laterality index of the corticospinal tract was not correlated with the functional ambulation category or Medical Research Council muscle scale score at admission or discharge. The FA laterality index of the ICP at the pontomedullary junction was positively correlated with the functional ambulation category and Medical Research Council muscle scale scores of all hemiplegic lower limb muscles at admission and discharge. The FA laterality index of the ICP at the pontomedullary junction was independently associated with the functional ambulation category according to the multivariate regression models. Conclusions- ICP degeneration occurs in the subacute and early chronic phase of middle cerebral artery stroke. The lower FA laterality index of the ICP was indicative of poorer ambulatory and lower limb function.

Laterality of cerebellar afferent and efferent pathways in a healthy right-handed population: A diffusion tensor imaging study.

The cerebellum communicates with the cerebral cortex through the cortico-ponto-cerebellar tract (CPCT, cerebellar afferent) and the dentato-rubro-thalamo-cortical tract (DRTCT, cerebellar efferent). This study explored the laterality of CPCT and DRTCT in a right-handed population. Forty healthy right-handed subjects (18 males and 22 females with age range of 26-79 years old) who underwent diffusion tensor imaging (DTI) were retrospectively enrolled. Bilateral CPCT, DRTCT, and the corticospinal tract (CST) were reconstructed using probabilistic diffusion tensor tractography (DTT). Tract volume (TV) and fractional anisotropy (FA) were compared between dominant and non-dominant tracts. Subjects were divided into age groups (20-40, 41-60, and 61-80 years), and the DTI-derived parameters of the groups were compared to determine age-related differences. TV and FA of non-dominant CPCT were higher than those of dominant CPCT, and the dominant CST was higher than the non-dominant CST. The TV and FA of DRTCT showed no side-to-side difference. The 61-80 years age group had the highest TV of the dominant and non-dominant DRTCT among the three groups and the highest FA of the non-dominant CPCT and DRTCT. The results revealed the structural characteristics of CPCT and DRTCT using probabilistic DTT. Normal asymmetric patterns and age-related changes in cerebellar white matter tracts may be important to researchers investigating cerebro-cerebellar structural connectivity.

Impact of video feedback system on medical students' perception of their clinical performance assessment.

BACKGROUND: Providing feedback on student performance in the clinical performance assessment (CPA) is meaningful in that it helps students understand their strengths and weaknesses. This study compared students' perception of their CPA scores before and after providing personalized video feedback. METHODS: Two identical online surveys of Year 1 medical students (N = 103) that had undergone CPA were conducted to evaluate students' perceptions about their CPA scores before and after video feedback. Students were given their test scores with assessment analysis reports immediately after completing the CPA. Top-scored students from each station agreed to provide their video-recorded performance to the rest of the students. RESULTS: After comparing their performance video and top-scored video at each station, medical students were more aware of their CPA total score, clinical performance examination (CPX) total score, score of each CPX station, section score for the CPX station, history taking section score, physical examination section score, and doctor-patient relationship section score. Moreover, students became more convinced of their own weaknesses from their history taking and patient education section after viewing video feedback than before. CONCLUSION: The use of the video feedback system might help students recognize their CPA results and identify their strengths and weaknesses.

Determining Peak Cough Flow Cutoff Values to Predict Aspiration Pneumonia Among Patients With Dysphagia Using the Citric Acid Reflexive Cough Test.

OBJECTIVE: To investigate the clinical usefulness of the peak cough flow generated during the citric acid reflexive cough test (0.28 mol/L) by determining the appropriate cutoff values that could accurately predict aspiration pneumonia within the first 6 months after onset. DESIGN: Retrospective analysis of a prospectively maintained database. SETTING: University-affiliated hospital. PARTICIPANTS: Patients (N=163) with first-ever diagnosed dysphagia attributable to cerebrovascular disease, who had undergone the citric acid reflexive cough test on the same day they underwent the instrumental assessment of swallowing, such as videofluoroscopy or the functional endoscopic swallowing test. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Peak cough flow (L/min) from the citric acid reflexive cough test. RESULTS: A final 163 patients had full medical records with 6-month follow-up. Receiver operating curve analysis showed that peak cough flow cutoff values set at 59 L/min were significantly associated with aspiration pneumonia (area under the curve [AUC] 95% confidence interval =0.88 [0.83-0.93]). This cutoff value significantly (P<.001) predicted the risk of aspiration pneumonia with an odds ratio of 21.56 (9.62-48.28). A multivariate regression logistic regression analysis model including initial dysphagia severity, low body mass index, and decreased level of cognition showed that inclusion of the peak cough flow from the citric acid reflexive cough test significantly improved the predictive model of aspiration pneumonia within the first 6 months after onset (AUC=0.91 vs 0.79). CONCLUSIONS: Those with reflexive cough strength less than 59 L/min may be at high risk of respiratory infections within the first 6 months after dysphagia onset. Objective measurement of reflexive cough strength may help to predict those at risk of aspiration pneumonia.

Holistic rubric vs. analytic rubric for measuring clinical performance levels in medical students.

BACKGROUND: Task-specific checklists, holistic rubrics, and analytic rubrics are often used for performance assessments. We examined what factors evaluators consider important in holistic scoring of clinical performance assessment, and compared the usefulness of applying holistic and analytic rubrics respectively, and analytic rubrics in addition to task-specific checklists based on traditional standards. METHODS: We compared the usefulness of a holistic rubric versus an analytic rubric in effectively measuring the clinical skill performances of 126 third-year medical students who participated in a clinical performance assessment conducted by Pusan National University School of Medicine. We conducted a questionnaire survey of 37 evaluators who used all three evaluation methods-holistic rubric, analytic rubric, and task-specific checklist-for each student. The relationship between the scores on the three evaluation methods was analyzed using Pearson's correlation. Inter-rater agreement was analyzed by Kappa index. The effect of holistic and analytic rubric scores on the task-specific checklist score was analyzed using multiple regression analysis. RESULTS: Evaluators perceived accuracy and proficiency to be major factors in objective structured clinical examinations evaluation, and history taking and physical examination to be major factors in clinical performance examinations evaluation. Holistic rubric scores were highly related to the scores of the task-specific checklist and analytic rubric. Relatively low agreement was found in clinical performance examinations compared to objective structured clinical examinations. Meanwhile, the holistic and analytic rubric scores explained 59.1% of the task-specific checklist score in objective structured clinical examinations and 51.6% in clinical performance examinations. CONCLUSION: The results show the usefulness of holistic and analytic rubrics in clinical performance assessment, which can be used in conjunction with task-specific checklists for more efficient evaluation.

Variable Heavy Chain Domain Derived from a Cell-Penetrating Anti-DNA Monoclonal Antibody for the Intracellular Delivery of Biomolecules.

Targeting and modification of important intracellular proteins using efficient vehicles are invaluable in diagnostic and therapeutic fields. Cell-penetrating antibodies and their fragments can be utilized as vehicles for the delivery of modifiers into cells. In this study, we explored the applicability of variable heavy chain (VH) domain as delivery vehicles for mammalian cells. The characteristics of the recombinant VH domain produced from a cell-penetrating monoclonal anti-double stranded DNA antibody 2C10 were analyzed using flow cytometry, confocal microscopy, cell proliferation assay, and cell cycle analysis in various mammalian cell lines. The VH domain penetrated into various cell lines in a time- and dose-dependent manner, although the internalization efficiency varied. The domain was localized in the nuclei as well as the cytoplasm of living cells. It was also internalized into cells mainly through the clathrin-mediated endocytosis pathway. We tested further its efficiency in delivering specific biomolecule(s) using the conjugates of the single domain molecule and small interfering RNA (siRNA) for the testicular nuclear auto-antigenic sperm protein (tNASP). It was found that the siRNA was successfully delivered by the VH domain into cancer cells, and knockdown effects from the delivered tNASP-siRNA were observed. The levels of the RNA transcript and protein of tNASP were decreased and the down-regulated tNASP inhibited cell proliferation and caused G0G1 phase arrest of the cell cycle. These results indicate that the recombinant 2C10 VH domain could be applied as an efficient vehicle capable of delivering valuable biomolecule into the cytoplasm or cell nuclei for clinical uses.

Oropharyngeal dysphagia in secondary normal pressure hydrocephalus due to corticobulbar tract compression: cases series and review of literature.

The association and mechanism involved in swallowing disturbance and normal pressure hydrocephalus (NPH) needs to be established. We report a case report where a patient who showed progressive swallowing dysfunction was diagnosed with secondary NPH. Tractography analysis showed corticobulbar tract compression by ventricular dilation. Drainage operation led to the recovery of tract volume with an improvement of swallowing function. We also report ten case series in which secondary NPH was associated with a swallowing disturbance. In these cases, dysphagia also showed improvement after shunt operation. We review the literature regarding the corticobulbar tract and its association with swallowing disturbance and the possible underlying pathophysiological mechanism in secondary NPH. This report highlights that swallowing disturbance may manifest in those with secondary NPH due to corticobulbar tract involvement. Our findings suggest that involvement of the corticobulbar tract may be a possible cause of dysphagia in secondary NPH that may be reversible after shunt operation.

Bioactivity-guided isolation and identification of anti-adipogenic compounds from Sanguisorba officinalis.

CONTEXT: Sanguisorba officinalis Linne (Rosaceae) is a medicinal plant used traditionally for the treatment of inflammatory and metabolic diseases in Korea, China, and Japan. In our previous study, a 50% ethanol extract inhibited fat accumulation in 3T3-L1 adipocytes. OBJECTIVE: This study investigates bioassay-guided fractionation, isolation, and identification of anti-adipogenic bioactive compounds in S. officinalis. MATERIALS AND METHODS: The bioassay-guided fractionation was conducted using effective differentiation of 3T3-L1 cells into adipocytes (with 50 µg/mL test material for 8 days) to isolate the inhibitory compounds from ethyl acetate fraction of S. officinalis 50% ethanol extract. The cytotoxicity of each fraction and isolated compound was tested using MTT assay (with 25-300 µg/mL test material). Structures of the isolated active compounds were elucidated using 1H NMR, 13 C NMR, HSQC, HMBC, FT-IR, and MS. RESULTS: An active ethyl acetate fraction obtained with solvent partition of the extract inhibited lipid accumulation (44.84%) on 3T3-L1 cells without cytotoxicity (102.3%) at the concentration of 50 µg/mL. The ethyl acetate fraction was determined to be mainly composed by isorhamnetin-3-O-d-glucuronide (1) and ellagic acid (2). Pure isorhamnetin-3-O-d-glucuronide (IC30 is 18.43 µM) and ellagic acid (IC30 is 19.32 µM) showed lipid accumulation inhibition on 3T3-L1 cells without cytotoxicity (117.5% and 104.3%) at the concentration of 20 µM, respectively. DISCUSSION AND CONCLUSIONS: These results suggested that S. officinalis is a potential natural ingredient for the prevention of obesity, which may due to bioactive compounds such as isorhamnetin-3-O-d-glucuronide and ellagic acid.