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Abdurahman Abibeker Omer,1 Meiraf Daniel Meshesha,2 Abraham Teka Ajema,3 Samuel D Yoo4 1Department of Internal Medicine, Dilchora Hospital, Dire Dawa, Ethiopia; 2Department of Internal Medicine, Dilla University, Dilla, Ethiopia; 3Clinical and treatment wing, ICAP at Columbia University, Hawassa, Ethiopia; 4Department of Internal Medicine, Jimma University, Jimma, EthiopiaCorrespondence: Meiraf Daniel Meshesha, Tel +251 096 089 0307, Email meirafdanielm@gmail.comIntroduction: The emergence of drug resistance in TB treatment is a major public health threat. However, there are limited studies which are directed towards identifying factors that explain the gap in achieving treatment targets.Objective: : This study aimed to assess the treatment outcome and its associated factors among patients with MDR/RR-TB in Dilchora Hospital Treatment Initiation Center from January 2014 to December 2018.Method: : A retrospective cross-sectional study was conducted on patients with MDR/RR TB who initiated treatment between January 2014 and December 2018. Data were extracted from patient medical charts using a structured questionnaire. SPSS version 26 was used for analysis. Reports are presented using percentages and frequency. Independently associated factors for unfavorable outcome were identified using binary logistic regression model. Adjusted and crude odds ratio with 95% CI was used. P-value less than 0.05 was used to declare statistical significance.Result: : A total of 146 patients were included in this study. The overall prevalence of unfavorable outcomes in this study for those with known outcomes was 8.6%. People living with HIV had a 6.47 times (95% CI: 1.14– 36.68) increased odds of death as compared to those who are HIV negative. For every 1kg/m2 increment in BMI, there was a 35.3% (AOR = 0.647; CI: 0.44– 0.95) reduction in the odds of death as compared to those who had a 1kg/m2 lower BMI. Each additional month without culture conversion also increased the odds of death 2.24 times (95%CI: 1.08– 4.66).Conclusion & Recommendation: : The findings of our study showed an appreciably low poor treatment outcome for this outpatient program. HIV screening and early initiation of HAART, early identification and treatment of those who are underweight and a critical follow-up to the time of sputum culture conversion could help in further improving the outcomes.Keywords: MDR/RR-TB, treatment outcome, Dire-Dawa

Botulinum toxin type A (BTX-A) injection is a commonly used therapeutic intervention for upper limb spasticity in stroke patients. This study was designed as a randomized, active-drug-controlled, double-blind, multicenter, phase 3 clinical trial to evaluate the safety and efficacy of Liztox ® in comparison to onabotulinum toxin A (Botox ® ) for individuals with post-stroke upper limb spasticity. The primary outcome was the alteration in wrist flexor muscle tone from the initial assessment to the fourth week, evaluated using the modified Ashworth scale (MAS). Secondary outcomes included MAS score changes for the wrist at weeks 8 and 12 from baseline; MAS score changes for finger and elbow flexors; and changes in the Disability Assessment Scale (DAS), Subject's Global Assessment (SGA), the Investigator's Global Assessment (IGA), and Caregiver Burden Scale (CBS) at weeks 4, 8, and 12 from baseline. The MAS score for wrist flexor spasticity decreased by -1.14 ± 0.59 in the Liztox ® group and -1.22 ± 0.59 in the Botox ® group from baseline to week 4. The difference [97.5% confidence interval (CI)] between the test and control groups was 0.08 [-∞, 0.26], confirming the non-inferiority of the test group compared to the control group. Furthermore, there were consistent improvements in the IGA, SGA, and CBS scores across all assessment intervals, with no statistically significant variances detected between the two groups. No safety-related concerns were reported during the study. In conclusion, Liztox ® injection proved to be a secure and efficacious intervention for managing upper extremity spasticity in post-stroke patients.

This meta-analysis aimed to compare the effects of robot-assisted training (RAT) with those of conventional therapy (CT), considering the potential sources of heterogeneity in the previous studies. We searched three international electronic databases (MEDLINE, Embase, and the Cochrane Library) to identify relevant studies. Risk of bias assessment was performed using the Cochrane's Risk of Bias 1.0 tool. The certainty of the evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations method. The meta-analyses for each outcome of the respective domains were performed using 24 randomized controlled trials (RCTs) on robot-assisted arm training (RAAT) for arm function, 7 RCTs on RAAT for activities of daily living (ADL), 12 RCTs on robot-assisted gait training (RAGT) for balance, 6 RCTs on RAGT for walking, and 7 RCTs on RAGT for ADL. The random-effects model for the meta-analysis revealed that RAAT has significant superiority over CT in improving arm function, and ADL. We also showed that RAGT has significant superiority over CT in improving balance. Our study provides high-level evidence for the superiority of RAT over CT in terms of functional recovery after stroke. Therefore, physicians should consider RAT as a therapeutic option for facilitating functional recovery after stroke., Competing Interests: Conflict of Interest: The authors have no potential conflicts of interest to disclose., (Copyright © 2023. Korean Society for Neurorehabilitation.)

Pirfenidone (PRF) is an anti-fibrotic agent that has been approved by the Food and Drug Administration (FDA) for the treatment of mild to moderate idiopathic pulmonary fibrosis. However, the current oral administration dosing regimen of PRF is complex and requires high doses. Patients are instructed to take PRF three times daily, with each dose consisting of up to three capsules or tablets (600 mg/d or 1.8 g/d of PRF) taken with food. To improve the dosing regimen, efforts are being made to develop an extended-release tablet with a zero-order release pattern. In this study, two types of extended-release matrix tablets were compared: non-channeled extended-release matrix tablets (NChMT) and channeled extended-release matrix tablets (ChMT). In vitro release tests, swelling and erosion index, rheology studies, and X-ray microcomputed tomography (XRCT), were conducted. The results indicated that ChMT maintained a zero-order release pattern with a constant release rate, while NChMT exhibited a decreased release rate in the latter half of the dissolution. ChMT exhibited accelerated swelling and erosion compared to other formulations, and this was made possible by the presence of channels within the tablet. These channels allowed for thorough wetting and swelling throughout the entire depth of the tablet. The formation of channels was confirmed through XRCT images. In conclusion, the presence of channels in ChMT tablets increased the rate of swelling and erosion, resulting in a zero-order release pattern. This development offers the potential to improve the dosage of PRF and reduce its associated side effects.

This clinical practice guideline (CPG) is the fourth edition of the Korean guideline for stroke rehabilitation, which was last updated in 2016. The development approach has been changed from a consensus-based approach to an evidence-based approach using the Grading of Recommendations Assessment Development and Evaluation (GRADE) method. This change ensures that the guidelines are based on the latest and strongest evidence available. The aim is to provide the most accurate and effective guidance to stroke rehabilitation teams, and to improve the outcomes for stroke patients in Korea. Fifty-five specialists in stroke rehabilitation and one CPG development methodology expert participated in this development. The scope of the previous clinical guidelines was very extensive, making it difficult to revise at once. Therefore, it was decided that the scope of this revised CPG would be limited to Part 1: Rehabilitation for Motor Function. The key questions were selected by considering the preferences of the target population and referring to foreign guidelines for stroke rehabilitation, and the recommendations were completed through systematic literature review and the GRADE method. The draft recommendations, which were agreed upon through an official consensus process, were refined after evaluation by a public hearing and external expert evaluation., Competing Interests: Among the development members, if there was even a slight interest in the result of the declaration of interest, it was excluded from the development process of individual clinical questions with interest and the official agreement process. Prior to reaching a formal consensus, a preliminary consensus was reached through a review meeting for each team, and an additional preliminary consensus meeting was held at the operating committee. The recommendations revised and supplemented through informal consensus were subsequently followed by a formal consensus-building process using the RAND-UCLA Appropriateness Method (RAM) method.Conflict of Interests: All researchers involved in the development of this clinical guideline were instructed to indicate any conflicting interests related to the study (involvement in similar clinical guideline development, employment, financial understanding, and other potential conflicts). All researchers except for six declared that they have no conflicting interests. Researchers with personal interests in the content of this clinical guideline have excluded themselves from making recommendations regarding specific items (botulinum toxin, virtual reality, robot rehabilitation, medication)., (Copyright © 2023. Korean Society for Neurorehabilitation.)

Dysarthria and dysphonia are common in patients with traumatic brain injury (TBI). Multiple factors may contribute to TBI-induced dysarthria, including poor vocalization, articulation, respiration, and/or resonance. Many patients suffer from dysarthria that persists after the onset of TBI, with negative effects on their quality of life. This study aimed to investigate the relationship between vowel quadrilateral parameters and Dysphoria Severity Index (DSI), which objectively reflects vocal function We retrospectively enrolled TBI patients diagnosed using computer tomography. Participants had dysarthria and dysphonia and underwent acoustic analysis. Praat software was used to measure vowel space area (VSA), formant centralization ratio (FCR), and the second formant (F2) ratio. For the 4 corner vowels (/a/,/u/,/i/, and/ae/), the resonance frequency of the vocal folds was measured and is shown as 2-dimensional coordinates for the formant parameters. Pear-son correlation and multiple linear regression analyses were performed between the variables. VSA showed a significant positive correlation with DSI/a/ ( R  = 0.221) and DSI/i/ ( R  = 0.026). FCR showed a significant negative correlation with DSI/u/ and DSI/i/. The F2 ratio showed a significant positive correlation with DSI/u/ and DSI/ae/. In the multiple linear regression analysis, VSA was found to be a significant predictor of DSI/a/ (β = 0.221, P  = .030, R 2  = 0.139). F2 ratio (β = 0.275, P  = .0.015) and FCR (β = -0.218, P  = .029) was a significant predictor of DSI/u/ (R 2  = 0.203). FCR was a significant predictor of DSI/i/ (β = -0.260, P  = .010, R 2  = 0.158). F2 ratio was a significant predictor of DSI/ae/ (β = 0.254, P  = .013, R 2  = 0.154). Vowel quadrilateral parameters, such as VSA, FCR, and F2 ratio, may be associated with dysphonia severity in TBI patients., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Respiratory dysfunction following supratentorial cerebral infarction leads to pneumonia and is a major cause of mortality. Decreased voluntary cough function impairs the ability to clear mucus or secretions from the airways and increases the risk of aspiration pneumonia. Peak cough flow (PCF) is one of the objective tools for evaluating voluntary cough function. Repetitive transcranial magnetic stimulation (rTMS) could be applied to the respiratory motor cortex to improve respiratory function. Little is known about the effect of rTMS on PCF in patients with supratentorial cerebral infarction during the subacute period. This study aimed to determine whether rTMS treatment could improve PCF in patients with supratentorial cerebral infarction. We retrospectively recruited patients with subacute supratentorial cerebral infarction who underwent a PCF test. The rTMS group received a combination of rTMS treatment for 2 weeks and conventional rehabilitation for 4 weeks. However, the control group underwent only conventional rehabilitation for 4 weeks. PCF tests were performed before and after treatment and the results were compared between the 2 groups. In total, 145 patients with supratentorial cerebral infarctions were recruited. The PCF parameters before and after treatment increased in both the rTMS and control groups. However, the rTMS group showed a greater increase in PCF values compared with the control group. In patients with supratentorial cerebral infarction, the combination of conventional rehabilitation and rTMS in the subacute period may be helpful in improving voluntary cough function compared with conventional rehabilitation alone., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Dysphonia and malnutrition are major problems in patients who have suffered an ischemic stroke. Tools to assess dysphonia severity include the dysphonia severity index (DSI) and maximum phonation time (MPT). This study aimed to investigate whether the nutritional biomarkers transferrin, albumin, and prealbumin could be predictors of dysphonia severity. A retrospective analysis was conducted between January 2018 and October 2022. A total of 180 patients who had suffered an ischemic stroke were included. Serum transferrin, albumin, and prealbumin levels were significantly correlated with DSI and MPT levels. In a multiple regression analysis, prealbumin and transferrin were significant predictors of DSI, whereas only prealbumin was a significant predictor of MPT. Serum transferrin, albumin, and prealbumin levels in patients who have suffered an ischemic stroke may correlate with dysphonia severity as assessed using DSI and MPT. These results may provide objective evidence that nutritional biomarkers affect dysphonia severity.

Aspiration pneumonia is a major, potentially fatal complication after ischemic stroke. Decreased coughing function is a significant risk factor for aspiration in ischemic stroke survivors. Peak cough flow (PCF) is a useful tool for assessing cough function. Vitamin D deficiency is frequent after ischemic stroke and is linked to a variety of muscle functions and physical activities. There has been no investigation of the correlation between vitamin D levels and PCF in ischemic stroke survivors. This study aimed to examine the relationship between serum vitamin D levels and PCF in patients with ischemic stroke. Patients with ischemic stroke who underwent PCF evaluation and serum vitamin D level measurements within 1 month of onset were retrospectively recruited. The association between PCF parameters and serum vitamin D levels was also analyzed. In total, 142 patients with ischemic stroke were included. PCF parameters and serum vitamin D levels were found to be significantly correlated. Moreover, serum vitamin D levels were shown to be a significant predictor of PCF parameters. Serum vitamin D levels were related to PCF parameters in patients with ischemic stroke. In addition, serum vitamin D level may serve as a predictor of coughing function in patients with ischemic stroke., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: This study aimed to determine which prodromal symptoms frequently occur in patients with Bell's palsy and evaluate the association between these symptoms and clinical severity of paresis or the severity of facial nerve injury., Materials and Methods: The study included 86 patients with Bell's palsy between August 2018 and April 2020. Severity levels of Bell's palsy and facial nerve damage were evaluated using the House-Brackmann (H-B) grading scale and electrodiagnostic study, respectively. Subsequently, a self-reported questionnaire on prodromal symptoms was administered. To assess the degree of recovery, the H-B grade was reported at 9 weeks and 6 months after the onset of paralysis., Results: The most common prodromal symptoms were postauricular pain, sensory decline in the tongue, headache on the affected side, myalgia, facial sensory decline on the affected side, taste impairment, and dry eye. Taste impairment was significantly correlated with severe facial paralysis reported at 9 weeks after onset ( P  < .05) and was not related to the severity of paresis assessed at initial examination or 6 months after onset or on electrodiagnostic findings., Conclusions: The prodromal symptoms of Bell's palsy were not associated with the severity of facial nerve injury in an electrodiagnostic study. Taste impairment was related to clinical severity of paralysis at subacute stage, 9 weeks after onset, but it was not associated with long-term prognosis.

Depressive and somatic symptoms are common after traumatic brain injury (TBI). Depression after TBI can relate to worsened cognitive functioning, functional impairment, higher rates of suicide attempts, and larger health care costs. Heart rate variability (HRV) represents the activity of the autonomic nervous system (ANS), which regulates almost all vascular, visceral, and metabolic functions. Several studies show a correlation between HRV, depression, and somatic symptoms in other diseases. However, studies on autonomic dysfunction, depression, and somatic symptoms in TBI patients are lacking. This study investigated the association between reduced ANS function, depression, and somatic symptoms in TBI patients. We retrospectively recruited 136 TBI patients who underwent 24 h ambulatory Holter electrocardiography to measure autonomic dysfunction within 1 month of onset. Patients who used BDI and PHQ-15 to evaluate depressive and somatic symptoms were included. Using Pearson's correlation analysis and multiple linear regression, the association between HRV parameters and BDI and PHQ-15 was determined. The HRV parameters and BDI and PHQ-15 showed statistical significance. In addition, HRV was shown to be a significantly associated factor of BDI and PHQ-15. HRV was associated with depressive and somatic symptom severity in TBI patients. Additionally, autonomic dysfunction may serve as an associated factor of depressive and somatic symptoms in patients with TBI.

There are many stroke patients with decreased phonation ability. Vitamin D is associated with weakness in muscle power and a decreased function of activity and is often accompanied by a deficiency of serum vitamin D in stroke patients. This study was conducted to evaluate the correlation between serum vitamin D level and phonetic function in subacute stroke patients. Among subacute stroke patients, patients with dysphonia were retrospectively recruited. Phonation function was assessed by acoustic analysis using the dysphonia severity index (DSI) and maximum phonation time for 4 corner vowels/a/,/i/,/u/, and/ae/. As a statistical method, the relationships of vitamin D levels with the maximum phonation time and DSI were evaluated using Pearson's correlation analysis and linear regression analysis. A total of 32 stroke patients with dysphonia were assessed. A positive correlation was found between vitamin D levels and the DSI of /a/, /u/, /i/, and/ae/. The DSI of/u/ was significantly lower in the group with vitamin D deficiency. Vitamin D level was associated with phonation function and its deficiency may be a factor in predicting phonation severity in stroke patients., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Malnutrition and autonomic dysfunction are associated with poor outcomes, mortality, and psychological problems after stroke. Relevant laboratory biomarkers include serum albumin, prealbumin, and transferrin. Heart rate variability (HRV), a noninvasive measurement, can objectively measure autonomic nervous system (ANS) function. The relationship between HRV and nutritional biomarkers in stroke patients has not been studied. This study aimed to examine the relationship between nutritional biomarkers and HRV parameters in stroke patients. We retrospectively recruited 426 patients with subacute stroke who were examined for nutritional biomarkers, such as serum albumin, prealbumin, and transferrin, and underwent 24 h ambulatory Holter electrocardiography. Patients were divided into groups according to their nutritional biomarker status. Differences in HRV parameters between nutritional biomarker-deficient and normal groups were assessed. Pearson's correlation and multiple regression analyses were used to verify the relationship between HRV parameters and nutritional biomarkers. HRV parameters were significantly lower in the nutritional biomarker-deficient groups. In addition, there was a significant association between HRV parameters and nutritional biomarkers. Serum albumin, prealbumin, and transferrin levels were associated with ANS function, as measured by HRV, and their deficiency may be a predictive factor for the severity of ANS dysfunction in stroke patients.

Dysphagia is associated with dysarthria in stroke patients. Vowel space decreases in stroke patients with dysarthria; destruction of the vowel space is often observed. We determined the correlation of destruction of acoustic vowel space with dysphagia in stroke patients. Seventy-four individuals with dysphagia and dysarthria who had experienced stroke were enrolled. For /a/, /ae/, /i/, and /u/ vowels, we determined formant parameter (it reflects vocal tract resonance frequency as a two-dimensional coordinate point), formant centralization ratio (FCR), and quadrilateral vowel space area (VSA). Swallowing function was assessed using the videofluoroscopic dysphagia scale (VDS) during videofluoroscopic swallowing studies. Pearson's correlation and linear regression were used to determine the correlation between VSA, FCR, and VDS. Subgroups were created based on VSA; vowel space destruction groups were compared using ANOVA and Scheffe's test. VSA and FCR were negatively and positively correlated with VDS, respectively. Groups were separated based on mean and standard deviation of VSA. One-way ANOVA revealed significant differences in VDS, FCR, and age between the VSA groups and no significant differences in VDS between mild and moderate VSA reduction and vowel space destruction groups. VSA and FCR values correlated with swallowing function. Vowel space destruction has characteristics similar to VSA reduction at a moderate-to-severe degree and has utility as an indicator of dysphagia severity., Competing Interests: The authors report no conflict of interest.

Background: Shoulder subluxation occurs in 17−64% of hemiplegic patients after stroke and develops mostly during the first three weeks of hemiplegia. A range of shoulder orthoses has been used in rehabilitation to prevent subluxation. However, there is little evidence of their efficacy. AIM: This study aimed to investigate whether there is a difference in the subluxation distance, pain, and functional level of the hemiplegic upper extremity among patients with two different shoulder orthoses. Design: This is a prospective, randomized controlled trial with intention-to-treat analysis. SETTING: Multicenter, rehabilitation medicine department of two university hospitals in South Korea. Population: Forty-one patients with subacute stroke with shoulder subluxation with greater than 0.5 finger width within 4 weeks of stroke were recruited between January 2016 and October 2021. Methods: The experimental group used an elastic dynamic sling while sitting and standing to support the affected arm for eight weeks. The control group used a Bobath sling while sitting and standing. The primary outcome was to assess the distance of the shoulder subluxation on radiography. The secondary outcomes were upper-extremity function, muscle power, activities of daily living, pain and spasticity. Result: The horizontal distance showed significant improvement in the elastic dynamic sling group, but there were no significant differences in the vertical distance between the elastic dynamic and Bobath sling groups. Both groups showed improvements in upper-extremity movements and independence in daily living after 4 and 8 weeks of using shoulder orthoses, and the differences within the groups were significant (p < 0.05). However, there were no significant differences in upper-extremity movements and independence in daily living between the two groups. Conclusions: The subluxation distance showed better results in the elastic dynamic sling, which has both proximal and distal parts, than in the Bobath sling, which holds only the proximal part. Both shoulder orthoses showed improvements in the modified Barthel index, upper-extremity function, and manual muscle testing.

Vitamin B12 (B12) is involved as a cofactor in the synthesis of myelin. A lack of B12 impairs peripheral nerve production, which can contribute to sarcopenia. In this cross-sectional study, we aimed to investigate the relationship between B12 insufficiency and sarcopenia in community-dwelling older Korean adults. A total of 2325 (1112 men; 1213 women) adults aged 70-84 years were recruited. The tools used for sarcopenia were based on the Asian Working Group for Sarcopenia (AWGS) guidelines. Individuals with low appendicular skeletal muscle mass index (ASMI) (<7.0 kg/m 2 for men; <5.4 kg/m 2 for women) and low hand grip strength (HGS) (<28 kg for men; <18 kg for women) were defined as the sarcopenia group. Among this group, those who showed low physical performance (≤9 points on the Short Physical Performance Battery (SPPB)) were defined as the severe sarcopenia group. B12 concentrations were classified into insufficient (<350 pg/mL) and sufficient (≥350 pg/mL). Univariate and multivariate logistic regression analyses were used to evaluate the relationship between sarcopenia and B12 levels. Low ASMI showed a high incidence in the B12-insufficient group. However, HGS, SPPB, and the severity of sarcopenia showed no correlation with B12. Further, insufficient B12 may affect muscle quantity rather than muscle strength or physical performance.

Objective: The incidence of hip fractures is increasing worldwide with the aging population, causing a challenge to healthcare systems due to the associated morbidities and high risk of mortality. After hip fractures in frail geriatric patients, existing comorbidities worsen and new complications are prone to occur. Comprehensive rehabilitation is essential for promoting physical function recovery and minimizing complications, which can be achieved through a multidisciplinary approach. Recommendations are required to assist healthcare providers in making decisions on rehabilitation post-surgery. Clinical practice guidelines regarding rehabilitation (physical and occupational therapies) and management of comorbidities/complications in the postoperative phase of hip fractures have not been developed. This guideline aimed to provide evidence-based recommendations for various treatment items required for proper recovery after hip fracture surgeries., Methods: Reflecting the complex perspectives associated with rehabilitation post-hip surgeries, 15 key questions (KQs) reflecting the complex perspectives associated with post-hip surgery rehabilitation were categorized into four areas: multidisciplinary, rehabilitation, community-care, and comorbidities/complications. Relevant literature from four databases (PubMed, EMBASE, Cochrane Library, and KoreaMed) was searched for articles published up to February 2020. The evidence level and recommended grade were determined according to the grade of recommendation assessment, development, and evaluation method., Results: A multidisciplinary approach, progressive resistance exercises, and balance training are strongly recommended. Early ambulation, weigh-bearing exercises, activities of daily living training, community-level rehabilitation, management of comorbidities/complication prevention, and nutritional support were also suggested. This multidisciplinary approach reduced the total healthcare cost., Conclusion: This guideline presents comprehensive recommendations for the rehabilitation of adult patients after hip fracture surgery.

The n + -base width of a two-terminal vertical thyristor fabricated with n ++ (top-emitter)-p + (base)-n + (base)-p ++ (bottom-emitter) epitaxial Si layers was designed to produce a cross-point memory cell without a selector. Both the latch-up and latch-down voltages increased linearly with the n + -base width, but the voltage increase slope of the latch-up was 2.6 times higher than that of the latch-down, and the memory window increased linearly with the n + -base width. There was an optimal n + -base width that satisfied cross-point memory cell operation; i.e. ∼180 nm, determined by confirming that the memory window principally determined the condition of operation as a cross-point memory cell (i.e. one half of the latch-up voltage being less than the latch-down voltage and a sufficient voltage difference existing between the latch-up and latch-down voltages). The vertical thyristor designed with the optimal n + -base width produced write/erase endurance cycles of ∼10 9 by sustaining a memory margin (I on /I off ) of 10 2 , and the cross-point memory cell array size of 1024 K sustained a sensing margin of 99 %, which is comparable with that of current dynamic random-access memory (DRAM). In addition, in the cross-point memory cell array, a ½ bias scheme (i.e. a memory array size of 1024 K for 0.02 W of power consumption) resulted in lower power consumption than a [Formula: see text] bias scheme (i.e. a memory array size of 256 K for 0.02 W of power consumption).

The evolutionarily conserved target of rapamycin (TOR) kinase acts as a master regulator that coordinates cell proliferation and growth by integrating nutrient, energy, hormone and stress signals in all eukaryotes 1,2 . Research has focused mainly on TOR-regulated translation, but how TOR orchestrates the global transcriptional network remains unclear. Here we identify ethylene-insensitive protein 2 (EIN2), a central integrator 3-5 that shuttles between the cytoplasm and the nucleus, as a direct substrate of TOR in Arabidopsis thaliana. Glucose-activated TOR kinase directly phosphorylates EIN2 to prevent its nuclear localization. Notably, the rapid global transcriptional reprogramming that is directed by glucose-TOR signalling is largely compromised in the ein2-5 mutant, and EIN2 negatively regulates the expression of a wide range of target genes of glucose-activated TOR that are involved in DNA replication, cell wall and lipid synthesis and various secondary metabolic pathways. Chemical, cellular and genetic analyses reveal that cell elongation and proliferation processes that are controlled by the glucose-TOR-EIN2 axis are decoupled from canonical ethylene-CTR1-EIN2 signalling, and mediated by different phosphorylation sites. Our findings reveal a molecular mechanism by which a central signalling hub is shared but differentially modulated by diverse signalling pathways using distinct phosphorylation codes that can be specified by upstream protein kinases.

Rationale: Hematoma of the iliopsoas muscle is a rare condition. Prolonged pressure conditions due to hematoma of the femoral nerve can cause severe pain in the affected groin, hip, and thigh, and quadriceps weakness. We report a rare case of a spontaneous iliopsoas muscle hematoma that caused sudden femoral neuropathy., Patient Concerns: A 71-year-old woman presented sudden left hip pain and knee extensor weakness. The pain was aggravated with left hip extension. She had a bilateral total hip replacement surgery due to avascular necrosis. She was diagnosed as mild stenosis of the cerebral artery and took aspirin to prevent cerebral artery atherosclerosis., Diagnosis: A hip computed tomography scan demonstrated a suspicious fluid collection at the left iliopsoas bursa. We considered the possibility of lower limb weakness due to neuralgic amyotrophy and performed electromyography and enhanced lumbosacral magnetic resonance imaging (MRI). Electromyography finding showed left femoral neuropathy of moderate severity around the inguinal area was diagnosed. On MRI, left iliopsoas bursitis or hematoma, and displacement of the left femoral nerve due to the iliopsoas bursitis/hematoma were observed., Intervention: Ultrasonography (US)-guided aspiration of the left iliopsoas hematoma was performed. We started steroid pulse therapy for 8 days., Outcomes: After US-guided aspiration and steroid pulse therapy, the patient's knee extension motor grade improved from grade 1 to 2, and the pain was slightly reduced. At 3 weeks after the aspiration procedure, her hip flexion motor grade had improved from grade 3+ to 4 at follow-up., Lessons: Imaging studies are fundamental to diagnose of iliopsoas hematoma. Electromyography examination plays an important role in determining the prognosis of patients and lesion site. Despite the negligible change in sitting position, hematoma can develop. Physicians should consider hematoma that cause femoral neuropathy.

Background: Bone loss after stroke escalates the risk of fractures, mainly in the hip, leading to further disability in individuals with stroke. We aimed to investigate the skeletal effect of bone mineral density (BMD) based on the duration of onset of stroke, compare the BMD of the paretic and non-paretic sides, and elucidate the relationship between BMD and disability variables., Methods: The 31 male hemiplegic stroke patients between 20 and 70 years of age with cerebral infarction or hemorrhage were considered in this study. Subacute and chronic cases included 13 and 18 patients with lag time from the onset of 1 to 6 months and beyond 6 months, respectively. BMD in the lumbar, paretic, and non-paretic hip as well as the disability variables were analyzed retrospectively., Results: The subacute group showed a significant reduction in the femoral neck BMD on the paretic side compared to that on the non-paretic side based on T-scores (P=0.013). Bone loss was significantly correlated with lower limb muscle strength and overall physical impairment (P&lt;0.05). The chronic group demonstrated significant reduction in femur neck and total femur BMD on the paretic side compared to that on the non-paretic side based on T-scores (P=0.002 and P&lt;0.001, respectively). T-scores of BMD in the chronic phase were not significantly associated with the clinical parameters., Conclusions: Early screening of bilateral hip BMD in the early stages after stroke, monitoring, and timely implementation of prevention strategies are important to minimize subsequent bone loss and prevent possible complications in patients who experience stroke.

Articulation disorder is associated with impaired control of respiration and speech organ movement. There are many cases of dysarthria and dysphonia in stroke patients. Dysphonia adversely affects communication and social activities, and it can interfere with everyday life. The purpose of this study is to assess the association between phonation abilities and the vowel quadrilateral in stroke patients.The subjects were stroke patients with pronunciation and phonation disorders. The resonance frequency was measured for the 4 corner vowels to measure the vowel space area (VSA) and formant centralization ratio (FCR). Phonation ability was evaluated by the Dysphonia Severity Index (DSI) and maximal phonation time (MPT) through acoustic evaluation for each vowel. Pearsons correlation analysis was performed to confirm the association, and multiple linear regression analysis was performed between variables.The correlation coefficients of VSA and MPT/u/ were 0.420, VSA and MPT/i/ were 0.536, VSA and DSI/u/ were 0.392, VSA and DSI /i/ were 0.364, and FCR and DSI /i/ were -0.448. Multiple linear regression analysis showed that VSA was a factor significantly influencing MPT/u/ (β = 0.420, P = .021, R = 0.147), MPT/i/ (β = 0.536, P = .002, R = 0.262), DSI/u/ (β = 0.564, P = .045, R = 0.256), and DSI/i/ (β = 0.600, P = .03, R = 0.302).The vowel quadrilateral can be a useful tool for evaluating the phonation function of stroke patients.

Background: Chronic obstructive pulmonary disease (COPD) and asthma exacerbations are associated with ill health, increased mortality, and health care costs. However, there is limited evidence regarding mortality and its predictors among patients treated for COPD and asthma exacerbations in low-income nations, particularly in Ethiopia., Methods: A-6 month prospective observational study was conducted from April 20-September 20, 2019. Data were collected on socio-demographic, baseline clinical characteristics and outcomes of asthma and COPD exacerbations. Data were entered into Epi-Data version 4.02.01 for cleaning and exported to STATA 14.0 for analysis. Kaplan-Meier (Log-rank test) was used to compare the baseline survival experience of the study participants and Cox proportional hazard regression analysis was conducted to determine the predictors of mortality. Adjusted hazard ratios (AHRs) with two-sided p-value <0.05 were considered statistically significant., Results: A total of 130 patients (60% males) were included. The median (interquartile range (IQR)) age of the study participants was 59(50-70) years. The median (IQR) survival time to death was 17.5 (10-26) days. The total proportion of in-hospital mortality was 10.78% (14/130), and the incidence rate of mortality was 2.56 per 1000 person-years. The duration of oxygen therapy ≥16hours/day (AHR = 6.330, 95% CI [1.092-36.679], and old age (AHR = 1.066, 95% CI [1.0001-1.136] were the independent predictors of in-hospital mortality., Conclusion: In this study, the in-hospital mortality rate was very high. Moreover, prolonged oxygen therapy (≥16hours/day) and old age were independently associated with in-hospital mortality. Therefore, special attention should be given to recipients of prolonged oxygen therapy and the elderly during hospital stay., Competing Interests: The authors have declared that no competing interests exist.

Objective: To compare the surgical outcomes of simple frenotomy and the 4-flap Z-frenuloplasty according to the articulation test values and tongue-tie classification in patients with ankyloglossia with articulation difficulty., Study Design: prospective randomized study., Setting: Tertiary academic center., Subjects: and methods: Children with ankyloglossia with articulation difficulty were randomly divided into 2 groups for surgical treatment. Patients were evaluated for the tongue-tie classification and articulation test before surgery. Three months after the operation, the frenulum classification and articulation test were re-evaluated to compare the differences in surgical outcome between the two surgical methods., Results: Out of 37 patients, 19 underwent the 4-flap Z-frenuloplasty and 18, the simple frenotomy. No differences were observed in the baseline characteristics of the patients assigned to both groups. Changes in the tongue-tie classification and improvement in the articulation test results were observed with both the surgical methods. Both surgical groups had significant improvement in the speech articulation test (consonants) but there was no difference in the speech outcomes between the surgical groups., Conclusion: Although there was no significant difference in the surgical outcome between the two surgical methods, ankyloglossia patients showed improvement in a Korean speech articulation test 3 months after undergoing surgery to release the lingual frenulum., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Coccidioidomycosis is an endemic disease in the Americas. No cases have been reported in Africa., Patient: A 23-year-old HIV seronegative Ugandan man was referred to Mulago National Referral Hospital in Kampala, Uganda with a 10-month history of haemoptysis and difficulty breathing, and a 6-month history of localized swellings on the extremities. He had associated weight loss and drenching sweats, but no fevers. He had taken anti-tuberculosis medicine for 2 months with no improvement. He had never travelled out of Uganda. On physical examination, he had cystic swellings and ulcerated lesions on the extremities. He had tachypnoea, crackles in the chest and mild hepatomegaly. Bronchoscopic examination showed two masses occluding the right main bronchus. Bronchoscopic biopsy showed findings consistent with coccidioidomycosis. The patient improved with antifungal treatment and was discharged., Conclusion: We report the first case of disseminated coccidioidomycosis with pulmonary and cutaneous manifestations in Africa., Learning Points: Coccidioidomycosis is an endemic disease in the Americas and may now be present in Africa.The patient had taken anti-tuberculosis medicine for 2 months with no improvement.Coccidioidomycosis should be considered in the differential diagnosis of tuberculosis., Competing Interests: Conflicts of Interests: The Authors declare that there are no competing interests., (© EFIM 2020.)

Introduction: A hiccup is myoclonus of a sudden involuntary contraction of the diaphragm. Hiccups have various causes, and brain stem stroke is one of the causes of central hiccups. Certain types of hiccups are caused by diseases that can be fatal. Therefore, it is beneficial for physicians to be familiar with the various cases of unusual hiccups. We report a case of hiccups triggered by urinary bladder filling in a brain stem stroke patient. To the best of our knowledge, previous reports have not described a similar case., Patient Concerns: We describe the case of a 54-year-old patient who had acute bilateral pontine hemorrhage. The patient had intermittent hiccups in the early stages of the stroke onset. The hiccups ceased by the administration of medication or stimulation of the pharyngeal or tracheal wall. Two months after the onset, the Foley catheter was removed to check if the patient could void the bladder voluntarily. Hiccups occurred whenever the bladder was filled with some amount of urine., Diagnosis: Pontine hemorrhage, neurogenic bladder, and quadriplegia., Interventions: When the hiccups occurred, the amount of urine in the bladder was checked using a transabdominal bladder ultrasonography scanner. After clean intermittent catheterization for bladder emptying, the hiccups subsided., Outcomes: The hiccups occurred 5 or 6 times a day, as often as the bladder was filling. He was unable to void the urine voluntarily for 5 days after the removal of the Foley catheter. Percutaneous suprapubic cystostomy was performed finally to remove the stimulation of bladder filling and the hiccups disappeared., Conclusion: Bladder filling is suspected to increase the sympathetic tone and cause a hiccup reflex. Bladder filling could be a factor triggering hiccups in pontine hemorrhage.

Background: Dysphagia and dysarthria tend to coexist in stroke patients. Dysphagia can reduce patients' quality of life, cause aspiration pneumonia and increased mortality., Objective: To evaluate correlations among swallowing function parameters and acoustic vowel space values in patients with stroke., Methods: Data from stroke patients with dysarthria and dysphagia were collected. The formant parameter representing the resonance frequency of the vocal tract as a two-dimensional coordinate point was measured for the /a/, /ae/, /i/, and /u/vowels, and the quadrilateral vowel space area (VSA) and formant centralization ratio (FCR) were measured. Swallowing function was evaluated by a videofluoroscopic swallowing study (VFSS) using the videofluoroscopic dysphagia scale (VDS) and penetration aspiration scale (PAS). Pearson's correlation and linear regression analyses were used to assess the correlation of VSA and FCR to VDS and PAS scores., Results: Thirty-one stroke patients with dysphagia and dysarthria were analyzed. VSA showed a negative correlation to VDS and PAS scores, while FCR showed a positive correlation to VDS score, but not to PAS score. VSA and FCR were significant factors for assessing dysphagia severity., Conclusions: VSA and FCR values were correlated with swallowing function and may be helpful in predicting dysphagia severity associated with stroke.

Though clinical practice guidelines (CPGs) for cardiac rehabilitation (CR) are an effective and widely used treatment method worldwide, they are as yet not widely accepted in Korea. Given that cardiovascular (CV) disease is the second leading cause of death in Korea, it is urgent that CR programs be developed. In 2008, the Government of Korea implemented CR programs at 11 university hospitals as part of its Regional Cardio-Cerebrovascular Center Project, and 3 additional medical facilities will be added in 2019. In addition, owing to the promotion of CR nationwide and the introduction of CR insurance benefits, 40 medical institutions nationwide have begun CR programs even as a growing number of medical institutions are preparing to offer CR. The purpose of this research was to develop evidence-based CPGs to support CR implementation in Korea. This study is based on an analysis of CPGs elsewhere in the world, an extensive literature search, a systematic analysis of multiple randomized control trials, and a CPG management, development, and assessment committee comprised of thirty-three authors-primarily rehabilitation specialists, cardiologists, and thoracic surgeons in 21 university hospitals and 2 general hospitals. Twelve consultants, primarily rehabilitation, sports medicine, and preventive medicine specialists, CPG experts, nurses, physical therapists, clinical nutritionists, and library and information experts participated in the research and development of these CPGs. After the draft guidelines were developed, 3 rounds of public hearings were held with staff members from relevant academic societies and stakeholders, after which the guidelines were further reviewed and modified. CR involves a more cost-effective use of healthcare resources relative to that of general treatments, and the exercise component of CR lowers CV mortality and readmission rates, regardless of the type of coronary heart disease and type and setting of CR. Individualized CR programs should be considered together with various factors, including differences in heart function and lifestyle, and doing so will boost participation and adherence with the CR program, ultimately meeting the final goals of the program, namely reducing the recurrence of myocardial infarction and mortality rates., Competing Interests: The authors have no financial conflicts of interest., (Copyright © 2019. The Korean Society of Cardiology.)

Background Context: Lumbosacral disc herniation (LDH) is one of the most frequent musculoskeletal diseases causative of sick leave in the workplace and morbidity in daily activities. Nonsurgical managements are considered as first line treatment before surgical treatment., Purpose: This clinical practice guideline (CPG) is intended to provide physicians who treat patients diagnosed with LDH with a guideline supported by scientific evidence to assist in decision-making for appropriate and reasonable treatments., Study Design/setting: A systematic review., Patient Sample: Studies of human subjects written in Korean or English that met the following criteria were selected: patients aged ≥18 years, clinical presentation of low back and radicular leg pain, diagnosis of LDH on radiological evaluation including computed tomography or magnetic resonance imaging., Outcomes Measures: Pain and functional evaluation scales such as visual analogue scale, numeric rating scale, and Oswestry disability index METHODS: The MEDLINE (PubMed), EMBASE, Cochrane Review, and KoreaMed databases were searched for articles regarding non-surgical treatments for LDH published up to July 2017. Of the studies fulfilling these criteria, those investigating clinical results after non-surgical treatment including physical and behavioral therapy, medication, and interventional treatment in terms of pain control and functional improvements were chosen for this study., Results: Nonsurgical treatments were determined to be clinically effective with regards to pain reduction and functional improvement in patients with LDH. Nevertheless, the evidence level was generally not evaluated as high degree, which might be attributed to the paucity of well-designed randomized controlled trials. Exercise and traction were strongly recommended despite moderate level of evidence. Epidural injection was strongly recommended with high degree of evidence and transforaminal approach was more strongly recommended than caudal approach., Conclusions: This CPG provides new and updated evidence-based recommendations for treatment of the patients with LDH, which suggested that, despite an absence of high degrees of evidence level, non-surgical treatments were clinically effective., (Copyright © 2019 Elsevier Inc. All rights reserved.)

This study investigated the time taken for upper extremity spasticity to develop and its regional difference after first-ever stroke onset in a nationwide multicenter study in South Korea. The retrospective observational study included 861 individuals with post-stroke spasticity in the upper limbs. Spasticity in the upper extremity joints was defined as a modified Ashworth Scale score ≥1. The median time to develop upper limb spasticity after stroke onset was 34 days. 12% of post-stroke spasticity cases developed between 2 months and 3 months and 13% developed after 3 months from onset. At the time of diagnosis of spasticity, most patients showed only a slight increase in muscle tone, which was observed most frequently in the elbow, followed by the wrist, and fingers. Younger stroke survivors were more spastic, and the severity of spasticity increased with time. Approximately half of the patients with post-stroke spasticity developed spasticity during the first month. However, post-stroke spasticity can develop more than 3 months after stroke onset. Therefore, it is important to assess spasticity, even in the chronic state., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: To evaluate correlations between values of articulation tests and language tests for children with articulation disorder in Korea., Methods: Data of outpatients with chief complaint of an articulation problem were retrospectively collected. Patients who underwent Urimal Test of Articulation and Phonation (U-TAP) with Assessment of Phonology and Articulation for Children (APAC), Preschool Receptive-Expressive Language Scale (PRES), or Receptive and Expressive Vocabulary Test (REVT) simultaneously were identified. Patients whose word-level percentages of correct consonants in U-TAP (UTAP&#95;wC) were more than 2 standard deviations below the mean as diagnostic criteria for articulation disorder were selected. Those whose receptive language age (P&#95;RLA), expressive language age (P&#95;ELA), or combined language age (P&#95;CLA) in PRES was delayed more than 24 months compared to their chronological age in months as diagnostic criteria for language disorder were excluded., Results: Thirty-three children aged 3-6 years were enrolled retrospectively. PRES and U-TAP showed significant correlations for most of value relationships. PRES and APAC showed significant correlations for all value relationships except for receptive language age. All values of REVT were significantly correlated with all values from U-TAP, but not with any value from APAC. Articulation tests U-TAP and APAC showed significant correlations between percentages of correct consonants. Language tests PRES and REVT showed significant correlations for all value relationships., Conclusion: This study suggests that articulation abilities and language abilities might be correlated in children with articulation disorder.

Background: Though clinical practice guidelines (CPGs) for cardiac rehabilitation (CR) are an effective and widely used treatment method worldwide, they are as yet not widely accepted in Korea. Given that cardiovascular disease is the second leading cause of death in Korea, it is urgent that CR programs be developed. In 2008, the Government of Korea implemented CR programs at 11 university hospitals as part of its Regional Cardio-Cerebrovascular Center Project, and 3 additional medical facilities will be added in 2019. In addition, owing to the promotion of CR nationwide and the introduction of CR insurance benefits, 40 medical institutions nationwide have begun CR programs even as a growing number of medical institutions are preparing to offer CR. The purpose of this research was to develop evidence-based CPGs to support CR implementation in Korea., Methods: This study is based on an analysis of CPGs elsewhere in the world, an extensive literature search, a systematic analysis of multiple randomized control trials, and a CPG management, development, and assessment committee comprised of 33 authors-primarily rehabilitation specialists, cardiologists, and thoracic surgeons in 21 university hospitals and 2 general hospitals. Twelve consultants, primarily rehabilitation, sports medicine, and preventive medicine specialists, CPG experts, nurses, physical therapists, clinical nutritionists, and library and information experts participated in the research and development of these CPGs. After the draft guidelines were developed, 3 rounds of public hearings were held with staff members from relevant academic societies and stakeholders, after which the guidelines were further reviewed and modified., Results: CR involves a more cost-effective use of healthcare resources relative to that of general treatments, and the exercise component of CR lowers cardiovascular mortality and readmission rates, regardless of the type of coronary heart disease and type and setting of CR., Conclusion: Individualized CR programs should be considered together with various factors, including differences in heart function and lifestyle, and doing so will boost participation and adherence with the CR program, ultimately meeting the final goals of the program, namely reducing the recurrence of myocardial infarction and mortality rates., Competing Interests: Conflict of interest No potential conflict of interest relevant to this article was reported.

Rationale: Cerebral, ocular, dental, auricular, skeletal anomalies (CODAS) syndrome is a very rare multisystem disorder, which shows malformations of the central nervous system, ears, eyes, teeth, and skeleton that was first reported in 1991. Only a few cases that sporadically occurred have been reported worldwide. The research investigating the pathogenesis and patterns of CODAS inheritance is still ongoing. There is no satisfactory treatment for this rare genetic disease yet. Due to the lack of curative medical treatment, rehabilitation could play a major role in treatment for genetic disease., Patient Concerns: To our best knowledge, the 2 children described in this study are the only CODAS syndromes siblings reported in the world so far. These Korean siblings show highly distinctive features consisting of developmental delay, cataracts, vulnerability to tooth decay, epiphyseal dysplasia, and anomalous ears., Diagnoses: CODAS syndrome., Interventions: Comprehensive long-term rehabilitation treatment during 5 years., Outcomes: We report on the progress of the comprehensive long-term rehabilitation treatment at 5-year follow-up. Their fine motor and language skills development improved similarly to that of same-aged children. We observed the positive effect of rehabilitation on the quality of life., Lessons: The therapy of genetic disorders is challenging for pediatric neurologists and pediatric physiatrists. We suggest that rehabilitation is the best treatment currently available for this genetic disease that yields satisfactory therapeutic effect.

DNA methylation plays an important role in diverse developmental processes in many eukaryotes, including the response to environmental stress. Abscisic acid (ABA) is a plant hormone that is up-regulated under stress. The involvement of DNA methylation in the ABA response has been reported but is poorly understood. DNA demethylation is a reverse process of DNA methylation and often induces structural changes of chromatin leading to transcriptional activation. In Arabidopsis ( Arabidopsis thaliana) , active DNA demethylation depends on the activity of REPRESSOR OF SILENCING 1 (ROS1), which directly excises 5-methylcytosine from DNA. Here we showed that ros1 mutants were hypersensitive to ABA during early seedling development and root elongation. Expression levels of some ABA-inducible genes were decreased in ros1 mutants, and more than 60% of their proximal regions became hypermethylated, indicating that a subset of ABA-inducible genes are under the regulation of ROS1-dependent DNA demethylation. Notable among them is NICOTINAMIDASE 3 ( NIC3 ) that encodes an enzyme that converts nicotinamide to nicotinic acid in the NAD + salvage pathway. Many enzymes in this pathway are known to be involved in stress responses. The nic3 mutants display hypersensitivity to ABA, whereas overexpression of NIC3 restores normal ABA responses. Our data suggest that NIC3 is responsive to ABA but requires ROS1-mediated DNA demethylation at the promoter as a prerequisite to transcriptional activation. These findings suggest that ROS1-induced active DNA demethylation maintains the active state of NIC3 transcription in response to ABA., (© 2019 American Society of Plant Biologists. All Rights Reserved.)

Acute cholecystitis (AC) is a rare but possible medical complication found in stroke patients. As many stroke patients present with neurologic symptoms, such as altered mental status, motor weakness, global aphasia, or dysarthria, clinical symptoms and signs of AC are often unexpressed or overlooked. As a result, the diagnosis of AC is often delayed with subsequent secondary complications in these stroke patients. This study aims to evaluate the clinical incidence, manifestations, and predictive factors of AC in stroke patients.A retrospective cohort study was conducted between January 2013 and December of 2017 of all stroke patients (n = 2699) who have been admitted to our stroke center of the university hospital. We evaluated patient demographics, presenting symptoms, vital signs, laboratory results, mean initial consecutive fasting time, mean total fasting time, modified Rankin Scale (mRS), as well as radiological findings of abdominal computed tomography (CT) or ultrasonography.AC was diagnosed in 28 of the 2699 patients (1.04%). Of these patients with AC, gallbladder stones (calculous cholecystitis) were found in 4 patients (14.3%), and 24 patients (85.7%) were diagnosed with a calculous cholecystitis. Subgroup analysis revealed that of the 28 stroke patients with AC, those who underwent neurosurgical intervention (n = 15) had increased incidence of AC compared with those who did not (2.3% vs 0.6%, respectively, P < .001). Furthermore, the initial consecutive fasting time, total fasting time, and mRS were all predictive factors (P < .05) for developing AC in stroke patients.The incidence of AC was higher in acute stroke patients who required neurosurgical intervention, with longer initial consecutive fasting time, total fasting time, and higher mRS. We recommend early enteral nutrition and to maintain a high degree of clinical suspicion to make an early diagnosis of AC in stroke patients for improved outcome.

For performance assessment of the lipid-based drug delivery systems (LBDDSs), in vitro lipolysis is commonly applied because traditional dissolution tests do not reflect the complicated in vivo micellar formation and solubilization processes. Much of previous research on in vitro lipolysis has mostly focused on rank-ordering formulations for their predicted performances. In this study, we have incorporated in vitro lipolysis with microsomal stability to quantitatively predict the oral bioavailability of a lipophilic antineoplastic drug bexarotene (BEX) administered in LBDDS. Two types of LBDDS were applied: lipid solution and lipid suspension. The predicted oral bioavailability values of BEX from linking in vitro lipolysis with microsomal stability for lipid solution and lipid suspension were 34.2 ± 1.6% and 36.2 ± 2.6%, respectively, whereas the in vivo oral bioavailability of BEX was tested as 31.5 ± 13.4% and 31.4 ± 5.2%, respectively. The predicted oral bioavailability corresponded well with the oral bioavailability for both formulations, demonstrating that the combination of in vitro lipolysis and microsomal stability can quantitatively predict oral bioavailability of BEX. In vivo intestinal lymphatic uptake was also assessed for the formulations and resulted in <1% of the dose, which confirmed that liver microsomal stability was necessary for correct prediction of the bioavailability., (Copyright © 2019. Published by Elsevier Inc.)

Tacrolimus is one of the most commonly used immunosuppressive agents in animal models of transplantation. However, in these models, oral administration is often problematic due to the lowered compliance associated with highly invasive surgery and due to malabsorption in the intestinal tract. Therefore, we carried out a study to determine the pharmacokinetics of tacrolimus after intramuscular (IM) injection and to determine the optimal IM dosing regimens in primate models. Six male cynomolgus monkeys (Macaca fascicularis) were used in the study. Doses of 0.1 mg/kg and 5 mg were administered via IM injection and oral administration, respectively, once to determine single-dose pharmacokinetics and once daily for 5 days to determine multiple-dose pharmacokinetics. According to pharmacokinetic model estimates, the inter- and intra-individual variabilities in bioavailability following IM injection were remarkably reduced compared with those following oral administration. Monte Carlo simulations revealed that C peak , C trough and AUC would also have less variability following IM injection compared with oral administration. In this study, we found that the pharmacokinetic characteristics of tacrolimus were more constant following IM injection compared with oral administration. These results suggest that IM injection can be an alternative route of administration fin non-human primate model studies., (Copyright © 2018 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

Thyristor random access memory without a capacitor has been highlighted for its significant potential to replace current dynamic random access memory. We fabricated a two-terminal (2-T) thyristor by wet chemical etching techniques on n + -p-n-p + silicon epitaxial layers, which have the proper thicknesses and carrier concentrations, as provided by technology computer-aided design simulation. The etched features such as etch rate, surface roughness, and morphologies, in a potassium hydroxide (KOH) and an isotropic etchant, were compared. The type of silicon etchant strongly affected the etched shapes of the side wall and therefore critically influenced the device performance with varying turn-on voltages. The turn-on voltage of thyristor fabricated with a KOH solution showed a consistent tendency of operation voltage in the range of 2.2-2.5 V regardless of the cell size, while the thyristor formulated with isotropic etchant had an operation voltage which increased from about 2.3-4.4 V as the device dimension decreased from 200 μm to 10 μm. The optimized 2-T thyristor showed a memory window of about 2 V, a nearly zero-subthreshold swing, and a current on-off ratio of about 10 4 -10 5 .

The intestinal lymphatic system plays an important role in the pathophysiology of multiple diseases including lymphomas, cancer metastasis, autoimmune diseases, and human immunodeficiency virus (HIV) infection. It is thus an important compartment for delivery of drugs in order to treat diseases associated with the lymphatic system. Lipophilic prodrug approaches have been used in the past to take advantage of the intestinal lymphatic transport processes to deliver drugs to the intestinal lymphatics. Most of the approaches previously adopted were based on very bulky prodrug moieties such as those mimicking triglycerides (TG). We now report a study in which a lipophilic prodrug approach was used to efficiently deliver bexarotene (BEX) and retinoic acid (RA) to the intestinal lymphatic system using activated ester prodrugs. A range of carboxylic ester prodrugs of BEX were designed and synthesised and all of the esters showed improved association with chylomicrons, which indicated an improved potential for delivery to the intestinal lymphatic system. The conversion rate of the prodrugs to BEX was the main determinant in delivery of BEX to the intestinal lymphatics, and activated ester prodrugs were prepared to enhance the conversion rate. As a result, an 4-(hydroxymethyl)-1,3-dioxol-2-one ester prodrug of BEX was able to increase the exposure of the mesenteric lymph nodes (MLNs) to BEX 17-fold compared to when BEX itself was administered. The activated ester prodrug approach was also applied to another drug, RA, where the exposure of the MLNs was increased 2.4-fold through the application of a similar cyclic activated prodrug. Synergism between BEX and RA was also demonstrated in vitro by cell growth inhibition assays using lymphoma cell lines. In conclusion, the activated ester prodrug approach results in efficient delivery of drugs to the intestinal lymphatic system, which could benefit patients affected by a large number of pathological conditions., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To evaluate the potential pharmacokinetic interactions of the anticancer agent gefitinib (Iressa®) and the oriental medications Guipi Decoction (, GPD, Guibi-tang in Korean) and Bawu Decoction (, BWD, Palmul-tang in Korean)., Methods: Methylcellulose (MC, control), GPD (1,200 mg/kg), or BWD (6,000 mg/kg) was orally administered to rats either as a single dose or multiple doses prior to gefitinib administration. To examine the effects of a single dose of the herbal medicines, gefitinib (10 mg/kg) was orally administered after 5 min or 1 h of MC or the herbal medicine pretreatments. To examine the effects of the multiple doses of the herbal medicines, gefitinib (10 mg/kg) was orally administered following 7 consecutive days of the administration of MC or each herbal medicine. The plasma concentrations of gefitinib were determined with liquid chromatography-tandem mass spectrometry assay. The plasma concentration-time profiles of gefitinib were analyzed with a noncompartmental analysis., Results: Gefitinib was rapidly absorbed and showed a monoexponential decline with an elimination half-life of 3.7-4.1 h. The pharmacokinetics of gefitinib was not affected by GPD pretreatment. However, a significantly lower maximum plasma concentration (C max , P<0.05) and area under the curve (P<0.05), and a delayed time to reach C max (T max , P<0.01) were observed in both single- and multipledose BWD-pretreated rats compared with the control rats., Conclusions: BWD and not GPD might delay and interfere with gefitinib absorption. Further evaluations of the clinical significance of these findings are needed.

Pungent spice constituents such as piperine, capsaicin and [6]-gingerol consumed via daily diet or traditional Chinese medicine, have been reported to possess various pharmacological activities. These dietary phytochemicals have also been reported to inhibit P-glycoprotein (P-gp) in vitro and act as an alternative to synthetic P-gp modulators. However, the in vivo effects on P-gp inhibition are currently unknown. This study aimed to test the hypothesis that phytochemical P-gp inhibitors, i.e., piperine, capsaicin and [6]-gingerol, modulate the in vivo tissue distribution of doxorubicin, a representative P-gp substrate. Mice were divided into four groups and each group was pretreated with intraperitoneal injections of control vehicle, piperine, capsaicin, or [6]-gingerol and doxorubicin (1 mg/kg) was administered via the penile vein. The concentrations of the phytochemicals and doxorubicin in the plasma and tissues were determined by LC-MS/MS. The overall plasma concentration-time profiles of doxorubicin were not significantly affected by piperine, capsaicin, or [6]-gingerol. In contrast, doxorubicin accumulation was observed in tissues pretreated with piperine or capsaicin. The tissue to plasma partition coefficients, K p , for the liver and kidney were higher in the piperine-pretreated group, while the K p for kidney, brain and liver were higher in the capsaicin-pretreated group. [6]-Gingerol did not affect doxorubicin tissue distribution. The data demonstrated that the phytochemicals modulated doxorubicin tissue distribution, which suggested their potential to induce food-drug interactions and act as a strategy for the delivery of P-gp substrate drugs to target tissues and tumors., Competing Interests: The authors declare no conflict of interest.

To overcome high temperature stress, plants have developed transcriptional cascades which express a large amount of chaperone proteins called heat shock proteins (HSPs). In our recent publication, we reported that STABILIZED1, as an U5-snRNP-interacting protein, is involved in the splicing of heat shock factor (HSF) and HSP transcripts during high temperature stress. This indicates that not only transcriptional regulation, but also post-transcriptional regulation by STA1, is essential for the full activation of HSF-HSP cascades and for thermotolerance. Here, we observed that the splicing of HSP transcripts was induced independent of STA1 at room temperature after heat acclimation, indicating that STA1 acts as a high temperature-specific splicing factor for the splicing of HSP transcripts. Our findings suggest the molecular mechanism for how HSF and HSP transcripts are spliced well under high temperature stress that blocks the splicing of overall transcripts.

Objective: To evaluate the association between balance function and asymmetry of knee extension strength in an elderly Korean population., Methods: The strength of the knee extensors in each leg was measured in 306 community-dwelling elderly subjects (age, 76.70±4.85 years) and 25 young healthy subjects (age, 34.23±8.93 years). Based on the difference in strength of both legs, the elderly subjects were divided into symmetric (n=128) and asymmetric (n=178) strength groups using an asymmetry cutoff 20%. We determined the postural control ability of the subjects using InBody posturography, Berg Balance Scale (BBS), Timed Up and Go test (TUG) and Short Physical Performance Battery (SPPB). The sway index (SI) of the subjects in four positions was assessed using posturography., Results: The group with asymmetric strength presented a significantly higher SI than the group with symmetric strength, in the normal position with eyes open and eyes open on pillows. In the normal position with the eyes closed and in postures with the eyes closed on pillows, the statistical analysis revealed no significant differences between the two groups. The three tests for physical performance (BBS, TUG, and SPPB) show no statistically significant difference between the two groups., Conclusion: The asymmetric strength group showed a significantly lower balance than the group with symmetric strength based on several posturographic parameters. Ambulatory elderly individuals with asymmetry in knee extension strength, showed deficits in balance control even in normal clinical tests., Competing Interests: CONFLICT OF INTEREST: No potential conflict of interest relevant to this article was reported.

Objective: To investigate the differences in biomechanical parameters measured by gait analysis systems between healthy subjects and subjects with plantar fasciitis (PF), and to compare biomechanical parameters between 'normal, barefooted' gait and arch building gait in the participants., Methods: The researchers evaluated 15 subjects (30 feet) with bilateral foot pain and 15 subjects (15 feet) with unilateral foot pain who had a clinical diagnosis of PF. Additionally, 17 subjects (34 feet) who had no heel pain were recruited. Subjects were excluded if they had a traumatic event, prior surgery or fractures of the lower limbs, a leg length discrepancy of 1 cm or greater, a body mass index greater than 35 kg/m 2 , or had musculoskeletal disorders. The participants were asked to walk with an arch building gait on a treadmill at 2.3 km/hr for 5 minutes. Various gait parameters were measured., Results: With the arch building gait, the PF group proved that gait line length and single support line were significantly decreased, and lateral symmetry of the PF group was increased compared to that of the control group. The subjects with bilateral PF displayed significantly increased maximum pressure over the heel and the forefoot during arch building gait. In addition, the subjects with unilateral PF showed significantly increased maximum pressure over the forefoot with arch building gait., Conclusion: The researchers show that various biomechanical differences exist between healthy subjects and those with PF. Employing an arch building gait in patients with PF could be helpful in changing gait patterns to normal biomechanics., Competing Interests: CONFLICT OF INTEREST: No potential conflict of interest relevant to this article was reported.

Objective: To assess the cross-sectional area (CSA) of the muscles for investigating the occurrence of asymmetry of the paraspinal (multifidus and erector spinae) and psoas muscles and its relation to the chronicity of unilateral lumbar radiculopathy using magnetic resonance imaging (MRI)., Methods: This retrospective study was conducted between January 2012 to December 2014. Sixty one patients with unilateral L5 radiculopathy were enrolled: 30 patients had a symptom duration less than 3 months (group A) and 31 patients had a symptom duration of 3 months or more (group B). Axial MRI measured the CSA of the paraspinal and psoas muscles at the middle between the lower margin of the upper vertebra and upper margin of the lower vertebra, and obtained the relative CSA (rCSA) which is the ratio of the CSA of muscles to that of the lower margin of L4 vertebra., Results: There were no differences in the demographics between the two groups. In group B, rCSA of the erector spinae at the L4-5 level, and that of multifidus at the L4-5 and L5-S1 levels, were significantly smaller on the involved side as compared with the uninvolved side. In contrast, no significant muscle asymmetry was observed in group A. The rCSA of the psoas was not affected in either group., Conclusion: The atrophy of the multifidus and erector spinae ipsilateral to the lumbar radiculopathy was observed only in patients suffering from unilateral radiculopathy for 3 months or more., Competing Interests: CONFLICT OF INTEREST: No potential conflict of interest relevant to this article was reported.