Bidirectional association between Parkinson's disease and obstructive sleep apnea: a cohort study.

STUDY OBJECTIVES: Chronic intermittent hypoxia due to obstructive sleep apnea (OSA) causes oxidative stress, which may contribute to the pathophysiology of Parkinson's disease (PD). However, the bidirectional relationship between PD and OSA has not been satisfactorily established. The objective of this study was to try to estimate whether there is a bidirectional relationship between PD and OSA through a retrospective cohort study in the South Korean population. METHODS: This study used data from the Korean National Health Information Database of the National Health Insurance Service, which contains data from 3.5 million individuals evenly distributed. In study 1, patients with OSA were matched in a 1:2 ratio with non-OSA controls. In study 2, patients with PD were matched in a 1:2 ratio with non-PD controls. A stratified Cox proportional hazards model was used to calculate hazard ratios. RESULTS: In study 1, which included 6,396 patients with OSA and 12,792 non-OSA controls, the incidence of PD per 10,000 person-years was 11.59 in the OSA group and 8.46 in the non-OSA group. The OSA group demonstrated a 1.54-fold higher incidence of PD than the non-OSA group (95% confidence interval, 1.14-2.07; P < .05). In study 2, which included 3,427 patients with PD and 6,854 non-PD controls, the incidence of OSA per 10,000 person-years was 14.97 in the PD group and 7.72 in the non-PD group. The PD group demonstrated a 1.92-fold higher incidence of OSA than the non-PD group (95% confidence interval, 1.32-2.78; P < .05). CONCLUSIONS: This study supports a possible bidirectional relationship between PD and OSA. CITATION: Jeon S-H, Hwang YS, Oh S-Y, et al. Bidirectional association between Parkinson's disease and obstructive sleep apnea: a cohort study. J Clin Sleep Med. 2023;19(9):1615-1623.

A Synthetic Time-Series Generation Using a Variational Recurrent Autoencoder with an Attention Mechanism in an Industrial Control System.

Data scarcity is a significant obstacle for modern data science and artificial intelligence research communities. The fact that abundant data are a key element of a powerful prediction model is well known through various past studies. However, industrial control systems (ICS) are operated in a closed environment due to security and privacy issues, so collected data are generally not disclosed. In this environment, synthetic data generation can be a good alternative. However, ICS datasets have time-series characteristics and include features with short- and long-term temporal dependencies. In this paper, we propose the attention-based variational recurrent autoencoder (AVRAE) for generating time-series ICS data. We first extend the evidence lower bound of the variational inference to time-series data. Then, a recurrent neural-network-based autoencoder is designed to take this as the objective. AVRAE employs the attention mechanism to effectively learn the long-term and short-term temporal dependencies ICS data implies. Finally, we present an algorithm for generating synthetic ICS time-series data using learned AVRAE. In a comprehensive evaluation using the ICS dataset HAI and various performance indicators, AVRAE successfully generated visually and statistically plausible synthetic ICS data.

A security scheme for distributing analysis codes supporting CDM-based research in a multi-center environment.

BACKGROUND: Although the common data model (CDM) has achieved a standardization of medical data and a de-identification of personal patient information, hospitals still store CDM data in an on-premises environment, making it difficult for researchers to access medical data. OBJECTIVE: In this study, for easy access to CDM data in a multi-institutional participatory CDM research environment and to encourage data-driven research, researchers outside hospital networks securely access and analyze CDM data in the target medical center, analyze it, and respond to the results through a public network. We propose an automated security framework that operates on a public network, such as the Internet. METHOD: The proposed scheme allows authenticated researchers to securely deliver CDM data analysis codes to a medical institution distributed on the network. The institutional servers automatically execute authenticated codes and return the results to the researcher safely. For this purpose, we designed a scheme based on cryptography. The scheme operates on a group of servers consisting of an authentication process, a signing process, a ticket-granting process, a relaying process, and a data analysis process located at the hospital providing medical CDM data. The scheme consists of four phases for a secure medical data analysis in a distributed environment: authentication, code signing, ticket issuing, and distribution and return. RESULTS: Although the CDM has de-identified patient privacy, the issue still needs to be carefully addressed. Therefore, we established four security objectives to verify that the proposed scheme can be operated safely and formally proved them using BAN logic. CONCLUSION: As a result of the proof using BAN logic, the proposed scheme was verified to achieve the proposed security goal. Although this scheme was designed solely for CDM, it can be applied to systems with similar environments and functional goals.

Measurement Issue in Antecollis.

Background: Antecollis is defined as an involuntary forward flexion of the neck. Previous reports have measured the neck flexion angles based on the line perpendicular to the ground. This led to an inflation of the neck flexion angles in patients who had combined forward truncal flexions, especially upper camptocormia. Methods: We examined the neck flexion angles and the upper camptocormia angle in the published photographs of antecollis. MEDLINE search was conducted using the following search terms: antecollis OR anterocollis. Lateral-view photographs of patients diagnosed with antecollis were collected. Neck flexion angles were measured with the classic 'perpendicular method' and the 'antecollis method' we developed. Results: Nine patient photographs were identified. While antecollis was the only described postural abnormality in eight cases, these patients exhibited upper camptocormia angles of 45° or larger. The mean neck flexion angle measured with the antecollis method was 49.7°, while the perpendicular method yielded 103.4°. Discussion: Upper camptocormia should be considered in the evaluation of antecollis. We propose a new method to measure neck flexion in relation to the torso, instead of the vertical line.

Long-Term Outcomes of Deep Brain Stimulation in Pantothenate Kinase-Associated Neurodegeneration-Related Dystonia.

OBJECTIVE: To investigate the long-term clinical outcomes of pallidal deep brain stimulation (GPi-DBS) in patients with pantothenate kinase-associated neurodegeneration (PKAN). METHODS: We reviewed the records of patients with genetically confirmed PKAN who received bilateral GPi-DBS for refractory dystonia and were clinically followed up for at least 2 years postoperatively at two centers in Korea. Pre- and postoperative Burke- Fahn-Marsden Dystonia Rating Scale motor subscale (BFMDRS-M) scores, disability subscale (BFMDRS-D) scores, and qualitative clinical information were prospectively collected. Descriptive analysis was performed for BFMDRS-M scores, BFMDRSD scores, and the orofacial, axial, and limb subscores of the BFMDRS-M at 6-12, 24-36, and 60-72 months postoperatively. RESULTS: Five classic-type, four atypical-type, and one unknown-type PKAN cases were identified. The mean preoperative BFMDRS-M score was 92.1 for the classic type and 38.5 for the atypical or unknown type, with a mean BFMDRS follow-up of 50.7 months and a clinical follow-up of 69.0 months. The mean improvements in BFMDRS-M score were 11.3%, 41.3%, and 30.5% at 6-12, 24-36, and 60-72 months, respectively. In four patients with full regular evaluations until 60-72 months, improvements in the orofacial, axial, and limb subscores persisted, but the disability scores worsened from 24-36 months post-operation compared to the baseline, mainly owing to the aggravation of eating and feeding disabilities. CONCLUSION: The benefits of GPi-DBS on dystonia may persist for more than 5 years in PKAN. The effects on patients' subjective disability may have a shorter duration despite improvements in dystonia owing to the complex manifestations of PKAN.

Development of Clinical Milestones in Parkinson's Disease After Bilateral Subthalamic Deep Brain Stimulation.

OBJECTIVE: Deep brain stimulation of the subthalamic nucleus (STN-DBS) in Parkinson's disease (PD) patients does not halt disease progression, as these patients will progress and develop disabling non-levodopa responsive symptoms. These features may act as milestones that represent the overall functionality of patients after DBS. The objective of this study was to investigate the development of clinical milestones in advanced PD patients who underwent bilateral STN-DBS. METHODS: The study evaluated PD patients who underwent STN-DBS at baseline up to their last follow-up using the Unified Parkinson's Disease Rating Scale and Hoehn and Yahr scale. The symptoms of hallucinations, dysarthria, dysphagia, frequent falls, difficulty walking, cognitive impairment and the loss of autonomy were chosen as the clinical milestones. RESULTS: A total of 106 patients with a mean age of 47.21 ± 10.52 years at disease onset, a mean age of 58.72 ± 8.74 years at surgery and a mean disease duration of 11.51 ± 4.4 years before surgery were included. Initial improvement of motor symptoms was seen after the surgery with the appearance of clinical milestones over time. Using the moderately disabling criteria, 81 patients (76.41%) developed at least one clinical milestone, while 48 patients (45.28%) developed a milestone when using the severely disabling criteria. CONCLUSION: STN-DBS has a limited effect on axial and nonmotor symptoms of the PD patients, in contrast to the effect on motor symptoms. These symptoms may serve as clinical milestones that can convey the status of PD patients and its impact on the patients and their caregivers. Therefore, advanced PD patients, even those treated with bilateral STN-DBS, will still require assistance and cannot live independently in the long run.

Resveratrol-enriched rice identical to original Dongjin rice variety with respect to major agronomic traits in different cultivation years and regions.

Resveratrol is synthesized by the catalysis of resveratrol synthases (RS) in a limited number of higher plants. Resveratrol shows potential health-promoting properties, including as an antioxidant and in preventing cardiovascular diseases. Recently, resveratrol-enriched rice has been produced as a novel source of resveratrol. This study aimed to investigate the major agronomic characteristics of resveratrol-enriched rice, Iksan526 (I526) and compared them with those of a nontransgenic and commercial rice variety, Dongjin (DJ). Transgene (RS) integration was confirmed using Southern blot analysis, and homologous recombination was achieved after digestion with the SacI restriction enzyme. The phenotypic traits of I526 grown in Iksan were similar to those grown in Milyang but not similar to those grown in Suwon. In Suwon, I526 had slightly earlier heading dates [i.e., number of days from sowing to heading) and shorter culm lengths. When I526 was treated with 0.4% Basta in the seedling stage, no significant difference was observed among all the agronomic traits compared with nontreated I526; particularly, the culm length, panicle length, number of panicles per hill, 1,000 grain weight of brown rice, and brown rice yield of the Basta-treated rice were similar to those of the nontreated I526, regardless of their cultivation region. The resveratrol content of I526 grown in Suwon and Milyang was increased by 18% and 37%, respectively, than that of I526 grown in the Iksan area. Therefore, DJ and I526 are not significantly different in terms of major agronomic traits depending on variety/year and variety/cultivation region. The results indicated that I526 has the potential to become a commercialized variety in the near future.

Proposal and Assessment of a De-Identification Strategy to Enhance Anonymity of the Observational Medical Outcomes Partnership Common Data Model (OMOP-CDM) in a Public Cloud-Computing Environment: Anonymization of Medical Data Using Privacy Models.

BACKGROUND: De-identifying personal information is critical when using personal health data for secondary research. The Observational Medical Outcomes Partnership Common Data Model (CDM), defined by the nonprofit organization Observational Health Data Sciences and Informatics, has been gaining attention for its use in the analysis of patient-level clinical data obtained from various medical institutions. When analyzing such data in a public environment such as a cloud-computing system, an appropriate de-identification strategy is required to protect patient privacy. OBJECTIVE: This study proposes and evaluates a de-identification strategy that is comprised of several rules along with privacy models such as k-anonymity, l-diversity, and t-closeness. The proposed strategy was evaluated using the actual CDM database. METHODS: The CDM database used in this study was constructed by the Anam Hospital of Korea University. Analysis and evaluation were performed using the ARX anonymizing framework in combination with the k-anonymity, l-diversity, and t-closeness privacy models. RESULTS: The CDM database, which was constructed according to the rules established by Observational Health Data Sciences and Informatics, exhibited a low risk of re-identification: The highest re-identifiable record rate (11.3%) in the dataset was exhibited by the DRUG_EXPOSURE table, with a re-identification success rate of 0.03%. However, because all tables include at least one "highest risk" value of 100%, suitable anonymizing techniques are required; moreover, the CDM database preserves the "source values" (raw data), a combination of which could increase the risk of re-identification. Therefore, this study proposes an enhanced strategy to de-identify the source values to significantly reduce not only the highest risk in the k-anonymity, l-diversity, and t-closeness privacy models but also the overall possibility of re-identification. CONCLUSIONS: Our proposed de-identification strategy effectively enhanced the privacy of the CDM database, thereby encouraging clinical research involving multiple centers.

Acute basilar artery occlusion with recurrent shivering: A case report.

RATIONALE: Shivering is an important physiological response of the body that causes muscle tremors to maintain temperature homeostasis. Traumatic brain injuries that affect the hypothalamus cause hypothermia, and physical removal of suprasellar tumors causes thermoregulation imbalance. However, no study has reported shivering due to ischemic stroke. PATIENT CONCERNS: A 58-year-old male patient was admitted to our emergency department to evaluate severe stenosis of the basilar artery. While waiting for further examination, he exhibited coarse shivering and severe dysarthria. DIAGNOSIS: Brain computed tomography angiography revealed occlusion of the entire basilar artery, and cerebral hypoperfusion was diagnosed in that area. INTERVENTIONS: Transfemoral cerebral angiography (TFCA) was immediately performed, followed by thrombectomy of the basilar artery. OUTCOMES: Neurological deficits, including shivering, were rapidly reversed. The same symptom reoccurred 5 hours later, and TFCA was performed for thrombectomy and stenting, and neurological symptoms immediately reversed. The patient's neurological symptoms did not worsen during hospitalization. LESSONS: Patients with acute basilar artery occlusion need prompt management because they have a higher mortality rate than those with other intracranial artery occlusions. When a patient exhibits neurological deficits accompanied by abrupt shivering for no specific reason, basilar artery occlusion must be considered.

Neural Correlates of Transient Mal de Debarquement Syndrome: Activation of Prefrontal and Deactivation of Cerebellar Networks Correlate With Neuropsychological Assessment.

Background: Mal de debarquement syndrome (MdDS) is characterized by a subjective perception of self-motion after exposure to passive motion, mostly after sea travel. A transient form of MdDS (t-MdDS) is common in healthy individuals without pathophysiological certainty. In the present cross-sectional study, the possible neuropsychiatric and functional neuroimaging changes in local fishermen with t-MdDS were evaluated. Methods: The present study included 28 fishermen from Buan County in South Korea; 15 (15/28, 53.6%) participants experienced t-MdDS for 1-6 h, and 13 were asymptomatic (13/28, 46.4%). Vestibular function tests were performed using video-oculography, the video head impulse test, and ocular and cervical vestibular-evoked myogenic potentials. Visuospatial function was also assessed by the Corsi block test. Brain imaging comprised structural MRI, resting-state functional MRI, and [18F]FDG PET scans. Results: The results of vestibular function tests did not differ between the fishermen with and those without t-MdDS. However, participants with t-MdDS showed better performance in visuospatial memory function than those without t-MdDS (6.40 vs. 5.31, p-value = 0.016) as determined by the Corsi block test. Structural brain MRIs were normal in both groups. [18F]FDG PET showed a relative hypermetabolism in the bilateral occipital and prefrontal cortices and hypometabolism in the vestibulocerebellum (nodulus and uvula) in participants with t-MdDS compared to those without t-MdDS. Resting-state functional connectivities were significantly decreased between the vestibular regions of the flocculus, superior temporal gyrus, and parietal operculum and the visual association areas of the middle occipital gyrus, fusiform gyrus, and cuneus in participants with t-MdDS. Analysis of functional connectivity of the significant regions in the PET scans revealed decreased connectivity between the prefrontal cortex and visual processing areas in the t-MdDS group. Conclusion: Increased visuospatial memory, altered metabolism in the prefrontal cortex, visual cognition cortices, and the vestibulocerebellum, and decreased functional connectivity between these two functional areas might indicate reductions in the integration of vestibular input and enhancement of visuospatial attention in subjects with t-MdDS. Current functional neuroimaging similarities from transient MdDS via chronic MdDS to functional dizziness and anxiety disorders suggest a shared mechanism of enhanced self-awareness as a kind of continuum or as overlap disorders.

Recurrent GANs Password Cracker For IoT Password Security Enhancement.

Text-based passwords are a fundamental and popular means of authentication. Password authentication can be simply implemented because it does not require any equipment, unlike biometric authentication, and it relies only on the users' memory. This reliance on memory is a weakness of passwords, and people therefore usually use easy-to-remember passwords, such as "iloveyou1234". However, these sample passwords are not difficult to crack. The default passwords of IoT also are text-based passwords and are easy to crack. This weakness enables free password cracking tools such as Hashcat and JtR to execute millions of cracking attempts per second. Finally, this weakness creates a security hole in networks by giving hackers access to an IoT device easily. Research has been conducted to better exploit weak passwords to improve password-cracking performance. The Markov model and probabilistic context-free-grammar (PCFG) are representative research results, and PassGAN, which uses generative adversarial networks (GANs), was recently introduced. These advanced password cracking techniques contribute to the development of better password strength checkers. We studied some methods of improving the performance of PassGAN, and developed two approaches for better password cracking: the first was changing the convolutional neural network (CNN)-based improved Wasserstein GAN (IWGAN) cost function to an RNN-based cost function; the second was employing the dual-discriminator GAN structure. In the password cracking performance experiments, our models showed 10%-15% better performance than PassGAN. Through additional performance experiments with PCFG, we identified the cracking performance advantages of PassGAN and our models over PCFG. Finally, we prove that our models enhanced password strength estimation through a comparison with zxcvbn.

Factors associated with temporal window failure in transcranial Doppler sonography.

BACKGROUND: Temporal window failure (TWF) is found in 8-20% of subjects. There are still insufficient studies about the factors affecting TWF. We aimed to elucidate the underlying causes of TWF. METHODS: We analyzed 376 patients who underwent both transcranial Doppler sonography and cerebral angiographic imaging. They were divided into two groups: with and without TWF. Demographics, cardiovascular factors, degree of stenosis from the proximal intracranial artery to the middle cerebral artery (MCA), MCA diameter, and skull features were examined. RESULTS: The subjects were 314 TWF-negative patients and 62 TWF-positive patients. The TWF-negative group was younger than that of the TWF-positive group (67.0 ± 12.1 vs. 75.2 ± 9.4, p < 0.001). The proportion of men in the TWF-negative group was higher than in the TWF-positive group (71% vs. 29%; p < 0.001). The TWF-negative group had a higher smoking rate than the TWF-positive group (34.4% vs. 12.9%; p = 0.001). In multivariate logistic regression analysis, age (odds ratio (OR), 1.05; p = 0.019), sex (OR, 4.64; p = 0.002), temporal bone thickness (OR, 6.03; p < 0.001), temporal bone density (OR, 0.996; p = 0.002), and soft tissue thickness (OR, 1.31; p = 0.004) significantly affected TWF. CONCLUSIONS: In addition to age, sex, temporal bone thickness, and temporal bone density which were previously reported as variables associated with TWF, we confirmed that soft tissue thickness of the temporal area is a new associated factor of TWF. Measuring soft tissue thickness of the temporal area for patients with suspected TWF could be useful in identifying measurement error due to technical problems.

Functional Chemical Components in Protaetia brevitarsis Larvae: Impact of Supplementary Feeds.

The goal of this study was to evaluate the influence of various supplementary feeds on the chemical composition and production of bioactive substances in Protaetia brevitarsis larvae. The primary feed-oak-fermented sawdust-was supplemented with a variety of substances, including aloe, apple, banana, sweet persimmon (S. persimmon) and sweet pumpkin (S. pumpkin). Crude protein and fat content were the highest in the control and S. pumpkin group, respectively. Supplementary feeds increased the content of unsaturated fatty acids, except in the group receiving S. pumpkin, in which oleic acid was the most abundant (58.2%-64.5%). Free essential amino acids in larvae receiving supplementary aloe were higher compared with the control group except for Lys and His. Polyphenol and flavonoid contents and the antioxidant activities of ABTS and DPPH were higher in all treated groups compared with the control group. Although supplementary feeds led to a decreased crude protein content in the treated larvae when compared with the control group, these treatments generally improved the levels of unsaturated fatty acids and antioxidative activity. Therefore, we suggest that among the supplementary foods tested, aloe is a better resource for P. brevitarsis based on crude protein content, free amino acids and other bioactive compounds such as unsaturated fatty acids and antioxidants.

Different imaging patterns of PCNSL and IVL: a case report.

BACKGROUND: Primary central nervous system lymphoma (PCNSL) is a rare, malignant, non-Hodgkin's lymphoma of the brain, leptomeninges, and rarely the spinal cord. PCNSL has characteristic magnetic resonance imaging (MRI) findings, and effective treatment strategies are available. It is characterized predominately by neurological symptoms, which are caused by tumor infiltration into the nervous system as well as ischemia. Chemotherapy is an effective treatment, if started prior to the ischemic damage. CASE PRESENTATION: A 62-year-old male patient with PCNSL presented with altered mental status. The initial brain MRI revealed high signal intensity on the T2-weighted images (T2WIs) of the putamen area of the right basal ganglia, and the clinical symptoms improved after steroid administration. However, the symptoms were later deteriorated, we considered the possibility of autoimmune encephalitis and, consequently, conducted an immunomodulatory therapy. In a follow-up brain MRI, enlargement lesions of T2WI in basal ganglia and pons were simultaneously enhanced. Subsequently, the patient's mental status deteriorated to a semi-coma and PCNSL was diagnosed after a surgical biopsy. Chemotherapy was started immediately; however, the patient died. CONCLUSIONS: Effective treatments are available for PCNSL and intravascular lymphoma; thus, their prognosis is generally good if they are diagnosed early. Herein, we report the case of a patient suspected with autoimmune encephalitis after brain MRI and treated with immunomodulation therapy. However, PCNSL was confirmed by a surgical biopsy. It is, therefore recommended to consider lymphoma in patients with neurological symptoms that are difficult to localize and rapidly progressive enhancing lesions showing a mass effect on brain MRI.

Femoral artery pseudoaneurysm after carotid artery stenting: Two case reports.

RATIONALE: Pseudoaneurysm, the most common complication of femoral artery catheterization, involves the formation of a space between the lumen and the surrounding fibrous tissue through the damaged arterial wall. In patients treated with antiplatelet and anticoagulant agents, the incidence of vascular complications increases with the increasing use of minimally invasive procedures. PATIENT CONCERNS: We experienced 2 cases of procedure-induced pseudoaneurysms. A 79-year-old man with right hemiparesis visited our hospital. Brain magnetic resonance imaging showed acute left middle cerebral artery territory infarction and severe stenosis of the left proximal carotid artery. The patient was prescribed apixaban and underwent carotid stenting through the right femoral artery. Hematoma and tenderness were observed in the right inguinal region after the procedure. The hemoglobin level decreased from 16.9 g/dL to 9.4 g/dL. Another 78-year-old man with left common carotid artery stenosis was admitted. We performed stent implantation through the right femoral artery and administered aspirin and clopidogrel. After the procedure, hematoma and tenderness of the puncture site were observed. The hemoglobin level decreased from 14.5 g/dL to 10.9 g/dL. DIAGNOSIS: Emergency computed tomography confirmed a pseudoaneurysm with a massive hematoma in the right inguinal area. The patients were diagnosed with infection-associated right pseudoaneurysm for which an emergency puncture site repair was performed. INTERVENTIONS: We performed resection of pseudoaneurysm and repaired puncture site. OUTCOMES: The hemoglobin level was stabilized postoperatively and vital sign remained stable. LESSONS: Pseudoaneurysm is an important complication of femoral artery puncture. The use of a hemostatic device was not superior to manual compression, and the incidence of this complication was significantly higher in patients who received anticoagulant or antiplatelet agents. A pseudoaneurysm may cause a bad prognosis. Therefore, the early detection of pseudoaneurysm and immediate treatment after femoral arterial puncture are needed.

Evaluation of tacrolimus sorption to PVC- and non-PVC-based tubes in administration sets: Pump method vs. drip method.

Tacrolimus sorption to tubes was evaluated using pump and drip methods For tubes, polyvinylchloride (PVC)- and non-PVC-based (polyurethane [PU] and polyolefin [PO]) tubes were used. First, inner surface properties of tubes were analyzed using field emission scanning electron microscopy and X-ray photoelectron spectroscopy. Tacrolimus was quantitatively analyzed using high-performance liquid chromatography with UV detection. For kinetic sorption analysis, diluted tacrolimus to 10µg/mL was passed through 1-m-long tubes at 10mL/h. Samples were collected at 1-4h. The inner surface of PO-based tubes was relatively smooth and soft compared with those of PVC- and PU-based tubes. Atomic compositions of tubes matched chemical formulas of polymers excluding low-level impurity in PVC-based tubes. Tacrolimus was successfully analyzed and linearly determined at 2.5-20µg/mL. From both methods, PVC- and PO-based tubes exhibited the highest and the lowest (<10%) sorption levels to tacrolimus, respectively. Tacrolimus was stably delivered using the pump method. Results suggested that the pump method can estimate tacrolimus sorption in administration set tubes and evaluate other sorptional drugs used at low concentrations. PO-based tubes also have promising potential as an alternative for administration set tubes.

Evaluation of Drug Sorption to PVC- and Non-PVC-based Tubes in Administration Sets Using a Pump.

Administration sets are delivery tools for the direct application of drugs into the body and are composed of a spike, a drip chamber, tubes, Luer adapters (connectors), a needle cover for protection, and other accessories. Drug sorption to tubes of administration sets is a critical issue in terms of safety and efficacy. Although drug sorption is an important factor in the quality of an administration set, there are no standard evaluation methods for the regulation of drug sorption to the tubes. Here, we describe an evaluation protocol for drug sorption to tubes of administration sets. Tubes made of polyvinyl chloride (PVC)- and non-PVC-based polymeric materials were cut to 1 m in length. Diazepam and tacrolimus were used as model drugs. In the kinetic sorption study, we selected the drug concentration and flow rate based on the clinical usage of these drugs. After the dilution of each drug in a glass bottle, the diluted drug solution was delivered through tubes of administration sets using a pump. Samples were collected in amber vials at appropriate time points and the drugs were analyzed using high-performance liquid chromatography. Drug concentrations and sorption levels to tubes of the administration sets were calculated. Acceptable criteria to ensure the quality of administration sets are recommended.

Diazepam sorption to PVC- and non-PVC-based tubes in administration sets with quantitative determination using a high-performance liquid chromatographic method.

Diazepam is highly sorbed to the plastic materials of administration sets for intravenous infusion. This can be detrimental as it should be delivered to the patient at the administered amount for efficacy and safety. We report here the sorption levels of diazepam onto various types of tubes in administration sets. The tube materials of the administration sets included polyvinylchloride (PVC) and the non-PVC materials such as polyurethane (PU) and polyolefin (PO) were used. Two conditions of diazepam administered in preclinical and clinical settings were tested using an infusion pump. Injections were prepared by diluting diazepam to 20mg/500mL and 10mg/100mL in 5% dextrose. Diluted diazepam solutions at the concentrations of 10mg/100mL and 20mg/500mL were separately delivered through 1m of tubing at 1mL/min for 1.05 and 4.05h. Samples were analyzed using a high-performance liquid chromatography with UV detection. PVC- and PU-based tubes showed higher sorption of diazepam than did PO-based tubes. PO-based tubes delivered more than 90% of the administered diazepam. The results showed that PO-based tubes of administration sets have a promising potential to deliver hydrophobic drugs like diazepam with minimal sorption levels. In addition, the tube materials in administration sets may be one of the critical factors to ensure drug efficacy and safety.

The potential of interleukin 12 receptor beta 2 (IL12RB2) and tumor necrosis factor receptor superfamily member 8 (TNFRSF8) gene as diagnostic biomarkers of oral lichen planus (OLP).

OBJECTIVE: This study evaluated the potential of interleukin 12 receptor beta 2 and tumor necrosis factor receptor superfamily member 8 as diagnostic biomarkers of oral lichen planus (OLP). MATERIALS AND METHODS: The mRNA expression of IL12RB2 and TNFRSF8 in FFPE OLP samples (OLP group, n = 38) were investigated with quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) analysis and compared to those of chronic non-specific mucositis (Non-OLP group, n = 25) and normal mucosa (Normal group, n = 18). Predictive modeling of the expression of IL12RB2 and TNFRSF8 was constructed using support vector machine (SVM), random forest (RF), linear discriminant analysis (LDA), neural network (NN) and naive Bayes (NB) methods. RESULTS: Normalized expression of IL12RB2 in the OLP group (3.78 ± 1.67) was significantly higher than the Normal group (1.97 ± 1.12), but lower than the Non-OLP group (6.86 ± 1.67). TNFRSF8 gene expression in the OLP group (7.46 ± 1.51) was significantly higher than the Normal group (2.90 ± 1.61), but no significant difference was found between the OLP and Non-OLP groups. The ratio of IL12RB2/TNFRSF8 in the OLP group (0.52 ± 0.23) was significantly lower than the Normal group (0.74 ± 0.39) and the Non-OLP group (1.07 ± 0.38). In the predictive modeling, the area under receiver operating characteristic (ROC) curves (AUC) ranged from 0.83-0.92 and their accuracy was higher than 0.75 in all methods. CONCLUSIONS: The IL12RB2/TNFRSF8 ratio can be a useful diagnostic tool for OLP.