The Effect of Marijuana on Postoperative Spine Patients' Emergency Department Visits, Readmission Rates, and Opioid Consumption.

OBJECTIVE: To compare postoperative opioid consumption with patients who tested negative for tetrahydrocannabinol (THC) preoperatively with those who were THC-positive and patients who were positive for THC and any other drug and to compare 90-day rates of postoperative emergency department (ED) visits and 90-day readmission rates, using morphine milligram equivalents (MMEs), for those three patient populations. METHODS: Three patient groups were confirmed with preoperative urine drug screens. Chart reviews were conducted to determine whether there was an ED visit or hospital readmission 90 days from the index procedure. MMEs were calculated for all patients. RESULTS: There were a total of 252 patients in the THC-negative control group, 54 in the THC-positive group, and 47 in the THC-and-opioid-positive group. The 90-day ED visit and 90-day readmission rates were not statistically significant among the groups. Both the multidrug and THC-only-positive patients showed a higher 90-day MME compared with the control patients. DISCUSSION: Our study demonstrates that THC used may increase opioid consumption. The THC patients to be cautious toward are the multidrug user. Although not statistically significant, multidrug patients were noted for a trend toward increased ED visits and readmissions.

Optimization of process parameters in micro-scale pneumatic aerosol jet printing for high-yield precise electrodes.

Aerosol jet printing (AJP) is a new non-contact direct writing technique designed to achieve precise and intricate patterns on various substrates. Specifically, the pneumatic AJP process breaks down the ink into fine particles, significantly reducing the risk of nozzle clogging and rendering it highly advantageous for industrial applications. This paper focuses on the optimization of the line electrode formation process using soluble silver clusters as the conductive ink, along with the aerosol formation procedure. The main parameters of the AJP process, namely sheath flow rate, atomizer flow rate, and dispensing speed, were identified and examined for their influence on line width and resistivity. Through this analysis, an operability window, including optimized conditions for printing high-quality lines using the AJP process, was established, along with a regression equation enabling the statistical estimation of line width. In summary, the outcomes of this investigation underscore the feasibility of an integrated printing system capable of precision control over line width, achieved through the optimization of AJP process parameters. Furthermore, it was established that pneumatic AJP offers robust process stability. The practical applicability of the proposed optimization techniques was assessed, highlighting their potential utilization in electrode formation processes within the electronic and display industry.

Efficacy of a Mobile-Based Multidomain Intervention to Improve Cognitive Function and Health-Related Outcomes Among Older Korean Adults with Subjective Cognitive Decline.

BACKGROUND: Subjective cognitive decline (SCD) is a self-reported experience of declining cognitive function showing normal performance in cognitive assessments, which is a known risk factor for dementia. Recent studies highlight the importance of nonpharmacological multidomain interventions that can target multiple risk factors of dementia in older adults. OBJECTIVE: This study investigated the efficacy of the Silvia program, a mobile-based multidomain intervention, to improve cognitive function and health-related outcomes of older adults with SCD. We compare its effects to a conventional paper-based multidomain program on various health indicators related to risk factors of dementia. METHODS: This prospective randomized controlled trial involved 77 older adults with SCD recruited from the Dementia Prevention and Management Center in Gwangju, South Korea during May to October 2022. Participants were randomly assigned to either the mobile- or paper-based group. Interventions were administered for 12 weeks, where pre- and post-assessments were conducted. RESULTS: The K-RBANS total score did not show significant differences between groups. The mobile group showed better improvement in K-PRMQ scores and PSS scores than the paper group. Differences within groups showed that mobile-based interventions significantly improved K-PRMQ, STAI-X-1, PSS, and EQ-5D-5 L scores, while paper-based interventions significantly improved PSS, and EQ-5D-5 L scores. Patient adherence rate was 76.6%. CONCLUSION: Overall, the Silvia program was effective for improving self-reported memory failures, stress, anxiety, and health-related quality of life in older adults with SCD. However, longer periods of administration for more than 12 weeks may be needed to achieve significant improvements in cognitive function by objective measures.

Oral Macrocystis pyrifera Fucoidan Administration Exhibits Anti-Inflammatory and Antioxidant Properties and Improves DSS-Induced Colitis in C57BL/6J Mice.

Inflammatory bowel disease (IBD) is a complex and multifactorial disorder characterised by relapsing and remitting inflammation of the intestinal tract. Oxidative stress (OS) is the result of an imbalance between production and accumulation of reactive oxygen species (ROS), which has been associated with inflammatory responses and implicated in the exacerbation of IBD. Fucoidan, a sulfated polysaccharide from brown seaweed, is a well-known anti-inflammatory agent and emerging evidence indicates that fucoidan extracts from Macrocystis pyrifera (MPF and DP-MPF) may also modulate oxidative stress. This study investigated the impact of fucoidan extracts, MPF and DP-MPF in a dextran sodium sulphate (DSS)-induced mouse model of acute colitis. 3% DSS was administered in C57BL/6J male mice over a period of 7 days, and MPF and DP-MPF were co-administered orally at a dose of 400 mg/kg body weight. Our results indicated that MPF and DP-MPF significantly prevented body weight loss, improved the disease activity index (DAI), restored colon lengths, reduced the wet colon weight, reduced spleen enlargement, and improved the overall histopathological score. Consistent with the reported anti-inflammatory functions, fucoidan extracts, MPF and DP-MPF significantly reduced the colonic levels of myeloperoxidase (MPO), nitric oxide (NO), malondialdehyde (MDA) and increased the levels of antioxidant enzymes, superoxide dismutase (SOD) and catalase (CAT). In addition, MPF and DP-MPF significantly inhibited levels of pro-inflammatory cytokines in colon-derived tissues. Collectively, our results indicate that MPF and DP-MPF exhibited anti-inflammatory and antioxidant effects representing a promising therapeutic strategy for the cure of IBD.

Effect of Passage Number of Conditioned Medium Collected from Equine Amniotic Fluid Mesenchymal Stem Cells: Porcine Oocyte Maturation and Embryo Development.

Oocyte in vitro maturation (IVM) is the most important first step in in vitro embryo production. One prerequisite for the success of IVM in oocytes is to provide a rich culture microenvironment that meets the nutritional needs of developing oocytes. We applied different equine amniotic fluid mesenchymal stem cell conditioned medium (eAFMSC-CM) from passages 7, 18, and 27 to porcine oocytes during IVM to determine its effects on oocyte development and subsequent embryo development, specifically. The eAFMSC-CM from passage 7 (eAFMSC-CMp7) has a considerable impact on 9 genes: BAX, BCL2, SOD2, NRF2, TNFAIP6, PTGS2, HAS2, Cx37, and Cx43, which are associated with cumulus cell mediated oocyte maturation. GSH levels and distribution of mitochondrial and cortical granules were significantly increased in oocytes incubated with eAFMSC-CMp7. In addition, catalase and superoxide dismutase activities were high after IVM 44 h with eAFMSC-CMp7. After in vitro fertilization, blastocyst quality was significantly increased in the eAFMSC-CMp7 group compared to control. Lastly, the antioxidant effect of eAFMSC-CMp7 substantially regulated the expression of apoptosis, pluripotency related genes and decreased autophagy activity in blastocysts. Taken together, this study demonstrated that the eAFMSC-CMp7 enhanced the cytoplasmic maturation of oocytes and subsequent embryonic development by generating high antioxidant activity.

Prevalence of latent tuberculosis infection among participants of the national LTBI screening program in South Korea - A problem of low coverage rate with current LTBI strategy.

Background: The Government of South Korea launched a national preemptive latent tuberculosis infection (LTBI) screening program in 2016, including more than 1. 6 million population in congregate settings. The objective of this study was to analyze LTBI prevalence and its risk factors in each setting. Additionally, the proportion of LTBI pool covered by the current national LTBI strategy was investigated. Methods: Database for results of interferon gamma release assay (IGRA), X-ray, and baseline demographic information was linked with National Health Information Database, national tuberculosis (TB) surveillance database, and national contact investigation database. Participants were categorized into three groups: Group A, workers of postpartum care centers, social welfare facilities and educational institutions; Group B, first year students in high school and out-of-school youths; and Group C, inmates of correctional facilities. Relative risks of LTBI by sex, age, place of living, income level, and comorbidities were calculated. Results: A total of 444,394 participants in Group A, 272,224 participants in Group B, and 11,511 participants in Group C who participated in the national LTBI screening program between 2017 and 2018 were included, with LTBI prevalence of 20.7, 2.0, and 33.2%, respectively. Age was the single most important risk factor in Group A and Group C. Low-income level was another risk factor commonly identified in all groups. Among participants with positive IGRA results, 2.7, 4.4, and 3.3% in Groups A, B and C, respectively, had past TB exposure history since 2013. Current LTBI guideline targeting high or moderate TB risk disease covered 6.5, 0.6, and 1.1% of participants with positive IGRA results in Groups A, B and C, respectively. Conclusion: Only a small proportion of participants with positive IGRA results could be covered by the current LTBI strategy. Expansion of LTBI strategy by identifying further high-TB risk group in the general population is required.

Pathway Analysis of Fucoidan Activity Using a Yeast Gene Deletion Library Screen.

Fucoidan, the sulfated fucose-rich polysaccharide derived from brown macroalgae, was reported to display some anti-cancer effects in in vitro and in vivo models that included apoptosis and cell cycle arrest. The proposed mechanisms of action involve enhanced immune surveillance and direct pro-apoptotic effects via the activation of cell signaling pathways that remain largely uncharacterized. This study aimed to identify cellular pathways influenced by fucoidan using an unbiased genetic approach to generate additional insights into the anti-cancer effects of fucoidan. Drug⁻gene interactions of Undaria pinnatifida fucoidan were assessed by a systematic screen of the entire set of 4,733 halpoid Saccharomyces cerevsiae gene deletion strains. Some of the findings were confirmed using cell cycle analysis and DNA damage detection in non-immortalized human dermal fibroblasts and colon cancer cells. The yeast deletion library screen and subsequent pathway and interactome analysis identified global effects of fucoidan on a wide range of eukaryotic cellular processes, including RNA metabolism, protein synthesis, sorting, targeting and transport, carbohydrate metabolism, mitochondrial maintenance, cell cycle regulation, and DNA damage repair-related pathways. Fucoidan also reduced clonogenic survival, induced DNA damage and G1-arrest in colon cancer cells, while these effects were not observed in non-immortalized human fibroblasts. Our results demonstrate global effects of fucoidan in diverse cellular processes in eukaryotic cells and further our understanding about the inhibitory effect of Undaria pinnatifida fucoidan on the growth of human cancer cells.

Structure-based design of inhibitors of the aspartic protease endothiapepsin by exploiting dynamic combinatorial chemistry.

Structure-based design (SBD) can be used for the design and/or optimization of new inhibitors for a biological target. Whereas de novo SBD is rarely used, most reports on SBD are dealing with the optimization of an initial hit. Dynamic combinatorial chemistry (DCC) has emerged as a powerful strategy to identify bioactive ligands given that it enables the target to direct the synthesis of its strongest binder. We have designed a library of potential inhibitors (acylhydrazones) generated from five aldehydes and five hydrazides and used DCC to identify the best binder(s). After addition of the aspartic protease endothiapepsin, we characterized the protein-bound library member(s) by saturation-transfer difference NMR spectroscopy. Cocrystallization experiments validated the predicted binding mode of the two most potent inhibitors, thus demonstrating that the combination of de novo SBD and DCC constitutes an efficient starting point for hit identification and optimization.

Synthesis of enantiomerically pure D- and L-bicyclo[3.1.0]hexenyl carbanucleosides and their antiviral evaluation.

Based upon the fact that L-nucleosides have been generally known to be less cytotoxic than D-counterparts, L-bicyclo[3.1.0]hexenyl carbanucleoside derivatives with a fixed north conformation were designed and synthesized by employing a novel synthetic strategy starting from (R)-epichlorohydrin in order to search for new anti-HIV agents with high potency and less cytotoxicity. A tandem alkylation, γ-lactonization, a chemoselective reduction of ester in the presence of γ-lactone functional group, a RCM reaction, and a Mitsunobu coupling reaction were used as key reactions. D-Counterpart nucleosides were also prepared according to the same synthetic method. Among the synthesized carbanucleosides, D-thymine nucleoside, D-2 and L-thymine nucleoside, L-2 exhibited excellent anti-HIV-1 and -2 activities, in MT-4 cells, which were higher than those of ddI, an anti-AIDS drug. Whereas D-2 exhibited high cytotoxicity in MT-4 cell lines, L-2 did not show any discernible cytotoxicity in all cell lines tested, reflecting that L-2 may be a good candidate for an anti-AIDS drug. L-2 also showed weak anti-HSV-2 activity without cytotoxicity. However, none of the synthesized nucleosides exhibited antiviral activities against RNA viruses including coxsakie, influenza, corona and polio viruses, maybe due to their 2',3'-dideoxy structure. Potent antiviral effects of D-2 and L-2 indicate that nucleosides belonging to a class of D4Ns can be an excellent candidate for anti-DNA virus agents. This research strongly supports L-nucleosides of a class of D4Ns to be a very promising candidate for antiviral agents due to its low cytotoxicity and a good antiviral activity.

Efficient and practical synthesis of L-hamamelose.

An efficient synthetic route of L-hamamelose was successfully accomplished starting from D-ribose. L-Hamamelose was synthesized in 42% overall yield with six reaction steps via a stereoselective Grignard reaction, a stereoselective crossed aldol reaction and a controlled oxidative cleavage of the double bond of a vinyl diol compound. During the oxidative cleavage of the double bond of the vinyl diol compound with osmium tetroxide and NaIO(4), an over-oxidative cleavage of alpha-hydroxyl aldehyde generated from ring opening of the first cleaved product, formyl lactol, did not occur, probably due to the stability of the lactol form. A plausible mechanism for the stereoselective crossed aldol reaction was suggested. The final target compound, L-hamamelose can play a very important role as a chiral building block in synthesizing a wide variety of enantiopure compounds.

Synthesis of pyrimidine analog of fluoroneplanocin A as potential anti-HCV agent.

N-hydroxycytosine nucleoside 3 was synthesized as potential anti-HCV agent, starting from D-ribose using an iodine-fluorine exchange reaction by a help of BuLi, a RCM reaction, a stereoselective reduction and a Mitsunobu reaction as the key steps.

Synthesis of novel cyclopropyl nucleoside analogues as potential antiherpetic agent.

Synthesis of novel cyclopropyl pyrimidine and purine nucleoside derivatives was successfully achieved using one pot reactions including an alkylation, an oxirane-ring opening reaction and a lactonization and a hydroboration-oxidation as the key steps in order to find new antiherpetic agent.

Synthesis and antiviral evaluation of conformationally fixed bicyclohexanyl nucleosides with ethenyl group at C3'-position.

Conformationally fixed bicyclo[3.1.0]hexanyl nucleosides 1 and 2 with C3'-ethenyl group were successfully synthesized and evaluated against various viruses. Carbenoid intramolecular cycloaddition and diastereoselective Grignard reaction were employed as the key reaction steps.

Synthesis and biological evaluation of 5''-iodoneplanocin A and its analogues.

5''-Iodoneplanocin A was enantiopurely synthesized as potential antiviral and antitumor agents starting from D-ribose using an addition-iodination-elimination reaction, a RCM reaction and an oxidative rearrangement.

Asymmetric synthesis and biological activity of L-bicyclocarba-d4T.

Novel L-bicyclocarba-d4T (1), an enantiomer of D-N-MCd4T has been enantiopurely synthesized as a potent anti-HIV agent starting from (R)-epichlorohydrin using tandem alkylation, chemoselective reduction of ester in the presence of lactone functional group, Grignard reaction, RCM reaction, and Mitsunobu reaction as key steps. L-N-MCd4T (1) was found to be very potent anti-HIV-1 (EC(50) = 6.76 microg/mL) agent with no cytotoxicity.

Design, enantiopure synthesis, and biological evaluation of novel iso-D-2',3'-dideoxy-3'-fluorothianucleoside derivatives as a bioisostere of lamivudine.

Novel iso D-2',3'-dideoxythianucleoside derivatives 1-3 were designed and asymmetrically synthesized to search for new anti-HIV agents. Final compounds 1-3 were evaluated against a variety of viruses including HIV-1 and 2. Only cytosine analog 3 showed a potent anti-VSV activity (EC(50) = 9.43 microg/mL). This result implies that iso 2',3'-dideoxy sugar templates might play a role of a sugar surrogate of nucleosides for the development of anti-RNA virus agent.

Asymmetric synthesis of apio fluoroneplanocin A analogs as potential AdoHcy hydrolase inhibitor.

Apio fluoroneplanocin A (apio F-NPA, 3) and its uracil analogue 4 have been designed and asymmetrically synthesized starting from D-ribose. Introduction of fluoro group into vinylic position of 5 was accomplished successfully over 5 steps employing key reactions such as iodination according to an addition-elimination reaction mechanism, stereo- and regioselective reduction of alpha,beta-unsaturated ketone, and electrophilic fluorination. This methodology can be adapted to the synthesis of fluoro compounds extensively.

Synthesis of enantiopure pseudo-L-vinylcyclopropyl nucleosides bearing quaternary carbon as potential anti-herpesvirus agent.

Pseudo-L-vinylcyclopropyl adenine and guanine nucleosides 11 and 12 were designed and enantiopurely synthesized starting from (S)-epichlorohydrin using tandem alkylation, regioselective oxirane-ring opening, and chemoselective reduction as key steps.

Asymmetric synthesis of novel pseudo-D-vinylcyclopropyl nucleosides bearing quaternary carbon as potential anti-herpesvirus agent.

Pseudo-D-vinylcyclopropyl nucleosides 10-12 bearing a quaternary carbon were designed and synthesized starting from (R)-epichlorohydrin using a tandem reaction of double alkylation and lactonization via oxirane-ring opening reaction, a Wittig reaction, and chemoselective reduction as potential anti-herpesvirus agent.

Design, synthesis, and biological evaluation of novel iso-D-2',3'-dideoxy-3'-fluorothianucleoside derivatives.

Novel iso-d-2',3'-dideoxythianucleoside derivatives 1-4 were designed and asymmetrically synthesized as a bioisostere of lamivudine to search for new anti-HIV agents. The information about using sulfur participation occurred on DAST fluorination and Mitsunobu reaction will be of great help in synthesizing sulfur-containing compounds. Final compounds 1-4 were evaluated against HIV-1 and 2, HSV-1 and 2, EMCV, Cox. B3, VSV, FluA (Taiwan), FluA (Johan.), FCV, and FIP. Only cytosine analogue 3 showed a potent anti-VSV activity (EC(50)=9.43microg/mL). This result implies that iso-2',3'-dideoxy sugar templates might play a role of a sugar surrogate of nucleosides for the development of anti-RNA virus agent.