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Background/Aims: Although pharmacist intervention for patients with chronic diseases has been shown to improve medication adherence, few studies have evaluated its effects on the objective clinical outcomes. We investigated the impact of pharmacist intervention on medication adherence and clinical outcomes in patients with ulcerative colitis (UC). Methods: Patients with UC and low medication adherence were divided into two groups, based on pharmacist intervention. Their medication possession ratio and nonadherence rate for 6 months before and after the baseline were investigated. The partial Mayo score, flare-up incidence, and factors influencing flare-up events for 1 year after the baseline were analyzed. Results: Of 99 patients, 33 and 66 were included in the intervention and control groups, respectively. The nonadherence rate significantly declined in the intervention group 6 months after the baseline (60.6% before vs 30.3% after; p=0.013). The groups showed a significant difference regarding time-related partial Mayo scores (p=0.002). Intervention was significantly negatively correlated with time and the partial Mayo score (r2=0.035, p=0.013). A significant difference was observed in the flare-up incidence (33.3% in the intervention group vs 54.6% in the control group; p=0.046). Multivariate logistic regression indicated that pharmacist intervention (adjusted odds ratio, 0.370; 95% confidence interval, 0.145 to 0.945; p=0.038) independently reduced the flareup risk. Conclusions: Pharmacist intervention significantly decreased the nonadherence rate, improved the partial Mayo score, and reduced the flare-up incidence compared with the control group in a cohort of UC patients identified to have low medication adherence.

Antibiotic-induced dysbiosis may affect the efficacy of immune checkpoint inhibitors. We investigated the impact of antibiotics on the clinical outcomes of nivolumab in patients with non-small cell lung cancer (NSCLC). Patients who received nivolumab for NSCLC between July 2015 and June 2018 and who were followed up until June 2020 were included in a retrospective cohort analysis. Of 140 eligible patients, 70 were on antibiotics. Overall survival (OS) was shorter in patients on antibiotics (ABX) compared to those not on antibiotics (NoABX) (p = 0.014). OS was negatively associated with piperacillin/tazobactam (PTZ) (HR = 3.31, 95% CI: 1.77–6.18), days of therapy (DOT) ≥ 2 weeks (HR = 2.56, 95% CI: 1.30–5.22) and DOT of PTZ. The defined daily dose (DDD) in PTZ (r = 0.27) and glycopeptides (r = 0.21) showed weak correlations with mortality. There was no difference in progression-free survival (PFS) between ABX and NoABX; however, PFS was negatively associated with the antibiotic class PTZ and DOT of PTZ. Therefore, the use of a broad-spectrum antibiotic, such as PTZ, the long-term use of antibiotics more than 2 weeks in total and the large amount of defined daily dose of specific antibiotics were associated with decreased survival in patients receiving nivolumab for NSCLC.

BACKGROUND:Nephrotoxicity of intravenous (IV) colistin has impeded its clinical use; aerosolized (AS) colistin may be an alternative, but safety data are lacking. Therefore, this study aimed to evaluate the incidence of acute kidney injury (AKI) and risk factors associated with IV and AS colistin administration. METHODS:A retrospective study was performed in a tertiary referral hospital. Data were collected before and after colistin administration between October 2012 and April 2016. Exclusion criteria were as follows: age less than 18 years, previous colistin administration, concurrent use of IV and AS colistin, dialysis before colistin use, and colistin use for less than 3 days. We compared AKI incidence following administration of IV versus AS colistin and analyzed risk factors for colistin-associated nephrotoxicity. RESULTS:A total of 464 patients were enrolled (n = 311, IV group; n = 153, AS group). Incidence of AKI was significantly higher in the IV group (IV vs AS, 20.26% vs 7.84%, p-value < 0.001). Duration of colistin use (OR 1.033, 95% CI 1.009-1.058, p-value 0.008) and presence of chronic kidney disease (OR 2.710, 95% CI 1.348-5.448, p-value 0.005) were associated with nephrotoxicity. There were no significant risk factors associated with AS colistin. CONCLUSIONS:Although AS colistin was not associated with any significant risk factors for nephrotoxicity, duration of colistin use and baseline kidney function may affect AS colistin-associated nephrotoxicity.

Summary: Live imaging of regenerative processes can reveal how animals restore their bodies after injury through a cascade of dynamic cellular events. Here, we present a comprehensive toolkit for live imaging of tissue regeneration in the flatworm Macrostomum lignano, including a high-throughput cloning pipeline, targeted cellular ablation, and advanced microscopy solutions. Using tissue-specific reporter expression, we examine how various structures regenerate. Enabled by a custom luminescence/fluorescence microscope, we overcome intense stress-induced autofluorescence to demonstrate genetic cellular ablation and reveal the limited regenerative capacity of neurons and their essential role during wound healing, contrasting muscle cells’ rapid regeneration after ablation. Finally, we build an open-source tracking microscope to continuously image freely moving animals throughout the week-long process of regeneration, quantifying kinetics of wound healing, nerve cord repair, body regeneration, growth, and behavioral recovery. Our findings suggest that nerve cord reconnection is highly robust and proceeds independently of regeneration.

Abstract Animal regeneration involves coordinated responses across cell types throughout the animal body. In endosymbiotic animals, whether and how symbionts react to host injury and how cellular responses are integrated across species remain unexplored. Here, we study the acoel Convolutriloba longifissura, which hosts symbiotic Tetraselmis sp. green algae and can regenerate entire bodies from tissue fragments. We show that animal injury causes a decline in the photosynthetic efficiency of the symbiotic algae, alongside two distinct, sequential waves of transcriptional responses in acoel and algal cells. The initial algal response is characterized by the upregulation of a cohort of photosynthesis-related genes, though photosynthesis is not necessary for regeneration. A conserved animal transcription factor, runt, is induced after injury and required for acoel regeneration. Knockdown of Cl-runt dampens transcriptional responses in both species and further reduces algal photosynthetic efficiency post-injury. Our results suggest that the holobiont functions as an integrated unit of biological organization by coordinating molecular networks across species through the runt-dependent animal regeneration program.

Abstract Background The success of cephalometric analysis depends on the accurate detection of cephalometric landmarks on scanned lateral cephalograms. However, manual cephalometric analysis is time-consuming and can cause inter- and intra-observer variability. The purpose of this study was to automatically detect cephalometric landmarks on scanned lateral cephalograms with low contrast and resolution using an attention-based stacked regression network (Ceph-Net). Methods The main body of Ceph-Net compromised stacked fully convolutional networks (FCN) which progressively refined the detection of cephalometric landmarks on each FCN. By embedding dual attention and multi-path convolution modules in Ceph-Net, the network learned local and global context and semantic relationships between cephalometric landmarks. Additionally, the intermediate deep supervision in each FCN further boosted the training stability and the detection performance of cephalometric landmarks. Results Ceph-Net showed a superior detection performance in mean radial error and successful detection rate, including accuracy improvements in cephalometric landmark detection located in low-contrast soft tissues compared with other detection networks. Moreover, Ceph-Net presented superior detection performance on the test dataset split by age from 8 to 16 years old. Conclusions Ceph-Net demonstrated an automatic and superior detection of cephalometric landmarks by successfully learning local and global context and semantic relationships between cephalometric landmarks in scanned lateral cephalograms with low contrast and resolutions.

Abstract Background Among interdental cleaning aids (ICAs), interdental brushes (IDBs) are in the spotlight because they can effectively remove plaque from interdental surfaces. Guidance on the correct use of ICAs, such as IDBs, is required to prevent dental plaque accumulation. Since it is impossible to confirm the interdental proximal surface unless extracted, it is difficult to conduct quantitative experiments. This study presented an efficient way to evaluate IDBs by realizing dental structures and embrasures using a Dental computer-aided design (CAD) software and a 3D printer. Methods Two different sizes of embrasure (0.7 and 1.2 mm) crown models were prepared with CAD software and a 3D printer. To evaluate the cleaning efficacy of IDBs of each size (0.6, 0.7, 0.8, 1.0, 1.2, and 1.5 mm diameters), the 9th cycle of brush move was performed where artificial plaque was spread and a digital camera was used to record the process. The pixels and percentage of cleaning from the recorded digital images were analyzed. Results The plateau was formed after the 5th brushing cycle under all conditions—after the 5th cycle, the cleaning efficacy of the two crown models was 69.3–86.4% and 49.8–75.4%. In these results, the optimal diameters for the IDB were 1.2 and 1.5 mm for embrasure sizes of 0.7 and 1.2 mm, respectively. Moreover, the cleaning efficacy was the highest at 86.4% and 75.4% after the 9th cycle. Conclusions The 3D-printed model base for the human oral embrasure structure is an adequate model to test artificial plaque removal using IDB. The use of IDBs for more than five cycles does not support the conventional idea that a greater number of IDB brushing moves is more effective in a statistically substantial manner.