Muramyl dipeptide alleviates estrogen deficiency-induced osteoporosis through canonical Wnt signaling.

Wnt signaling is a positive regulator of bone formation through the induction of osteoblast differentiation and down-regulation of osteoclast differentiation. We previously reported that muramyl dipeptide (MDP) increases bone volume by increasing osteoblast activity and attenuating osteoclast activity in receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoporotic model mice. In this study, we investigated whether MDP could alleviate post-menopausal osteoporosis through Wnt signaling regulation in an ovariectomy (OVX)-induced mouse osteoporosis model. MDP-administered OVX mice exhibited higher bone volume and bone mineral density than mice of the control group. MDP significantly increased P1NP in the serum of OVX mice, implying increased bone formation. The expression of pGSK3ß and ß-catenin in the distal femur of OVX mice was lower than that in the distal femur of sham-operated mice. Yet, the expression of pGSK3ß and ß-catenin was increased in MDP-administered OVX mice compared with OVX mice. In addition, MDP increased the expression and transcriptional activity of ß-catenin in osteoblasts. MDP inhibited the proteasomal degradation of ß-catenin via the down-regulation of its ubiquitination by GSK3ß inactivation. When osteoblasts were pretreated with Wnt signaling inhibitors, DKK1 or IWP-2, the induction of pAKT, pGSK3ß, and ß-catenin was not observed. In addition, nucleotide oligomerization domain-containing protein 2-deficient osteoblasts were not sensitive to MDP. MDP-administered OVX mice exhibited fewer tartrate-resistant acid phosphatase (TRAP)-positive cells than did OVX mice, attributed to a decrease in the RANKL/OPG ratio. In conclusion, MDP alleviates estrogen deficiency-induced osteoporosis through canonical Wnt signaling and could be an effective therapeutic for the treatment of post-menopausal bone loss. © 2023 The Pathological Society of Great Britain and Ireland.

Lipoteichoic acid inhibits osteoclast differentiation and bone resorption via interruption of gelsolin-actin dissociation.

Bone resorption can be caused by excessive differentiation and/or activation of bone-resorbing osteoclasts. While microbe-associated molecular patterns can influence the differentiation and activation of bone cells, little is known about the role of lipoteichoic acid (LTA), a major cell wall component of Gram-positive bacteria, in the regulation of bone metabolism. In this study, we investigated the effect of LTA on bone metabolism using wild-type Staphylococcus aureus and the LTA-deficient mutant strain. LTA-deficient S. aureus induced higher bone loss and osteoclast differentiation than wild-type S. aureus. LTA isolated from S. aureus (SaLTA) inhibited osteoclast differentiation from committed osteoclast precursors in the presence of various osteoclastogenic factors by downregulating the expression of NFATc1. Remarkably, SaLTA attenuated the osteoclast differentiation from committed osteoclast precursors of TLR2-/- or MyD88-/- mice and from the committed osteoclast precursors transfected with paired immunoglobulin-like receptor B-targeting siRNA. SaLTA directly interacted with gelsolin, interrupting the gelsolin-actin dissociation which is a critical process for osteoclastogenesis. Moreover, SaLTA suppressed the mRNA expression of dendritic cell-specific transmembrane protein, ATPase H+ transporting V0 subunit D2, and Integrin, which encode proteins involved in cell-cell fusion of osteoclasts. Notably, LTAs purified from probiotics, including Bacillus subtilis, Enterococcus faecalis, and Lactobacillus species, also suppressed Pam2CSK4- or RANKL-induced osteoclast differentiation. Taken together, these results suggest that LTAs have anti-resorptive activity through the inhibition of osteoclastogenesis by interfering with the gelsolin-actin dissociation and may be used as effective therapeutic agents for the prevention or treatment of inflammatory bone diseases.

Gut microbiota composition and metabolite profiling in smokers: a comparative study between emphysema and asymptomatic individuals with therapeutic implications.

BACKGROUND: Diet has a crucial role in the gut microbiota, and dysbiosis in the gut and lungs has been suggested to be associated with chronic obstructive pulmonary disease. We compared the diet, microbiome and metabolome between asymptomatic smokers and those with emphysema. METHODS: We enrolled 10 asymptomatic smokers with preserved lung function and 16 smokers with emphysema with severe airflow limitation. Dietary intake information was gathered by a self-reported questionnaire. Sputum and faecal samples were collected for microbial and metabolomics analysis. A murine model of emphysema was used to determine the effect of metabolite supplementation. RESULTS: Despite having a similar smoking history with emphysema patients, asymptomatic smokers had higher values of body mass index, fibre intake and faecal acetate level. Linear discriminant analysis identified 17 microbial taxonomic members that were relatively enriched in the faeces of asymptomatic smokers. Analysis of similarity results showed dissimilarity between the two groups (r=0.287, p=0.003). Higher acetate level was positively associated with forced expiratory volume in one second in the emphysema group (r=0.628, p=0.012). Asymptomatic smokers had a greater number of species associated with acetate and propionate (r>0.6) than did those with emphysema (30 vs 19). In an emphysema mouse model, supplementation of acetate and propionate reduced alveolar destruction and the production of proinflammatory cytokines, and propionate decreased the CD3+CD4+IL-17+ T-cell population in the lung and spleen. CONCLUSION: Smokers with emphysema showed differences in diet, microbiome and short-chain fatty acids compared with asymptomatic smokers. Acetate and propionate showed therapeutic effects in a smoking-induced murine model of emphysema.

Establishment of multicenter COVID-19 therapeutics preclinical test system in Republic of Korea.

Throughout the recent COVID-19 pandemic, South Korea led national efforts to develop vaccines and therapeutics for SARS-CoV-2. The project proceeded as follows: 1) evaluation system setup (including Animal Biosafety Level 3 (ABSL3) facility alliance, standardized nonclinical evaluation protocol, and laboratory information management system), 2) application (including committee review and selection), and 3) evaluation (including expert judgment and reporting). After receiving 101 applications, the selection committee reviewed pharmacokinetics, toxicity, and efficacy data and selected 32 final candidates. In the nonclinical efficacy test, we used golden Syrian hamsters and human angiotensin-converting enzyme 2 transgenic mice under a cytokeratin 18 promoter to evaluate mortality, clinical signs, body weight, viral titer, neutralizing antibody presence, and histopathology. These data indicated eight new drugs and one repositioned drug having significant efficacy for COVID-19. Three vaccine and four antiviral drugs exerted significant protective activities against SARS-CoV-2 pathogenesis. Additionally, two anti-inflammatory drugs showed therapeutic effects on lung lesions and weight loss through their mechanism of action but did not affect viral replication. Along with systematic verification of COVID-19 animal models through large-scale studies, our findings suggest that ABSL3 multicenter alliance and nonclinical evaluation protocol standardization can promote reliable efficacy testing against COVID-19, thus expediting medical product development.

Classification of Breathing Signals According to Human Motions by Combining 1D Convolutional Neural Network and Embroidered Textile Sensor.

Research on healthcare and body monitoring has increased in recent years, with respiratory data being one of the most important factors. Respiratory measurements can help prevent diseases and recognize movements. Therefore, in this study, we measured respiratory data using a capacitance-based sensor garment with conductive electrodes. To determine the most stable measurement frequency, we conducted experiments using a porous Eco-flex and selected 45 kHz as the most stable frequency. Next, we trained a 1D convolutional neural network (CNN) model, which is a type of deep learning model, to classify the respiratory data according to four movements (standing, walking, fast walking, and running) using one input. The final test accuracy for classification was >95%. Therefore, the sensor garment developed in this study can measure respiratory data for four movements and classify them using deep learning, making it a versatile wearable in the form of a textile. We expect that this method will advance in various healthcare fields.

Laparoscopic Extraperitoneal Approach for Lateral Pelvic Node Dissection in Rectal Cancer: Techniques and Short-Term Outcomes.

BACKGROUND: Lateral pelvic lymph node dissection has been performed selectively in rectal cancer cases; however, it involves highly skilled techniques because of the complex adjacent anatomical structures. MATERIALS AND METHODS: Laparoscopic EP-LPND was performed in Korea University Anam Hospital from June 2018, and short-term surgical outcomes were analyzed from June to December 2018. Among the patients with histologically diagnosed rectal adenocarcinoma, patients who were suspected Lateral pelvic lymph node metastasis at magnetic resonance imaging were selected for this procedure. RESULTS: Seven patients underwent laparoscopic extraperitoneal approach for lateral pelvic lymph node dissection in the study period. The mean number of retrieved lymph node was 4.57, and metastatic lymph nodes were identified in 3 patients (42.8%). All of the lymph nodes with suspected metastasis preoperatively were removed in postoperative images. There was no immediate postoperative complication beyond the moderate grade associated with lateral pelvic lymph node dissection. The median follow-up was 9 months, and there were no local recurrence nor complications related to sexual and voiding functions. CONCLUSIONS: The laparoscopic extraperitoneal approach might be an efficient way to perform lateral pelvic lymph node dissection using the same principles as the conventional method without violation of the peritoneum.

Midline incision vs. transverse incision for specimen extraction is not a significant risk factor for developing incisional hernia after minimally invasive colorectal surgery: multivariable analysis of a large cohort from a single tertiary center in Korea.

BACKGROUND: Incisional hernia (IH) is a commonly encountered problem even in the era of minimally invasive surgery (MIS). Numerous studies on IH are available in English literature, but there are lack of data from the Eastern part of the world. This study aimed to evaluate the risk factors as well as incidence of IH by analyzing a large cohort collected from a single tertiary center in Korea. METHODS: Among a total number of 4276 colorectal cancer patients who underwent a surgical resection from 2006 to 2019 in Korea University Anam Hospital, 2704 patients (2200 laparoscopic and 504 robotic) who met the inclusion criteria were analyzed. IH was confirmed by each patient's diagnosis code registered in the hospital databank based on physical examination and/or computed tomography findings. Clinical data including specimen extraction incision (transverse or vertical midline) were compared between IH group and no IH group. Risk factors of developing IH were assessed by utilizing univariable and multivariable analyses. RESULTS: During the median follow-up of 41 months, 73 patients (2.7%) developed IH. Midline incision group (n = 1472) had a higher incidence of IH than that of transverse incision group (n = 1232) (3.5% vs. 1.7%, p = 0.003). The univariable analysis revealed that the risk factors of developing IH were old age, female gender, obesity, co-morbid cardiovascular disease, transverse incision for specimen extraction, and perioperative bleeding requiring transfusion. However, on multivariable analysis, specimen extraction site was not significant in developing IH and transfusion requirement was the strongest risk factor. CONCLUSIONS: IH development after MIS is uncommon in Korean patients. Multivariable analysis suggests that specimen extraction site can be flexibly chosen between midline and transverse incisions, with little concern about risk of developing IH. Careful efforts are required to minimize operative bleeding because blood transfusion is a strong risk factor for developing IH.

Dynamic molecular conformational change leading to energy transfer in F8-5% BSP copolymer revealed by single-molecule spectroscopy.

Polyfluorene-based copolymers such as poly(9,9-dioctylfluorene)-alt-5% [bis-N,N'-(4-butylphenyl)-bis-N,N'-phenyl-1,4-phenylenediamine] (F8-5% BSP) are efficient blue-emitting polymers with various electronic phases: F8 blue-emitting glassy phase, F8 ordered more red-emitting ß-phase, and F8/BSP charge transfer (CT) state. Polymer light-emitting device performance and color purity can be significantly improved by forming ß-phase segments. However, the role of the ß-phase on energy transfer (ET) among glassy F8, ß-phase, and F8/BSP CT state is unclear. Herein, we identify dynamic molecular conformation-controlled ET from locally excited states to either the CT state or ß-phase in light-emitting copolymers. By conducting single-molecule spectroscopy for single F8-5% BSP chains, we find inefficient intra-chain ET from glassy segments to the CT state, while efficient ET from the glassy to the ß-phase. Spontaneous and reversible CT on-off emission is observed both in the presence and absence of the ß-phase. The density functional theory calculations reveal the origin of the on-chain CT state and indicate this CT emission on-off switching behavior could be related to molecule torsional motion between BSP and F8 units. The population of the CT state by ET can be increased via through-space interaction between the F8 block and the BSP unit on a self-folded chain. Temperature-dependent single-molecule spectroscopy confirms such interaction showing a gradual increase in intensity of the CT emission with the temperature. Based on these observations, we propose the dynamic molecular motion-induced conformation change as the origin of the glassy-to-CT ET, and thermal energy may provide the activation for such a change to enhance the ET from glassy or ß-phases to the CT state.

Ultrasensitive Strain Sensor Based on Pre-Generated Crack Networks Using Ag Nanoparticles/Single-Walled Carbon Nanotube (SWCNT) Hybrid Fillers and a Polyester Woven Elastic Band.

Flexible strain sensors are receiving a great deal of interest owing to their prospective applications in monitoring various human activities. Among various efforts to enhance the sensitivity of strain sensors, pre-crack generation has been well explored for elastic polymers but rarely on textile substrates. Herein, a highly sensitive textile-based strain sensor was fabricated via a dip-coat-stretch approach: a polyester woven elastic band was dipped into ink containing single-walled carbon nanotubes coated with silver paste and pre-stretched to generate prebuilt cracks on the surface. Our sensor demonstrated outstanding sensitivity (a gauge factor of up to 3550 within a strain range of 1.5-5%), high stability and durability, and low hysteresis. The high performance of this sensor is attributable to the excellent elasticity and woven structure of the fabric substrate, effectively generating and propagating the prebuilt cracks. The strain sensor integrated into firefighting gloves detected detailed finger angles and cyclic finger motions, demonstrating its capability for subtle human motion monitoring. It is also noteworthy that this novel strategy is a very quick, straightforward, and scalable method of fabricating strain sensors, which is extremely beneficial for practical applications.

One-Step Sixfold Cyanation of Benzothiadiazole Acceptor Units for Air-Stable High-Performance n-Type Organic Field-Effect Transistors.

Reported here is a new high electron affinity acceptor end group for organic semiconductors, 2,1,3-benzothiadiazole-4,5,6-tricarbonitrile (TCNBT). An n-type organic semiconductor with an indacenodithiophene (IDT) core and TCNBT end groups was synthesized by a sixfold nucleophilic substitution with cyanide on a fluorinated precursor, itself prepared by a direct arylation approach. This one-step chemical modification significantly impacted the molecular properties: the fluorinated precursor, TFBT IDT, a poor ambipolar semiconductor, was converted into TCNBT IDT, a good n-type semiconductor. The electron-deficient end group TCNBT dramatically decreased the energy of the highest occupied and lowest unoccupied molecular orbitals (HOMO/LUMO) compared to the fluorinated analogue and improved the molecular orientation when utilized in n-type organic field-effect transistors (OFETs). Solution-processed OFETs based on TCNBT IDT exhibited a charge-carrier mobility of up to µe ≈0.15 cm2 V-1 s-1 with excellent ambient stability for 100 hours, highlighting the benefits of the cyanated end group and the synthetic approach.

Prospective study of oncologic outcomes after laparoscopic modified complete mesocolic excision for non-metastatic right colon cancer (PIONEER study): study protocol of a multicentre single-arm trial.

BACKGROUND: The introduction of complete mesocolic excision (CME) with central vascular ligation (CVL) for right-sided colon cancer has improved the oncologic outcomes. Recently, we have introduced a modified CME (mCME) procedure that keeps the same principles as the originally described CME but with a more tailored approach. Some retrospective studies have reported the favourable oncologic outcomes of laparoscopic mCME for right-sided colon cancer; however, no prospective multicentre study has yet been conducted. METHODS: This study is a multi-institutional, prospective, single-arm study evaluating the oncologic outcomes of laparoscopic mCME for adenocarcinoma arising from the right side of the colon. A total of 250 patients will be recruited from five tertiary referral centres in South Korea. The primary outcome of this study is 3-year disease-free survival. Secondary outcome measures include 3-year overall survival, incidence of surgical complications, completeness of mCME, and distribution of metastatic lymph nodes. The quality of laparoscopic mCME will be assessed on the basis of photographs of the surgical specimen and the operation field after the completion of lymph node dissection. DISCUSSION: This is a prospective multicentre study to evaluate the oncologic outcomes of laparoscopic mCME for right-sided colon cancer. To the best of our knowledge, this will be the first study to prospectively and objectively assess the quality of laparoscopic mCME. The results will provide more evidence about oncologic outcomes with respect to the quality of laparoscopic mCME in right-sided colon cancer. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03992599 (June 20, 2019). The posted information will be updated as needed to reflect protocol amendments and study progress.

A highly sensitive molecular structural probe applied to in situ biosensing of metabolites using PEDOT:PSS.

A large amount of research within organic biosensors is dominated by organic electrochemical transistors (OECTs) that use conducting polymers such as poly(3,4-ethylene dioxythiophene) doped with poly(styrenesulfonate) (PEDOT:PSS). Despite the recent advances in OECT-based biosensors, the sensing is solely reliant on the amperometric detection of the bioanalytes. This is typically accompanied by large undesirable parasitic electrical signals from the electroactive components in the electrolyte. Herein, we present the use of in situ resonance Raman spectroscopy to probe subtle molecular structural changes of PEDOT:PSS associated with its doping level. We demonstrate how such doping level changes of PEDOT:PSS can be used, for the first time, on operational OECTs for sensitive and selective metabolite sensing while simultaneously performing amperometric detection of the analyte. We test the sensitivity by molecularly sensing a lowest glucose concentration of 0.02 mM in phosphate-buffered saline solution. By changing the electrolyte to cell culture media, the selectivity of in situ resonance Raman spectroscopy is emphasized as it remains unaffected by other electroactive components in the electrolyte. The application of this molecular structural probe highlights the importance of developing biosensing probes that benefit from high sensitivity of the material's structural and electrical properties while being complimentary with the electronic methods of detection.

Modulation of macrophage subtypes by IRF5 determines osteoclastogenic potential.

Bone-resorbing osteoclasts are differentiated from macrophages (MΦ) by M-CSF and RANKL. MΦ can be mainly classified into M1 and M2 MΦ, which are proinflammatory and anti-inflammatory, respectively, but little is known about their osteoclastogenic potential. Here, we investigated the osteoclastogenic potential of MΦ subtypes. When the two MΦ subtypes were differentiated into osteoclasts using M-CSF and RANKL, M2 MΦ more potently differentiated into osteoclasts than M1 MΦ. M2 MΦ generated with IL-4 or IL-10 also showed enhanced osteoclast differentiation compared with M1 MΦ induced by IFN-γ and lipopolysaccharide. In addition, robust bone-resorptive capacity and giant actin rings, which are features of mature osteoclasts, were observed in M2, but not M1 MΦ, under the osteoclast differentiation condition. Osteoclast differentiation was significantly increased in CD206+ M2 MΦ but not in CD86+ M1 MΦ. Compared with M1 MΦ, c-Fms and RANK were highly expressed in M2 MΦ. Enhanced osteoclastogenesis of M2 MΦ was mediated through sustained ERK activation, followed by efficient c-Fos and NFATc1 induction. Notably, the osteoclastogenic potential of M1 MΦ converted into M2 MΦ by exposure to M-CSF was higher than that of M2 MΦ converted into M1 MΦ by exposure to GM-CSF. Silencing IRF5, which is responsible for M1 MΦ polarization, increased osteoclast differentiation by enhancing c-Fms expression and activation of ERK, c-Fos, CREB, and NFATc1, which was inhibited by overexpression of IRF5. Collectively, M2 MΦ are suggested to be more efficient osteoclast precursors than M1 MΦ because of the attenuated expression of IRF5.

Streptococcus gordonii induces bone resorption by increasing osteoclast differentiation and reducing osteoblast differentiation.

Streptococcus gordonii is commonly found in the periapical endodontic lesions of patients with apical periodontitis, a condition characterized by inflammation and periapical bone loss. Since bone metabolism is controlled by osteoclastic bone resorption and osteoblastic bone formation, we investigated the effects of S. gordonii on the differentiation and function of osteoclasts and osteoblasts. For the determination of bone resorption activity in vivo, collagen sheets soaked with heat-killed S. gordonii were implanted on mouse calvaria, and the calvarial bones were scanned by micro-computed tomography. Mouse bone marrow-derived macrophages (BMMs) were stimulated with M-CSF and RANKL for 2 days and then differentiated into osteoclasts in the presence or absence of heat-killed S. gordonii. Tartrate-resistant acid phosphatase staining was performed to determine osteoclast differentiation. Primary osteoblast precursors were differentiated into osteoblasts with ascorbic acid and ß-glycerophosphate in the presence or absence of heat-killed S. gordonii. Alkaline phosphatase staining and alizarin red S staining were conducted to determine osteoblast differentiation. Western blotting was performed to examine the expression of transcription factors including c-Fos, NFATc1, and Runx2. Heat-killed S. gordonii induced bone destruction in a mouse calvarial implantation model. The differentiation of RANKL-primed BMMs into osteoclasts was enhanced in the presence of heat-killed S. gordonii. Heat-killed S. gordonii increased the expression of c-Fos and NFATc1, which are essential transcription factors for osteoclast differentiation. On the other hand, heat-killed S. gordonii inhibited osteoblast differentiation and reduced the expression of Runx2, an essential transcription factor for osteoblast differentiation. S. gordonii exerts bone resorptive activity by increasing osteoclast differentiation and reducing osteoblast differentiation, which may be involved in periapical bone resorption.

Lactobacilus nuruki sp. nov., isolated from Nuruk, a Korean fermentation starter.

A rod-shaped, Gram-stain-positive, non-flagellated, facultatively anaerobic bacterium, designated SYF10-1aT, was isolated from Nuruk, a Korean traditional fermentation starter. It grew at 4-40 °C (optimum 37 °C), at pH 3.0-9.0 (optimum, pH 7.0) and with 0-5 % (w/v) NaCl. Phylogenetic analysis using 16S rRNA gene sequences revealed that strain SYF10-1aT belonged to the genus Lactobacillus and showed the highest sequence similarity of 98.7 % to Lactobacillus crustorum LMG 23699T. A comparison of two housekeeping genes, pheS and rpoA, supported the suggestion that strain SYF10-1aT fell within the radius of the genus Lactobacillus, but was clearly separated from its closest related species. The average nucleotide identity value and digital DNA-DNA hybridization value between strain SYF10-1aT and the most closely related species,L. crustorum LMG 23699T, were 80.5 and 33.3 %, respectively. The predominant cellular fatty acids were C16 : 0, C18 : 1ω9c, C18 : 1ω7c and summed feature 3 (including iso-C15 : 0 2-OH and/or C16 : 1ω7c). Polar lipids were diphosphatidylglycerol, phosphatidylglycerol, two unidentified aminolipids and two unidentified glycolipids. The cell-wall peptidoglycan was of the A4α type with an interpeptide bridge comprising l-Lys-d-Asp. The DNA G+C content was 34.2 mol%. On the basis of this taxonomic study, strain SYF10-1aT represents a novel species within the genus Lactobacillus, for which the name Lactobacillus nuruki sp. nov. is proposed. The type strain is SYF10-1aT (=KACC 18726T=NBRC 112011T).

Photo-stability study of a solution-processed small molecule solar cell system: correlation between molecular conformation and degradation.

Solution-processed organic small molecule solar cells (SMSCs) have achieved efficiency over 11%. However, very few studies have focused on their stability under illumination and the origin of the degradation during the so-called burn-in period. Here, we studied the burn-in period of a solution-processed SMSC using benzodithiophene terthiophene rhodamine:[6,6]-phenyl C71 butyric acid methyl ester (BTR:PC71BM) with increasing solvent vapour annealing time applied to the active layer, controlling the crystallisation of the BTR phase. We find that the burn-in behaviour is strongly correlated to the crystallinity of BTR. To look at the possible degradation mechanisms, we studied the fresh and photo-aged blend films with grazing incidence X-ray diffraction, UV-vis absorbance, Raman spectroscopy and photoluminescence (PL) spectroscopy. Although the crystallinity of BTR affects the performance drop during the burn-in period, the degradation is found not to originate from the crystallinity changes of the BTR phase, but correlates with changes in molecular conformation - rotation of the thiophene side chains, as resolved by Raman spectroscopy which could be correlated to slight photobleaching and changes in PL spectra.

Population Pharmacokinetics and Dose Optimization of Teicoplanin during Venoarterial Extracorporeal Membrane Oxygenation.

The pharmacokinetics (PK) of drugs are known to be significantly altered in patients receiving extracorporeal membrane oxygenation (ECMO). However, clinical studies of the PK of drugs administered during ECMO are scarce, and the proper dosing adjustment has yet to be established. We developed a population PK model for teicoplanin, investigated covariates influencing teicoplanin exposure, and suggested an optimal dosing regimen for ECMO patients. Samples for PK analysis were collected from 10 adult patients, and a population PK analysis and simulations were performed to identify an optimal teicoplanin dose needed to provide a >50% probability of target attainment at 72 h using a trough concentration target of >10 µg/ml for mild to moderate infections and a trough concentration target of >15 µg/ml for severe infections. Teicoplanin was well described by a two-compartment PK model with first-order elimination. The presence of ECMO was associated with a lower central volume of distribution, and continuous renal replacement therapy (CRRT) was associated with a higher peripheral volume of distribution. For mild to moderate infections, an optimal dose was a loading dose (LD) of 600 mg and a maintenance dose (MD) of 400 mg for ECMO patients not receiving CRRT and an LD of 800 mg and an MD of 600 mg for those receiving CRRT. For severe infections, an optimal dose was an LD of 1,000 mg and an MD of 800 mg for ECMO patients not receiving CRRT and an LD of 1,200 mg and an MD of 1,000 mg for those receiving CRRT. In conclusion, doses higher than the standard doses are needed to achieve fast and appropriate teicoplanin exposure during ECMO. (This study has been registered at ClinicalTrials.gov under identifier NCT02581280.).

Do measures of depressive symptoms function differently in people with spinal cord injury versus primary care patients: the CES-D, PHQ-9, and PROMIS®-D.

PURPOSE: To evaluate whether items of three measures of depressive symptoms function differently in persons with spinal cord injury (SCI) than in persons from a primary care sample. METHODS: This study was a retrospective analysis of responses to the Patient Health Questionnaire depression scale, the Center for Epidemiological Studies Depression scale, and the National Institutes of Health Patient-Reported Outcomes Measurement Information System (PROMIS®) version 1.0 eight-item depression short form 8b (PROMIS-D). The presence of differential item function (DIF) was evaluated using ordinal logistic regression. RESULTS: No items of any of the three target measures were flagged for DIF based on standard criteria. In a follow-up sensitivity analyses, the criterion was changed to make the analysis more sensitive to potential DIF. Scores were corrected for DIF flagged under this criterion. Minimal differences were found between the original scores and those corrected for DIF under the sensitivity criterion. CONCLUSIONS: The three depression screening measures evaluated in this study did not perform differently in samples of individuals with SCI compared to general and community samples. Transdiagnostic symptoms did not appear to spuriously inflate depression severity estimates when administered to people with SCI.