Discovery of Novel Small Molecule Dual Inhibitor Targeting Toll-Like Receptors 7 and 9.

The aberrant secretion of proinflammatory cytokines by immune cells is the principal cause of inflammatory diseases, such as systemic lupus erythematosus and rheumatoid arthritis. Toll-like receptor 7 (TLR7) and TLR9, sequestered to the endosomal compartment of dendritic cells and macrophages, are closely associated with the initiation and progression of these diseases. Therefore, the development of drugs targeting dysregulated endosomal TLRs is imperative to mitigate systemic inflammation. Here, we applied the principles of computer-aided drug discovery to identify a novel low-molecular-weight compound, TLR inhibitory compound 10 (TIC10), and its potent derivative (TIC10g), which demonstrated dual inhibition of TLR7 and TLR9 signaling pathways. Compared to TIC10, TIC10g exhibited a more pronounced inhibition of the TLR7- and TLR9-mediated secretion of the proinflammatory cytokine tumor necrosis factor-α in a mouse macrophage cell line and mouse bone marrow dendritic cells in a concentration-dependent manner. While TIC10g slightly prevented TLR3 and TLR8 activation, it had no impact on cell surface TLRs (TLR1/2, TLR2/6, TLR4, or TLR5), indicating its selectivity for TLR7 and TLR9. Additionally, mechanistic studies suggested that TIC10g interfered with TLR9 activation by CpG DNA and suppressed downstream pathways by directly binding to TLR9. Western blot analysis revealed that TIC10g downregulated the phosphorylation of the p65 subunit of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinases (MAPKs), including extracellular-signal-regulated kinase, p38-MAPK, and c-Jun N-terminal kinase. These findings indicate that the novel ligand, TIC10g, is a specific dual inhibitor of endosomal TLRs (TLR7 and TLR9), disrupting MAPK- and NF-κB-mediated proinflammatory gene expression.

Developing centrifugal force real-time digital PCR for detecting extremely low DNA concentration.

Digital PCR (dPCR) is a technique for absolute quantification of nucleic acid molecules. To develop a dPCR technique that enables more accurate nucleic acid detection and quantification, we established a novel dPCR apparatus known as centrifugal force real-time dPCR (crdPCR). This system is efficient than other systems with only 2.14% liquid loss by dispensing samples using centrifugal force. Moreover, we applied a technique for analyzing the real-time graph of the each micro-wells and distinguishing true/false positives using artificial intelligence to mitigate the rain, a persistent issue with dPCR. The limits of detection and quantification were 1.38 and 4.19 copies/µL, respectively, showing a two-fold higher sensitivity than that of other comparable devices. With the integration of this new technology, crdPCR will significantly contribute to research on next-generation PCR targeting absolute micro-analysis.

Enrichment and MALDI-TOF MS Analysis of Phosphoinositides in Brain Tissue.

Triazolium cyclodextrin click cluster (+CCC) is an ideal scaffold to specifically bind phosphoinositides (PIPs) via multivalent electrostatic interaction. A new enrichment material, triazolium cyclodextrin click cluster-magnetic agarose bead conjugate (+CCC-MAB), was synthesized and applied to the PIP enrichment of brain tissue. The enriched sample was analyzed using MALDI-TOF MS in negative ion mode without any derivatization. The PIP extract of brain tissue is known to contain abundant lipid interferences. By employing magnetic pull-down separation using +CCC-MAB, we effectively removed the weak-binding interferences in the PIP extract, thereby improving the signal-to-noise ratio (S/N) of the PIPs. Our +CCC-MAB-based PIP enrichment enabled us to analyze 16 PIP species in brain tissue. Six species with high S/N were assigned by MS/MS, while the remaining 10 species with low S/N were characterized by an empirical selection guide based on the biological relevance of PIPs. We conclude that +CCC-MAB-based PIP enrichment is a promising MALDI sample preparation method for specific PIP analysis in brain tissue.

An Analysis of John Bowlby's Mourning Stages in Family Art Therapy as a Way to Help the Family Mourning Process.

Purpose: Pediatric palliative care is a rapidly developing multidisciplinary approach that supports children with life-limiting conditions and their families. However, there is limited evidence on how to effectively support bereaved parents and siblings. The purpose of this study is to explore the therapeutic impact of art therapy for bereaved families, in accordance with John Bowlby's four-stage theory of mourning. Methods: This single-case study employed the consensual qualitative research method. Art therapy records of bereaved families were reviewed individually, and records from one case were selected. Verbal statements made during the art therapy sessions and photocopies of the artworks were analyzed to understand the mourning process of the family. Results: A total of 113 statements and 12 artworks from 19 art therapy sessions were analyzed. As the art therapy progressed, each family member exhibited a pattern of engaging in more positive and healthy conversations in daily life, demonstrating the final stage of mourning reorganization and recovery. The family dynamics also revealed that they reconstructed their inner world and redefined the meaning of loss, which is the final stage of mourning. The art therapy provided a safe environment for the family, allowing them to fulfill their wishes and regain the strength needed for recovery. Conclusion: This study suggests that art therapy supports bereaved families in alleviating their psychological difficulties, engaging in a healthy mourning process, and functioning as members of society. Further research is needed to better understand the effect of art therapy as a bereavement support tool in pediatric palliative care.

A Small-Scale Hopper Design Using a Power Spring-Based Linear Actuator.

Hopping locomotion has the potential to enable small-scale robots to maneuver lands quickly while overcoming obstacles bigger than themselves. To make this possible, in this paper, we propose a novel design of a high-power linear actuator for a small-scale hopper. The key design principle of the linear actuator is to use a power spring and an active clutch. The power spring provides a near constant torque along the wide range of output displacement. The active clutch controls the moving direction and operation timing of the linear actuator, which enables the hopper to take off at the right timing. As a result, the hopper has a size of 143 mm, a mass of 45.9 g, and hops up to 0.58 m.

MiR-155-5p Elevated by Ochratoxin A Induces Intestinal Fibrosis and Epithelial-to-Mesenchymal Transition through TGF-ß Regulated Signaling Pathway In Vitro and In Vivo.

Ochratoxin A (OTA) is a mycotoxin that induces fibrosis and epithelial-to-mesenchymal transitions (EMT) in kidneys and livers. It enters our bodies through food consumption, where it is absorbed in the intestines. However, the impact of OTA on the intestines is yet to be studied. MicroRNA (miRNAs) are small non-coding single-stranded RNAs that block the transcription of specific mRNAs and are, therefore, involved in many biochemical processes. Our findings indicate that OTA can induce EMT and intestinal fibrosis both in vivo and in vitro. This study examines the impact of OTA on intestinal toxicity and the role of miRNAs in this process. Following OTA treatment, miR-155-5p was the most elevated miRNA by next-generation sequencing. Our research showed that OTA increased miR-155-5p levels through transforming growth factor ß (TGF-ß), leading to the development of intestinal fibrosis and EMT. Additionally, the study identified that the modulation of TGF-ß and miR-155-5p by OTA is linked to the inhibition of CCAAT/enhancer-binding protein ß (C/EBPß) and Smad2/3 accumulation in the progression of intestinal fibrosis.

Measurement of interspinous motion in dynamic cervical radiographs using a deep learning-based segmentation model.

OBJECTIVE: Interspinous motion (ISM) is a representative method for evaluating the functional fusion status following anterior cervical discectomy and fusion (ACDF) surgery, but the associated measuring difficulty and potential errors in the clinical setting remain concerns. The aim of this study was to investigate the feasibility of a deep learning-based segmentation model for measuring ISM in patients who underwent ACDF surgery. METHODS: This study is a retrospective analysis of flexion-extension dynamic cervical radiographs from a single institution and a validation of a convolutional neural network (CNN)-based artificial intelligence (AI) algorithm for measuring ISM. Data from 150 lateral cervical radiographs from the normal adult population were used to train the AI algorithm. A total of 106 pairs of dynamic flexion-extension radiographs from patients who underwent ACDF at a single institution were analyzed and validated for measuring ISM. To evaluate the agreement power between human experts and the AI algorithm, the authors assessed the interrater reliability using the intraclass correlation coefficient and root mean square error (RMSE) and performed a Bland-Altman plot analysis. They processed 106 pairs of radiographs from ACDF patients into the AI algorithm for autosegmenting the spinous process created using 150 normal population radiographs. The algorithm automatically segmented the spinous process and converted it to a binary large object (BLOB) image. The rightmost coordinate value of each spinous process from the BLOB image was extracted, and the pixel distance between the upper and lower spinous process coordinate value was calculated. The AI-measured ISM was calculated by multiplying the pixel distance by the pixel spacing value included in the DICOM tag of each radiograph. RESULTS: The AI algorithm showed a favorable prediction power for detecting spinous processes with an accuracy of 99.2% in the test set radiographs. The interrater reliability between the human and AI algorithm of ISM was 0.88 (95% CI 0.83-0.91), and its RMSE was 0.68. In the Bland-Altman plot analysis, the 95% limit of interrater differences ranged from 0.11 to 1.36 mm, and a few observations were outside the 95% limit. The mean difference between observers was 0.02 ± 0.68 mm. CONCLUSIONS: This novel CNN-based autosegmentation algorithm for measuring ISM in dynamic cervical radiographs showed strong agreement power to expert human raters and could help clinicians to evaluate segmental motion following ACDF surgery in clinical settings.

Perfluorooctanoic acid (PFOA) and hexafluoropropylene oxide-dimer acid (GenX): Hepatic stress and bile acid metabolism with different pathways.

Per- and polyfluoroalkyl substances (PFASs) and perfluoroalkyl ether carboxylic acids (PFECAs) are organic chemicals that are widely used in the manufacture of a wide range of human-made products. Many monitoring findings revealed the presence of PFASs and PFECAs in numerous environmental sources, including water, soil, and air, which drew more attention to both chemicals. Because of their unknown toxicity, the discovery of PFASs and PFECAs in a variety of environmental sources was viewed as a cause for concern. In the present study, male mice were given orally one of the typical PFASs, perfluorooctanoic acid (PFOA), and one of the representative PFECAs, hexafluoropropylene oxide-dimer acid (HFPO-DA). The liver index showing hepatomegaly rose significantly after 90 d of exposure to PFOA and HFPO-DA, respectively. While sharing similar suppressor genes, both chemicals demonstrated unique hepatotoxic mechanisms. In different ways, these two substances altered the expression of hepatic stress-sensing genes as well as the regulation of nuclear receptors. Not only are bile acid metabolism-related genes in the liver altered, but cholesterol metabolism-related genes as well. These results indicate that PFOA and HFPO-DA both cause hepatotoxicity and bile acid metabolism impairment with distinct mechanisms.

Changes in Shoulder Trauma during the COVID-19 Pandemic: A South Korean Survey.

Background: This study aimed to investigate the changes in the incidence of shoulder trauma and surgery 1 year after the outbreak of coronavirus disease 2019 (COVID-19) with social restriction compared with 1 year before the pandemic. Methods: Patients managed in our orthopedic trauma center between February 18, 2020, and February 17, 2021 (COVID-19 period) for shoulder trauma were compared with patients managed for the same duration a year ago (non-COVID-19 period; February 18, 2019, to February 17, 2020). The incidence of shoulder trauma, surgery, and mechanism of injury were compared between these periods. Results: The total number of shoulder trauma cases was lower in the COVID-19 period than in the non-COVID-19 period, although the difference was not significant (160 vs. 180 cases, p = 0.278). In addition, traumatic shoulder surgeries decreased during the COVID-19 period (57 vs. 69 cases, p = 0.285). The incidence of shoulder trauma according to four diagnostic classifications (contusion, sprain/subluxation, fracture, and dislocation) and fracture/dislocation types did not differ between the periods. During the COVID-19 period, accidental falls outdoors (45 vs. 67, p = 0.038) and sports-related injuries (15 vs. 29, p = 0.035) significantly decreased, but accidental falls at home (52 vs. 37, p = 0.112) increased compared with those during the non-COVID-19 period, although the difference was not significant. The monthly incidence of shoulder trauma decreased 2 months after the first outbreak (significant in March, p = 0.019), then steadily increased and significantly decreased during the second outbreak (August, p = 0.012). However, the third outbreak (December, p = 0.077) had little effect on the incidence of shoulder trauma. The number of monthly traumatic shoulder surgeries showed a similar pattern to the monthly incidence of shoulder trauma. Conclusions: During the COVID-19 pandemic, annual shoulder trauma cases and surgeries decreased compared to those in the non-COVID-19 period, even though the difference was insignificant. The incidence of shoulder trauma and surgery was significantly reduced in the early COVID-19 period; however, the effect of the pandemic on orthopedic trauma practice was minimal after approximately half a year. Decreases in falls outdoors and sports-related injuries, but an increase in falls at home, were observed during the COVID-19 pandemic.

Salty taste test for a low-salt diet to control blood pressure.

BACKGROUND: Reducing salt intake helps prevent complications of cerebrovascular disease. To help patients accept a low-sodium diet, the salty taste test is used to evaluate how much salt an individual actually consumes. The aim of this study was to help patients with hypertension reduce their salt intake by helping them recognize the difference between their subjective perception of saltiness and the objective test results. METHODS: We enrolled workers who visited a local occupational health institution in the period from April to August 2019. Demographic and physical characteristics were recorded. Blood pressure measurement and use of medication were also recorded. A questionnaire was used to investigate whether people liked or disliked salty food, i.e., preference for saltiness, and whether they usually ate salty, normal, or fresh food, i.e., the subjective perception of saltiness. Subsequently, the taste determination kit provided by the Ministry of Food and Drug Safety was used to objectively test saltiness at various salty taste concentrations. The Ministry of Food and Drug Safety program (No. 10-093760) was used as the salty taste judgment tool. RESULTS: A total of 86 workers were surveyed. Eleven of 18 workers (61.1%) who reported usually eating fresh food actually ate normal or salty food. Thirteen of 37 workers (35.1%) who reported eating normal food actually ate salty food. Thirteen of 31 workers (41.9%) who reported eating salty food actually ate fresh or normal food. Of 46 workers who reported disliking salty food, 14 (30.4%) actually ate salty food, while 20 (43.5%) ate normal food. The subjective perception and preference for saltiness were not significantly correlated with the objective test results (P = ​​0.085 and P = 0.110, respectively). As for the subjective perception and preference for saltiness, Cohen's weighted kappa for the taste judgment result were 0.23 and 0.22, respectively, indicating a low degree of agreement. CONCLUSIONS: In dietary counseling to prevent cerebrovascular and cardiovascular diseases, rather than relying on the subjective perception of saltiness, a salty taste test should be performed such that people can recognize their salty food eating habits through objective evaluation.

Ochratoxin A induces endoplasmic reticulum stress and fibrosis in the kidney via the HIF-1α/miR-155-5p link.

Ochratoxin A (OTA) is a ubiquitous fungal toxin found in agricultural products and foods that is toxic to both humans and animals. OTA mainly affects kidney, but the mechanisms underlying OTA-induced nephrotoxicity remain not fully understood. MicroRNA (miRNA) is involved in key cellular processes. The toxic mechanism and regulatory effects of miRNAs on OTA toxicity in kidney, and particularly the role of HIFα-1/miR-155-5p on OTA-caused ER stress and fibrosis, were investigated in this study. OTA induced hypoxia-like conditions such as ER stress and fibrosis in HK-2 cells and renal tissues via modulating HIF-1α, which was followed by regulation of ER stress-related proteins (GRP78 and ATF-4), as well as fibrosis-related markers (fibronectin, α-SMA, and E-cadherin). Notably, a total of 62 miRNAs showed significant differential expression in kidney of OTA-treated mice. Under OTA exposure, HIF-1α enhanced miR-155-5p expression, causing ER stress and fibrosis in HK-2 cells. HIF-1α knockdown decreased OTA-induced miR-155-5p expression as well as ER stress and fibrotic responses, whereas miR-155-5p overexpression restored this. Our data suggest that OTA enhances ER stress and fibrosis in the kidney through upregulating the HIF-1α/miR-155-5p link.

Risk factors for hardware-related complications after extra-articular distal humerus fracture fixation using an anatomical locking plate.

PURPOSE: We aimed to identify the incidence and risk factors of hardware-related complications in patients treated with anatomical locking plate fixation for extra-articular distal humerus fractures. METHODS: From 2013 to 2020, patients with extra-articular distal humerus fractures who underwent open reduction and internal fixation with an extra-articular distal humerus locking plate (EADHP) were retrospectively reviewed and categorized according to the presence/absence of hardware-related complications. Hardware-related complications were defined as the occurrence of skin prominence on the plate and discomfort in activities of daily living. Patient demographics, the lateral condylar angle, lateral body length, shaft-condylar angle of the humerus, and plate length were analyzed. RESULTS: Of the 29 patients, 10 (34%) did not develop hardware-related complications (group A), whereas 19 (66%) did (group B). Patient demographics did not differ between the groups. However, the number of patients who underwent hardware removal was significantly greater in group B (16/19) than in group A (4/10; p = 0.032). Radiologic assessment revealed no significant difference in the lateral condylar or shaft-condylar angle. However, the lateral body length was greater in group A than in group B (44.5 ± 4.8 vs. 39.5 ± 3.7, p = 0.007). The plate length significantly differed between the groups. Twelve of 19 (63%) patients in group B received short-hole plates (six holes), while nine of ten (90%) patients in group A received long-hole plates (eight holes). In the multivariable analysis, the lateral body length of the distal humerus (p = 0.047, odds ratio = 0.734, 95% confidence interval: 0.542-0.996) and plate length (p = 0.036, odds ratio = 0.076, 95% confidence interval: 0.542-0.996) were associated with hardware-related complications. CONCLUSIONS: Most patients developed hardware-related complications, particularly with short plates, mainly because of the narrow lateral body length of the distal humerus. Surgeons should be careful to secure EADHP in the appropriate position, especially when short plates are used in patients with narrow lateral body length.

Changes in Shoulder Trauma during the COVID-19 Pandemic: A South Korean Survey

Background@#This study aimed to investigate the changes in the incidence of shoulder trauma and surgery 1 year after the outbreak of coronavirus disease 2019 (COVID-19) with social restriction compared with 1 year before the pandemic. @*Methods@#Patients managed in our orthopedic trauma center between February 18, 2020, and February 17, 2021 (COVID-19 period) for shoulder trauma were compared with patients managed for the same duration a year ago (non–COVID-19 period; February 18, 2019, to February 17, 2020). The incidence of shoulder trauma, surgery, and mechanism of injury were compared between these periods. @*Results@#The total number of shoulder trauma cases was lower in the COVID-19 period than in the non–COVID-19 period, although the difference was not significant (160 vs. 180 cases, p = 0.278). In addition, traumatic shoulder surgeries decreased during the COVID-19 period (57 vs. 69 cases, p = 0.285). The incidence of shoulder trauma according to four diagnostic classifications (contusion, sprain/subluxation, fracture, and dislocation) and fracture/dislocation types did not differ between the periods. During the COVID-19 period, accidental falls outdoors (45 vs. 67, p = 0.038) and sports-related injuries (15 vs. 29, p = 0.035) significantly decreased, but accidental falls at home (52 vs. 37, p = 0.112) increased compared with those during the non–COVID-19 period, although the difference was not significant. The monthly incidence of shoulder trauma decreased 2 months after the first outbreak (significant in March, p = 0.019), then steadily increased and significantly decreased during the second outbreak (August, p = 0.012).However, the third outbreak (December, p = 0.077) had little effect on the incidence of shoulder trauma. The number of monthly traumatic shoulder surgeries showed a similar pattern to the monthly incidence of shoulder trauma. @*Conclusions@#During the COVID-19 pandemic, annual shoulder trauma cases and surgeries decreased compared to those in the non–COVID-19 period, even though the difference was insignificant. The incidence of shoulder trauma and surgery was significantly reduced in the early COVID-19 period; however, the effect of the pandemic on orthopedic trauma practice was minimal after approximately half a year. Decreases in falls outdoors and sports-related injuries, but an increase in falls at home, were observed during the COVID-19 pandemic.

Hyaluronic Acid Nanoparticles as a Topical Agent for Treating Psoriasis.

Although conventional topical approaches for treating psoriasis have been offered as an alternative, there are still unmet medical needs such as low skin-penetrating efficacy and off-target adverse effects. A hyaluronic acid nanoparticle (HA-NP) formed by self-assembly of HA-hydrophobic moiety conjugates has been broadly studied as a nanocarrier for long-term and target-specific delivery of drugs, owing to their excellent physicochemical and biological characteristics. Here, we identify HA-NPs as topical therapeutics for treating psoriasis using in vivo skin penetration studies and psoriasis animal models. Transcutaneously administered HA-NPs were found to be accumulated and associated with pro-inflammatory macrophages in the inflamed dermis of a psoriasis mouse model. Importantly, HA-NP exerted potent therapeutic efficacy against psoriasis-like skin dermatitis in a size-dependent manner by suppressing innate immune responses and restoring skin barrier function without overt toxicity signs. The therapeutic efficacy of HA-NPs on psoriasis-like skin dermatitis was due to the outermost hydrophilic HA shell layer of HA-NPs, independent of the molecular weight of HA and hydrophobic moiety, and comparable with that of other conventional psoriasis therapeutics widely used in the clinical settings. Overall, HA-NPs have the potential as a topical nanomedicine for treating psoriasis effectively and safely.

A Phase 3, Multicenter, Randomized, Controlled Trial to Evaluate Immune Equivalence and Safety of Multidose and Single-dose Formulations of Vi-DT Typhoid Conjugate Vaccine in Healthy Filipino Individuals 6 Months to 45 Years of Age.

Trial Design: Phase 3, randomized, controlled, multicenter, equivalence trial. Methods: Recruitment of participants occurred between 04Februray2020 and 15July2020 at four centers in the Philippines: University of the East - Ramon Magsaysay Memorial Medical Center Inc., Quezon City; University of Philippines Manila - National Institute of Health, Ermita Manila; Asian Hospital and Medical Center, Metro Manila, Philippines Study; and Medical Research Unit, Tropical Disease Foundation, Makati City, Metro Manila, Philippines. Participants: 1800 adults and children 6-months to 45-years of age. Interventions: Participants received a single injection of multidose (MD) or single dose (SD) Vi-DT as test vaccines or meningococcal conjugate vaccine as a comparator. Objective: To evaluate immune equivalence of SD and MD formulations of Vi-DT, and to assess the safety of both formulations compared with comparator vaccine. Outcome Measurement: Blood draw for immunogenicity was performed at baseline prior to vaccine receipt and at four weeks after vaccination for a subset of participants to determine anti-Vi IgG geometric mean titers (GMT) and seroconversion rates. The primary outcome was comparison of anti Vi-IgG seroconversion and GMT between the two formulations of Vi-DT at 4 weeks following vaccine administration. Immune equivalence of MD and SD formulations was confirmed when the two-tailed 95% confidence interval (CI) of the GMT ratio is within [0.67, 1.5] at a two-sided significance level of 0.05. All participants were followed for safety events for six months after vaccine administration. Randomization: Participants were randomized to receive SD Vi-DT, MD Vi-DT, or meningococcal conjugate vaccines in 2.5:2.5:1 allocation ratio. Blinding: Study participants and observers were blinded to treatment assignment. Findings: Immune equivalence of SD (n=252) and MD (n=247) formulations was confirmed by anti-Vi IgG GMT ratio of 1.14 (95%CI: 0.91, 1.43) with respective GMTs in the MD and SD groups of 640.62 IU/mL (95%CI: 546.39, 751.11) and 562.57 IU/mL (95%CI: 478.80, 661.00) (p=0.259). Similarly, anti-Vi IgG seroconversion rate difference between the two formulations of ‒0.43% (95%CI: -4.42, 3.56) confirmed immune equivalence with corresponding seroconversion rates of 98.38% (95%CI: 95.91, 99.37) and 98.81% (95%CI: 96.56, 99.59) in MD and SD Vi-DT formulations, respectively (p=0.722). Both formulations of Vi-DT had a satisfactory safety profile - all five serious adverse events reported during the study were unrelated to the investigational product. Interpretation: The MD and SD formulations of Vi-DT elicited robust and equivalent immune responses following one dose vaccination, and both formulations demonstrated a favorable safety profile. Trial Registration: ClinicalTrials.gov: NCT04204096. Funding: This study was funded by the Bill & Melinda Gates Foundation (OPP 1115556).

Prevalence of sarcopenia and mortality rate in older adults with hip fracture.

BACKGROUND: Several international study groups adopted appendicular skeletal muscle mass (ASM) index adjusted by (1) height squared, (2) weight, and (3) body mass index (BMI) in the diagnosis of sarcopenia. However, different prevalence rates of sarcopenia by each index and clinical implications were not well known. The purpose of this study was to compare the differences in (1) the percentage of sarcopenia in hip fracture patients and (2) the relative mortality rate according to the sarcopenia criteria of three ASM indices. METHODS: Between January 2009 and December 2020, 1003 older adult hip fracture patients at a tertiary institution were eligible and retrospectively reviewed for this study. Based on the ASM measured on dual-energy X-ray absorptiometry, three indices were calculated, and sarcopenia was diagnosed. The proportion of sarcopenia was evaluated according to each index. One, two, and five-year mortality rates were compared between each sarcopenia group and a normal musculature group, based on ASM criteria. RESULTS: The proportion of sarcopenia patients differed according to three ASM indices. The proportion of sarcopenic patients by ASM/height2 index was higher than those of the other two indices in both male and female hip fracture patients. In male patients, 61% were sarcopenic by ASM/height2 index, 37% by ASM/weight index, and 44% by ASM/BMI index. In female patients, 26%, 11%, and 14% were sarcopenic, respectively. Among the three indices, only ASM/height2 had significant correlations with all 1-, 2-, and 5-year mortality rates. CONCLUSIONS AND IMPLICATIONS: The prevalence of sarcopenia in hip fracture patients differed substantially according to ASM indices. Sarcopenic hip fracture patients had a higher mortality rate than those with normal musculature. The 1-year, 2-year, and 5-year mortality rates were discriminated by ASM/height2 criteria in both men and women. Future prospective studies in a larger cohort are warranted.

Positivity of Rapid Antigen Testing for SARS-CoV-2 With Serial Followed-up Nasopharyngeal Swabs in Hospitalized Patients due to COVID-19.

Despite the accuracy of nucleic acid amplification tests (NAATs), rapid antigen tests (RATs) for severe acute respiratory syndrome coronavirus-2 are widely used as point-of-care tests. A total of 282 pairs of reverse transcription-polymerase chain reaction and Standard Q COVID-19 Ag tests were serially conducted for 68 patients every 3-4 days until their discharge. Through a field evaluation of RATs using direct nasopharyngeal swabs, the sensitivities were 84.6% and 87.3% for E and RNA-dependent RNA polymerase (RdRp) genes, respectively, for specimens with cycle thresholds (Cts) < 25. The Ct values of E and RdRp genes for 95% detection rates by RATs were 16.9 and 18.1, respectively. The sensitivity of RAT was 48.4% after the onset of symptoms, which was not sufficient. RAT positivity gradually decreased with increased time after symptom onset and had continuously lower sensitivity than NAATs.

Immune persistence and response to booster dose of Vi-DT vaccine at 27.5 months post-first dose.

Vaccination with typhoid conjugate vaccines (TCV) is a major part of typhoid prevention. However, little is known about long-term immune persistence following vaccination with TCVs. In this phase-2, randomized double-blind trial (NCT03527355), 285 children aged 6-23 months were randomized to one of three groups: (1) the group that received a first dose of Vi polysaccharide conjugated to diphtheria-toxoid (Vi-DT) vaccine followed by an "early booster" at 24 weeks, (2) the group that which received a first dose of Vi-DT followed by a "late booster" at 96 or 110 weeks, and (3) comparator group. Safety and immunogenicity of anti-Vi IgG GMTs were assessed at weeks 0, 4, 24, 28, 60, 96, 110, and 114 since the first dose. Here, we describe persistence of immune responses at weeks 60, 96, 110, and 114 post first dose. The anti-Vi IgG seroconversion rate after 27.5 months of follow-up was 88.16% (95% CI: 79.00, 93.64) in late-booster and 94.76% (95% CI: 86.91, 97.88) in early booster Vi-DT groups (p = 0.081). Whereas anti-Vi IgG GMTs were significantly higher in the early booster group (11.95 [95% CI: 9.65, 14.81]) than prebooster GMTs in the late booster group (5.50 [95% CI: 4.44, 6.80], p < 0.0001). GMT in the late booster group significantly increased to 351.76 (95% CI: 265.01, 466.93) (p < 0.0001) when measured 4 weeks after they received their "late-booster" shot. In conclusion, late booster dosing with Vi-DT at 27.5 months post first dose was safe and elicited robust anti-Vi IgG immune responses. Anti-Vi IgG seroconversion rates were persistently comparable in early and late-booster Vi-DT groups.

Comparison of 3-month cytogenetic and molecular assays for early assessment of long-term clinical impact after BCR-ABL1 tyrosine kinase inhibitor treatment in chronic myeloid leukemia.

To compare the clinical significance of 3-month cytogenetic and molecular monitoring, we analyzed 1,410 paired cytogenetic and molecular data from 705 chronic-phase chronic myeloid leukemia patients. Based on early cytogenetic response (ECyR, Ph+≤35 %) and molecular response (EMR, BCR-ABL1IS≤10 %) at 3 months, the patients were divided into four groups (group 1: ECyR + EMR, n = 560; group 2: no ECyR + EMR, n = 27; group 3: ECyR + no EMR, n = 55; group 4: no ECyR + no EMR, n = 63). By 10 years, major molecular response (MMR), deep molecular response (MR4.5), overall survival (OS), and progression-free survival (PFS) rates were significantly high in group 1 (P < 0.001). Comparing groups 2 and 3, the MMR (P = 0.096), MR4.5 (P = 0.945), OS (P = 0.832), and PFS (P = 0.627) rates tended to be higher in group 2, although not significantly. Thus, the cytogenetic assay can not only be useful but its addition may also provide a more precise prediction of MR4.5.

Positivity of Rapid Antigen Testing for SARS-CoV-2 With Serial Followed-up Nasopharyngeal Swabs in Hospitalized Patients due to COVID-19

Despite the accuracy of nucleic acid amplification tests (NAATs), rapid antigen tests (RATs) for severe acute respiratory syndrome coronavirus-2 are widely used as point-of-care tests. A total of 282 pairs of reverse transcription-polymerase chain reaction and Standard Q COVID-19 Ag tests were serially conducted for 68 patients every 3–4 days until their discharge. Through a field evaluation of RATs using direct nasopharyngeal swabs, the sensitivities were 84.6% and 87.3% for E and RNA-dependent RNA polymerase (RdRp) genes, respectively, for specimens with cycle thresholds (Cts) < 25. The Ct values of E and RdRp genes for 95% detection rates by RATs were 16.9 and 18.1, respectively. The sensitivity of RAT was 48.4% after the onset of symptoms, which was not sufficient. RAT positivity gradually decreased with increased time after symptom onset and had continuously lower sensitivity than NAATs.