The effects of medial soft tissue release for varus deformity during medial open wedge supramalleolar osteotomy: a cadaveric study.

This study was performed to investigate the effects of fibular osteotomy and release of medial soft tissues including posterior tibial tendon (PTT), and deep deltoid ligaments, which act as medial stabilizing structures in medial open wedge SMO. Twelve fresh frozen human legs were obtained and disarticulated below the knee. Experiments were conducted in four steps. First, medial open wedge tibial osteotomy was performed. Second, fibular osteotomy was performed in an inferomedial direction at the same level as the tibial osteotomy. Third, the deep deltoid ligament was released from tibial attachments. Forth, total tenotomy of the PTT was performed behind the medial malleolus. After finishing each step, contact area and peak and mean pressures were measured in the tibiotalar and talofibular joints. Fibular osteotomy after medial open wedge SMO significantly decreased mean pressure in the tibiotalar joint, mean and peak pressures in the talofibular joint. Medial soft tissue release resulted in a remarkable lateral shift and decreased tibiotalar joint loading. However, no remarkable change was observed in the tibiotalar joint during releasing medial soft tissues. The overall peak pressure distribution tended to shift more laterally compared to the value of normal alignment. In conclusion, concomitant fibular osteotomy and release of the deltoid ligament and PTT provide a useful means of minimizing tibiotalar joint stress. Supplementary Information: The online version contains supplementary material available at 10.1007/s13534-024-00370-7.

Shortcomings in the Evaluation of Blood Glucose Forecasting.

OBJECTIVE: Recent years have seen an increase in machine learning (ML)-based blood glucose (BG) forecasting models, with a growing emphasis on potential application to hybrid or closed-loop predictive glucose controllers. However, current approaches focus on evaluating the accuracy of these models using benchmark data generated under the behavior policy, which may differ significantly from the data the model may encounter in a control setting. This study challenges the efficacy of such evaluation approaches, demonstrating that they can fail to accurately capture an ML-based model's true performance in closed-loop control settings. METHODS: Forecast error measured using current evaluation approaches was compared to the control performance of two forecasters-a machine learning-based model (LSTM) and a rule-based model (Loop)-in silico when the forecasters were utilized with a model-based controller in a hybrid closed-loop setting. RESULTS: Under current evaluation standards, LSTM achieves a significantly lower (better) forecast error than Loop with a root mean squared error (RMSE) of 11.57 ±0.05 mg/dL vs. 18.46 ±0.07 mg/dL at the 30-minute prediction horizon. Yet in a control setting, LSTM led to significantly worse control performance with only 77.14% (IQR 66.57-84.03) time-in-range compared to 86.20% (IQR 78.28-91.21) for Loop. CONCLUSION: Prevailing evaluation methods can fail to accurately capture the forecaster's performance when utilized in closed-loop settings. SIGNIFICANCE: Our findings underscore the limitations of current evaluation standards and the need for alternative evaluation metrics and training strategies when developing BG forecasters for closed-loop control systems.

Effects of Black and White Mulch on Mycelial Growth of Tuber Species in Korean Field Environment.

Truffles, belonging to the genus Tuber, are ectomycorrhizal (ECM) fungi that form underground ascocarps and primarily establish symbiosis with oaks and hazels. The cultivation of Tuber spp. involves transplanting inoculated seedlings that have formed ectomycorrhiza with Tuber species, with mulching being effective for truffle cultivation. In this study, we investigated the effects of mulching on the mycelial growth of four Tuber species (T. himalayense, T. koreanum, T. melanosporum, and T. borchii) in the Korean natural environment, highlighting the potential for Korea as a truffle cultivation site. We developed and tested species-specific primers for quantifying the soil mycelial biomass of Tuber spp. by qRT-PCR, determined the superior mulch color for mycelial growth, and identified the Tuber species exhibiting the highest growth rate in the Korean field environment. Our results demonstrated that white mulch significantly enhanced mycelial growth in Tuber species than black mulch, likely owing to its ability to maintain low soil temperatures, control weeds, and improve host plant growth. Among the Tuber species, T. himalayense showed the greatest growth potential in the Korean natural environment. Additionally, a significant and positive correlation was observed between the mycelial biomass of Tuber species and the growth of inoculated seedlings, as measured by the total stem length and the number of leaves, thereby indicating the importance of symbiosis between ECM fungi and host plants. This study provides valuable insights into truffle cultivation in Korea and highlights the potential of using white mulch to promote mycelial growth, thereby contributing essential data for understanding the appropriate environmental conditions for Tuber spp. cultivation in Korea. Further study is needed to assess the long-term impact of mulching and to explore the effectiveness of other mulching materials.

Socioeconomic status and physical activity disparities in older adults: Implications for COVID-19 related diabetes cognitive dysfunction.

Objectives: This study aims to investigate the influence of socioeconomic status (SES) on variations in physical activity (PA) levels and diabetes-related cognitive dysfunction and impairment amidst disruptions caused by the COVID-19 pandemic. Methods: With the sample of old population, comprising about 20 thousand from the Fact-Finding Survey on the Status of Senior Citizens (FSSSC) released by Ministry of Health and Welfare of South Korea in 2017 and 2020, we empirically tested the direct and indirect effects of SES on cognitive dysfunction using structural equation modeling (SEM). Two SEMs provided the comparison on the effects of COVID-19. Results: Household income had a negative impact on the likelihood of dementia diagnosis via PA related diabetes during the pandemic (p < 0.001), whereas no effects of household income on dementia diagnosis were found in 2017, due to no direct effect of PA on diabetes confirmation in 2017. The disparity in PA based on SES becomes more prominent among the older individuals during the pandemic (z = 11.7) than 2017 (z = 6.0), emphasizing the significance of PA in mitigating diabetes-induced cognitive dysfunction during the pandemic. SES affects access to PA, contributing to diabetes-induced cognitive dysfunctions in the older population with lower SES during the pandemic. Conclusion: PA may serve as a preventive measure against diabetes-induced cognitive dysfunction and dementia in the older population. Thorough investigation of these mechanisms is imperative to establish the role of PA in preventing diabetes-induced cognitive impairment, particularly among the older population with lower SES.

Combination Therapy Approach to Overcome the Resistance to PI3K Pathway Inhibitors in Gynecological Cancers.

The PI3K signaling pathway plays an essential role in cancer cell proliferation and survival. PI3K pathway inhibitors are now FDA-approved as a single agent treatment or in combination for solid tumors such as renal cell carcinoma or breast cancer. However, despite the high prevalence of PI3K pathway alterations in gynecological cancers and promising preclinical activity in endometrial and ovarian cancer models, PI3K pathway inhibitors showed limited clinical activity in gynecological cancers. In this review, we provide an overview on resistance mechanisms against PI3K pathway inhibitors that limit their use in gynecological malignancies, including genetic alterations that reactivate the PI3K pathway such as PIK3CA mutations and PTEN loss, compensatory signaling pathway activation, and feedback loops causing the reactivation of the PI3K signaling pathway. We also discuss the successes and limitations of recent clinical trials aiming to address such resistance mechanisms through combination therapies.

Atypical Presentations of Hydroxychloroquine Retinopathy: A Case Series Study.

Background/Objective: Hydroxychloroquine retinopathy, traditionally characterized by parafoveal or pericentral outer retinal damage, is explored for atypical presentations in Asian patients. This challenges conventional beliefs regarding onset, retinopathy pattern, and associated visual field defects. Methods: Ninety-five patients diagnosed with hydroxychloroquine retinopathy at Hanyang University Hospital underwent screening from January 2010 to December 2023. Swept-source optical coherence tomography (SS-OCT), ultra-widefield fundus autofluorescence (UWF-FAF), and automated visual fields (VF) were employed for detailed structural and functional evaluations. Multifocal electroretinography was performed in selected cases requiring additional objective evidence of retinal toxicity. Results: Among 95 patients, 14 (14.7%) exhibited atypical presentations, including very early onset (n = 1), (far) peripheral-dominant damages (n = 4), perivascular involvement (n = 1), bitemporal hemianopsia due to nasal extensive lesions (n = 1), unilateral involvement (n = 2), and asymmetric involvement in retinopathy pattern or severity between the eyes (n = 7). These findings underscore the importance of utilizing expanded imaging techniques, such as ultra-widefield FAF imaging, to identify atypical presentations of retinal involvement. Conclusions: Screening physicians should consider these atypical presentations to ensure timely diagnosis and appropriate management in patients undergoing hydroxychloroquine treatment.

Antiviral activity of pimecrolimus against dengue virus type 2 infection in vitro and in vivo.

Dengue virus (DENV) infection is a public health concern in several countries and is associated with severe diseases, such as dengue hemorrhagic fever and dengue shock syndrome. DENVs are transmitted to humans via the bites of infected Aedes mosquitoes, and no antiviral therapeutics are currently available. In this work, we aimed to identify antiviral drugs against DENV type 2 (DENV2) infections and selected pimecrolimus as a potential antiviral drug candidate. Pimecrolimus significantly inhibited DENV2-mediated cell death and replication in vitro. We also confirmed a decrease in the number of plaques formed as well as in the envelope protein levels of DENV2. The time-of-addition and course experiments revealed that pimecrolimus inhibited DENV2 infection during the early stages of the virus replication cycle. In an experimental mouse model, orally administered pimecrolimus alleviated body weight loss and lethality caused by DENV2 infection, which we used as readouts of the drug's antiviral potency. Furthermore, pimecrolimus significantly inhibited the DENV2 load and ameliorated focal necrosis in the liver and spleen. Taken together, our in vitro and in vivo findings suggest that pimecrolimus is a promising antiviral drug candidate for the treatment of DENV2 infection.

A 13-Year Trend Analysis of HIV Epidemiology in the Philippines (2010 to 2022).

PURPOSE: This article describes the trends and contributing factors in the human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS) epidemiology in the Philippines from 2010 to 2022. This is the first trend analysis of the Philippine HIV/AIDS situation. DESIGN: Using time trend research design, 13-year longitudinal epidemiological data were collected and analyzed to present a dynamic perspective of the Philippine HIV/AIDS epidemic. METHODS: Secondary data analysis of HIV surveillance public documents from 2010 to 2022 was conducted. The Centers for Disease Control's socioecological model was used to guide the literature and interpretation of findings. Frequency, percentage distribution, and Sieve-bootstrap t-test for linear trends were used to analyze the results. FINDINGS: There is an increased trend in HIV incidence, late diagnosis, and AIDS-related mortality in all geographical regions in the country from 2010-2022. The majority of HIV cases are males, ages 25-34, and reside in the nation's capital. Increased HIV incidence among overseas workers, sex workers, and HIV-positive blood products were noted. CONCLUSION: Trends in Philippine HIV epidemiology are contrary to global trends. Community-based HIV prevention programs targeting specific high-risk populations are needed. CLINICAL EVIDENCE: Community health nurses in the Philippines play a critical role in reversing the rising trend of HIV/AIDS. They are positioned to lead targeted education and prevention programs for high-risk groups using the socioecological model to implement community-based strategies that address factors contributing to the epidemic. Their efforts in early detection and linkage to care are essential in reducing late diagnosis and AIDS-related mortality.

Deep Learning Segmentation of Ascites on Abdominal CT Scans for Automatic Volume Quantification.

"Just Accepted" papers have undergone full peer review and have been accepted for publication in Radiology: Artificial Intelligence. This article will undergo copyediting, layout, and proof review before it is published in its final version. Please note that during production of the final copyedited article, errors may be discovered which could affect the content. Purpose To evaluate the performance of an automated deep learning method in detecting ascites and subsequently quantifying its volume in patients with liver cirrhosis and ovarian cancer. Materials and Methods This retrospective study included contrast-enhanced and noncontrast abdominal-pelvic CT scans of patients with cirrhotic ascites and patients with ovarian cancer from two institutions, National Institutes of Health (NIH) and University of Wisconsin (UofW). The model, trained on The Cancer Genome Atlas Ovarian Cancer dataset (mean age, 60 years ± 11 [SD]; 143 female), was tested on two internal (NIH-LC and NIH-OV) and one external dataset (UofW-LC). Its performance was measured by the Dice coefficient, standard deviations, and 95% confidence intervals, focusing on ascites volume in the peritoneal cavity. Results On NIH-LC (25 patients; mean age, 59 years ± 14; 14 male) and NIH-OV (166 patients; mean age, 65 years ± 9; all female), the model achieved Dice scores of 85.5% ± 6.1% (CI: 83.1%-87.8%) and 82.6% ± 15.3% (CI: 76.4%-88.7%), with median volume estimation errors of 19.6% (IQR: 13.2%-29.0%) and 5.3% (IQR: 2.4%- 9.7%), respectively. On UofW-LC (124 patients; mean age, 46 years ± 12; 73 female), the model had a Dice score of 83.0% ± 10.7% (CI: 79.8%-86.3%) and median volume estimation error of 9.7% (IQR: 4.5%-15.1%). The model showed strong agreement with expert assessments, with r2 values of 0.79, 0.98, and 0.97 across the test sets. Conclusion The proposed deep learning method performed well in segmenting and quantifying the volume of ascites in concordance with expert radiologist assessments. ©RSNA, 2024.

Is intensive chemotherapy and allogeneic stem cell transplantation mandatory for curing Philadelphia chromosome-positive acute lymphoblastic leukemia in young patients in the era of multitarget agents?

INTRODUCTION: The treatment outcomes for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) have improved with various tyrosine kinase inhibitors (TKIs) and bispecific T-cell engagers. Although allogeneic stem cell transplantation (allo-SCT) is the standard treatment for young patients with Ph+ALL, its role remains debatable in the era of TKIs and blinatumomab. AREAS COVERED: There are some issues regarding Ph+ALL. First, do young patients require intensive chemotherapy (IC) in the era of multitarget agents? Second, which TKI is preferred for frontline therapy? Third, should allo-SCT be performed in patients achieving complete remission with ponatinib and IC? Fourth, can chemo-free treatment lead to a cure without allo-SCT? We searched relevant literature from the last 30 years on PubMed; reviewed the role of chemo-free therapies and combinations of ponatinib and IC; and assessed the necessity of allo-SCT in young patients with Ph+ALL. EXPERT OPINION: Allo-SCT may not be needed, even in young patients with Ph+ALL treated with ponatinib-based IC or combined ponatinib and blinatumomab as frontline therapy. When adopting a ponatinib-based chemo-minimized regimen for induction, allo-SCT is needed with posttransplant ponatinib maintenance. Continuous exposure to ponatinib at pre- or post-transplant is regarded as one of the most important factor for the success of treatment.

A phase 2 trial exploring the significance of homologous recombination status in patients with platinum sensitive or platinum resistant relapsed ovarian cancer receiving combination cediranib and olaparib.

OBJECTIVE: Combination cediranib/olaparib has reported activity in relapsed ovarian cancer. This phase 2 trial investigated the activity of cediranib/olaparib in relapsed ovarian cancer and its association with homologous recombination deficiency (HRD). METHODS: Seventy patients were enrolled to cohorts of either platinum-sensitive or platinum-resistant ovarian cancer and received olaparib tablets 200 mg twice daily and cediranib tablets 30 mg once daily under a continuous dosing schedule. HRD testing was performed on pre-treatment, on-treatment and archival biopsies by sequencing key homologous recombination repair (HRR) genes and by genomic LOH analysis. The primary objective for the platinum-sensitive cohort was the association of HRD, defined as presence of HRR gene mutation, with progression-free survival (PFS). The primary objective for the platinum-resistant cohort was objective response rate (ORR), with a key secondary endpoint evaluating the association of HRD status with activity. RESULTS: In platinum-sensitive ovarian cancer (N = 35), ORR was 77.1% (95% CI 59.9-89.6%) and median PFS was 16.4 months (95% CI 13.2-18.6). Median PFS in platinum-sensitive HRR-HRD cancers (N = 22) was 16.8 months (95% CI 11.3-18.6), and 16.4 months (95% CI 9.4-NA) in HRR-HR proficient cancers (N = 13; p = 0.57). In platinum-resistant ovarian cancer (N = 35), ORR was 22.9% (95% CI 10.4-40.1%) with median PFS 6.8 months (95% CI 4.2-9.1). Median PFS in platinum-resistant HRR-HRD cancers (N = 7) was 10.5 months (95% CI 3.6-NA) and 5.6 months (95% CI 3.6-7.6) in HRR-HR proficient cancers (N = 18; p = 0.23). CONCLUSIONS: Cediranib/olaparib had clinical activity in both platinum-sensitive and -resistant ovarian cancer. Presence of HRR gene mutations was not associated with cediranib/olaparib activity in either setting.

Deep-learning-based pelvic automatic segmentation in pelvic fractures.

With the recent increase in traffic accidents, pelvic fractures are increasing, second only to skull fractures, in terms of mortality and risk of complications. Research is actively being conducted on the treatment of intra-abdominal bleeding, the primary cause of death related to pelvic fractures. Considerable preliminary research has also been performed on segmenting tumors and organs. However, studies on clinically useful algorithms for bone and pelvic segmentation, based on developed models, are limited. In this study, we explored the potential of deep-learning models presented in previous studies to accurately segment pelvic regions in X-ray images. Data were collected from X-ray images of 940 patients aged 18 or older at Gachon University Gil Hospital from January 2015 to December 2022. To segment the pelvis, Attention U-Net, Swin U-Net, and U-Net were trained, thereby comparing and analyzing the results using five-fold cross-validation. The Swin U-Net model displayed relatively high performance compared to Attention U-Net and U-Net models, achieving an average sensitivity, specificity, accuracy, and dice similarity coefficient of 96.77%, of 98.50%, 98.03%, and 96.32%, respectively.

Diagnosis of Glaucoma Based on Few-Shot Learning with Wide-Field Optical Coherence Tomography Angiography.

This study evaluated the utility of incorporating deep learning into the relatively novel imaging technique of wide-field optical coherence tomography angiography (WF-OCTA) for glaucoma diagnosis. To overcome the challenge of limited data associated with this emerging imaging, the application of few-shot learning (FSL) was explored, and the advantages observed during its implementation were examined. A total of 195 eyes, comprising 82 normal controls and 113 patients with glaucoma, were examined in this study. The system was trained using FSL instead of traditional supervised learning. Model training can be presented in two distinct ways. Glaucoma feature detection was performed using ResNet18 as a feature extractor. To implement FSL, the ProtoNet algorithm was utilized to perform task-independent classification. Using this trained model, the performance of WF-OCTA through the FSL technique was evaluated. We trained the WF-OCTA validation method with 10 normal and 10 glaucoma images and subsequently examined the glaucoma detection effectiveness. FSL using the WF-OCTA image achieved an area under the receiver operating characteristic curve (AUC) of 0.93 (95% confidence interval (CI): 0.912-0.954) and an accuracy of 81%. In contrast, supervised learning using WF-OCTA images produced worse results than FSL, with an AUC of 0.80 (95% CI: 0.778-0.823) and an accuracy of 50% (p-values < 0.05). Furthermore, the FSL method using WF-OCTA images demonstrated improvement over the conventional OCT parameter-based results (all p-values < 0.05). This study demonstrated the effectiveness of applying deep learning to WF-OCTA for glaucoma diagnosis, highlighting the potential of WF-OCTA images in glaucoma diagnostics. Additionally, it showed that FSL could overcome the limitations associated with a small dataset and is expected to be applicable in various clinical settings.

The Impact of Physical Activity on Thyroid Health: Insights From Representative Data in Korea.

CONTEXT: Thyroid hormones are essential for energy metabolism related to thermogenesis and oxygen consumption. OBJECTIVE: This study evaluated the potential association of thyroid function including thyroid peroxidase antibodies (TPOAb) with physical activity in nationally representative data. DESIGN/SETTING/PARTICIPANTS: This retrospective cohort study used data from the Korean National Health and Nutrition Examination Survey between 2013 and 2015. Physical activity (PA) was assessed using metabolic equivalents based on the validated Korean version of the International Physical Activity Questionnaire Short Form. PA level was categorized into 3 groups of high, moderate, and low. Participants with abnormal thyroid function test, restricted activity, or previous history of thyroid disease were excluded in the study. RESULTS: A total of 5372 participants was finally selected. The free T4 level was lowest in the low PA group, while TSH was not significantly different among the groups. TPOAb titers increased in the following order: moderate PA, low PA, and high PA. After adjustment for confounding factors, moderate PA was associated with a high T4 level and a decrease in TSH and TPOAb with significance. However, there were no significant changes in free T4, TSH, or TPOAb titer in the high PA group. In a subanalysis, females with moderate PA showed a significant decrease in TSH and TPOAb. In both males and females, insulin sensitivity was increased with moderate PA. In obese participants, TSH negatively correlated with PA, and free T4 levels decreased in the low PA. The sensitivity to thyroid hormone did not differ in our study. CONCLUSION: The present study found an association between thyroid function and moderate PA. Therefore, moderate-intensity PA should be recommended to improve thyroid function.

Pressure change at ankle joint in supramalleolar osteotomy with or without fibular osteotomy according to different types of varus ankle.

The need for additional fibular osteotomy (FO) when performing supramalleolar osteotomy (SMO) in the varus ankle arthritis (VAA) is controversial. Some cadaveric studies have been performed to prove this; however, it is difficult to implement deformities including talar tilting and translation in cadavers. In this study, we created a model of VAA with the tilting and translation using three-dimensional (3-D) finite element (FE) analysis and analyzed the results of SMO with or without FO depending on the types of VAA. The validated normal foot and ankle 3-D FE model was constructed including the ankle cartilages of the talar dome and tibia plafond. The VAA models were determined and reconstructed by following the classification of VAA, VAA with medial translation for stage 3a, VAA with varus tilting (7.5°) for stage 3b. The postoperative SMO models (SMO with and without FO) were reconstructed by corresponding to each VAA models. The FE analysis conditions were commonly applied. The boundary condition of ankle joint was defined as "sliding condition" and applied 0.002 friction coefficient to realize lubricative property. Loading condition was assumed as a two-leg standing position and half of the subject body weight (325 N) was loaded on center of ground to vertical direction. Contact pressure changes were predicted at the medial ankle cartilage. As a result, in VAA with medial translation, isolated SMO may provide sufficient pressure reduction at the medial ankle joint. However, in VAA with varus tilting, SMO combined with FO could appropriately relieve concentrated pressure at the medial ankle joint.

The CHK1 inhibitor prexasertib in BRCA wild-type platinum-resistant recurrent high-grade serous ovarian carcinoma: a phase 2 trial.

The multi-cohort phase 2 trial NCT02203513 was designed to evaluate the clinical activity of the CHK1 inhibitor (CHK1i) prexasertib in patients with breast or ovarian cancer. Here we report the activity of CHK1i in platinum-resistant high-grade serous ovarian carcinoma (HGSOC) with measurable and biopsiable disease (cohort 5), or without biopsiable disease (cohort 6). The primary endpoint was objective response rate (ORR). Secondary outcomes were safety and progression-free survival (PFS). 49 heavily pretreated patients were enrolled (24 in cohort 5, 25 in cohort 6). Among the 39 RECISTv1.1-evaluable patients, ORR was 33.3% in cohort 5 and 28.6% in cohort 6. Primary endpoint was not evaluable due to early stop of the trial. The median PFS was 4 months in cohort 5 and 6 months in cohort 6. Toxicity was manageable. Translational research was an exploratory endpoint. Potential biomarkers were investigated using pre-treatment fresh biopsies and serial blood samples. Transcriptomic analysis revealed high levels of DNA replication-related genes (POLA1, POLE, GINS3) associated with lack of clinical benefit [defined post-hoc as PFS < 6 months]. Subsequent preclinical experiments demonstrated significant cytotoxicity of POLA1 silencing in combination with CHK1i in platinum-resistant HGSOC cell line models. Therefore, POLA1 expression may be predictive for CHK1i resistance, and the concurrent POLA1 inhibition may improve the efficacy of CHK1i monotherapy in this hard-to-treat population, deserving further investigation.

Investigating the safety profiles of exogenous melatonin and associated adverse events: A pharmacovigilance study using WHO-VigiBase.

Melatonin, a pineal hormone that modulates circadian rhythms, sleep, and neurotransmitters, is widely used to treat sleep disorders. However, there are limited studies on the safety of melatonin. Therefore, we aimed to present the overall patterns of adverse events (AEs) following melatonin administration and identify potential safety signals associated with melatonin. Using VigiBase, a global individual case safety report (ICSRs) database managed by the World Health Organization (WHO), we conducted a retrospective, observational, pharmacovigilance study of melatonin between January 1996 and September 2022. Disproportionality analysis was conducted using two comparator settings: all other drugs and other sleep medications. We used multivariable logistic regression to estimate reporting odds ratios (RORs) with 95% confidence intervals (CIs) to compare the frequencies of AEs reporting between melatonin and each comparator setting. Furthermore, we assessed adverse events of special interests (AESIs) that could potentially be associated with melatonin. Signals were identified when the following criteria were met: cases ≥3, x2 ≥ 4, IC025 ≥ 0, and the lower end of the 95% CI of ROR > 2. These signals were then compared with the AE information on the drug labels provided by regulatory bodies. A total of 35 479 AE reports associated with melatonin were identified, with a higher proportion of reports from females (57.1%) and individuals aged 45-64 years (20.8%). We identified 21 AEs that were commonly detected as safety signals in the disproportionality analyses, including tic, educational problems, disturbance in social behavior, body temperature fluctuation, and growth retardation. In AESI analyses, accidents and injuries (adjusted ROR 2.97; 95% CI, 2.80-3.16), fall (2.24; 2.12-2.37), nightmare (4.90; 4.37-5.49), and abnormal dreams (3.68; 3.19-4.25) were detected as a signal of melatonin when compared to all other drugs, whereas those signals were not detected when compared to other sleep medications. In this pharmacovigilance study, exogenous melatonin showed safety profiles comparable to other sleep medications. However, several unexpected potential safety signals were identified, underscoring the need for further investigation at the population level.

Comparison of the Usefulness of Computer-Assisted Three-Dimensional Analysis and Weight-Bearing Radiographs in Ankle Osteoarthritis.

Background: To evaluate the degree of deformation in patients with ankle osteoarthritis (OA), it is essential to measure the three-dimensional (3D), in other words, stereoscopic alignment of the ankle, subtalar, and foot arches. Generally, measurement of radiological parameters use two-dimensional (2D) anteroposterior and lateral radiographs in a weight-bearing state; however, computer-aided 3D analysis (Disior) using weight-bearing cone-beam computed tomography (CBCT) has recently been introduced. Methods: In this study, we compared the 2D human radiographic method with a stereoscopic image in patients with ankle arthritis. We enrolled 57 patients diagnosed with OA (28 left and 29 right) and obtained both standing radiographs and weight-bearing CBCT. Patients were divided by the Takakura stage. The interclass correlation coefficient (ICC) for each result was confirmed. Results: On the ICC between 2D radiographs and 3D analysis, the tibiotalar surface angle and lateral talo-1st metatarsal angle showed a good ICC grade (> 0.6), while other parameters did not have significant ICC results. Three-dimension was superior to radiographs in terms of statistical significance. Conclusions: We demonstrated that 2D and stereoscopic images are useful for the diagnosis of OA. Our study also confirmed that the radiographic features affected by ankle OA varied. However, according to the results, the typical radiography is not sufficient to diagnose and determine a treatment plan for ankle OA. Therefore, the method of using 3D images should be considered.

Actinidia polygama Water Extract (APWE) Protects Against UVB-Induced Photoaging via MAPK/AP-1 and TGFß-Smad Pathway.

BACKGROUND: Actinidia polygama (silver vine) has been used in oriental medicine to treat gout, rheumatoid arthritis, and inflammation. Actinidia polygama water extract (APWE) is named PB203. OBJECTIVE: To investigate whether PB203 has anti-photoaging effects and to understand the molecular mechanism underlying such effects. METHODS: The antioxidant effect was assessed by 1,1-diphenyl-2-picrylhydrazyl assay and 2',7'-dichlorodihydrofluorescein diacetate staining in ultraviolet B (UVB)-irradiated HaCaT cells with or without PB203 treatment. Type I collagen, matrix metalloproteinase-1 (MMP-1), tissue inhibitor of metalloproteinase (TIMP-1), hyaluronic acid (HA), hyaluronan synthase 1 (HAS1) and HAS2 levels were measuring by enzyme-linked immunosorbent assay or reverse transcription quantitative polymerase chain reaction. Also, we investigate the effects of PB203 on wrinkle formation, and the potential mechanisms underlying such effects were investigated in UVB-induced wrinkle mouse model mice. RESULTS: PB203 alleviated the UVB-induced reactive oxygen species production, phosphorylation of JNK, ERK, and p38, and formation of AP-1. In addition, PB203 inhibited the decreases in type I collagen and TIMP-1 levels, and the increase in MMP-1 levels in UVB-exposed HaCaT cells. In UVB-induced wrinkle mouse model, PB203 inhibited the decreases in elastin and type I collagen levels as well as the increases in MMP-1 expression, wrinkle formation, and skin dehydration. Furthermore, PB203 increased the expression of filaggrin, HAS1, and HAS2, improving the skin barrier function. CONCLUSION: Taken together, we found that PB203 is as a potent candidate to serve as a functional ingredient or therapeutic agent to improve UVB-mediated skin aging.