The Making of a Flight Feather: Bio-architectural Principles and Adaptation.

The evolution of flight in feathered dinosaurs and early birds over millions of years required flight feathers whose architecture features hierarchical branches. While barb-based feather forms were investigated, feather shafts and vanes are understudied. Here, we take a multi-disciplinary approach to study their molecular control and bio-architectural organizations. In rachidial ridges, epidermal progenitors generate cortex and medullary keratinocytes, guided by Bmp and transforming growth factor ß (TGF-ß) signaling that convert rachides into adaptable bilayer composite beams. In barb ridges, epidermal progenitors generate cylindrical, plate-, or hooklet-shaped barbule cells that form fluffy branches or pennaceous vanes, mediated by asymmetric cell junction and keratin expression. Transcriptome analyses and functional studies show anterior-posterior Wnt2b signaling within the dermal papilla controls barbule cell fates with spatiotemporal collinearity. Quantitative bio-physical analyses of feathers from birds with different flight characteristics and feathers in Burmese amber reveal how multi-dimensional functionality can be achieved and may inspire future composite material designs. VIDEO ABSTRACT.

A novel HDAC6 inhibitor interferes microtubule dynamics and spindle assembly checkpoint and sensitizes cisplatin-induced apoptosis in castration-resistant prostate cancer.

BACKGROUND: Metastatic castration-resistant prostate cancer (CRPC), the most refractory prostate cancer, inevitably progresses and becomes unresponsive to hormone therapy, revealing a pressing unmet need for this disease. Novel agents targeting HDAC6 and microtubule dynamics can be a potential anti-CRPC strategy. METHODS: Cell proliferation was examined in CRPC PC-3 and DU-145 cells using sulforhodamine B assay and anchorage-dependent colony formation assay. Flow cytometric analysis of propidium iodide staining was used to determine cell-cycle progression. Cell-based tubulin polymerization assay and confocal immunofluorescence microscopic examination determine microtubule assembly/disassembly status. Protein expressions were determined using Western blot analysis. RESULTS: A total of 82 novel derivatives targeting HDAC6 were designed and synthesized, and Compound 25202 stood out, showing the highest efficacy in blocking HDAC6 (IC50, 3.5 nM in enzyme assay; IC50, 1.0 µM in antiproliferative assay in CRPC cells), superior to tubastatin A (IC50, 5.4 µM in antiproliferative assay). The selectivity and superiority of 25202 were validated by examining the acetylation of both α-tubulin and histone H3, detecting cell apoptosis and HDACs enzyme activity assessment. Notably, 25202 but not tubastatin A significantly decreased HDAC6 protein expression. 25202 prolonged mitotic arrest through the detection of cyclin B1 upregulation, Cdk1 activation, mitotic phosphoprotein levels, and Bcl-2 phosphorylation. Compound 25202 did not mimic docetaxel in inducing tubulin polymerization but disrupted microtubule organization. Compound 25202 also increased the phosphorylation of CDC20, BUB1, and BUBR1, indicating the activation of the spindle assembly checkpoint (SAC). Moreover, 25202 profoundly sensitized cisplatin-induced cell death through impairment of cisplatin-evoked DNA damage response and DNA repair in both ATR-Chk1 and ATM-Chk2 pathways. CONCLUSION: The data suggest that 25202 is a novel selective and potent HDAC6 inhibitor. Compound 25202 blocks HDAC6 activity and interferes microtubule dynamics, leading to SAC activation and mitotic arrest prolongation that eventually cause apoptosis of CRPC cells. Furthermore, 25202 sensitizes cisplatin-induced cell apoptosis through impeding DNA damage repair pathways.

Multitask deep learning on mammography to predict extensive intraductal component in invasive breast cancer.

OBJECTIVES: To develop a multitask deep learning (DL) algorithm to automatically classify mammography imaging findings and predict the existence of extensive intraductal component (EIC) in invasive breast cancer. METHODS: Mammograms with invasive breast cancers from 2010 to 2019 were downloaded for two radiologists performing image segmentation and imaging findings annotation. Images were randomly split into training, validation, and test datasets. A multitask approach was performed on the EfficientNet-B0 neural network mainly to predict EIC and classify imaging findings. Three more models were trained for comparison, including a single-task model (predicting EIC), a two-task model (predicting EIC and cell receptor status), and a three-task model (combining the abovementioned tasks). Additionally, these models were trained in a subgroup of invasive ductal carcinoma. The DeLong test was used to examine the difference in model performance. RESULTS: This study enrolled 1459 breast cancers on 3076 images. The EIC-positive rate was 29.0%. The three-task model was the best DL model with an area under the curve (AUC) of EIC prediction of 0.758 and 0.775 at the image and breast (patient) levels, respectively. Mass was the most accurately classified imaging finding (AUC = 0.915), followed by calcifications and mass with calcifications (AUC = 0.878 and 0.824, respectively). Cell receptor status prediction was less accurate (AUC = 0.625-0.653). The multitask approach improves the model training compared to the single-task model, but without significant effects. CONCLUSIONS: A mammography-based multitask DL model can perform simultaneous imaging finding classification and EIC prediction. CLINICAL RELEVANCE STATEMENT: The study results demonstrated the potential of deep learning to extract more information from mammography for clinical decision-making. KEY POINTS: • Extensive intraductal component (EIC) is an independent risk factor of local tumor recurrence after breast-conserving surgery. • A mammography-based deep learning model was trained to predict extensive intraductal component close to radiologists' reading. • The developed multitask deep learning model could perform simultaneous imaging finding classification and extensive intraductal component prediction.

Risk Factors of Long-Term Sequelae After Transcatheter Closure of Perimembranous Ventricular Septal Defect in Young Children.

BACKGROUND: Complications arising from transcatheter closure of perimembranous ventricular septal defects (pmVSD) in children, such as residual shunts and aortic regurgitation (AR), have been observed. However, the associated risk factors remain unclear. This study identified risk factors linked with residual shunts and AR following transcatheter closure of pmVSD in children aged 2-12 years. METHODS AND RESULTS: The medical records of 63 children with pmVSD and a pulmonary-to-systemic blood flow ratio <2.0 who underwent transcatheter closure between 2011 and 2018 were analyzed with a minimum 3-year follow-up. The success rate of transcatheter closure was 98.4%, with no emergency surgery, permanent high-degree atrioventricular block, or mortality. Defects ≥4.5 mm had significantly higher odds of persistent residual shunt (odds ratio [OR] 6.85; P=0.03). The use of an oversize device (≥1.5 mm) showed a trend towards reducing residual shunts (OR 0.23; P=0.06). Age <4 years (OR 27.38; 95% confidence interval [CI] 2.33-321.68) and perimembranous outlet-type VSD (OR 11.94, 95% CI 1.10-129.81) were independent risk factors for AR progression after closure. CONCLUSIONS: Careful attention is crucial for pmVSDs ≥4.5 mm to prevent persistent residual shunts in transcatheter closure. Assessing AR risk, particularly in children aged <4 years, is essential while considering the benefits of pmVSD closure.

Biomechanical analysis of plate versus K-wire fixation for metacarpal shaft fractures with wedge-shaped bone defects.

BACKGROUND: Metacarpal shaft fracture is a common type of hand fracture. Numerous studies have explored fixing transverse fractures in the midshaft of the metacarpal bone. However, this section of the metacarpal bone is often susceptible to high-energy injury, resulting in comminuted fracture or bone loss. In such cases, wedge-shaped bone defects can develop in the metacarpal shaft, increasing the difficulty of performing fracture fixation. Notably, the research on this type of fracture fixation is limited. This study compared the abilities of four fixation methods to fix metacarpal shaft fractures with wedge-shaped bone defects. METHODS: In total, 28 artificial metacarpal bones were used. To create wedge-shaped bone defects, an electric saw was used to create metacarpal shaft fractures at the midshaft of each bone. The artificial metacarpal bones were then divided into four groups for fixation. The bones in the first group were fixed with a dorsal locked plate (DP group), those in the second group were fixed with a volar locked plate (VP group), and those in the third group were fixed by combining dorsal and volar locked plates (DP + VP group), and those in the fourth group were fixed with two K-wires (2 K group). Cantilever bending tests were conducted using a material testing machine to measure yielding force and stiffness. The four groups' fixation capabilities were then assessed through analysis of variance and Tukey's test. RESULTS: The DP + VP group (164.1±44.0 N) achieved a significantly higher yielding force relative to the 2 K group (50.7 ± 8.9 N); the DP group (13.6 ± 3.0 N) and VP group (12.3 ± 1.0 N) did not differ significantly in terms of yielding force, with both achieving lower yielding forces relative to the DP + VP group and 2 K group. The DP + VP group (19.8±6.3 N/mm) achieved the highest level of stiffness, and the other three groups did not differ significantly in terms of stiffness (2 K group, 5.4 ± 1.1 N/mm; DP group, 4.0 ± 0.9 N/mm; VP group, 3.9 ± 1.9 N/mm). CONCLUSIONS: The fixation method involving the combined use of dorsal and volar locked plates (DP + VP group) resulted in optimal outcomes with respect to fixing metacarpal shaft fractures with volar wedge bone defects.

Risk factors of stent migration in esophageal cancer patients who underwent fully-covered self-expanding metal stents for malignant dysphagia or tracheoesophageal fistula.

BACKGROUND: More than 50% of esophageal cancer patients are diagnosed with advanced diseases and commonly experience dysphagia, some of whom even have tracheoesophageal fistula. Self-expandable metal stent (SEMS) is one of the recommended palliative methods, although complications such as chest pain and stent migration are not uncommon. The goal of this study was to examine the predictors of stent migration. METHODS: We conducted a retrospective cohort study to include patients with esophageal cancer and dysphagia/tracheoesophageal fistula. Clinicopathological information, stent characteristics and patient outcomes were collected for analysis, while side-effects of SEMS were recorded, potential predictors were examined, and patients' nutritional outcomes were compared in the migration and non-migration groups. RESULTS: A total of 54 patients with esophageal cancer who received fully covered SEMS between 2013 and 2022 were included. We found tumor across the esophagogastric junction (adjusted odds ratio (OR) = 32.64, P = 0.01) and the female sex (adjusted OR = 12.5, P = 0.02) were significant predictors for stent migration. There was a decreasing tendency in body mass index/body weight in migration and non-migration groups, but the former had a steeper downslope. CONCLUSION: Fully covered SEMS is a safe and effective strategy to palliate dysphagia or fistula. Tumor across esophagogastric junction and the female sex were higher risk predictors of stent migration. A careful patient selection would optimize the effects of SEMS placement, especially in those with short-expected lifespan.

Mechanistic study of dual-function inhibitors targeting topoisomerase II and Rad51-mediated DNA repair pathway against castration-resistant prostate cancer.

BACKGROUND: Castration-resistant prostate cancer (CRPC) is refractory to hormone treatment and the therapeutic options are continuously advancing. This study aims to discover the anti-CRPC effects and underlying mechanisms of small-molecule compounds targeting topoisomerase (TOP) II and cellular components of DNA damage repair. METHODS: Cell proliferation was determined in CRPC PC-3 and DU-145 cells using anchorage-dependent colony formation, sulforhodamine B assay and flow cytometric analysis of CFSE staining. Flow cytometric analyses of propidium iodide staining and JC-1 staining were used to examine the population of cell-cycle phases and mitochondrial membrane potential, respectively. Nuclear extraction was performed to detect the nuclear localization of cellular components in DNA repair pathways. Protein expressions were determined using Western blot analysis. RESULTS: A series of azathioxanthone-based derivatives were synthesized and examined for bioactivities in which WC-A13, WC-A14, WC-A15, and WC-A16 displayed potent anti-CRPC activities in both PC-3 and DU-145 cell models. These WC-A compounds selectively downregulated both TOP IIα and TOP IIß but not TOP I protein expression. WC-A13, WC-A14, and WC-A15 were more potent than WC-A16 on TOP II inhibition, mitochondrial dysfunction, and induction of caspase cascades indicating the key role of amine-containing side chain of the compounds in determining anti-CRPC activities. Furthermore, WC-A compounds induced an increase of γH2AX and activated ATR-Chk1 and ATM-Chk2 signaling pathways. P21 protein expression was also upregulated by WC-A compounds in which WC-A16 showed the least activity. Notably, WC-A compounds exhibited different regulation on Rad51, a major protein in homologous recombination of DNA in double-stranded break repair. WC-A13, WC-A14, and WC-A15 inhibited, whereas WC-A16 induced, the nuclear translocation of Rad51. CONCLUSION: The data suggest that WC-A compounds exhibit anti-CRPC effects through the inhibition of TOP II activities, leading to mitochondrial stress-involved caspase activation and apoptosis. Moreover, WC-A13, WC-A14, and WC-A15 but not WC-A16 display inhibitory activities of Rad51-mediated DNA repair pathway which may increase apoptotic effect of CRPC cells.

Cross-cultural adaptation and validation of the Traditional Chinese version of the Core Outcome Measures Index in patients with low back pain.

PURPOSE: This study aimed to carry out a cross-cultural adaptation of the Core Outcome Measures Index (COMI) for use in Traditional Chinese-speaking patients with low back pain (LBP) and to investigate its psychometric properties. METHODS: A total of 224 patients with LBP > 6 weeks who visited our spine center from May 2018 to May 2019 were included in the study. Patients completed a booklet of questionnaires including the following: (1) pain Numeric Rating Scale, (2) Oswestry Disability Index, (3) Roland-Morris Disability Questionnaire, (4) EuroQol-five dimension (EQ-5D), and (5) COMI. Patients were sent a second booklet (also containing a transition question to indicate any change in condition) to be completed again within one month after the first. Fifty-two patients did not receive any intervening treatment (group 1), while the other 172 patients received medical treatment (group 2) between the two questionnaires. RESULTS: The intraclass correlation coefficient (ICC) for the COMI summary score was 0.94 (95% CI 0.89-0.97); the standard error of measurement (SEM) was 0.41 and the minimum detectable change (MDC) score was 1.14. The COMI summary scores showed a low floor effect (1.8%) and ceiling effect (0.4%). All COMI item scores demonstrated the hypothesized correlations with their corresponding full-length questionnaires except for the pain item (correlation stronger than hypothesized). Standardized response means (SRM) for the COMI items in the treated group were between 0.58 and 1.30. Regarding the ability of the COMI change score to differentiate between good and poor outcomes, the area under the receiver operating characteristic (AUROC) curve was 0.77 [standard error (SE) 0.07, 95% confidence interval (CI) 0.68-0.84] and the minimal clinically important change (MCIC) score was ≥ 1.85 points. CONCLUSION: The Traditional Chinese COMI represents a practical and reliable tool for the assessment of Traditional Chinese-speaking patients with back problems.

New classification for bone type at dental implant sites: a dental computed tomography study.

OBJECTIVE: This study proposed a new classification method of bone quantity and quality at the dental implant site using cone-beam computed tomography (CBCT) image analysis, classifying cortical and cancellous bones separately and using CBCT for quantitative analysis. METHODS: Preoperative CBCT images were obtained from 128 implant patients (315 sites). First, measure the crestal cortical bone thickness (in mm) and the cancellous bone density [in grayscale values (GV) and bone mineral density (g/cm3)] at the implant sites. The new classification for bone quality at the implant site proposed in this study is a "nine-square division" bone classification system, where the cortical bone thickness is classified into A: > 1.1 mm, B:0.7-1.1 mm, and C: < 0.7 mm, and the cancellous bone density is classified into 1: > 600 GV (= 420 g/cm3), 2:300-600 GV (= 160 g/cm3-420 g/cm3), and 3: < 300 GV (= 160 g/cm3). RESULTS: The results of the nine bone type proportions based on the new jawbone classification were as follows: A1 (8.57%,27/315), A2 (13.02%), A3 (4.13%), B1 (17.78%), B2 (20.63%), B3 (8.57%) C1 (4.44%), C2 (14.29%), and C3 (8.57%). CONCLUSIONS: The proposed classification can complement the parts overlooked in previous bone classification methods (bone types A3 and C1). TRIAL REGISTRATION: The retrospective registration of this study was approved by the Institutional Review Board of China Medical University Hospital, No. CMUH 108-REC2-181.

Recurrent Exacerbations and Evolution into Polymyositis in a Patient with Interstitial Pneumonia with Autoimmune Features: A Case Report and Literature Review.

Interstitial pneumonia with autoimmune features (IPAF) is a new disease entity proposed in 2015. Numerous questions regarding IPAF require clarification, including diagnostic criteria, standard managements for stable disease and exacerbation, and prognosis. We report a case of a 67-year-old Asian woman who presented with progressive dyspnea. Chest computed tomography (CT) scans revealed nonspecific interstitial pneumonia. Serologic testing indicated positive anti-Jo-1 without presence of extrathoracic manifestations. An IPAF diagnosis was made after a multidisciplinary discussion. The patient experienced a severe exacerbation requiring mechanical ventilation, and she was successfully salvaged with methylprednisolone pulse therapy and single-dose cyclophosphamide. During the one-year follow-up, she reported bilateral leg muscle weakness with noticeably elevated serum creatine kinase, suggesting polymyositis. The development of malignancy was also noted 15 months after the initial presentation, and the patient eventually died. This report demonstrated successful salvage treatment with glucocorticoid pulse therapy for IPAF with acute exacerbation. However, the maintenance therapy failed to control disease progression. The treatment strategies for exacerbation and stable disease in IPAF remain unknown and need further studies. Given the high risk of evolution into a defined connective tissue disease (CTD), regular evaluation of the clinical features and biomarkers of CTDs is essential for patients with IPAF.

The Operational Feasibility of Vaccination Programs Targeting Influenza Risk Groups in the World Health Organization (WHO) African and South-East Asian Regions.

BACKGROUND: Influenza vaccination is uncommon in low-resource settings. We evaluated aspects of operational feasibility of influenza vaccination programs targeting risk groups in the World Health Organization (WHO) African (AFR) and South-East Asian (SEAR) Regions. METHODS: We estimated routine immunization and influenza vaccination campaign doses, doses per vaccinator, and cold storage requirements for 1 simulated country in each region using evidence-based population distribution, vaccination schedule, and vaccine volumes. Influenza vaccination targeted persons <5 years, pregnant women, persons with chronic diseases, persons ≥65 years, and healthcare workers (HCW). For the AFR country, we compared vaccine volumes to actual storage capacities. RESULTS: Targeting HCW had a small operational impact, and subsequent findings exclude this group. During 3-month influenza vaccination campaigns, monthly doses delivered in the AFR country increased from 15.0% for ≥65 years to 93.1% for <5 years and in the SEAR country from 19.6% for pregnant women to 145.0% for persons with chronic diseases. National-level cold storage capacity requirements increased in the AFR country from 4.1% for ≥65 years to 20.3% for <5 years and in the SEAR country from 3.9% for pregnant women to 28.8% for persons with chronic diseases. Subnational-level cold storage capacity requirements increased in the AFR country from 5.9% for ≥65 years to 36.8% for <5 years and the SEAR country from 17.6% for pregnant women to 56.0% for persons with chronic diseases. CONCLUSIONS: Influenza vaccination of most risk groups will require substantial increases in doses, doses per vaccinator, and cold storage capacity in countries where infrastructure and resources are limited.

Operando photoelectron spectroscopy analysis of graphene field-effect transistors.

In this study, operando photoelectron spectroscopy was used to characterize the performance of graphene field-effect transistors under working conditions. By sweeping the back-gate voltages, the carrier concentration of the graphene channel on the 150 nm Si3N4/Si substrate was tuned. From the C1s core level spectra acquired under the application of different gate voltages, the binding energy shifts caused by electric-field effects were obtained and analyzed. Together with the C1s peak shape information and the photoluminescence spectrum of the Si3N4/Si substrate, the presence of local potential across the x-ray beam spot associated with defects and gate leakage current in amorphous Si3N4was identified. The presence of defects in Si3N4/Si substrate could not only screen the partial electric field generated by the back gate but also serve as long-range scattering centers to the carriers, thus affecting charge transport in the graphene channel. Our findings will help further investigate the dielectric/graphene interface properties and accelerate the utilization of graphene in real device applications.

Optical determination of layered-materials InSe thickness via RGB contrast method and regression analysis.

Indium selenide (InSe) features intriguing thickness-dependent optoelectronic properties, and a simple, and precise way to identify the thickness is essential for the rapid development of InSe research. Here, a red, green, and blue (RGB) color contrast method with regression analysis for quantitative correlation of three optical contrasts from RGB channels with the InSe thickness (1-35 nm), is demonstrated. The lower accuracy of the thickness identification obtained from the individual channels was discussed. Moreover, the effective refractive indices in the three RGB regions can be extracted from the Fresnel equation and numerical analysis by finding the best fit to the experimental optical contrast. After further consideration of the wavelength-dependent refractive indices, the slope of the regression line between the estimated thickness and that obtained from the atomic force microscope was improved from 1.59 ± 0.05 to 0.97 ± 0.02. The complex refractive index spectra of InSe (1-10 layers) generated fromab initionumerical calculation results were also adopted to identify the InSe thickness. Compared to dispersion, the evolution of the band structure had less effect on thickness identification. This work could be extended to other layered materials, facilitate the thickness-dependent study of layered materials, and expedite the realization of their practical applications.

Intermittent parathyroid hormone treatment affects the bone structural parameters and mechanical strength of the femoral neck after ovariectomy-induced osteoporosis in rats.

BACKGROUND: Menopause-induced decline in estrogen levels in women is a main factor leading to osteoporosis. The objective of this study was to investigate the effect of intermittent parathyroid hormone (PTH) on bone structural parameters of the femoral neck in ovariectomized rats, in addition to correlations of maximum fracture force. METHODS: Fifteen female Wister rats were divided into three groups: (1) control group; (2) ovariectomized (OVX) group; and (3) OVX + PTH group. All rats were then killed and the femurs extracted for microcomputed tomography scanning to measure volumetric bone mineral density (vBMD) and bone structural parameters of the femoral neck. Furthermore, the fracture forces of femoral neck were measured using a material testing system. RESULTS: Compared with the control and OVX + PTH groups, the OVX group had significantly lower aBMD, bone parameter, and mechanical strength values. A comparison between OVX and OVX + PTH groups indicated that PTH treatment increased several bone parameters. However, the OVX + PTH groups did not significantly differ with the control group with respect to the bone structural parameters, except for trabecular bone thickness of cancellous bone, which was greater. In addition, among the bone structural parameters, the CSA and BSI of cortical bone were significantly correlated with the maximum fracture force of the femoral neck, with correlations of, respectively, 0.682 (p = 0.005) and 0.700 (p = 0.004). CONCLUSION: Intermittent PTH helped treat ovariectomy-induced osteoporosis of cancellous bone and cortical bone in the femoral necks of rats. The ability of the femoral neck to resist fracture was highly correlated with the two parameters, namely cross-sectional area (CSA) and bone strength index (= vBMD × CSA), of cortical bone in the femoral neck and was less correlated with aBMD or other bone structural parameters.

Biomechanical Evaluation and Factorial Analysis of the 3-Dimensional Printing Self-Designed Metallic Reconstruction Plate for Mandibular Segmental Defect.

PURPOSE: Reconstruction plates are frequently used to treat mandibular segmental defects. The aim of this study is to compare the biomechanical performance of a 3-dimensional-printed self-designed titanium alloy reconstruction plate with that of the traditional reconstruction plate in mandible reconstruction. The analyzed parameters of the self-designed reconstruction plate, including plate length (100 mm and 125 mm), plate thickness (2.1, 2.4, and 2.7 mm), and bone mass (100, 75, and 50%), were also evaluated. METHODS: An artificial mandible with anatomical geometry was used to develop the self-designed reconstructed plate. Both in vitro experiments and finite element simulations were performed for the biomechanical comparison of the self-designed and traditional reconstruction plates. In finite element analysis, 3 major muscle forces of mandible movement were set as the loading condition, and the displacement of the condyle was fixed in all directions as the boundary condition. RESULTS: The biomechanical performances (stresses in the plate and strains in bone) of the self-designed reconstruction plate were superior to those of the traditional plate. Factorial analysis indicated that plate length and thickness had significant effects on decreasing stresses of the plate and mandibular bone. CONCLUSIONS: The self-designed reconstruction plate might have a benefit to reduce the stresses/strains in plate itself and surrounding bone.

Incisor liability and its effects among East Asian children.

BACKGROUND/PURPOSE: Incisor liability is the discrepancy in the sum of the mesiodistal crown width between the primary and permanent incisors. Incisor liability affects the integrity and eruption of the permanent incisors during the transition from the primary to permanent dentition. This study investigated the incisor liability in the primary dentition of Taiwanese children. METHODS: The digital periapical films of 203 upper arches of 105 boys and 98 girls and 195 lower arches of 119 boys and 76 girls aged between 3 and 6 years were selected in this retrospective study. The mesiodistal crown widths of the primary and permanent incisors were measured using the medical imaging software for both arches. Differences in incisor liability values were statistically analyzed. RESULTS: The mean ± standard deviation of the incisor liability values were 8.32 ± 1.88 and 6.91 ± 1.13 mm for the upper and lower arches, respectively, in all children. The incisor liability was closely related with the total crown widths of the permanent incisors for upper and lower arches. The incisor liability values were higher among boys than girls for the upper but not lower arch. CONCLUSION: Incisor liability differs depending on ethnicity. In Taiwanese children, incisor liability was closely related with the crown widths of the permanent incisors. The incisor liability values of boys were higher than those of girls in the upper arch but not the lower arch.

Lowering the Intraocular Pressure in Rats and Rabbits by Cordyceps cicadae Extract and Its Active Compounds.

Cordyceps cicadae (CC), an entomogenous fungus that has been reported to have therapeutic glaucoma, is a major cause of blindness worldwide and is characterized by progressive retinal ganglion cell (RGC) death, mostly due to elevated intraocular pressure (IOP). Here, an ethanolic extract of C. cicadae mycelium (CCME), a traditional medicinal mushroom, was studied for its potential in lowering IOP in rat and rabbit models. Data showed that CCME could significantly (60.5%) reduce the IOP induced by microbead occlusion after 56 days of oral administration. The apoptosis of retinal ganglion cells (RGCs) in rats decreased by 77.2%. CCME was also shown to lower the IOP of normal and dextrose-infusion-induced rabbits within 60 min after oral feeding. There were dose effects, and the effect was repeatable. The active ingredient, N6-(2-hydroxyethyl)-adenosine (HEA), was also shown to alleviate 29.6% IOP at 0.2 mg/kg body weight in this rabbit model. CCME was confirmed with only minor inhibition in the phosphorylated myosin light chain 2 (pMLC2) pathway.

Effects of essential oil mixtures on nitrogen metabolism and odor emission via in vitro simulated digestion and in vivo growing pig experiments.

BACKGROUND: Essential oils (EOs) are extensively used in swine production because of their bioactive action in gut health. In addition, some EOs have the potential to reduce waste emission. The present study aimed to find an optimal combination of carvacrol, thymol and cinnamaldehyde to promote nitrogen utilization and reduce waste emission by a model in vitro and an animal study. RESULTS: In the study in vitro, various dosages of essential oils (EOs) were used to evaluate the effect on nitrogen metabolism through a three-step model. Compared with other EO combinations, 2EO (10 ppm cinnamaldehyde and 20 ppm thymol), and 3EO (10 ppm cinnamaldehyde, 20 ppm thymol and 200 ppm carvacrol) displayed greater nitrogen digestibility, lesser ammonia production and lower activity of microbial enzymes. In the animal study, growing male Landrace × Yorkshire pigs (initial body weight: 31.8 ± 3.3 kg, n = 18) were randomly divided into three groups and fed the control, 2EO or 3EO diet for 4 weeks. Pigs fed 3EO exhibited the greatest nitrogen digestibility (85.4%, P < 0.05). EO supplementation decreased the emission of ammonia (130-140 vs. 223 mg g-1 ) and total fecal nitrogen (8.0-9.9 vs. 12.4 g d-1 ) (P < 0.05). Microbial protease and urease activities were inhibited by EO treatments (P < 0.01). Both 2EO and 3EO reduced the content of indole and 3-methylindole (P < 0.01), whereas only 2EO caused a decrease in p-cresol (P < 0.1). CONCLUSION: 2EO was suitable for reducing waste emission and odorous compounds in growing pigs, whereas 3EO was optimal for increasing nitrogen utilization and partially reducing waste odorous compounds. © 2021 Society of Chemical Industry.

Comparison of the Efficacies of Direct-Acting Antiviral Treatment for HCV Infection in People Who Inject Drugs and Non-Drug Users.

Background and Objectives: Hepatitis C virus (HCV) is a major cause of liver disease worldwide. People who inject drugs (PWIDs) constitute the majority of patients with HCV infection in the United States and Central Asia. There are several obstacles to treating HCV infection in PWIDs because PWIDs are often accompanied by concurrent infection, low compliance, substance abuse, and risky behavior. The aim of the study is to compare the efficacies of direct-acting antiviral (DAA) therapy for HCV infection in PWIDs and those without opioid injection. Materials and Methods: In this retrospective cohort study, we included 53 PWIDs with HCV infections treated on site in a methadone program and 106 age- and sex-matched patients with HCV infections who had no history of opioid injection (ratio of 1:2). All eligible subjects received anti-HCV treatment by DAA agents in our hospital from March 2018 to December 2020. The charts of these patients were carefully reviewed for demographic data, types of DAA agents, and treatment outcomes. The primary outcome measure was sustained virological response (SVR). Results: PWIDs and non-drug users had different HCV genotype profiles (p = 0.013). The former had higher proportions of genotype 3 (18.9% vs. 7.5%) and genotype 6 (24.5% vs. 14.2%) than the latter. The two patient groups had comparable rates of complete drug refilling (100.0% vs. 91.1%) and frequency of loss to follow-up (3.8% vs. 0.9%). However, PWIDs had a lower SVR rate of DAA treatment than non-drug users (92.2% vs. 99.0%; p = 0.04). Further analysis showed that both human immunodeficiency virus (HIV) coinfection and history of PWID were risk factors associated with treatment failure. The subjects with coinfection with HIV had lower SVR rates than those without HIV infection (50.0% vs. 96.5%; p = 0.021). Conclusions: PWIDs with HCV infections have higher proportions of HCV genotype 3 and genotype 6 than non-drug users with infections. DAA therapy can achieve a high cure rate (>90%) for HCV infection in PWID, but its efficacy in PWID is lower than that in non-drug users.

Safety Assessment of HEA-Enriched Cordyceps cicadae Mycelium: A Randomized Clinical Trial.

Objective:Cordyceps cicadae, a medicinal fungus, is assessed as having many functions: anti-cancer, anti-fatigue, anti-aging, immune-boosting, renal and liver protection. Since the industrial production of C. cicadae mycelium consistently manufactures bioactive compounds superior to wild fruiting bodies, there is a need to confirm the toxicity of liquid fermented C. cicadae mycelium. Studies showed the toxicity evaluation of C. cicadae mycelium in animal models, but safety reports in clinical studies are scarce. As such, a safety assessment of oral N6-(2-hydroxyethyl) adenosine (HEA-enriched) C. cicadae mycelium in humans is provided here.Method: After 49 participants ingested granules of 1.05 g of freeze-dried C. cicadae mycelium once a day for 3 months, their blood samples were collected at the beginning and end of the experiment for analysis.Results: There were no significant differences between the initial and final measurements in renal and liver function. Also, there was no influence on blood electrolytes as well as blood lipid levels. In clinical observation, there were also no side effects or adverse feelings mentioned by participants.Conclusion: These results suggested that HEA-enriched C. cicadae mycelium produced by liquid fermentation is safe and can be developed as a functional health food.