mtDNA amplifies beryllium sulfate-induced inflammatory responses via the cGAS-STING pathway in 16HBE cells.

Beryllium sulfate (BeSO4) can cause inflammation through the mechanism, which has not been elucidated. Mitochondrial DNA (mtDNA) is a key contributor of inflammation. With mitochondrial damage, released mtDNA can bind to specific receptors (e.g., cGAS) and then activate related pathway to promote inflammatory responses. To investigate the mechanism of mtDNA in BeSO4-induced inflammatory response in 16HBE cells, we established the BeSO4-induced 16HBE cell inflammation model and the ethidium bromide (EB)-induced ρ016HBE cell model to detect the mtDNA content, oxidative stress-related markers, mitochondrial membrane potential, the expression of the cGAS-STING pathway, and inflammation-related factors. Our results showed that BeSO4 caused oxidative stress, decline of mitochondrial membrane potential, and the release of mtDNA into the cytoplasm of 16HBE cells. In addition, BeSO4 induced inflammation in 16HBE cells by activating the cGAS-STING pathway. Furthermore, mtDNA deletion inhibited the expression of cGAS-STING pathway, IL-10, TNF-α, and IFN-ß. This study revealed a novel mechanism of BeSO4-induced inflammation in 16HBE cells, which contributes to the understanding of the molecular mechanism of beryllium and its compounds-induced toxicity.

MicroRNA-210-3p mediates trabecular meshwork extracellular matrix accumulation and ocular hypertension - Implication for novel glaucoma therapy.

Elevation of intraocular pressure (IOP) is a major, controllable risk factor of primary open-angle glaucoma (POAG). Transforming growth factor-ß2 (TGF-ß2)-induced excessive accumulation of extracellular matrix (ECM) in the trabecular meshwork (TM) has been demonstrated to contribute significantly to the development of high IOP. We previously showed that treatment with salidroside (Sal), a plant-derived glucoside, can ameliorate the TGF-ß2-induced ECM expression in cultured human TM cells and reduce TGF-ß2-induced ocular hypertension in mice. In the current study, its underlying molecular mechanism associated with microRNA-210-3p (miR-210-3p) was characterized. We discovered that, in TM tissues of POAG patients, there was an increase in miR-210-3p. And miR-210-3p mediated a portion of the pathological effects of TGF-ß2 in vitro (excessive accumulation of ECM in cultured human TM cells) and in vivo (mouse ocular hypertension and ECM accumulation in the TM). Most interestingly, miR-210-3p was down-regulated by Sal, which appeared to mediate a significant portion of its IOP-lowering effect. Thus, these results shed light on the probable molecular mechanisms of TGF-ß2 and Sal and indicate that manipulation of miR-210-3p level/activity represents a potential new therapeutic strategy for POAG.

Direct oral mucosal epithelial transplantation supplies stem cells and promotes corneal wound healing to treat refractory persistent corneal epithelial defects.

Persistent corneal epithelial defects (PED) can lead to irreversible blindness, seriously affecting the social function and life quality of these patients. When it comes to refractory PED, such as limbal stem cell deficiency (LSCD), that does not respond to standard managements, stem cell therapy is an ideal method. Oral mucosal epithelium (OME) abundant with stem cells within the base, is a promising autologous biomaterial, with much resemblance to corneal epithelial structures. In this experiment, uncultured autologous rat OME was directly applied to alkali burned corneas. Clinical evaluations and histological analyses showed that the transplantation accelerated the healing process, presenting faster re-epithelization and better formation of corneal epithelial barrier. To further investigate the therapeutic mechanism, oral epithelium was transplanted to de-epithelialized cornea in vitro for organ culture. It could be observed that the oral epithelial cells could migrate to the corneal surface and form smooth and stratified epithelium. Immunofluorescence staining results showed that the re-formed epithelium derived from OME, maintained stemness and transformed to corneal epithelial phenotype to some extent. Corneal stroma may provide the suitable microenvironment to promote the trans-differentiation of oral stem cells. Thus, both in vivo and in vitro experiments suggested that oral epithelium could play a positive role in treating refractory PED.

Hyperammonemia in a septic patient with Ureaplasma parvum arthritis: a case report.

BACKGROUND: Septic arthritis requires prompt diagnosis and treatments. Rare pathogens should be considered when patients respond poorly to the initial antibiotic treatments. Ureaplasma parvum is an opportunistic pathogen that commonly resides in the human urogenital tract. Its infection commonly causes hyperammonemia. Hyperammonemia from Ureaplasma parvum septic arthritis has never been reported previously. CASE PRESENTATION: A 65-year-old male presented with fever and left lower leg pain and swelling for more than ten days. Septic arthritis and sepsis were considered after laboratory tests and arthrocentesis. However, he responded poorly to the antibiotic treatments, including cefoperazone-sulbactam, imipenem-cilastatin, and linezolid. His mental status deteriorated rapidly with elevated blood ammonia levels with unremarkable liver function test and sonogram examination results. Despite the treatments with lactulose, L-ornithine L-aspartate, mannitol, and hemodialysis therapy to lower his ammonia level, his blood ammonia level remained persistently high. Finally, metagenomic sequencing of the left knee synovial fluid reported Ureaplasma parvum, which was considered to contribute to his hyperammonemia. CONCLUSION: Ureaplasma parvum could cause septic arthritis with hyperammonemia. Genetic tests, such as polymerase chain reaction and next-generation sequencing techniques, could provide a sensitive and fast diagnosis of Ureaplasma parvum.

Play During Growth: the Effect of Sports on Bone Adaptation.

PURPOSE OF REVIEW: The development of exercise interventions for bone health requires an understanding of normative growth trends. Here, we summarize changes in bone during growth and the effect of participating in sports on structural and compositional measures in different bones in males and females. RECENT FINDINGS: Growing females and males have similar normalized density and bone area fraction until age 16, after which males continue increasing at a faster rate than females. All metrics for both sexes tend to plateau or decline in the early 20s. Areal BMD measures indicate significant heterogeneity in adaptation to sport between regions of the body. High-resolution CT data indicate changes in structure are more readily apparent than changes in density. While adaptation to sport is spatially heterogeneous, participation in weight-bearing activities that involve dynamic muscle contractions tends to result in increased bone adaptation.

Effects of lens extraction versus laser peripheral iridotomy on anterior segment morphology in primary angle closure suspect.

PURPOSE: To compare the anatomical effects on anterior segment by lens extraction (LE, phacoemulsification with posterior chamber intraocular lens implantation) and laser peripheral iridotomy (LPI) in primary angle closure suspect (PACS) eyes. METHODS: This prospective comparative cohort trial included a total of 122 consecutive patients identified as PACS aged 52 to 80 years. LE or LPI was performed based on each patient's choice. The anterior segment optical coherence tomography (ASOCT) and gonioscopy were conducted at baseline and 4 weeks post-operation. Outcome measures include percentage of residual angle closure, mean angle width (modified Shaffer grade), angle opening distance (AOD), trabecular iris angle (TIA), trabecular iris space area (TISA), anterior chamber depth (ACD), iris curvature (I-Curve), lens vault (LV), intraocular pressure (IOP), and best-corrected visual acuity (BCVA). RESULTS: All anterior angle parameters (AOD, TIA, and TISA) were significantly greater after LE than LPI (P < 0.001 for all). ACD (P < 0.001) increased, LV (P < 0.001) decreased, IOP (P < 0.001) decreased, and BCVA (P < 0.001) increased after LE. However, no significant changes were found in ACD (P = 0.782), LV (P = 0.616), IOP (P = 0.112), and BCVA (P = 0.131) after LPI. In both groups, I-Curve decreased after the operation, but the iris was flatter after LE than LPI (P < 0.001). Gonioscopically, the LE group achieved a larger post-operative angle width (modified Shaffer grade) than LPI (P < 0.001) and all anterior chamber angles were open (defined as posterior pigmented trabecular meshwork (PTM) visible with static gonioscopy) after operation. Nevertheless, after LPI, 12 eyes (20.0%) still had two or more quadrants and 32 eyes (53.3%) still had at least one quadrant in which the posterior PTM could not be observed. CONCLUSIONS: Compared with LPI, LE resulted in a wider anterior chamber angle, a deeper anterior chamber, and a lower IOP in PACS eyes. Moreover, no residual angle closure was observed after LE, which could morphologically prevent the progress of angle closure. TRIAL REGISTRATION: ChiCTR1800016511.

Long-Term Results for a One-Stage Surgery Technique for Patients With Craniofacial Plexiform Neurofibroma.

BACKGROUND: Neurofibromatosis (NF) is an autosomal dominant genetic disorder, and NF type 1 (NF1) is one of the most common forms. Plexiform neurofibroma (PNF) is one of the characteristic expressions of NF1. The proper treatment for patients with craniofacial PNF is surgery. The evaluation methods for the surgical outcome of these patients are still controversial. As a consequence, a one-stage surgical technique and an appropriate evaluation method for patients with craniofacial PNF were discussed in this article. METHODS: This research is a retrospective study. Nine patients with craniofacial PNF were included in this study. They had undergone a one-stage surgical technique of tumor debulking and nasolabial fold reconstruction. Three methods had been applied to evaluate the surgical outcome. RESULTS: Significant improvement was observed in 8 patients. Eight patients were assessed by the relatively objective evaluation method. Obvious symmetry improvement was calculated using Mimics software in 7 patients. CONCLUSION: The surgical technique could achieve good surgical outcomes in both functional and cosmetic terms. Additionally, the relatively objective evaluation technique based on Mimics software could be a more convincing method for evaluating the surgical outcomes of craniofacial patients with PNF.

Targeting Imbalance between IL-1ß and IL-1 Receptor Antagonist Ameliorates Delayed Epithelium Wound Healing in Diabetic Mouse Corneas.

Patients with diabetes mellitus often develop corneal complications and delayed wound healing. How diabetes might alter acute inflammatory responses to tissue injury, leading to delayed wound healing, remains mostly elusive. Using a streptozotocin-induced type I diabetes mellitus mice and corneal epithelium-debridement wound model, we discovered that although wounding induced marked expression of IL-1ß and the secreted form of IL-1 receptor antagonist (sIL-1Ra), diabetes suppressed the expressions of sIL-1Ra but not IL-1ß in healing epithelia and both in whole cornea. In normoglycemic mice, IL-1ß or sIL-1Ra blockade delayed wound healing and influenced each other's expression. In diabetic mice, in addition to delayed reepithelization, diabetes weakened phosphatidylinositol 3-kinase-Akt signaling, caused cell apoptosis, diminished cell proliferation, suppressed neutrophil and natural killer cell infiltrations, and impaired sensory nerve reinnervation in healing mouse corneas. Local administration of recombinant IL-1Ra partially, but significantly, reversed these pathological changes in the diabetic corneas. CXCL10 was a downstream chemokine of IL-1ß-IL-1Ra, and exogenous CXCL10 alleviated delayed wound healing in the diabetic, but attenuated it in the normal corneas. In conclusion, the suppressed early innate/inflammatory responses instigated by the imbalance between IL-1ß and IL-1Ra is an underlying cause for delayed wound healing in the diabetic corneas. Local application of IL-1Ra accelerates reepithelialization and may be used to treat chronic corneal and potential skin wounds of diabetic patients.

Reconstruction of conjunctival epithelium-like tissue using a temperature-responsive culture dish.

PURPOSE: To study the feasibility of engineering conjunctival epithelial cell sheets on a temperature-responsive culture dish for ocular surface reconstruction. METHODS: Rabbit conjunctival epithelial cells (rCjECs) were cultured in DMEM/F-12 (1:1) medium. The morphology and phenotype of the rCjECs were confirmed with phalloidin staining, periodic acid-Schiff (PAS) staining, and immunocytochemistry. The rCjECs cultured on a temperature-responsive culture dish for 10 days produced confluent conjunctival epithelial cell sheets. Then, the phenotype, structure, and function of the conjunctival epithelial cell sheets were examined. RESULTS: The conjunctival epithelial cells were compact, uniform, and cobblestone shape. All cultured conjunctival epithelial cells were harvested as intact cell sheets by reducing the culture temperature to 20 °C. Conjunctival epithelial cells were stratified in four to five cell layers similar to the conjunctival epithelium. CCK-8 analysis, 5-bromo-2'-deoxyuridine (BrdU) staining, and the live and dead viability assay confirmed that viable proliferation cells were retained in the cell sheets. Immunohistochemistry for CK4, CK19, and MUC5AC showed the cell sheets still maintained characteristics of the conjunctival epithelium. CONCLUSIONS: A temperature-responsive culture dish enables fabrication of viable conjunctival epithelial cell sheets with goblet cells and proliferative cells. Conjunctival epithelial cell sheets will be promising for reconstruction of the conjunctival epithelium.

Adenosine triphosphate-induced rabbit corneal endothelial cell proliferation in vitro via the P2Y2-PI3K/Akt signaling axis.

PURPOSE: To investigate the effect of the ATP-P2Y2-PI3K/Akt signaling axis on promoting rabbit corneal endothelial cell (RCEC) proliferation in vitro. METHODS: Five concentrations of adenosine triphosphate (ATP; 1, 10, 25, 50 and 100 µM) were added to RCECs, and the cell proliferation was detected using Cell Counting Kit-8 (CCK8) and Ki67 immunohistochemical staining. Other P2Y2 receptor agonists and antagonists were added to the cells, and the proliferation effect was evaluated using CCK8 to determine the involvement of the P2Y2 receptor. Changes in the expression of phosphorylated Akt in RCECs treated with different concentrations of extracellular ATP and the duration of extracellular ATP on Akt phosphorylation were investigated using Western blotting. The pharmacological profiles with or without the PI3K/Akt pathway inhibitors were also determined using Western blotting. RESULTS: We found that 10 µM ATP strongly promoted RCEC proliferation in vitro. Additionally, 25 µM ATP had a proliferation effect, whereas other concentrations (1, 50 and 100 µM) had no effect compared with the control group. Selective P2Y2 receptor agonists (UTP, ATPγS and Ap4A) showed the same promotion effect, while P2Y2 antagonists and PI3K/Akt inhibitors inhibited the effect of ATP. Moreover, phosphorylated Akt could be induced by the addition of extracellular ATP at all five concentrations and lasted for 1 h. This phosphorylation was prevented by PI3K/Akt inhibitors and a P2Y2 antagonist. CONCLUSIONS: These findings showed that 10 µM ATP markedly promoted RCEC proliferation via the P2Y2-PI3K/Akt signaling axis.

A novel approach to modulating response inhibition: Multi-channel beta transcranial alternating current stimulation.

BACKGROUND: Deficits in response inhibition are associated with numerous psychiatric disorders. Previous studies have revealed the crucial role of the right inferior frontal gyrus (rIFG), pre-supplementary motor area (preSMA), and beta activity in these brain regions in response inhibition. Multi-channel transcranial alternating current stimulation (tACS) has garnered significant attention for its ability to modulate neural oscillations in brain networks. In this study, we employed multi-channel tACS targeting rIFG-preSMA network to investigate its impact on response inhibition in healthy adults. METHODS: In Experiment 1, 70 healthy participants were randomly assigned to receive 20 Hz in-phase, anti-phase, or sham stimulation over rIFG-preSMA network. Response inhibition was assessed using the stop-signal task during and after stimulation, and impulsiveness was measured via the Barratt Impulsiveness Scale. Additionally, 25 participants received stimulation at the left supraorbital area to account for potential effects of the "return" electrode. Experiment 2, consisting of 25 participants, was conducted to validate the primary findings of Experiment 1, including both in-phase and sham stimulation conditions, based on prior estimations derived from the results of Experiment 1. RESULTS: In Experiment 1, we found that in-phase stimulation significantly improved response inhibition compared with sham stimulation, whereas anti-phase stimulation did not. These findings were consistently replicated in Experiment 2. We also conducted an exploratory analysis of the multi-channel tACS impact, revealing that its effects primarily emerged during the post-stimulation phase. Furthermore, individuals with higher baseline attentional impulsiveness showed greater improvements in the in-phase stimulation group. CONCLUSIONS: These results demonstrate that in-phase beta-tACS over rIFG-preSMA network can effectively improve response inhibition in healthy adults and provides a new potential treatment for patients with deficits in response inhibition.

Long-term effects of mild cataract extraction versus laser peripheral iridotomy on anterior chamber morphology in primary angle-closure suspect eyes.

AIM: To compare lens extraction (LE) and laser peripheral iridotomy (LPI) on anterior segment morphology in primary angle-closure suspect (PACS) eyes. METHODS: This prospective clinical trial included 144 patients with PACS who underwent either LPI or LE. Ultrasound biomicroscopy (UBM) and gonioscopy were performed before and 1 month and 2 years after operation. Main outcomes included UBM parameters and the percentage of residual angle closure. RESULTS: At both 1 month and 2 years of follow-up, LE showed a better effect of relieving anterior chamber crowding and widening the drainage angle, as obtaining a larger anterior chamber depth (ACD), angle opening distance, trabecular iris angle (TIA), trabecular iris space area, trabecular ciliary process distance (TCPD) and a smaller iris curvature (I-Curv) and lens vault (LV) (p<0.001). In the LPI group, angle width increased (angle opening distance at 500 µm from the scleral spur, TIA and trabecular iris space area at 500 µm from the scleral spur) and I-Curv decreased (p<0.001) at 1 month postoperatively, with no significant changes in ACD, LV or TCPD. However, at 2 years after LPI, the angle narrowed with the increase in LV over time, and the proportion of residual angle closure also increased from 21.7% to 30.4% (p<0.001). In contrast, after LE, the widened angle width, flattened iris, deepened ACD, decreased LV and increased TCPD all showed good sustainability in the comparison between 1-month and 2-year follow-up. No residual angle closure was observed either at 1 month or 2 years after LE. CONCLUSIONS: LE was prior to LPI in widening the drainage angle. After LPI, there was a narrowing of the angle and an increase in the proportion of residual angle closure over time. LE could achieve a wider angle with no residual angle closure, and the anterior segment parameters were sustainable. TRIAL REGISTRATION NUMBER: ChiCTR1800016511.

Maternal separation leads to dynamic changes of visceral hypersensitivity and fecal metabolomics from childhood to adulthood.

We assessed dynamic changes in visceral hypersensitivity and fecal metabolomics through a mouse model of irritable bowel syndrome (IBS) from childhood to adulthood. A mouse model of IBS was constructed with maternal separation (MS) in early life. Male mice aged 25, 40, and 70 days were used. Visceral sensitivity was assessed by recording the reaction between the abdominal withdrawal reflex and colorectal distension. Metabolomics was identified and quantified by liquid chromatography-tandem mass spectrometry. The visceral sensitivity of the MS group was significantly higher than that of the non-separation (NS) group in the three age groups. The top four fecal differential metabolites in the different age groups were lipids, lipid molecules, organic heterocyclic compounds, organic acids and derivatives, and benzenoids. Five identical differential metabolites were detected in the feces and ileal contents of the MS and NS groups at different ages, namely, benzamide, taurine, acetyl-L-carnitine, indole, and ethylbenzene. Taurine and hypotaurine metabolism were the most relevant pathways at P25, whereas histidine metabolism was the most relevant pathway at P40 and P70. Visceral hypersensitivity in the MS group lasted from childhood to adulthood. The different metabolites and metabolic pathways detected in MS groups of different ages provide a theoretical basis for IBS pathogenesis.

Vitamin D improves irritable bowel syndrome symptoms: A meta-analysis.

Background & aims: Approximately 5%-10% of the population in most geographical regions suffer from irritable bowel syndrome (IBS), which creates a significant burden on individual patients, their families, and society. Recent advances in IBS therapies have indicated that vitamin D supplementation is potential to relieve its symptoms, but evidence of this is lacking. This meta-analysis aimed to estimate the effect of vitamin D on gastrointestinal (GI) symptoms in IBS patients. Methods: The PubMed, Embase, and Cochrane Central Register of Controlled Trials databases were searched from their inception to March 2022. Statistical analyses were performed with Stata 12.0 and Review Manager 5.4, and statistical significance was defined as P < 0.05. The pooled results are presented as weighted mean differences (WMD) and 95% confidence intervals (CI). Results: The meta-analysis including 6 randomized controlled trials (RCT) with 572 patients found a significant difference in IBS symptom severity score (WMD, -34.88; 95% CI, -62.48 to -7.27; P = 0.013; random-effects model) but no significant difference in IBS quality of life score (WMD, 3.33; 95% CI, -5.12 to -11.77; P = 0.440; random-effects model). Conclusions: Overall, IBS patients may benefit from vitamin D supplementation to reduce the GI symptoms.

Low FODMAP Diet Relieves Visceral Hypersensitivity and Is Associated with Changes in Colonic Microcirculation in Water Avoidance Mice Model.

(1) Background: Irritable bowel syndrome (IBS) is a global public health problem, the pathogenesis of which has not been fully explored. Limiting fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) can relieve symptoms in some patients with IBS. Studies have shown that normal microcirculation perfusion is necessary to maintain the primary function of the gastrointestinal system. Here, we hypothesized that IBS pathogenesis might be related to abnormalities in colonic microcirculation. A low-FODMAP diet could alleviate visceral hypersensitivity (VH) by improving colonic microcirculation; (2) Methods: C57BL/6 mice were raised to establish an IBS-like rodent model using water avoidance (WA) stress or SHAM-WA as a control, one hour per day for ten days. The mice in the WA group were administered different levels of the FODMAP diet: 2.1% regular FODMAP (WA-RF), 10% high FODMAP diet (WA-HF), 5% medium FODMAP diet (WA-MF), and 0% low FODMAP diet (WA-LF) for the following 14 days. The body weight and food consumption of the mice were recorded. Visceral sensitivity was measured as colorectal distention (CRD) using the abdominal withdrawal reflex (AWR) score. Colonic microcirculation was assessed using laser speckle contrast imaging (LCSI). Vascular endothelial-derived growth factor (VEGF) was detected using immunofluorescence staining; (3) Results: The threshold values of CRD pressure in the WA-RF, WA-HF, and WA-MF groups were significantly lower than those in the SHAM-WA group. Moreover, we observed that colonic microcirculation perfusion decreased, and the expression of VEGF protein increased in these three groups of mice. Interestingly, a low-FODMAP dietary intervention could reverse this situation. Specifically, a low-FODMAP diet increased colonic microcirculation perfusion, reduced VEGF protein expression in mice, and increased the threshold of VH. There was a significant positive correlation between colonic microcirculation and threshold for VH; (4) Conclusions: These results demonstrate that a low-FODMAP diet can alter VH by affecting colonic microcirculation. Changes in intestinal microcirculation may be related to VEGF expression.

Validity of evaluating spinal kinetics without participant-specific kinematics.

Musculoskeletal models are commonly used to estimate in vivo spinal loads under various loading conditions. Typically, participant-specific measured kinematics (PSMK) are coupled with participant-specific models, but obtaining PSMK data can be costly and infeasible in large studies or clinical practice. Thus, we evaluated two alternative methods to estimate spinal loads without PSMK: 1) ensemble average kinematics (EAK) based on kinematics from all participants; and 2) using separately measured individual kinematics (SMIK) from multiple other participants as inputs, then averaging the resulting loads. This study compares the dynamic spine loading patterns and peak loads in older adults performing five lifting tasks using PSMK, EAK and SMIK. Median root mean square errors of EAK and SMIK methods versus PSMK ranged from 18 to 72% body weight for compressive loads and from 2 to 25% body weight for shear loads, with median cross-correlations ranging from 0.931 to 0.991. The root mean square errors and cross-correlations between repeated PSMK trials fell within similar ranges. Compressive peak loads evaluated by EAK and SMIK were not different than PSMK in 12 of 15 cases, while by comparison repeated PSMK trials were not different in 13 of 15 cases. Overall, the resulting spine loading magnitudes and profiles using EAK or SMIK were not notably different than using a PSMK approach, and differences were not greater than between two PSMK trials. Thus, these findings indicate that these approaches may be used to make reasonable estimates of dynamic spinal loading without direct measurement of participant kinematics.

Effect of Lens Vault on the Accuracy of Intraocular Lens Calculation Formulas in Shallow Anterior Chamber Eyes.

PURPOSE: To explore the impact of preoperative lens vault (LV) on the accuracy of the Barrett Universal Ⅱ, Haigis, Hoffer Q, Hoffer QST, Holladay 1, Kane, and SRK/T formulas in eyes with a shallow anterior chamber. DESIGN: Retrospective case series. METHODS: Included were 409 eyes with anterior chamber depth (ACD) shallower than 3.0 mm that underwent phacoemulsification. Eyes were divided into a short axial length (AL) group (<22.00 mm) and a normal AL group (22.00 ≤ AL < 24.50 mm). Each group was further divided into a small LV subgroup (LV <0.95 mm) and a large LV subgroup (LV ≥0.95 mm) according to the median of the preoperative LV. Postoperative refraction was measured 3 months after surgery. Mean absolute error (MAE) was calculated and compared for each formula. The correlation between LV and the mean numeric error predicted by each formula was analyzed. RESULTS: Overall, the Barrett and Kane formulas generated the smallest MAE in both short AL and normal AL groups (P < .05 for both). In short AL eyes with small LV, the Haigis formula performed better than other traditional formulas (P < .05 for all). In normal AL eyes with a small LV, the Barrett and Kane formulas showed higher accuracy (P < .05 for all), and other formulas were comparable. In either subgroup with a large LV, the Haigis formula created a significant higher MAE (P < .001 for all), followed by Hoffer QST. Positive correlations were found between LV and mean numeric errors predicted by all formulas, except for Barrett and Kane formulas (P < .001 for all), indicating a postoperative hyperopic shift with an increased LV. CONCLUSIONS: In shallow anterior chamber eyes with a large LV, the Haigis and Hoffer QST formulas taking preoperative ACD into calculation surprisingly showed a larger prediction error. However, the Barrett and the Kane formulas, which include both ACD and lens thickness as predictive parameters, showed good accuracy in both small and large LV subgroups. Therefore, although formulas referring to preoperative ACD are generally believed to achieve better refractive results in patients with a shallow anterior chamber, LV may be valuable to consider when choosing an IOL power calculation formula.

Multidirectional basketball activities load different regions of the tibia: A subject-specific muscle-driven finite element study.

The tibia is a common site for bone stress injuries, which are believed to develop from microdamage accumulation to repetitive sub-yield strains. There is a need to understand how the tibia is loaded in vivo to understand how bone stress injuries develop and design exercises to build a more robust bone. Here, we use subject-specific, muscle-driven, finite element simulations of 11 basketball players to calculate strain and strain rate distributions at the midshaft and distal tibia during six activities: walking, sprinting, lateral cut, jumping after landing, changing direction from forward-to-backward sprinting, and changing direction while side shuffling. Maximum compressive strains were at least double maximum tensile strains during the stance phase of all activities. Sprinting and lateral cut had the highest compressive (-2,862 ± 662 µÎµ and -2,697 ± 495 µÎµ, respectively) and tensile (973 ± 208 µÎµ and 942 ± 223 µÎµ, respectively) strains. These activities also had the highest strains rates (peak compressive strain rate = 64,602 ± 19,068 µÎµ/s and 37,961 ± 14,210 µÎµ/s, respectively). Compressive strains principally occurred in the posterior tibia for all activities; however, tensile strain location varied. Activities involving a change in direction increased tensile loads in the anterior tibia. These observations may guide preventative and management strategies for tibial bone stress injuries. In terms of prevention, the strain distributions suggest individuals should perform activities involving changes in direction during growth to adapt different parts of the tibia and develop a more fatigue resistant bone. In terms of management, the greater strain and strain rates during sprinting than jumping suggests jumping activities may be commenced earlier than full pace running. The greater anterior tensile strains during changes in direction suggest introduction of these types of activities should be delayed during recovery from an anterior tibial bone stress injury, which have a high-risk of healing complications.

LncRNA TP73-AS1 Exacerbates the Non-Small-Cell Lung Cancer (NSCLC) Process via Regulating miR-125a-3p-Mediated ACTN4.

Background: LncRNA TP73-AS1 has been revealed to exert a noteworthy impact on the occurrence and advancement of different cancers. In this study, we explored the function of TP73-AS1 in tumor growth, cell progression as well as the relevant molecular mechanism in non-small-cell lung cancer (NSCLC). Methods: QRT-PCR was employed to assess the expression of TP73-AS1, miR-125a-3p, and actinin alpha 4 (ACTN4) in NSCLC cells. The biological effect of TP73-AS1 on NSCLC cells was assessed by cell transfection, CCK8, and transwell experiments. We further predicted the interaction among RNAs (TP73-AS1, miR-125a-3p, and ACTN4) through bioinformatics online tools and verified via luciferase reporter, RNA immunoprecipitation, and qRT-PCR assays. Xenograft models of SPC-A1 cells were conducted to test how TP73-AS1 regulates tumorigenesis. Western blot, as well as the immunohistochemistry (IHC) assays, was utilized to measure the expression levels. Functions of TP73-AS1 in NSCLC progression through the miR-125a-3p/ACTN4 axis were investigated by rescue experiments. Results: Knockdown of TP73-AS1 suppressed the growth and simultaneously attenuated the migration and invasion ability of NSCLC SPC-A1 and A549 cells. Bioinformatics and molecular mechanism assays demonstrated that TP73-AS1 could bind to miR-125a-3p/ACTN4 and regulate their expression. Moreover, the rescued-function experiment demonstrated that suppressing miR-125a-3p or elevating ACTN4 turned around the suppression effect of sh-TP73-AS1 on NSCLC progression. TP73-AS1 inhibition could also inhibit the NSCLC tumor growth and correspondingly regulated the expression of miR-125a-3p and ACTN4 in the tumor xenograft model. Conclusion: The present study indicated that TP73-AS1 affects NSCLC progression through a new competitive RNA (ceRNA) regulatory network of miR-125a-3p/ACTN4, providing an underlying target for NSCLC treatment in the future.

Effect of fatigue loading and rest on impact strength of rat ulna.

Stress fracture is a common injury among athletes and military personnel and is associated with fatigue-initiated damage and impact loading. The recovery of bending strength has been shown to be a function of the rest days allowed after fatigue loading in rodents and the aim of this study was to investigate if similar results would occur under impact conditions. In this study, cyclic axial compression load was applied in vivo on the right forelimbs while left forelimbs served as controls. Two rest groups were used: one day of rest and seven days of rest. Afterwards, all ulnae were scanned using micro-Computed Tomography followed by impact testing. The micro-CT scan confirmed the formation of woven bone on loaded ulnae after seven days rest. The peak impact force was 37.5% higher in the control (mean = 174.96 ± 33.25 N) specimens compared to the loaded bones (mean = 130.34 ± 22.37 N). Fourier-transformed infrared spectroscopy analyses suggested no significant change of chemical composition in the cortical region between the loaded and control ulnae, but woven bone region had lower carbonate and amide I content than contralateral controls (p < 0.05). We find that cyclic fatigue loading had a negative effect on bone's impact response. Bones that experienced fatigue loading became less stiff, weaker, and more prone to fracture when subjected to impact. The formation of woven bone after seven days of rest did not restore the stiffness upon impact and confirm that rest time is crucial to the recovery of fatigue damage.