Notes

AHR/ROS-mediated mitochondria apoptosis plays a part in benzo[a]pyrene-induced center disorders along with the shielding effects of resveratrol supplement.
In older elderly group, the aRR of death in the THA group compared to the HA group was 2.16 (95% confidence interval [CI], 1.20-3.87;
= 0.010) within the in-hospital period, 3.57 (95% CI, 2.00-6.40;
< 0.001) within 30-days, and 1.96 (95% CI, 1.21-3.18;
= 0.006) within 60-days.

In patients older than 80 years, THA was associated with higher postoperative mortality compared to HA. We recommend the use of HA rather than THA in these patients.
In patients older than 80 years, THA was associated with higher postoperative mortality compared to HA. We recommend the use of HA rather than THA in these patients.
Meniscal tears are commonly observed in patients with knee osteoarthritis (OA), however, clinical significance of such lesions detected by magnetic resonance imaging is in many cases unclear. This study aimed to determine the clinical effectiveness of arthroscopic partial meniscectomy (APM) compared with non-operative care in patients with knee OA.

We used existing systematic reviews with updates of latest studies. Three randomized controlled studies were selected, where two studies compared the effects of APM plus physical therapy (PT) with PT alone and one compared APM alone and PT alone. While 1 study exclusively included OA patients, 2 studies included 21.1 and 12% of patients with no radiographic OA. Patients with knee locking were unanimously excluded.

Upon comparison of APM plus PT and PT alone, there was no significant difference observed in knee function, physical activity, or adverse events. Knee pain was observed to be significantly lower in the APM plus PT group at 6 months, but there was no difference between the two groups at 12 and 24 months. With respect to the comparison between APM alone and PT alone, PT was non-inferior based on the criteria for knee function during 24 months; however, knee pain was significantly reduced in the APM alone group.

Our study showed that knee pain was significantly improved in the APM group compared to non-operative care group at 6 months and over 24 months. Our result was based on only 3 randomized controlled trials (RCTs) revealing a significant knowledge gap, hence demanding more high-quality RCTs in OA patients.

PROSPERO Identifier CRD42020215965.
PROSPERO Identifier CRD42020215965.
In the Korean medical system, the severity classification for a specific disease depends primarily on its nationwide admission rate in tertiary hospitals. Inversely, one of the important designation criteria for a tertiary hospital is the hospital's treatment ratio of patients classified as having a specific severe disease. Most diseases requiring pediatric orthopaedic surgery (POS) are not currently classified as high severity in terms of disease severity. We investigated the admission rates for the representative POS diseases in tertiary hospitals and compared these rates with those for adult orthopaedic surgery (AOS) diseases.

Seven POS diagnoses and three AOS diagnoses were selected based on frequency of admission. Nationwide sample data were used to investigate the admission rates for these representative diagnoses from 2008 to 2017.

Six of the seven frequent POS diagnoses presented high admission rates in tertiary hospitals (62.5-92.3%). In contrast, all frequent AOS diagnoses presented low admissildren may not receive appropriate professional care. Therefore, for the disease severity, POS diseases should be classified differently from general AOS diseases by using different criteria reflecting the patient's age.Circulating tumor cells (CTCs) are reported as the precursor of tumor metastases, implying that stifling CTCs would be beneficial for metastasis prevention. However, challenges remain for the application of therapies that aim at CTCs due to lack of effective CTC-targeting strategy and sensitive therapeutic agents. Herein, a general CTC-intervention strategy based on neutrophil cyto-pharmaceuticals is proposed for suppressing CTC colonization and metastasis formation. Breast cancer 4T1 cells are infused as the mimic CTCs, and 4T1 cells trapped are first elucidated in neutrophil extracellular traps (NETs) expressing high levels of hypoxia-inducible factor-1α (HIF-1α) due to NET formation and thus promoting tumor cell colonization through enhanced migration, invasion and stemness. After verifying HIF-1α as a potential target for metastasis prevention, living neutrophil cyto-pharmaceuticals (CytPNEs) loaded with HIF-1α inhibitor are fabricated to therapeutically inhibit HIF-1α. It is demonstrated that CytPNEs can specially convey the HIF-1α inhibitor to 4T1 cells according to the inflammatory chemotaxis of neutrophils and down-regulate HIF-1α, thereby inhibiting metastasis and prolonging the median survival of mice bearing breast cancer lung metastasis. The research offers a new perspective for understanding the mechanism of CTC colonization, and puts forward the strategy of targeted intervention of CTCs as a meaningful treatment for tumor metastasis.
Approximately a third of all extremely preterm infants diagnosed with bronchopulmonary dysplasia will require home oxygen therapy (HOT). 5(NEthylNisopropyl)Amiloride Lack of consensus-based guidelines has led to significant variability in outpatient HOT management in the United States. link2 A common assessment performed before discontinuing oxygen is a formal polysomnogram (PSG). PSGs are potentially undesirable due to cost, lack of convenient access, and parental stress, so alternative testing to determine the optimal timing of safe oxygen discontinuation are needed.

We compared nocturnal recorded home oximetry (RHO) with PSG data in a cohort of patients from the RHO trial for patients who had recordings performed simultaneously to or within 24 h of their PSG. The RHO trial was a randomized, unblinded, multi-center trial comparing two oxygen management strategies. Parameters of oxygenation were compared between PSG and RHO, and nonoximegtry findings from the PSG that changed clinical management were identified.

A total of 53 infants randomized to obtain a PSG as part of the RHO trial (55%) completed a PSG, and of those, 32 (64%) completed both a PSG with comparison RHO. There were more white infants in both groups than other races and ethnicities. Bland-Altman analysis showed a strong agreement of oxygen saturation time below 90% SpO
between PSG and RHO results (slope = 1.014, p = 0.24). Results agreed in 96% of cases.

RHO is a safe and effective alternative to PSG to assist in determination of discontinuing HOT in infants with BPD without other risks for sleep-disordered breathing.
RHO is a safe and effective alternative to PSG to assist in determination of discontinuing HOT in infants with BPD without other risks for sleep-disordered breathing.Biological tissues hinge on blood perfusion and mechanical toughness to function. link3 Injectable hydrogels that possess both high permeability and toughness have profound impacts on regenerative medicine but remain a long-standing challenge. To address this issue, injectable, pore-forming double-network hydrogels are fabricated by orchestrating stepwise gelation and phase separation processes. The interconnected pores of the resulting hydrogels enable direct medium perfusion through organ-sized matrices. The hydrogels are amenable to cell encapsulation and delivery while promoting cell proliferation and spreading. They are also pore insensitive, tough, and fatigue resistant. When tested in biomimetic perfusion bioreactors, the hydrogels maintain physical integrity under prolonged, high-frequency biomechanical stimulations (>6000 000 cycles at 120 Hz). The excellent biomechanical performance suggests the great potential of the new injectable hydrogel technology for repairing mechanically dynamic tissues, such as vocal folds, and other applications, such as tissue engineering, biofabrication, organs-on-chips, drug delivery, and disease modeling.Microbes embedded in hydrogels comprise one form of living material. Discovering formulations that balance potentially competing for mechanical and biological properties in living hydrogels-for example, gel time of the hydrogel formulation and viability of the embedded organisms-can be challenging. In this study, a pipeline is developed to automate the characterization of the gel time of hydrogel formulations. Using this pipeline, living materials comprised of enzymatically crosslinked silk and embedded E. coli-formulated from within a 4D parameter space-are engineered to gel within a pre-selected timeframe. Gelation time is estimated using a novel adaptation of microrheology analysis using differential dynamic microscopy (DDM). In order to expedite the discovery of gelation regime boundaries, Bayesian machine learning models are deployed with optimal decision-making under uncertainty. The rate of learning is observed to vary between artificial intelligence (AI)-assisted planning and human planning, with the fastest rate occurring during AI-assisted planning following a round of human planning. For a subset of formulations gelling within a targeted timeframe of 5-15 min, fluorophore production within the embedded cells is substantially similar across treatments, evidencing that gel time can be tuned independent of other material properties-at least over a finite range-while maintaining biological activity.Polymyxin B (PMB) has reemerged as a last-line therapy for infections caused by multidrug-resistant gram-negative pathogens, but dosing is challenging because of its narrow therapeutic window and pharmacokinetic (PK) variability. Population PK (POPPK) models based on suitably powered clinical studies with appropriate sampling strategies that take variability into consideration can inform PMB dosing to maximize efficacy and minimize toxicity and resistance. Here we reviewed published PMB POPPK models and evaluated them using an external validation data set (EVD) of patients who are critically ill and enrolled in an ongoing clinical study to assess their utility. Seven published POPPK models were employed using the reported model equations, parameter values, covariate relationships, interpatient variability, parameter covariance, and unexplained residual variability in NONMEM (Version 7.4.3). The predictive ability of the models was assessed using prediction-based and simulation-based diagnostics. Patient characteristics and treatment information were comparable across studies and with the EVD (n = 40), but the sampling strategy was a main source of PK variability across studies. All models visually and statistically underpredicted EVD plasma concentrations, but the two-compartment models more accurately described the external data set. As current POPPK models were inadequately predictive of the EVD, creation of a new POPPK model based on an appropriately powered clinical study with an informed PK sampling strategy would be expected to improve characterization of PMB PK and identify covariates to explain interpatient variability. Such a model would support model-informed precision dosing frameworks, which are urgently needed to improve PMB treatment efficacy, limit resistance, and reduce toxicity in patients who are critically ill.Excessive reactive oxygen species (ROS) generated after myocardial infarction (MI) result in the oxidative injury in myocardium. Implantation of antioxidant biomaterials, without the use of any type of drugs, is very appealing for clinical translation, leading to the great demand of novel biomaterials with high efficiency of ROS elimination. In this study, a segmented polyurethane (PFTU) with a high density of ROS-scavenging backbone units is synthesized by the reaction of poly(thioketal) dithiol (PTK) and poly(propylene fumarate) diol (PPF) (soft segments), thioketal diamine (chain extender), and 1,6-hexamethylene diisocyanate (HDI). Its chemical structure is verified by gel permeation chromatography (GPC), 1 H nuclear magnetic resonance (1 H NMR) spectroscopy, and Fourier transform infrared (FTIR) spectroscopy. The electrospun composite PFTU/gelatin (PFTU/Gt) fibrous patches show good antioxidation capacity and ROS-responsive degradation in vitro. Implantation of the PFTU/gelatin patches on the heart tissue surface in MI rats consistently decreases the ROS level, membrane peroxidation, and cell apoptosis at the earlier stage, which are not observed in the non-ROS-responsive polyurethane patch.
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