L-glutamic acid-g-poly hydroxyethyl methacrylate nanoparticles: acute and sub-acute toxicity and biodistribution potential in mice

The aim of this safety study in mice was to determine in vivo toxicity and biodistribution potential of a single and multiple doses of L-glutamic acid-g-p(HEMA) polymeric nanoparticles as a drug delivery system. The single dose did not cause any lethal effect, and its acute oral LD₅₀ was >2.000 mg/kg body weight (bw). Multiple doses (25, 50, or 100 mg/kg bw) given over 28 days resulted in no significant differences in body and relative organ weights compared to control. These results are supported by biochemical and histological findings. Moreover, nanoparticle exposure did not result in statistically significant differences in micronucleus counts in bone marrow cells compared to control. Nanoparticle distribution was time-dependent, and they reached the organs and even bone marrow by hour 6, as established by ex vivo imaging with the IVIS^® spectrum imaging system. In conclusion, L-glutamic acid-g-p(HEMA) polymeric nanoparticles appear biocompatible and have a potential use as a drug delivery system.KEY WORDS: biocompatibility, blood biochemistry, genotoxicity, histology, in vivo toxicity, micronucleus test, polymers     

The gut microbiota at the intersection of bile acids and intestinal carcinogenesis: An old story,yet mesmerizing

The prevalence of colorectal cancer (CRC) has markedly increased worldwide in the last decade. Alterations of bile acid metabolism and gut microbiota have been reported to play vital roles in intestinal carcinogenesis. About trillions of bacteria have inhabited in the human gut and maintained the balance of host metabolism. Bile acids are one of numerous metabolites that are synthesized in the liver and further metabolized by the gut microbiota, and are essential in maintaining the normal gut microbiota and lipid digestion. Multiple receptors such as FXR, GPBAR1, PXR, CAR and VDR act as sensors of bile acids have been reported. In this review, we mainly discussed interplay between bile acid metabolism and gut microbiota in intestinal carcinogenesis. We then summarized the critical role of bile acids receptors involving in CRC, and also addressed the rationale of multiple interventions for CRC management by regulating bile acids–microbiota axis such as probiotics, metformin, ursodeoxycholic acid and fecal microbiota transplantation. Thus, by targeting the bile acids–microbiota axis may provide novel therapeutic modalities in CRC prevention and treatment.     

Comparison of the anatomic and hearing outcomes of cartilage type 1 tympanoplasty in pediatric and adult patients

European Archives of Oto-Rhino-Laryngology - As a graft material cartilage produces an excellent anatomical result with a low risk of re-perforation. However, there is a controversy among surgeons...     

Filtration efficiency of surgical sterilization fabric for respiratory protection during COVID-19 pandemic

BackgroundDue to COVID-19 and high demand for respirators, some healthcare professionals have been using the Halyard H600 fabric as an alternative to N95 respirators without testing the filtration efficiency of the fabric with established scientific methods. The purpose of this study was to assess the efficiency of the Halyard H600 as a respirator filtering material as compared to the NIOSH-certified N95 and P100 filters, and determine if H600 is a good alternative for respiratory protection for healthcare professionals during the COVID-19 pandemic.MethodsThree filter types (Halyard H600, N95, and P100) were challenged with salt particles inside an exposure chamber at a flow rate of 43 LPM and relative humidity of 40 ± 2%. N95 and P100 respirator filters were tested initially to establish the validity of the chamber, followed by the Halyard H600 fabric. Particle penetration was measured using an aerosol spectrometer. The filtration efficiency was calculated for different particle sizes by measuring the particle number concentration upstream and downstream of the filter. The pressure drop across the filter materials was measured using a manometer.ResultsThe efficiency of the P100 for particles ≥250 nm was 100%. The N95 efficiency was 97 ± 1% at 275 nm, 99 ± 0% at 324 nm, and 100% for larger particles. The Halyard H600 fabric had a variable efficiency with an average of 62 ± 28% at 275 nm, 89 ± 8% at 324 nm, and 100% efficiency for particles >450 nm. The pressure drop values for P100 and N95 were 32 and 8 mmH₂O, respectively. The Halyard H600 fabric resistance increased dramatically from 30 mmH₂O at the start of the exposure to 65 mmH₂O after 16-minutes of exposure.ConclusionThe high variability in filter efficiency for particles ≤324 nm and the increased fabric breathing resistance demonstrate that the Halyard H600 has an inferior performance and is not a good substitute for N95 and P100. Thus, the use of the Halyard H600 fabric for respiratory protection is not recommended.     

PLR联合VTI评估急性循环衰竭容量反应性的单中心随机对照研究

目的探讨被动抬腿试验(PLR)联合左室流出道速度时间积分(VTI)评估外科ICU中急性循环衰竭(ACF)早期容量反应性的价值。方法采取前瞻性观察队列研究方法选取急性循环衰竭患者先后进行被动抬腿试验和容量负荷试验,试验前后采用经胸超声心动图测量每搏量(SV),做左室流出道速度时间积分(VTI),定义试验前后SV增加(ΔSV)≥15%为有容量反应性,根据有无容量反应将患者分为有反应组和无反应组,观察两组PLR前后相关血流动力学参数的变化及其相关性,最后采用受试者工作特征曲线(ROC曲线)评价VTI预测容量反应性的价值。结果研究共计纳入60例患者,其中有容量反应35例,无容量反应性25例;有容量反应性组PLR前后平均动脉压MAP(67±19 vs 73±13 mm Hg,P=0.02)、每搏量SV(48±11 vs 56±10 ml,P=0.03)、VTI(14±4 vs 18±5 cm,P=0.04)的变化存在显著统计学差异;PLR前后与容量负荷试验前后ΔSV呈显著正相关性(r=0.8846,P<0.0001);PLR后下腔静脉塌陷指数(c IVC)、ΔVTI与ΔSV呈显著正相关性(r=0.8034,P<0.001;r=9212,P<0.001),而CVP与ΔSV无显著相关性(r=-0.1121,P=3947);PLR后ΔVTI预测容量反应性AUC(ROC曲线下面积)为0.8686±0.04(P<0.001),其中ΔVTI>8.75%预测容量反应性敏感性和特异性分别为90.63%和85.00%,阳性预测率和阴性预测率分别为90.67%和84.00%。结论 PLR联合VTI可以准确预测外科ICU中急性循环衰竭患者容量反应性,可指导临床液体治疗。     

MRI compatible MS2 nanoparticles designed to cross the blood–brain-barrier: providing a path towards tinnitus treatment

Fundamental challenges of targeting specific brain regions for treatment using pharmacotherapeutic nanoparticle (NP) carriers include circumventing the blood–brain-barrier (BBB) and tracking delivery. Angiopep-2 (AP2) has been shown to facilitate the transport of large macromolecules and synthetic nanoparticles across the BBB. Thus, conjugation of AP2 to an MS2 bacteriophage based NP should also permit transport across the BBB. We have fabricated and tested a novel MS2 capsid-based NP conjugated to the ligand AP2. The reaction efficiency was determined to be over 70%, with up to two angiopep-2 conjugated per MS2 capsid protein. When linked with a porphyrin ring, manganese (Mn²⁺) remained stable within MS2 and was MRI detectable. Nanoparticles were introduced intracerebroventricularly or systemically. Systemic delivery yielded dose dependent, non-toxic accumulation of NPs in the midbrain. Design of a multifunctional MRI compatible NP platform provides a significant step forward for the diagnosis and treatment of intractable brain conditions, such as tinnitus.     

Orbital foreign body penetrating from the cheek

This study emphasizes the importance of diagnostic first aid procedures to avoid the consequences of trauma due to foreign body. A 20-year-old man referred to our hospital with a history of having a sharp penetrating injury to his right eye. Computed tomography evaluation reported right globe perforation and intraorbital glass foreign body measuring 4 x 7 cm was removed. Perforated eye was repaired and traumatic cuts were sutured. Orbital and ocular injuries are common, and delays in management may lead to complication. A team approach is the best technique for these patients.     

Chronic osteomyelitis: 20 years after mandible fracture

Abstract  – Chronic osteomyelitis is a persistent abscess of the bone that is characterized by the usual complex of inflammatory processes, including necrosis of mineralized and marrow tissues, suppuration, resorption, sclerosis, and hyperplasia. The purpose of this paper is to report a case of chronic osteomyelitis seen 20 years after mandible fracture.