Computer-aided design of dry powder inhalers using computational fluid dynamics to assess performance

Dry powder inhalers (DPIs) are gaining popularity for the delivery of drugs. A cost effective and efficient delivery device is necessary. Developing new DPIs by modifying an existing device may be the simplest way to improve the performance of the devices. The aim of this research was to produce a new DPIs using computational fluid dynamics (CFD). The new DPIs took advantages of the Cyclohaler® and the Rotahaler®. We chose a combination of the capsule chamber of the Cyclohaler® and the mouthpiece and grid of the Rotahaler®. Computer-aided design models of the devices were created and evaluated using CFD. Prototype models were created and tested with the DPI dispersion experiments. The proposed model 3 device had a high turbulence with a good degree of deagglomeration in the CFD and the experiment data. The %fine particle fraction (FPF) was around 50% at 60?L/min. The mass median aerodynamic diameter was around 2.8–4?μm. The FPF were strongly correlated to the CFD-predicted turbulence and the mechanical impaction parameters. The drug retention in the capsule was only 5–7%. In summary, a simple modification of the Cyclohaler® and Rotahaler® could produce a better performing inhaler using the CFD-assisted design.     

Deferoxamine promotes recovery of traumatic spinal cord injury by inhibiting ferroptosis

Ferroptosis is an iron-dependent novel cell death pathway. Deferoxamine, a ferroptosis inhibitor, has been reported to promote spinal cord injury repair. It has yet to be clarified whether ferroptosis inhibition represents the mechanism of action of Deferoxamine on spinal cord injury recovery. A rat model of Deferoxamine at thoracic 10 segment was established using a modified Allen's method. Ninety 8-week-old female Wistar rats were used. Rats in the Deferoxamine group were intraperitoneally injected with 100 mg/kg Deferoxamine 30 minutes before injury. Simultaneously, the Sham and Deferoxamine groups served as controls. Drug administration was conducted for 7 consecutive days. The results were as follows:(1) Electron microscopy revealed shrunken mitochondria in the spinal cord injury group.(2) The Basso, Beattie and Bresnahan locomotor rating score showed that recovery of the hindlimb was remarkably better in the Deferoxamine group than in the spinal cord injury group.(3) The iron concentration was lower in the Deferoxamine group than in the spinal cord injury group after injury.(4) Western blot assay revealed that, compared with the spinal cord injury group, GPX4, xCT, and glutathione expression was markedly increased in the Deferoxamine group.(5) Real-time polymerase chain reaction revealed that, compared with the Deferoxamine group, mRNA levels of ferroptosis-related genes Acyl-CoA synthetase family member 2(ACSF2) and iron-responsive element-binding protein 2(IREB2) were up-regulated in the Deferoxamine group.(6) Deferoxamine increased survival of neurons and inhibited gliosis. These findings confirm that Deferoxamine can repair spinal cord injury by inhibiting ferroptosis. Targeting ferroptosis is therefore a promising therapeutic approach for spinal cord injury.     

Is dose modification or discontinuation of nilotinib necessary in nilotinib-induced hyperbilirubinemia?

Nilotinib is a specific breakpoint cluster region-Abelson leukemia virus-tyrosine kinase inhibitor that is used as an effective first- or second-line treatment in imatinib-resistant chronic myelogenous leukemia (CML) patients. Hepatotoxicity due to nilotinib is a commonly reported side effect; however, abnormal liver function test (LFT) results have been reported in asymptomatic cases. When alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels are more than five-fold the upper limit of the normal (ULN) or when the serum total bilirubin level is more than three-fold the ULN, dose modification or discontinuation of nilotinib is recommended, resulting in decreased levels of hematological indicators in certain patients with CML. Nilotinib-induced hyperbilirubinemia typically manifests as indirect bilirubinemia without elevated ALT or AST levels. Such abnormal liver functioning is thus not attributed to the presence of a true histologic lesion of the liver. The underlying mechanism may be related to the inhibition of uridine diphosphate glucuronosyltransferase activity. Therefore, nilotinib dose adjustment is not recommended for this type of hyperbilirubinemia, and in the absence of elevated liver enzyme levels or presence of abnormal LFT findings, physicians should consider maintaining nilotinib dose intensity without modifications.     

Growth Hormone Induces Recurrence of Infantile Hemangiomas After Apparent Involution: Evidence of Growth Hormone Receptors in Infantile Hemangioma

Infantile hemangiomas (IHs) are the most common benign tumor of infancy, characterized by a natural history of early proliferation in the first months of life to eventual involution during childhood, often with residual fibrofatty tissue. Once involution has been achieved, IHs do not typically recur. We present two cases of exogenous growth hormone therapy resulting in the recurrence of IHs in late childhood, supported by radiological, immunohistochemical, in vitro, and in vivo evidence.     

Association Between Patient and Physician Sex and Physician-Estimated Stroke and Bleeding Risks in Atrial Fibrillation

Background

Physicians treating nonvalvular atrial fibrillation (AF) assess stroke and bleeding risks when deciding on anticoagulation. The agreement between empirical and physician-estimated risks is unclear. Furthermore, the association between patient and physician sex and anticoagulation decision-making is uncertain.

Effect of corneal stromal pocket irrigation in small-incision lenticule extraction

ObjectivesTo investigate the effect of corneal stromal pocket irrigation after small-incision lenticule extraction (SMILE) on visual acuity, intraocular pressure (IOP), corneal parameters and complications after surgery.MethodsA total of 242 eyes of 121 patients undergoing SMILE were enrolled in this prospective controlled study, and it was designed for one eye to randomly undergo SMILE with balanced salt solution irrigation of the corneal stromal pocket, while the other eye was not. The uncorrected distance visual acuity (UDVA) and slit lamp examination were recorded at 1 hour, 1 day, 1 week, and 1 month. Postoperative corneal density, corneal biomechanical, corneal endothelial cell number, and anterior OCT images were compared at 1 day, 1 week, and 1 month.ResultsCompared with the nonirrigation group, the irrigation group showed significantly higher UDVA at 1 day postoperatively (P < 0.05), but there was no significant difference during the rest of the postoperative period (1 hour, 1 week, and 1 month). In addition, no significant differences were found in IOP, corneal density, corneal biomechanics, corneal endothelial cells, and corneal morphology. No visual decline or severe postoperative complications were found in the patients in this study.ConclusionsInterlamellar irrigation did not affect IOP, corneal parameters, morphology, complications, or UDVA at 1 hour, 1 week, and 1 month after the operation, but it may promote UDVA 1 day after the operation.Subject terms: Refractive errors, Outcomes research, Surgery     

胸腔镜肺小结节切除术前微弹簧圈定位的临床应用研究

目的:研究孤立性肺结节(SPN)胸腔镜术前CT引导下双弹簧圈精准标记定位的应用价值。方法:回顾分析43例SPN胸腔镜术前定位病例资料，包括双弹簧圈组22例，Hook-wire定位组21例。统计双弹簧圈定位的术中、术后并发症，衔接期时间以及作楔形切除所用时间，并将两组结果进行对比分析。结果:两组病例定位均取得成功；双弹簧圈组的气胸发生率(9.0%)，肺出血发生率(9.0%)，胸痛发生率(9.0%)均低于Hook-wire组，其中肺出血发生率与Hook-wire组比较，差异有统计学意义(P＜0.01)；衔接时间双弹簧圈组（15.38±8.32）h长于Hook-wire组（4.21±3.29）h，差异有统计学意义（P＜0.05）；作楔形切除所用时间双弹簧圈组(21.01±7.14)min与Hook-wire组(18.22±5.18)min差异无统计学意义(P＞0.05)。结论:采用双微弹簧圈进行SPN胸腔镜手术前精准标记定位安全可靠、效果良好，与Hook-wire定位比较并发症发生率更低，并可获得更长的衔接期，具有较高的应用价值。