Mohawk promotes the maintenance and regeneration of the outer annulus fibrosus of intervertebral discs.

The main pathogenesis of intervertebral disc (IVD) herniation involves disruption of the annulus fibrosus (AF) caused by ageing or excessive mechanical stress and the resulting prolapse of the nucleus pulposus. Owing to the avascular nature of the IVD and lack of understanding the mechanisms that maintain the IVD, current therapies do not lead to tissue regeneration. Here we show that homeobox protein Mohawk (Mkx) is a key transcription factor that regulates AF development, maintenance and regeneration. Mkx is mainly expressed in the outer AF (OAF) of humans and mice. In Mkx(-/-) mice, the OAF displays a deficiency of multiple tendon/ligament-related genes, a smaller OAF collagen fibril diameter and a more rapid progression of IVD degeneration compared with the wild type. Mesenchymal stem cells overexpressing Mkx promote functional AF regeneration in a mouse AF defect model, with abundant collagen fibril formation. Our results indicate a therapeutic strategy for AF regeneration

A novel in vivo corneal trans-epithelial electrical resistance measurement device

Purpose: To develop a device that is capable of easily measuring corneal transepithelial electrical resistance (TER) and changes in the corneal barrier function. Methods: We had previously developed an in vivo method for measuring corneal TER using intraocular electrode. This method can be used to precisely measure the decline of the corneal barrier function after instillation of benzalkonium chloride (BAC). In order to lessen the invasiveness of that procedure, we further refined the method for measuring the corneal TER by developing electrodes that could be placed on the cornea and in the conjunctival sac instead of inserting them into the anterior chamber. TER was then calculated by subtracting the electrical resistance, which lacked the corneal epithelial input, from the whole electrical resistance that was measured between the electrodes. Slit lamp examination and scanning electron microscopy (SEM) were used to determine safety of the new device. Corneal TER changes after exposure to 0.02% BAC were determined using the new device as well as SEM and transmission electron microscopy (TEM). Results: Slit lamp examination before and after exposure of rabbits\u27 corneas to the sensor confirmed safety of the device. SEM examination revealed no difference of the corneal epithelium which exposed to the new device with normal corneas. SEM and TEM pictures revealed damaged microvilli and tight junctions after instillation of 0.02% BAC. TER change after treatment with 0.02%BAC was similar to those determined by the established anterior chamber method. Conclusion: We succeeded to develop a less invasive device for corneal TER measurement in vivo in animals. This new device may be applicable in the future for clinical use in humans

Microdosimetric evaluation of secondary particles in a phantom produced by carbon 290 MeV/nucleon ions at HIMAC

Microdosimetric single event spectra as a function of depth in a phantom for the 290 MeV/nucleon therapeutic carbon beam at HIMAC were measured by using a tissue equivalent proportional counter (TEPC). Two types of geometries were used: one is a fragment particle identification measurement (PID-mode) with time of flight (TOF) method without a backward phantom, and the other is an in-phantom measurement (IPM-mode) with a backward phantom.On the PID-mode geometry, fragments produced by carbon beam in a phantom are identified by the deltaE-TOF distribution between two scintillation counters positioned up- and down-stream relative to the tissue equivalent proportional counter (TEPC). Lineal energy distributions for carbon and five ion fragments (proton, helium, lithium, beryllium and boron) were obtained in the lineal-energy range of 0.1-1000 keV/um at eight depths (7.9-147.9 mm) in an acrylic phantom. In the IPM-mode geometry, the total lineal energy distributions measured at eight depths (61.9-322.9 mm) were compared with the distributions in the PID-mode. Both spectra are consistent with each other. This shows that the PID-mode measurement can be discussed as the equivalent of the phantom measurement. The dose distribution of the carbon beam and fragments were obtained separately. In the depth dose curve, the Bragg peak was observed.Relative biological effectiveness (RBE) for the carbon beam in the acrylic phantom was obtained based on a biological response function as a lineal-energy. The RBE of carbon beam had a maximum of 4.5 at the Bragg peak. Downstream of the Bragg peak, the RBE rapidly decreases. The RBE of fragments is dominated by Boron particles around the Bragg peak region

Microdosimetric study for secondary neutrons in phantom produced by a 290 MeV/nucleon carbon beam

Absorbed doses from main charged-particle beams and charged-particle fragments have been measured with high accuracy for particle therapy, but there are few reports for doses from neutron components produced as fragments. This study describes the measurements on neutron doses produced by carbon beams; microdosimetric distributions of secondary neutrons produced by 290 MeV/nucleon carbon beams have been measured by using a tissue equivalent proportional counter at the Heavy Ion Medical Accelerator in Chiba, Japan at the National Institute of Radiological Sciences. The microdosimetric distributions of the secondary neutron were measured on the distal and lateral faces of a body-simulated acrylic phantom (300 mm heightx300 mm width x253 mm thickness). To confirm the dose measurements, the neutron energy spectra produced by incident carbon beams in the acrylic phantom were simulated by the particle and heavy ion transport code system. The absorbed doses obtained by multiplying the simulated neutron energy spectra with the kerma factor calculated by MCNPX agree with the corresponding experimental data fairly well. Downstream of the Bragg peak, the ratio of the neutron dose to the carbon dose at the Bragg peak was found to be a maximum of 1.4x10−4 and the ratio of neutron dose was a maximum of 3.0x10−7 at a lateral face of the acrylic phantom. The ratios of neutrons to charged particle fragments were 11% to 89% in the absorbed doses at the lateral and the distal faces of the acrylic phantom. We can conclude that the treatment dose will not induce serious secondary neutron effects at distances greater than 90 mm from the Bragg peak in carbon particle therapy

Timing of Complications Following Surgery for Distal Femur Fractures in Older Adults

Introduction The purpose of this study was to identify the timing and nature of complications associated with distal femur fracture surgery in patients aged 65 and older using the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database. Methods The ACS NSQIP database was queried for adults aged 65 and older who received surgical treatment for a distal femur fracture between 01 January 2015 and 31 December 2021. Cox regression models and risk tables adjusted for baseline clinical characteristics were created for 14 complications (Superficial Surgical Site Infection (SSI), Deep SSI, Organ/Space SSI, Pneumonia, Pulmonary Embolism (PE), Deep Venous Thrombosis (DVT), Urinary Tract Infection (UTI), Stroke/Cerebrovascular accident (CVA), Myocardial Infarction (MI), Renal Failure, Cardiac Arrest (CA), Re-operation, Sepsis, and Death within 30 days of surgery). Model summaries were used to identify significant variables with a Bonferroni correction applied. Results A total of 3956 adults met inclusion criteria and were included in analysis. The most common complications were UTI (5.2%), death (4.1%), and pneumonia (3.4%). Complications typically occurred within 14 days after surgery, except for SSI, which occurred between post-op days 11 and 24. Conclusions Distal femur fractures are a substantial source of morbidity and mortality in the older adult population. Our findings underscore the need for comprehensive preoperative risk assessment and patient management strategies to mitigate the impact of identified risk factors in this vulnerable population