Magnetic Properties of Amorphous Ta/CoFeB/MgO/Ta Thin Films on Deformable Substrates with Magnetic Field Angle and Tensile Strain.

Recently, the application of cobalt iron boron (CoFeB) thin films in magnetic sensors has been widely studied owing to their high magnetic moment, anisotropy, and stability. However, most of these studies were conducted on rigid silicon substrates. For diverse applications of magnetic and angle sensors, it is important to explore the properties of ferromagnetic thin films grown on nonrigid deformable substrates. In this study, representative deformable substrates (polyimide (PI), polyethylene naphthalate (PEN), and polydimethylsiloxane (PDMS)), which can be bent or stretched, were used to assess the in-plane magnetic field angle-dependent properties of amorphous Ta/CoFeB/MgO/Ta thin films grown on deformable substrates. The effects of substrate roughness, tensile stress, deformable substrate characteristics, and sputtering on magnetic properties, such as the coercive field (Hc), remanence over saturation magnetization (Mr/Ms), and biaxial characteristics, were investigated. This study presents an unconventional foundation for exploring deformable magnetic sensors capable of detecting magnetic field angles.

Subacute inhalation toxicity study of synthetic amorphous silica nanoparticles in Sprague-Dawley rats.

Synthetic amorphous silica nanoparticles (SiNPs) are one of the most applied nanomaterials and are widely used in a broad variety of industrial and biomedical fields. However, no recent long-term inhalation studies evaluating the toxicity of SiNPs are available and results of acute studies are limited. Thus, we conducted a subacute inhalation toxicity study of SiNPs in Sprague-Dawley rats using a nose-only inhalation system. Rats were separated into four groups and target concentrations selected in this study were as follows: control (fresh air), low- (0.407 ± 0.066 mg/m3), middle- (1.439 ± 0.177 mg/m3) and high-concentration group (5.386 ± 0.729 mg/m3), respectively. The rats were exposed to SiNPs for four consecutive weeks (6 hr/day, 5 days/week) except for control group of rats which received filtered fresh air. After 28-days of inhalation exposure to SiNPs, rats were sacrificed after recovery periods of one, seven and 28 days. Although there were minimal toxic changes such as temporary decrease of body weight after exposure, increased levels of red blood cells (RBCs) and hemoglobin (Hb) concentration, the lung histopathological findings and inflammatory markers in bronchoalveolar lavage (BAL) fluid including polymorphonuclear (PMN) leukocyte, lactate dehydrogenase (LDH), albumin and protein did not show significant changes at any recovery period. The results of this study suggest that the subacute inhalation of SiNPs had no toxic effects on the lung of rats at the concentrations and selected time points used in this study.

Open-wedge high tibial osteotomy versus unicompartmental knee arthroplasty: no difference in progression of patellofemoral joint arthritis.

PURPOSE: The purpose of this retrospective comparative study was to evaluate and compare, radiographically and clinically, progression of osteoarthritis (OA) in the patellofemoral (PF) compartment after open-wedge high tibial osteotomy (OWHTO), and unicompartmental knee arthroplasty (UKA) over a minimum follow-up of 5 years. METHODS: In this study, 42 knees in an OWHTO group were compared with 59 knees in a UKA group in terms of radiographic parameters, such as the grading system for OA progression in the PF compartment, and clinical parameters, such as the PF pain and function scores over a minimum follow-up of 5 years. RESULTS: There was no significant difference of OA progression in the PF compartment between the two groups on knee radiography. Compared with the preoperative grades, the UKA group showed significant progression of OA in the medial PF compartment at the final follow-up, whereas the medial PF compartment showed significant stepwise progression by only one grade when compared to the OWHTO group. The PF pain and function scores showed no statistical differences between the two groups at the final follow-up, regardless of OA progression. CONCLUSIONS: There was no significant difference between OWHTO and UKA in terms of progression of OA in the PF compartment or deterioration of PF function score over a minimum follow-up of 5 years. However, the medial PF compartment of the UKA group was minimal, and worsened or progressed by only one grade. LEVEL OF EVIDENCE: III.

Total knee arthroplasty after failed high tibial osteotomy: a systematic review of open versus closed wedge osteotomy.

PURPOSE: Medial opening wedge high tibial osteotomy (HTO) has become increasingly popular as an alternative to lateral closing wedge osteotomy for the treatment of medial compartment knee osteoarthritis with varus deformity. The present systematic review was conducted to provide an objective analysis of total knee arthroplasty (TKA) outcomes following previous knee osteotomy (medial opening wedge vs. lateral closing wedge). METHODS: A literature search of online databases (MEDLINE, EMBASE, Cochrane Library database) was made, in addition to manual search of major orthopaedic journals. The methodological quality of each of the studies was assessed on the Newcastle-Ottawa Scale and Effective Practice and Organization of Care. A total of ten studies were included in the review. There were eight studies with Level IV and two studies with Level III evidence. RESULTS: Eight studies reported clinical and radiologic scores. Comparative studies between TKA following medial opening and lateral closing wedge HTO did not demonstrate statistically significant clinical and radiologic differences. The revision rates were similar. However, more technical issues during TKA surgery after lateral closing wedge HTO were mentioned than the medial open wedge group. The quadriceps snip, tibial tubercle osteotomy, and lateral soft tissue release were more frequently needed in the lateral closing wedge HTO group. In addition, because of loss of proximal tibia bone geometry in the lateral closing wedge HTO group, concerns such as tibia stem impingement in the lateral tibial cortex was noted. CONCLUSION: The present systematic review suggests that TKA after medial opening and lateral closing wedge HTO showed similar performance. Clinical and radiologic outcome including revision rates did not statistically differ from included studies. However, there are more surgical technical concerns in TKA conversion from lateral closing wedge HTO than from the medial opening wedge HTO group. LEVEL OF EVIDENCE: IV.

Size-dependent clearance of gold nanoparticles from lungs of Sprague-Dawley rats after short-term inhalation exposure.

Gold nanoparticles are known to be distributed to many tissues following their oral, inhalation, or intravenous exposure. Information on the biodistribution and clearance of gold nanoparticles from these tissues is, therefore, important to understand their behavior in vivo. To study the effect of size on the biodistribution of gold nanoparticles, Sprague-Dawley rats were exposed by inhalation to small gold nanoparticles (13 nm in diameter on average) at an exposure concentration of 12.8 ± 2.42 µg/m(3), and to large gold nanoparticles (105 nm in diameter on average) at an exposure concentration of 13.7 ± 1.32 µg/m(3). The experimental animals were exposed to the gold nanoparticles and the control animals to fresh air for 5 days (6 h/day), followed by a recovery period of 1, 3, and 28 days in fresh air. None of the exposed animals exhibited any toxic response to the gold nanoparticles. Despite the difference in size, both small and large gold nanoparticles deposited mainly in rat lungs. Their biodistribution from the lungs to secondary target organs was significantly higher with the small compared to the large gold nanoparticles. While the large gold nanoparticles were only found in the blood, the small gold nanoparticles were detected in the liver, spleen, brain, testes, and blood. In addition, the elimination half-life of the small gold nanoparticles from the lungs was significantly shorter than that of the large gold nanoparticles. The present data may, therefore, suggest that the smaller gold nanoparticles are able to translocate from the lungs, the primary exposure organ to extrapulmonary organs at a faster rate than the larger gold nanoparticles and thus confirming previous observations reported in the literature.

Serum levels of IL-8 and ICAM-1 as biomarkers for progressive massive fibrosis in coal workers' pneumoconiosis.

Coal workers' pneumoconiosis (CWP) is characterized as a chronic inflammation of the lung associated with activation of macrophages and endothelial cells in the lung. The aim of the present study was to compare the levels of serum interleukin-8 (IL-8), macrophage inflammatory protein-1α (MIP-α), and intercellular adhesion molecule-1 (ICAM-1) as biomarkers for progressive massive fibrosis (PMF) in 106 subjects (27 non-CWP and 79 CWP patients). The levels of serum IL-8 (P<0.001) and ICAM-1 (P=0.001) of subjects with PMF were higher than those of non-CWP subjects. The IL-8 levels of PMF subjects were also higher than those of simple CWP subjects (P=0.003). Among the subjects without PMF, IL-8 levels in the subjects with International Labour Organization (ILO) category II or III were higher than those in the subjects with ILO category 0 (P=0.006) and with category I (P=0.026). These results suggest that high serum levels of IL-8 and ICAM-1, which are important as neutrophil attractants and adhesion molecules, are associated with PMF.

In vivo genotoxicity evaluation of lung cells from Fischer 344 rats following 28 days of inhalation exposure to MWCNTs, plus 28 days and 90 days post-exposure.

Despite their useful physico-chemical properties, carbon nanotubes (CNTs) continue to cause concern over occupational and human health due to their structural similarity to asbestos. Thus, to evaluate the toxic and genotoxic effect of multi-wall carbon nanotubes (MWCNTs) on lung cells in vivo, eight-week-old rats were divided into four groups (each group = 25 animals), a fresh air control (0 mg/m(3)), low (0.17 mg/m(3)), middle (0.49 mg/m(3)), and high (0.96 mg/m(3)) dose group, and exposed to MWCNTs via nose-only inhalation 6 h per day, 5 days per week for 28 days. The count median length and geometric standard deviation for the MWCNTs determined by TEM were 330.18 and 1.72 nm, respectively, and the MWCNT diameters ranged from 10 to 15 nm. Lung cells were isolated from five male and five female rats in each group on day 0, day 28 (only from males) and day 90 following the 28-day exposure. The total number of animals used was 15 male and 10 female rats for each concentration group. To determine the genotoxicity of the MWCNTs, a single cell gel electrophoresis assay (Comet assay) was conducted on the rat lung cells. As a result of the exposure, the olive tail moments were found to be significantly higher (p < 0.05) in the male and female rats from all the exposed groups when compared with the fresh air control. In addition, the high-dose exposed male and middle and high-dose exposed female rats retained DNA damage, even 90 days post-exposure (p < 0.05). To investigate the mode of genotoxicity, the intracellular reactive oxygen species (ROS) levels and inflammatory cytokine levels (TNF-α, TGF- ß, IL-1, IL-2, IL-4, IL-5, IL-10, IL-12 and IFN-γ) were also measured. For the male rats, the H2O2 levels were significantly higher in the middle (0 days post-exposure) and high- (0 days and 28 days post-exposure) dose groups (p < 0.05). Conversely, the female rats showed no changes in the H2O2 levels. The inflammatory cytokine levels in the bronchoalveolar lavage (BAL) fluid did not show any statistically significant difference. Interestingly, the short-length MWCNTs deposited in the lung cells were persistent at 90 days post-exposure. Thus, exposing lung cells to MWCNTs with a short tube length may induce genotoxicity.

Analysis of carbon nanotube levels in organic matter: an inter-laboratory comparison to determine best practice.

Carbon nanotubes (CNTs) are increasingly being used in industrial applications, but their toxicological data in animals and humans are still sparse. To assess the toxicological dose-response of CNTs and to evaluate their pulmonary biopersistence, their quantification in tissues, especially lungs, is crucial. There are currently no reference methods or reference materials for low levels of CNTs in organic matter. Among existing analytical methods, few have been fully and properly validated. To remedy this, we undertook an inter-laboratory comparison on samples of freeze-dried pig lung, ground and doped with CNTs. Eight laboratories were enrolled to analyze 3 types of CNTs at 2 concentration levels each in this organic matrix. Associated with the different analysis techniques used (specific to each laboratory), sample preparation may or may not have involved prior digestion of the matrix, depending on the analysis technique and the material being analyzed. Overall, even challenging, laboratories' ability to quantify CNT levels in organic matter is demonstrated. However, CNT quantification is often overestimated. Trueness analysis identified effective methods, but systematic errors persisted for some. Choosing the assigned value proved complex. Indirect analysis methods, despite added steps, outperform direct methods. The study emphasizes the need for reference materials, enhanced precision, and organized comparisons.

Home cage locomotor changes in non-human primates after prolonged welding-fume exposure.

To define the relationship between the brain concentration of manganese and neurological signs, such as locomotion, after prolonged welding-fume exposure, cynomolgus monkeys were acclimated for 1 month and then divided into three concentration groups: unexposed, low concentration (31 mg/m(3) total suspended particulate (TSP), 0.9 mg/m(3) of Mn), and high concentration (62 mg/m(3) TSP, 1.95 mg/m(3) of Mn) of TSP. The monkeys were exposed to manual metal-arc stainless steel (MMA-SS) welding fumes for 2 h per day over 8 months in an inhalation chamber system equipped with an automatic fume generator. The home cage locomotor activity and patterns were determined using a camera system over 2-4 consecutive days. After 25 and 32 weeks of exposure, the home cage locomotor activity of the high-concentration primates was found to be 5-6 times higher than that of the unexposed primates, and this increased locomotor activity was maintained for 7 weeks after ceasing the welding-fume exposure, eventually subsiding to three times higher after 13 weeks of recovery. Therefore, the present results, along with our previous observations of a high magnetic resonance imaging (MRI) T1 signal in the globus pallidus and increased blood Mn concentration, indicate that prolonged welding-fume exposure can cause neurobehavioral changes in cynomolgus monkeys.

Ultrafine particle characteristics in a rubber manufacturing factory.

BACKGROUND: According to epidemiological research, exposure to rubber fumes can cause various types of cancer and can lead to an increase in death rate because of cardiovascular diseases. OBJECTIVES: In this study, we have assessed the characteristics of ultrafine particles emitted into the air during the manufacturing of rubber products using waste tires. METHODS: To assess the aerosol distribution of rubber fumes in the workplace from a product during curing, we have performed particle number concentration mapping using a handheld condensation particle counter. The particle number concentration of each process, count median diameter (CMD), and nanoparticle ratio (<100nm) were determined using an electrical low-pressure impactor (ELPI), and the surface area concentration was determined using a surface area monitor. The shape and composition of the sampled rubber fumes were analyzed using an ELPI-transmission electron microscopy grid method. Further, the rubber fume mass concentration was determined according to the Methods for the Determination of Hazardous Substances 47/2. RESULTS: The results of particle mapping show that the rubber fumes were distributed throughout the air of the workplace. The concentration was the highest during the final process of the work. The particle number concentration and the surface area concentration were 545 000cm(-3) and 640 µm(2) cm(-3), respectively, approximately 10- and 4-fold higher than those in the outdoor background. During the final process, the CMD and the nanoparticle ratio were 26nm and 94%, respectively. Most of the rubber fume particles had a compact shape because of the coagulation between particles. The main components of these fumes were silicon and sulfur, and heavy metals such as zinc were detected in certain particles. The filter concentration of the rubber fumes was 0.22mg m(-3), lower than the UK workplace exposure limit of 0.6mg m(-3). CONCLUSIONS: Therefore, the rubber manufacturing process is a potentially dangerous process that produces a high concentration of specific nanoparticles.

Lab on a chip for detecting Clara cell protein 16 (CC16) for potential screening of the workers exposed to respirable silica aerosol.

Early detection of pulmonary responses to silica aerosol exposure, such as lung inflammation as well as early identification of silicosis initiation, is of great importance in disease prevention of workers. In this study, to early screen the health condition of the workers who are exposed to respirable silica dusts, an immunoassay lab on a chip (LOC) was designed, developed and fully characterized for analyzing Clara cell protein 16 (CC16) in serum which has been considered as one of the potential biomarkers of lung inflammation or lung damage due to the respirable silica dusts. Sandwich immunoassay of CC16 was performed on the LOC developed with a custom-designed portable analyzer using artificial serums spiked with CC16 protein first and then human serums obtained from the coal mine workers exposed to the respirable silica-containing dusts. The dynamic range of CC16 assay performed on the LOC was in a range of 0.625-20 ng/mL, and the achieved limit of detection (LOD) was around 0.35 ng/mL. The assay results of CC16 achieved from both the developed LOC and the conventional 96 well plate showed a reasonable corelation. The correlation between the conventional reader and the developed portable analyzer was found to be reasonable, resulting in R2 ~ 0.93. This study shows that the LOC developed for the early detection of CC16 can be potentially applied for the development of a field-deployable point-of-care testing (POCT) for the early monitoring of the field workers who are exposed to silica aerosol.

Where is the Target Point to Prevent Cortical Hinge Fracture in Medial Closing-Wedge Distal Femoral Varus Osteotomy?

The purpose of this study was to investigate whether the location of the hinge affects the incidence of hinge fracture during medial closing-wedge distal femoral varus osteotomy (DFVO). Twenty knees from 10 fresh-frozen human cadavers (mean age, 75 ± 17 years) were used to perform uniplanar medial closing-wedge DFVO with a 7-mm wedge. Each specimen was randomly assigned to either group A (supracondylar hinge) or group B (lateral condylar hinge). The incidence of hinge fracture and stability was compared between both groups after uniplanar medial closing-wedge DFVO. In group A, 8 of 10 knees had a lateral cortex fracture during closure of the osteotomy gap, and all fractured knees were unstable. Two knees with an intact lateral cortical hinge showed stability under manual valgus and varus forces. After intentional breakage of the lateral cortical hinge, both knees were found to be unstable under the same force. In group B, 2 of 10 knees had a lateral cortex fracture, and 8 knees had no fractures. All specimens were found to be stable under manual valgus and varus forces. After intentional breakage of the lateral cortical hinge in group B, 2 knees were unstable, while 8 knees remained stable. This study showed a significantly higher incidence of lateral cortical hinge fracture and instability in group A than in group B during closure of the osteotomy gap.

Recovery from welding-fume-exposure-induced MRI T1 signal intensities after cessation of welding-fume exposure in brains of cynomolgus monkeys.

The shortening of the MRI T1 relaxation time, indicative of a high signal intensity in a T1-weighted MRI, is known as a useful biomarker for Mn exposure after short-term welding-fume exposure. A previous monkey experimental study found that the T1 relaxation times decreased time-dependently after exposure, and a visually detectable high signal intensity appeared after 150 days of exposure. The nadir for the shortening of the T1 relaxation time was also previously found to correspond well with the blood Mn concentration in welders, suggesting a correlation between a prolonged high blood Mn concentration and shortened T1 relaxation time. Accordingly, to clarify the clearance of the brain Mn concentration after the cessation of welding-fume exposure, cynomolgus monkeys were assigned to 3 groups-unexposed, low dose (31 mg/m(3) total suspended particulate (TSP), 0.9 mg Mn/m(3)), and high dose (62 mg/m(3) TSP, 1.95 mg Mn/m(3))-and exposed to manual metal-arc stainless steel (MMA-SS) welding fumes for 2 h per day for 8 mo in an inhalation chamber system equipped with an automatic fume generator. After reaching the peak MRI T1 signal intensity (shortest T1 relaxation time), the monkeys were allowed to recover by ceasing the welding-fume exposure. Within 2 mo, the MRI T1 signal intensities for the exposed monkeys returned to nearly the same level as those for the unexposed monkeys, indicating the potential for recovery from a high MRI T1 signal intensity induced by welding-fume exposure, even after prolonged exposure. Clearance of the Mn tissue concentration was also demonstrated in the globus pallidus, plus other tissues from the brain, liver, spleen, and blood. In contrast, there was no clearance of the lung concentrations of Mn, indicating that a soluble form of Mn was transported to the blood and brain. Therefore, the solubility of Mn in welding fumes would appear to be an important determinant as regards the retention of blood Mn levels and brain tissue Mn concentrations in welders.

Distal Femoral Varus Osteotomy for Valgus Arthritis of the Knees: Systematic Review of Open versus Closed Wedge Osteotomy.

PURPOSE: The purpose of this review is to compare the clinical and radiological outcomes between open and closed wedge distal femoral varus osteotomy (DFO). METHODS: A literature search of online databases (MEDLINE, EMBASE, and Cochrane Library database) was made in addition to manual search of major orthopedic journals. Data were searched from the time period of January 1990 to October 2016. A modified Coleman Methodology Score system was used to assess the methodologic quality of the included studies. A total of 20 studies were included in the review. All studies were level IV evidence. RESULTS: Comparative analysis of open and closed wedge DFO did not demonstrate clinical and radiological differences. The survival rates were also similar. Five studies (56%) on open wedge DFO mentioned the need for either bone grafting or substitute for osteotomy gap filling and reported higher incidences of reoperation for plate removal than the closed wedge DFO studies. CONCLUSIONS: The present systematic review showed similar performance between open and closed wedge DFO. Outcomes including survival rates were not statistically significantly different. However, additional bone grafting or substitutes were often needed to prevent delayed union or nonunion for open wedge techniques. Additional operations for plate removal were commonly required due to plate irritation in both techniques.

Short-term inhalation study of graphene oxide nanoplates.

Graphene oxides possess unique physicochemical properties with important potential applications in electronics, pharmaceuticals, and medicine. However, the toxicity following inhalation exposure to graphene oxide has not yet been clarified. Therefore, this study conducted a short-term graphene oxide inhalation toxicity analysis using a nose-only inhalation exposure system and male Sprague-Dawley rats. A total of four groups (15 rats per group) were exposed: (1) control (fresh air), (2) low concentration (0.76 ± 0.16 mg/m3), (3) moderate concentration (2.60 ± 0.19 mg/m3), and (4) high concentration (9.78 ± 0.29 mg/m3). The rats were exposed to graphene oxide for 6 h/day for 5 days, followed by recovery for 1, 3, and 21 days. No significant body or organ weight changes were noted after the short-term exposure or during the recovery period. Similarly, no significant systemic effects of toxicological importance were noted in the hematological assays, bronchoalveolar lavage fluid (BAL) inflammatory markers, BAL fluid cytokines, or blood biochemical assays following the graphene oxide exposure or during the post-exposure observation period. Moreover, no significant differences were observed in the BAL cell differentials, such as lymphocytes, macrophages, or polymorphonuclear cells. Graphene oxide-ingested alveolar macrophages as a spontaneous clearance reaction were observed in the lungs of all the concentration groups from post 1 day to post 21 days. Histopathological examination of the liver and kidneys did not reveal any significant test-article-relevant histopathological lesions. Importantly, similar to previously reported graphene inhalation data, this short-term nose-only inhalation study found only minimal or unnoticeable graphene oxide toxicity in the lungs and other organs.

Effect of manganese exposure on the neuroendocrine system in welders.

To evaluate the effect of occupational exposure to manganese (Mn) on serum prolactin (PRL) and the interrelationship among other hypophyseal-pituitary hormones, a cross-sectional study was conducted on 251 welders and 100 age-matched, office workers. We analyzed serum PRL, dopamine (DA), thyroid stimulating hormone releasing hormone (TRH), follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone (TST) and measured current airborne Mn concentration in the welders. Cumulative exposure index (CEI) of airborne Mn was calculated. CEI and the present Mn level of the welders were 1.4+/-1.1mg/m3 year (range: 0.0-4.9) and 0.4+/-3.84 mg/m3 (range: 0.0-3.8), respectively. TRH, FSH and LH were higher in welders (5.08 pg/ml, 7.40 and 4.91 mIU/ml, respectively) than in office workers (3.91 pg/ml, 6.15 and 4.00 mIU/ml, respectively) (p<0.05). DA was decreased and TRH was increased significantly with increasing CEI. DA increased up to CEI 2.0mg/m3 year or mean Mn level up to 0.2mg/m3, then decreased. PRL showed increasing tendency above the CEI and mean Mn level at which DA started to decrease. PRL was positively associated with DA in the office workers. However, such a normal feedback control of DA on PRL was not observed in the welders. Structural equation model (SEM) analysis showed that CEI was positively related to TRH and negatively related to DA. TRH increased PRL. PRL increased LH and perhaps FSH, and on the other hand, decreased TST. These results showed that Mn suppresses the inhibitory feedback control of DA on the hypophyseal-pituitary axis. In conclusion, we postulate that suppressed dopaminergic inhibitory function on the hypophyseal-pituitary axis might be the mechanism for the increased PRL exhibited in the welders.

Changes in blood manganese concentration and MRI t1 relaxation time during 180 days of stainless steel welding-fume exposure in cynomolgus monkeys.

Welders are at risk of being exposed to high concentrations of welding fumes and developing pneumoconiosis or other welding-fume exposure-related diseases. Among such diseases, manganism resulting from welding-fume exposure remains a controversial issue, as although the movement of manganese into specific brain regions has been established, the similar movement of manganese presented with other metals, such as welding fumes, has not been clearly demonstrated as being similar to that of manganese alone. Meanwhile, the competition between Mn and iron for iron transporters, such as transferrin and DMT-1, to the brain has also been implicated in the welding-fume exposure. Thus, the increased signal intensities in the basal ganglia, including the globus pallidus and subcortical frontal white matter, based on T1-weighted magnetic resonances in welders, require further examination as regards the correspondence with an increased manganese concentration. Accordingly, to investigate the movement of manganese after welding-fume exposure, 6 cynomolgus monkeys were acclimated for 1 mo and assigned to 3 dose groups: unexposed, low dose of (total suspended particulate [TSP] 31 mg/m3, 0.9 mg/m3 of Mn), and high dose of total suspended particulate (62 mg/m3 TSP, 1.95 mg/m3 of Mn). The primates were exposed to manual metal-arc stainless steel (MMA-SS) welding fumes for 2 h/day in an inhalation chamber system equipped with an automatic fume generator for 6 mo. Magnetic resonance imaging (MRI) studies of the basal ganglia were conducted before the initiation of exposure and thereafter every month. During the exposure, the blood chemistry was monitored every 2 wk and the concentrations of metal components in the blood were measured every 2 wk and compared with ambient manganese concentrations. The manganese concentrations in the blood did not show any significant increase until after 2 mo of exposure, and then reached a plateau after 90 days of exposure, showing that an exposure period of at least 60 days was required to build up the blood Mn concentration. Furthermore, as the blood Mn concentration continued to build, a continued decrease in the MRI T1 relaxation time in the basal ganglia was also detected. These data suggested that prolonged inhalation of welding fumes induces a high MRI T1 signal intensity with an elevation of the blood manganese level. The presence of a certain amount of iron or other metals, such as Cr and Ni, in the inhaled welding fumes via inhalation was not found to have a significant effect on the uptake of Mn into the brain or the induction of a high MRI T1 signal intensity.

Comparison of high MRI T1 signals with manganese concentration in brains of cynomolgus monkeys after 8 months of stainless steel welding-fume exposure.

Several pharmacokinetic studies on inhalation exposure to manganese (Mn) have already demonstrated that Mn readily accumulates in the olfactory and brain regions. However, a shortening of the magnetic resonance imaging (MRI) T1 relaxation time or high T1 signal intensity in specific sites of the brain, including the globus pallidus and subcortical frontal white matter, as indicative of tissue manganese accumulation has not yet been clearly established for certain durations of known doses of welding-fume exposure in experimental animals. Accordingly, to investigate the movement of manganese after welding-fume exposure, six cynomolgus monkeys were acclimated and assigned to three dose groups: unexposed, low dose (31 mg/m(3) total suspended particulate [TSP], 0.9 mg/m(3) of Mn), and high dose (62 mg/m(3) TSP, 1.95 mg/m(3) of Mn) of total suspended particulate. The primates were exposed to manual metal arc stainless steel (MMA-SS) welding fumes for 2 h per day in an inhalation chamber system equipped with an automatic fume generator. Magnetic resonance imaging (MRI) studies were conducted before the initiation of exposure and thereafter every month. The tissue Mn concentrations were then measured after a plateau was reached regarding the shortening of the MRI T1 relaxation time. A dose-dependent increase in the Mn concentration was found in the lungs, while noticeable increases in the Mn concentrations were found in certain tissues, such as the liver, kidneys, and testes. Slight increases in the Mn concentrations were found in the caudate, putamen, frontal lobe, and substantia nigra, while a dose-dependent noticeable increase was only found in the globus pallidus. Therefore, the present results indicated that a shortening of the MRI T1 relaxation time corresponded well with the Mn concentration in the globus pallidus after prolonged welding-fume exposure.

A Combined Closing Wedge Distal Femoral Osteotomy and Medial Reefing Procedure for Recurrent Patellar Dislocation with Genu Valgum.

PURPOSE: Recurrent patellar dislocation is often associated with genu valgum. The purpose of this study was to analyze the short-term results of single-incision, closing-wedge distal femoral osteotomy (CWDFO) combined with medial reefing and lateral release for recurrent patellar instability with genu valgum. MATERIALS AND METHODS: Combined CWDFO/medial reefing/lateral release was performed on 10 knees. Clinical evaluation was based on pre- and postoperative Knee Society Score (KSS) and Kujala patellofemoral score. Radiographic evaluation was performed with reference to the weight-bearing line (WBL), the femorotibial angle (FTA), and the mechanical lateral distal femoral angles in the knee-standing view. RESULTS: At a mean follow-up of 20±11.7 months (range, 12-42 months), KSS scores improved significantly, from 46.7±5.2 preoperatively to 87±4.4 postoperatively (p<0.001), as did the Kujala score, from 44±8 preoperatively to 86.6±6.8 postoperatively (p<0.001). The WBL decreased significantly, from 76±7% preoperatively to 41±11% postoperatively (p<0.001). The FTA was improved significantly, from 12.7±1.7° preoperatively to 4±4° postoperatively (p<0.001), as was the mLDFA, from 83±4° preoperatively to 91±1.3° postoperatively (p<0.001). CONCLUSION: Use of single-incision CWDFO combined with medial reefing and lateral release prevents patellar dislocation, corrects deformity, and improves clinical outcomes.

Engineering of multifunctional temperature-sensitive liposomes for synergistic photothermal, photodynamic, and chemotherapeutic effects.

Heterogeneity of cancer cells and drug resistance require multiple therapeutic approaches for comprehensive treatment. In this study, temperature-sensitive liposomes containing anti-cancer agent tanespimycin (17-AAG) and photosensitizer IR 820 were developed for combination of phototherapy and chemotherapy. The temperature-sensitive liposomes composed of DPPC, cholesterol, DSPE-PEG, 17-AAG, and IR 820 (LP-AI) at weight ratio of 35/15/3/2/2 were formulated as a thin film using extrusion and evaluated for particle size, morphology and drug release profile. Furthermore, the anticancer effect of combined therapy was examined in vitro and in vivo in SCC-7 and MCF-7 cell lines. As a result, LP-AI was prepared at particle size of 166.7±1.3nm, PDI of 0.153±0.012, and ζ-potential of -32.6±0.8mV. After NIR irradiation (660 and 808nm laser), LP-AI could generate heat and ROS and enhance drug release from nanoparticles which were useful to kill the cancer cells. These were confirmed by in vitro cytotoxicity as well as in vivo effective ablation of tumors. In conclusion, fast drug release and enhanced treatment efficacy of LP-AI indicate the potential of integrating photo- and chemotherapy for synergistic anti-cancer effects.