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In situ switching of the associated anions of a rotaxane catalyst between Cl - and TFPB - exposes its dialkylammonium and imidazolium stations, respectively, thereby selectively catalyzing the reactions of a mixture of trans-cinnamaldehyde and an aliphatic thiol to yield the Michael adduct and the thioacetal product, respectively., (© 2023 Wiley-VCH GmbH.)

We examined the incidence and causative factors of surgical site infection (SSI) following osteosynthesis for pelvic ring injury by reviewing the data of 97 consecutive patients with pelvic ring injuries treated between 2014 and 2019. Osteosyntheses, including internal or external skeletal fixation with plates or screws, were performed based on fracture type and patient's condition. Fractures were treated surgically, with a 36 months minimum follow-up period. Eight (8.2%) patients experienced SSI. The most common causative pathogen was Staphylococcus aureus. Patients with SSI had significantly worse functional outcomes at 3, 6, 12, 24, and 36 months than those without. For patients with SSI, the average Merle d'Aubigné and Majeed scores at 3, 6, 12, 24, and 36 months after injury were 2.4, 4.1, 8.0, 11.0, and 11.3, and 25.5, 32.1, 47.9, 61.9, and 63.3, respectively. Patients with SSI had a higher likelihood of undergoing staged operations (50.0 vs. 13.5%, p = 0.02), more surgeries for associated injuries (6.3% vs. 2.5%, p = 0.04), higher likelihood of Morel-Lavallee lesions (50.0% vs. 5.6%, p = 0.002), higher incidence of diversional colostomy (37.5% vs. 9.0%, p = 0.05), and longer intensive care unit stay (11.1 vs. 3.9 days, p = 0.001) than those without. The contributing factors for SSI were Morel-Lavallee lesions (odds ratio [OR] 4.55, 95% confidence interval [95% CI] 3.34-50.0) and other surgeries for associated injuries (OR 2.37, 95% CI 1.07-5.28). Patients with SSI after osteosynthesis for pelvic ring injuries may have worse short-term functional outcomes., (© 2023. The Author(s).)

Purpose: Open pelvic fractures have high mortality rates, and survivors may have ongoing functional deficits from severe trauma and invasive life-saving procedures. However, there are limited reports regarding the functional status evaluation following open pelvic fractures. We aimed to report the treatment experiences and short-term functional outcomes of patients with open pelvic fractures., Methods: We retrospectively reviewed the data of 19 consecutive patients with pelvic fractures who underwent treatment at a single institute between January 2014 and June 2018. The resuscitation protocol, osteosynthesis strategy, reduction quality of the pelvic ring, and functional outcomes were analyzed., Results: The incidence and mortality rates in patients with open pelvic fractures were 4.9 and 21.6%, respectively. Ten, one, and seven of the open wounds related to the pelvic fractures were located in Faringer zones I, II, and III, respectively. Fractures of four patients were categorized as classes 1 and 2, and those of 11 patients as class 3, according to the Jones-Powell classification. Eleven of 19 (57.9%) and 9 of 19 (47.5%) revealed excellent reduction quality by Matta/Torenetta and Lefaivre criteria, respectively. The Merle d'Aubigné score improved at each evaluation but stagnated after 24 months. The Majeed hip score also improved at the 12-month evaluation but the improvement stopped thereafter. At a 3-year follow-up, the patients with excellent reduction of the pelvic ring showed the highest functional performances., Conclusion: Improvements in functional status of patients with open pelvic fractures can be anticipated based on the reduction quality of the pelvis ring., (© 2022. The Author(s).)

Background: Reasons for the increased use of closed reduction and internal fixation (CRIF) for traumatic sacral fractures (SFs) are unclear in the literature. Therefore, we aimed to report the annual changes in the number of patients, mechanisms of injury, fracture patterns, and fixation methods., Methods: In this retrospective study, we extracted data of 271 patients (mean age, 37.5 years) from the trauma register over an 8-year period. Annual records regarding the number of patients, injury mechanisms, fracture types, and treatment options were statistically analyzed to examine the interactions among these factors., Results: The number of patients with SFs increased significantly each year. The rate of admission to the intensive care unit after resuscitation was high (64.9%). Arbeitsgemeinschaft für Osteosynthesefragen (AO) type C pelvic ring injury (PRI), Dennis zone II injury, Roy-Camille type 2 injury, and U/H-type injury were the most common fracture types. Trans-iliac trans-sacral screws were mainly used in AO type B PRI, and their use significantly increased each year. For AO type C PRI, open reduction and internal fixation (ORIF) with rigid fixation was the main treatment, and the use of CRIF with iliosacral screws decreased each year. Stepwise statistical analysis revealed that the increase in AO type B PRI and ORIF for anterior PRI were the factors contributing to the increased use of CRIF for SFs., Conclusions: While the use of osteosynthesis for SFs is increasing, an increased use of CRIF for traumatic SFs has also been observed in clinical practice. This increase can be attributed to the increase in AO type B PRIs and ORIF for anterior PRIs., (© 2022. The Author(s).)

Background: For hip posterior fracture-dislocation, the current consensus is to perform joint reduction within 6 h to prevent sequelae. However, whether a closed reduction (CR) should be performed at the emergency department (ED) or in the operation theater (OT) remains debatable. We aimed to assess the incidence and factors predictive of CR failure at the ED in patients with hip posterior fracture-dislocation., Methods: Patients with hip posterior fracture-dislocation between 2009 and 2019 were included. Age, sex, body mass index (BMI), injury severity score, new injury severity score, time from injury to first reduction attempt (TIR), presence of associated femoral head fracture, posterior wall marginal impaction, and posterior wall fragment size were compared between patients with CR success and patients with CR failure at the ED., Results: Fifty-five patients with hip posterior fracture-dislocation experienced CR attempts at the ED and were enrolled in the study. Thirty-eight (69.1%) hips were reduced successfully at the ED, and 17 (30.9%) experienced failure. No significant differences in age, sex, BMI, presence of femoral head fracture, marginal impaction, or size of the posterior wall fragment were found between the groups. TIR was significantly shorter in the successful CR group (2.24 vs. 4.11 h, p = 0.01). According to receiver operating characteristic curve analysis, 3.5 h was the cut-off time., Conclusions: For patients with hip posterior fracture-dislocation, TIR was a critical factor for successful CR. If the time interval exceeds 3.5 h from injury, the success rate of bedside CR at the ER is likely to decrease, and the OT should be prepared in case of failed bedside CR., (© 2022. The Author(s).)

Background: To date, no study has compared the surgical outcomes between posterior wall acetabular fractures with and without associated femoral head fractures. Therefore, we evaluated whether an associated femoral head fracture increases the incidence of fracture sequelae, including post-traumatic osteoarthritis (PTOA) and osteonecrosis of the femoral head (ONFH), following osteosynthesis for posterior wall acetabular fractures., Methods: This retrospective clinical study enrolled 183 patients who underwent osteosynthesis for posterior wall acetabular fractures between 2009 and 2019 at a level-1 trauma center. The incidence of PTOA, ONFH, and conversion to total hip arthroplasty (THA) was reviewed., Results: The incidence of PTOA, ONFH, and conversion to THA following osteosynthesis were 20.2%, 15.9%, and 17.5%, respectively. The average time for conversion to THA was 18.76 ± 20.15 months (range, 1-82). The results for the comparison of patients with associated femoral head fractures and isolated posterior wall acetabular fractures were insignificant (PTOA: 27.3% vs. 15.7%, p = 0.13; ONFH: 18.2% vs. 14.3%, p = 0.58; conversion to THA: 20.4% vs. 15.7%, p = 0.52). Upon evaluating other variables, only marginal impaction negatively affected ONFH incidence (odds ratio: 2.90)., Conclusions: Our methods failed to demonstrate a significant difference in the rate of PTOA, ONFH, or conversion to THA in posterior wall acetabular fractures with and without an associated femoral head fracture. Beyond femoral head fractures, the marginal impaction of the acetabulum could have led to early sequelae., Level of Evidence: Level III., (© 2022. The Author(s).)

Background: Data on the functional outcomes of patients with open pelvic fractures after osteosynthesis are limited, and whether open fracture is a risk factor for worse outcomes, as compared with closed fracture, remains unclear. This study aimed to compare the functional outcomes of patients with open and closed pelvic fractures and evaluate potential factors that might affect outcomes., Methods: Overall, 19 consecutive patients with open pelvic fractures and 78 patients with closed pelvic fractures between January 2014 and June 2018 were retrospectively reviewed. All fractures were surgically treated, with a minimal follow-up period of three years. Patients' demographic profile, associated injuries, management protocol, quality of reduction, and outcomes were recorded and analyzed., Results: Patients with open pelvic fractures had higher new injury severity score, higher incidence of diverting colostomy, and longer length of stay. Both radiological and functional evaluations revealed no significant differences between the two groups at 1-year and 3-year evaluations. Multiple logistic regression analysis identified poor radiological outcomes (using Lefaivre criteria) and longer length of stay as risk factors for worse short-term functional outcomes. At 3-year evaluation, fair-to-poor radiological outcomes (using Matta/Tornetta and Lefaivre criteria) and the presence of diverting colostomy were potential risk factors., Conclusions: Compared with closed pelvic fracture, open pelvic fracture was not an indicator of worse functional outcomes. Functional outcomes may be comparable between patients with open and closed pelvic fractures at different time points within three years postoperatively. Achieving anatomical reduction in a fracture is crucial, because it might affect patient satisfaction., (© 2021. The Author(s).)

To elucidate the accuracy, efficacy, and safety of percutaneous iliosacral screw (ISS) and trans-iliac trans-sacral screw (TITS) insertion using a single C-arm fluoroscopy intensifier. Additionally, the potential risk factors that might cause mal-positioned screws were identified. Patients with pelvic ring injuries who underwent percutaneous screw fixation in a single medical institute were divided into an ISS group (n = 59) and a TITS group (n = 62) and assessed. The angles deviated from ideal orientation (ADIO) of the implanted screw were measured, and potential risk factors for mal-positioned screws were analyzed. Overall, the reduction quality of the pelvic ring was good or excellent in 70 patients (82.4%) by Matta's criteria and in 48 patients (56.5%) by Lefaivre's criteria. ADIO measurements of the ISS and TITS groups via multi-planar computed tomography were 9.16° ± 6.97° and 3.09° ± 2.8° in the axial view, respectively, and 5.92° ± 3.65° and 2.10° ± 2.01° in the coronal view, respectively. Univariate statistical analysis revealed body mass index as the single potential risk factor of mal-positioned screws. With careful preoperative planning and intraoperative preparations, placing ISS and TITS under the guidance of single C-arm fluoroscopy intensifier is a reliable and safe technique. Caution should be exercised when performing this procedure in patients with a high body mass index., (© 2022. The Author(s).)

Purpose: The purpose of this study is to evaluate the outcome and prognosis of complete synovectomy performed under arthroscopic surgery in the treatment of diffuse pigmented villonodular synovitis (DPVNS) of the knee., Methods: We retrospectively reviewed 7 cases (6 female and 1 male) diagnosed with diffuse pigmented villonodular synovitis (DPVNS) of knee from 2013 to 2017. All of these cases were treated with knee arthroscopy-assisted complete synovectomy. The follow-up period ranged from 36 months to 60 months (average: 48.0 months). The pain score, range of motion and functional outcome of the knee joint were evaluated after surgery. Symptoms and signs were monitored and magnetic resonance imaging (MRI) were routinely requested to note for possible recurrence during clinical follow up., Results: During and after the surgeries of complete synovectomy under arthroscope by the same surgeon, no complications were noted in the ward or the clinic. Significant improvements were achieved in terms of the range of motion and Lysholm knee function score. There was no recurrence of DPVNS observed in our patients during a follow-up of 4 years., Conclusions: Intra-articular DPVNS of the knee can successfully be treated by complete synovectomy under arthroscope. This case series emphasized the technique of multiple portals and cycling different shavers to achieve satisfactory outcomes.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer mortality. Cancer stem cells (CSCs) are responsible for the maintenance, metastasis, and relapse of various tumors. The effects of CSCs on the tumorigenesis of HCC are still not fully understood, however. We have recently established two new rat HCC cell lines HTC and TW-1, which we isolated from diethylnitrosamine-induced rat liver cancer. Results showed that TW-1 expressed the genetic markers of CSCs, including CD133, GSTP1, CD44, CD90, and EpCAM. Moreover, TW-1 showed higher tolerance to sorafenib than HTC did. In addition, tumorigenesis and metastasis were observed in nude mice and wild-type rats with TW-1 xenografts. Finally, we combined highly expressed genes in TW-1/HTC with well-known biomarkers from recent HCC studies to predict HCC-related biomarkers and able to identify HCC with AUCs > 0.9 after machine learning. These results indicated that TW-1 was a novel rat CSC line, and the mice or rat models we established with TW-1 has great potential on HCC studies in the future.

Background: Open pelvic fractures are caused by high-energy traumas and are accompanied by organ injuries. Despite improvements in pre-hospital care, the acute mortality rate following open pelvic fractures remains high. This study aimed to report experiences in managing open pelvic fractures, identify potential independent predictors that contribute to acute mortality in such patients, and generate a scoring formula to predict mortality rate., Methods: Open pelvic fracture patients managed during a 42-month period were retrospectively studied. Logistic regression analysis was used to determine predictors of acute mortality. Using the Youden index, threshold values of predictors were selected. Significant predictors were weighted to create a scoring formula. The area under the curve (AUC) was tested in this specific group., Results: The incidence of open pelvic fractures in all pelvic fractures was 4.9% (37/772), and the overall mortality rate was 21.6% (8/37). All the successfully resuscitated patients entered the reconstruction stage survived and underwent the complete treatment course. Univariate and multivariate logistic regression analyses revealed that the revised trauma score (RTS) was the single independent predictor of acute mortality. A scoring formula was generated following the statistical analysis. The probability of mortality was 0% and 100% when the score was above and below -2, respectively. This model predicted mortality with an AUC of 0.948 (95% confidence interval 0.881-1.000, P < 0.01)., Conclusion: The RTS may be a potential predictor of acute mortality in open pelvic fracture patients. Further work would be required to validate the clinical efficacy of the generated scoring formula.

Micro-exons are exons of very small size (usually 3-30 nts). Some micro-exons are alternatively spliced. Their functions, regulation and evolution are largely unknown. Here, we present an example of an alternatively spliced 3 bp micro-exon (micro-Ex8) in the homothorax (hth) gene in Drosophila. Hth is involved in many developmental processes. It contains a MH domain and a TALE-class homeodomain (HD). It binds to another homeodomain Exd via its MH domain to promote the nuclear import of the Hth-Exd complex and serve as a cofactor for Hox proteins. The MH and HD domains in Hth as well as the HTh-Exd interaction are highly conserved in evolution. The alternatively spliced micro-exon lies between the exons encoding the MH and HD domains. We provide clear proof that the micro-Ex8 is produced by alternative splicing from a 48 bp full-length exon 8 (FL-Ex8) and the micro-Ex8 is the first three nt is FL-Ex8. We found that the micro-Ex8 is the ancient form and the 3 + 48 organization of alternatively spliced overlapping exons only emerged in the Schizophora group of Diptera and is absolutely conserved in this group. We then used several strategies to test the in vivo function of the two types of isoforms and found that the micro-Ex8 and FL-Ex8 isoforms have largely overlapping functions but also have non-redundant functions that are tissue-specific, which supports their strong evolutionary conservation. Since the different combinations of protein interaction of Hth with Exd and/or Hox can have different DNA target specificity, our finding of alternatively spliced isoforms adds to the spectrum of structural and functional diversity under developmental regulation.

Background: In most institutions, arterial embolization (AE) remains a standard procedure to achieve hemostasis during the resuscitation of patients with pelvic fractures. However, the actual benefits of AE are controversial. In this study, we aimed to explore AE-related outcomes following resuscitation at our center and to assess the predictive value of contrast extravasation (CE) during computed tomography (CT) for patients with hemodynamically unstable closed pelvic fractures., Methods: We retrospectively reviewed data from patients who were treated for closed pelvic fractures at a single center between 2014 and 2017. Data regarding the AE and clinical parameters were analyzed to determine whether poor outcomes could be predicted., Results: During the study period, 545 patients were treated for closed pelvic fractures, including 131 patients who underwent angiography and 129 patients who underwent AE. Nonselective bilateral internal iliac artery embolization (nBIIAE) was the major AE strategy (74%). Relative to the non-AE group, the AE group had higher values for injury severity score, shock at hospital arrival, and unstable fracture patterns. The AE group was also more likely to require osteosynthesis and develop surgical site infections (SSIs). Fourteen patients (10.9%) experienced late complications following the AE intervention, including 3 men who had impotence at the 12-month follow-up visit and 11 patients who developed SSIs after undergoing AE and osteosynthesis (incidence of SSI: 11/75 patients, 14.7%). Nine of the 11 patients who developed SSI after AE had undergone nBIIAE. The positive predictive value of CE during CT was 29.6%, with a negative predictive value of 91.3%. Relative to patients with identifiable CE, patients without identifiable CE during CT had a higher mortality rate (30.0% vs. 11.0%, p = 0.03)., Conclusion: Performing AE for pelvic fracture-related hemorrhage may not be best practice for patients with no CE detected during CT or for unstable patients who do not respond to resuscitation after exclusion of other sources of hemorrhage. Given the high incidence of SSI following nBIIAE, this procedure should be selected with care. Given their high mortality rate, patients without CE during imaging might be considered for other hemostasis procedures, such as preperitoneal pelvic packing.

In this Letter, we report high-speed integrated 14 µm in diameter micro-light-emitting diode (μLED) arrays with the parallel configuration, including ${2} \times {2}$2×2, ${2} \times {3}$2×3, ${2} \times {4}$2×4, and ${2} \times {5}$2×5 arrays. The small junction area of μLED (${\sim}{191}\;\unicode{x00B5}{\rm m}^2$∼191µm 2 ) in each element facilitates the operation of higher injection current density up to ${13}\;{{\rm kA/cm}^2}$13kA/cm 2 , leading to the highest modulation bandwidth of 615 MHz. The optical power of ${2} \times {5}$2×5 array monotonically increases (${\sim}{10}$∼10 times higher) as the number of arrays increases (1 to 10), while retaining the fast modulation bandwidth. A clear eye diagram up to 1 Gbps without any equalizer further shows the capability of this high-speed transmitter for VLC. These results mean that tailoring the optical power of μLEDs in a parallel-biased integrated array can further enhance the data transmission rate without degradation of the modulation bandwidth.

The type 2 transmembrane serine protease matriptase is involved in many pathophysiological processes probably via its enzymatic activity, which depends on the dynamic relationship between zymogen activation and protease inhibition. Matriptase shedding can prolong the life of enzymatically active matriptase and increase accessibility to substrates. We show here that matriptase shedding occurs via a de novo proteolytic cleavage at sites located between the SEA domain and the CUB domain. Point or combined mutations at the four positively charged amino acid residues in the region following the SEA domain allowed Arg-186 to be identified as the primary cleavage site responsible for matriptase shedding. Kinetic studies further demonstrate that matriptase shedding is temporally coupled with matriptase zymogen activation. The onset of matriptase shedding lags one minute behind matriptase zymogen activation. Studies with active site triad Ser-805 point mutated matriptase, which no longer undergoes zymogen activation or shedding, further suggests that matriptase shedding depends on matriptase zymogen activation, and that matriptase proteolytic activity may be involved in its own shedding. Our studies uncover an autonomous mechanism coupling matriptase zymogen activation, proteolytic activity, and shedding such that a proportion of newly generated active matriptase escapes HAI-1-mediated rapid inhibition by shedding into the extracellular milieu.

Cardiac myxoma is the most common cardiac tumour. Most lesions occur sporadically, but occasional lesions develop in patients with Carney complex, a syndrome characterized by cardiac myxoma, spotty pigmentation, and endocrine overactivity. Two-thirds of patients with Carney complex harbour germline mutations in PRKAR1A, which encodes the type I regulatory subunit of protein kinase A (PKA). Most studies have not found a mutation in PRKAR1A in sporadic cardiac myxoma cases. Recent studies identified frequent mutations in PRKACA, which encodes the catalytic subunit of PKA, in cortisol-secreting adrenocortical adenoma cases. To determine whether the PRKACA mutation is involved in the tumourigenesis of cardiac myxoma, we performed Sanger sequencing of 41 specimens of sporadic cardiac myxoma to test for the presence of mutations in the coding regions and intron-exon boundaries of PRKACA. Mutations were identified in four cases (9.7%). In contrast to the point mutations identified in adrenocortical adenoma, all mutations were in-frame microinsertions of 18-33 bp clustered in exons 7 and 8. The mutated PRKACA proteins lost their ability to bind to PRKAR1A, and thereby lead to constitutive activation of the PKA pathway. Together with previous reports of PRKAR1A mutations in syndromic cardiac myxoma, our study demonstrates the importance of the PKA pathway in the tumourigenesis of cardiac myxoma. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd., (Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)

Purpose: Pipkin type IV femoral head (FH) fracture was thought as poor prognosis. There were several surgical approaches and treatments for this difficult fracture. However, there was no one treatment superior to another. We reviewed a serious of patients with Pipkin type IV FH fracture underwent surgery via a modified Gibson approach., Methods: We reviewed a consecutive series of nine patients with Pipkin type IV FH fracture under surgery via a modified Gibson approach between 2012 and 2013. The surgical procedure was completely described, and the radiological outcome and the functional outcome were also reviewed., Results: The mean follow-up duration was 17 (12-30) months. The mean Merle d'Aubigne score was 16 (8-19). Seven patients had anatomical reductions, and two had imperfect reductions by Matta's grading. There was no early posttraumatic osteoarthritis during the follow-up period. One patient with early post-traumatic osteonecrosis 3 months after index surgery underwent total hip arthroplasty., Conclusions: Through this surgery approach to fix the FH and the acetabulum, the radiological and the functional results were satisfactory. We still need more patients with prospective study to find an optimal surgical approach for Pipkin type IV FH fracture.

Hydrocephalus is a brain disorder derived from CSF accumulation due to defects in CSF clearance. Although dysfunctional apical cilia in the ependymal cell layer are causal to the onset of hydrocephalus, mechanisms underlying proper ependymal cell differentiation are largely unclear. SNX27 is a trafficking component required for normal brain function and was shown previously to suppress γ-secretase-dependent amyloid precursor protein and Notch cleavage. However, it was unclear how SNX27-dependent γ-secretase inhibition could contribute to brain development and pathophysiology. Here, we describe and characterize an Snx27-deleted mouse model for the ependymal layer defects of deciliation and hydrocephalus. SNX27 deficiency results in reductions in ependymal cells and cilia density, as well as severe postnatal hydrocephalus. Inhibition of Notch intracellular domain signaling with γ-secretase inhibitors reversed ependymal cells/cilia loss and dilation of lateral ventricles in Snx27-deficient mice, giving strong indication that Snx27 deletion triggers defects in ependymal layer formation and ciliogenesis through Notch hyperactivation. Together, these results suggest that SNX27 is essential for ependymal cell differentiation and ciliogenesis, and its deletion can promote hydrocephalus pathogenesis., Significance Statement: Down's syndrome (DS) in humans and mouse models has been shown previously to confer a high risk for the development of pathological hydrocephalus. Because we have previously described SNX27 as a component that is consistently downregulated in DS, we present here a robust Snx27-deleted mouse model that produces hydrocephalus and associated ciliary defects with complete penetrance. In addition, we find that γ-secretase/Notch modulation may be a candidate drug target in SNX27-associated hydrocephalus such as that observed in DS. Based on these findings, we anticipate that future study will determine whether modulation of a SNX27/Notch/γ-secretase pathway can also be of therapeutic interest to congenital hydrocephalus., (Copyright © 2016 the authors 0270-6474/16/3612586-12$15.00/0.)

Background: Treatment of supraintercondylar (AO/OTA 33-C) and supracondylar (AO/OTA 33-A) femur fractures is generally challenging. Standard treatments include open reduction and internal fixation. However, optimal implants are now being well-defined. This study focus on the comparison between clinical and functional outcomes of fractures treated with condylar buttress plates (CBPs)., Methods: We treated 87 patients with supraintercondylar or supracondylar femur fracture from 2004 to 2008, including 30 supraintercondylar and 24 supracondylar fractures treated with CBPs. Both knee and function scores (per Knee Society) were given to clinical and functional outcomes, and concomitant knee function was assessed per Mize criteria., Results: Union rate of supraintercondylar fractures was 90 % (27/30) and supracondylar fractures was 91.7 % (22/24) (P = 0.68). In supraintercondylar group, 16.7 % revealed postoperative varus deformity, whereas none in supracondylar group (P = 0.045). Knee Society knee score was 73.6 in supraintercondylar group and 85.5 in supracondylar group (P = 0.009); and function score was 62.5 in supraintercondylar group and 83.1 in supracondylar group (P = 0.023). A satisfactory result based on modified Mize criteria was achieved in 50 % of supraintercondylar fractures and in 79.1 % of supracondylar fractures (P = 0.09)., Conclusions: Use of CBPs for supraintercondylar and supracondylar femur fractures treatment led to a high union rate. However, a high rate of varus deformity occurred in patients with supraintercondylar but not supracondylar fractures. Moreover, CBP treatment in patients with supracondylar fractures led to better functional outcomes than those with supraintercondylar fractures.

Objective: To report the perioperative results and surgical outcomes of patients with vertical unstable sacral fractures who underwent lumbopelvic fixation through a modified subcutaneous route for iliac screw fixation., Summary of Background Data: Treating vertical unstable sacral fractures is still challenging for orthopedic surgeons. Among various methods for treating these fractures, lumbopelvic fixation provides a high reduction quality and promising stability for early weight-bearing ambulation. However, wound healing disturbance and surgical site infection (SSI) are the drawbacks of this extensive technique, especially after inserting iliac screws., Methods: Here, we provide an alternative subcutaneous route for iliac screw insertion during lumbopelvic fixation surgery to lessen soft tissue retraction and injury, and thus decrease soft tissue complications., Results: Using this modified technique, 28 patients with vertical unstable sacral fractures were treated between 2012 and 2014. One patient had an SSI (infection rate: 3.5%). All fractures were united with a mean sacral kyphosis correction angle of 10.5°. The mean Majeed score of the 17 patients during the 12-month follow-up was 84.5., Conclusions: The subcutaneous route for iliac screw insertion is a simple, safe, and effective technique when performing lumbopelvic fixation for vertical unstable sacral fractures., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Unlabelled: Proteolytic generation of amyloidogenic amyloid β (Aβ) fragments from the amyloid precursor protein (APP) significantly contributes to Alzheimer's disease (AD). Although amyloidogenic APP proteolysis can be affected by trafficking through genetically associated AD components such as SORLA, how SORLA functionally interacts with other trafficking components is yet unclear. Here, we report that SNX27, an endosomal trafficking/recycling factor and a negative regulator of the γ-secretase complex, binds to the SORLA cytosolic tail to form a ternary complex with APP. SNX27 enhances cell surface SORLA and APP levels in human cell lines and mouse primary neurons, and depletion of SNX27 or SORLA reduces APP endosome-to-cell surface recycling kinetics. SNX27 overexpression enhances the generation of cell surface APP cleavage products such as soluble alpha-APP C-terminal fragment (CTFα) in a SORLA-dependent manner. SORLA-mediated Aβ reduction is attenuated by downregulation of SNX27. This indicates that an SNX27/SORLA complex functionally interacts to limit APP distribution to amyloidogenic compartments, forming a non-amyloidogenic shunt to promote APP recycling to the cell surface., Significance Statement: Many genes have been identified as risk factors for Alzheimer's disease (AD), and a large proportion of these genes function to limit production or toxicity of the AD-associated amyloid β (Aβ) peptide. Whether and how these genes precisely operate to limit AD onset remains an important question. We identify binding and trafficking interactions between two of these factors, SORLA and SNX27, and demonstrate that SNX27 can direct trafficking of SORLA and the Aβ precursor APP to the cell surface to limit the production of Aβ. Diversion APP to the cell surface through modulation of this molecular complex may represent a complimentary strategy for future development in AD treatment., (Copyright © 2016 the authors 0270-6474/16/367996-16$15.00/0.)

Progressive supranuclear palsy (PSP) is a movement disorder characterized by tau neuropathology where the underlying mechanism is unknown. An SNP (rs1768208 C/T) has been identified as a strong risk factor for PSP. Here, we identified a much higher T-allele occurrence and increased levels of the pro-apoptotic protein appoptosin in PSP patients. Elevations in appoptosin correlate with activated caspase-3 and caspase-cleaved tau levels. Appoptosin overexpression increased caspase-mediated tau cleavage, tau aggregation, and synaptic dysfunction, whereas appoptosin deficiency reduced tau cleavage and aggregation. Appoptosin transduction impaired multiple motor functions and exacerbated neuropathology in tau-transgenic mice in a manner dependent on caspase-3 and tau. Increased appoptosin and caspase-3-cleaved tau were also observed in brain samples of patients with Alzheimer's disease and frontotemporal dementia with tau inclusions. Our findings reveal a novel role for appoptosin in neurological disorders with tau neuropathology, linking caspase-3-mediated tau cleavage to synaptic dysfunction and behavioral/motor defects., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Focused ultrasound (FUS) exposure in the presence of microbubbles can temporally open the blood-brain barrier (BBB) and is an emerging technique for non-invasive brain therapeutic agent delivery. Given the potential to deliver large molecules into the CNS via this technique, we propose a reliable strategy to synergistically apply FUS-BBB opening for the non-invasive and targeted delivery of non-viral genes into the CNS for therapeutic purpose. In this study, we developed a gene-liposome system, in which the liposomes are designed to carry plasmid DNA (pDNA, containing luciferase reporter gene) to form a liposomal-plasmid DNA (LpDNA) complex. Pulsed FUS exposure was delivered to induce BBB opening (500-kHz, burst length=10ms, 1% duty cycle, PRF=1Hz). The longitudinal expression of luciferase was quantitated via an in vivo imaging system (IVIS). The reporter gene expression level was confirmed via immunoblotting, and histological staining was used to identify transfected cells via fluorescent microscopy. In a comparison of gene transduction efficiency, the LpDNA system showed better cell transduction than the pDNA system. With longitudinal observation of IVIS monitoring, animals with FUS treatment showed significant promotion of LpDNA release into the CNS and demonstrated enhanced expression of genes upon sonication with FUS-BBB opening, while both the luciferase and GDNF protein expression were successfully measured via Western blotting. The gene expression peak was observed at day 2, and the gene expression level was up to 5-fold higher than that in the untreated hemisphere (compared to a 1-fold increase in the direct-inject positive-control group). The transfection efficiency was also found to be LpDNA dose-dependent, where higher payloads of pDNA resulted in a higher transfection rate. Immunoblotting and histological staining confirmed the expression of reporter genes in glial cells as well as astrocytes. This study suggests that IV administration of LpDNA in combination with FUS-BBB opening can provide effective gene delivery and expression in the CNS, demonstrating the potential to achieve non-invasive and targeted gene delivery for treatment of CNS diseases., (Copyright © 2015 Elsevier B.V. All rights reserved.)

NKX6-1 is a homeobox transcription factor participating in the development and regulation of endocrine function of pancreatic islets. This study evaluated the potential use of NKX6-1 as a diagnostic marker for well-differentiated neuroendocrine tumors (WDNETs). In total, 178 primary and 26 metastatic WDNETs of different origins were analyzed through immunohistochemistry for NKX6-1, TTF-1, CDX2, ISL1, and polyclonal PAX8. NKX6-1 was expressed in 36 of the 44 (82%) primary pancreatic WDNETs, 12 of the 18 (67%) primary duodenal WDNETs, and rarely in pulmonary, gastric, and appendiceal WDNETs. The specificity of using NKX6-1 as a marker for pancreatic and duodenal WDNETs is 93%. Of the 26 metastatic WDNETs, NKX6-1 was expressed only in the tumors of pancreatic origin (sensitivity: 63%, specificity: 100%). The combinatorial use of NKX6-1, CDX2, TTF-1, and ISL1 distinguished WDNETs of different origins with high specificity. Our results indicated that the inclusion of NKX6-1 in an immunohistochemical panel will be beneficial for identifying the primary sites of WDNETs.

The ability of cells to rapidly detect and react to alterations in their chemical environment, such as pH, ionic strength and redox potential, is essential for cell function and survival. We present here evidence that cells can respond to such environmental alterations by rapid induction of matriptase autoactivation. Specifically, we show that matriptase autoactivation can occur spontaneously at physiological pH, and is significantly enhanced by acidic pH, both in a cell-free system and in living cells. The acid-accelerated autoactivation can be attenuated by chloride, a property that may be part of a safety mechanism to prevent unregulated matriptase autoactivation. Additionally, the thio-redox balance of the environment also modulates matriptase autoactivation. Using the cell-free system, we show that matriptase autoactivation is suppressed by cytosolic reductive factors, with this cytosolic suppression being reverted by the addition of oxidizing agents. In living cells, we observed rapid induction of matriptase autoactivation upon exposure to toxic metal ions known to induce oxidative stress, including CoCl2 and CdCl2. The metal-induced matriptase autoactivation is suppressed by N-acetylcysteine, supporting the putative role of altered cellular redox state in metal induced matriptase autoactivation. Furthermore, matriptase knockdown rendered cells more susceptible to CdCl2-induced cell death compared to control cells. This observation implies that the metal-induced matriptase autoactivation confers cells with the ability to survive exposure to toxic metals and/or oxidative stress. Our results suggest that matriptase can act as a cellular sensor of the chemical environment of the cell that allows the cell to respond to and protect itself from changes in the chemical milieu.

In the root of rice (Oryza sativa), abscisic acid (ABA) treatment, salinity, or water deficit stress induces the expression of a family of four genes, REPETITIVE PROLINE-RICH PROTEIN (RePRP). These genes encode two subclasses of novel proline-rich glycoproteins with highly repetitive PX₁PX₂ motifs, RePRP1 and RePRP2. RePRP orthologs exist only in monocotyledonous plants, and their functions are virtually unknown. Rice RePRPs are heavily glycosylated with arabinose and glucose on multiple hydroxyproline residues. They are significantly different from arabinogalactan proteins that have glycan chains composed of arabinose and galactose. Transient and stable expressions of RePRP-green fluorescent protein reveal that a fraction of this protein is localized to the plasma membrane. In rice roots, ABA treatment increases RePRP expression preferentially in the elongation zone. Overexpression of RePRP in transgenic rice reduces root cell elongation in the absence of ABA, similar to the effect of ABA on wild-type roots. Conversely, simultaneous knockdown of the expression of RePRP1 and RePRP2 reduces the root sensitivity to ABA, indicating that RePRP proteins play an essential role in ABA/stress regulation of root growth and development. Moreover, rice RePRPs specifically interact with a polysaccharide, arabinogalactan, in a dosage-dependent manner. It is suggested that RePRP1 and RePRP2 are functionally redundant suppressors of root cell expansion and probably act through interactions with cell wall components near the plasma membrane.

Background: Shoulder hemiarthroplasty is a widely accepted method for treating complex proximal humeral fractures, and the deltopectoral approach is the most popular route for this procedure. The purpose of the current study was to define and compare outcomes of shoulder hemiarthroplasty when using deltopectoral or anterolateral deltoid-splitting approaches., Materials and Methods: Two cohorts of patients were compared for clinical and radiographic outcomes at the same postoperative follow-up periods: a deltopectoral group (DP group) of 15 patients, from November 2004 to April 2007, and an anterolateral deltoid-splitting group (DS group) of 17 patients, from May 2007 to December 2009. Pain scores, goniometric measurements of the range of motion, and Constant scores were recorded for clinical assessment. Radiographic evaluations were recorded for stem osteolysis, tuberosity absorption, joint subluxation, and acromiohumeral distance., Results: The 2 groups did not differ significantly in demographic data, preoperative fracture classification, surgical timing, early postoperative radiographic findings, and 2-year radiographic results. The DS group had less immediate postoperative pain (P = .025). At the 2-year follow-up assessment, the groups did not difference significantly in shoulder abduction and forward flexion. All prostheses survived until the 2-year assessment., Conclusion: When performing shoulder hemiarthroplasty for complex proximal humeral fractures, we found that the anterolateral deltoid-splitting approach provides an easier route for assessing posterior fracture fragments and managing rotator cuff tissue. The anterolateral deltoid-splitting approach was shown to be an acceptable alternative route for shoulder hemiarthroplasty than the standard deltopectoral approach., (Copyright © 2013 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.)

Background: Both pelvic fractures and femoral shaft fractures are caused by high-energy injuries. When unstable pelvic fractures and femoral shaft fractures occur concomitantly, the optimal treatment method is controversial. The aim of this study was to establish a reasonable principle for treating such complicated injuries., Methods: Forty patients sustaining unstable pelvic fractures and concomitant femoral shaft fractures were treated in a 7-year period. The initial management of the fractures was started at the emergency service according to the Advanced Trauma Life Support protocol. Unstable pelvic fractures were wrapped by cloth sheets and femoral shaft fractures were immobilized with a splint. Angiography was performed on patients with unstable hemodynamic status. The definitive treatment for combined fractures was performed after stabilizing the hemodynamics. Closed nailing was used for femoral shaft fractures, and pelvic fractures were treated with various techniques., Results: The mortality rate was 12.5% (5/40) during admission. Thirty-three patients were followed up for an average of 32 months (range, 12-76 months). There were 33 cases of unstable pelvic fractures and 36 instances of femoral shaft fractures. The union rate for pelvic fractures was 100% (33/33), while femoral shaft fractures had a 94.4% (34/36) union rate. The average healing time was 3.3 months (range, 1.6-8.1 months) and 4.1 months (range, 2.5-18.2 months) for pelvic and femoral shaft fractures, respectively. After fracture, 34 hips (94%) achieved a satisfactory result in the Harris hip score and 30 knees (83%) achieved a satisfactory result in the Mize knee score., Conclusions: Stabilization of the hemodynamics in patients with combined fractures should be the first aim. Angiography to stop arterial bleeding in the pelvis is often life-saving. The definitive treatment for combined fractures, such as pelvic fractures and femoral shaft fractures, should wait until hemodynamics is stabilized.

The purpose of this study is to assess the preclinical therapeutic efficacy of magnetic resonance imaging (MRI)-monitored focused ultrasound (FUS)-induced blood-brain barrier (BBB) disruption to enhance Temozolomide (TMZ) delivery for improving Glioblastoma Multiforme (GBM) treatment. MRI-monitored FUS with microbubbles was used to transcranially disrupt the BBB in brains of Fisher rats implanted with 9L glioma cells. FUS-BBB opening was spectrophotometrically determined by leakage of dyes into the brain, and TMZ was quantitated in cerebrospinal fluid (CSF) and plasma by LC-MS\MS. The effects of treatment on tumor progression (by MRI), animal survival and brain tissue histology were investigated. Results demonstrated that FUS-BBB opening increased the local accumulation of dyes in brain parenchyma by 3.8-/2.1-fold in normal/tumor tissues. Compared to TMZ alone, combined FUS treatment increased the TMZ CSF/plasma ratio from 22.7% to 38.6%, reduced the 7-day tumor progression ratio from 24.03 to 5.06, and extended the median survival from 20 to 23 days. In conclusion, this study provided preclinical evidence that FUS BBB-opening increased the local concentration of TMZ to improve the control of tumor progression and animal survival, suggesting its clinical potential for improving current brain tumor treatment.

A novel mesophilic, hydrogenotrophic methanogen, designated strain TNR(T), was isolated from an anaerobic, propionate-degradation enrichment culture that was originally established from a rice field soil sample from Taiwan. Cells were non-motile rods, 2.0-6.5 µm long by 0.3 µm wide. Filamentous (up to about 100 µm) and coccoid (about 1 µm in diameter) cells were also observed in cultures in the late exponential phase of growth. Strain TNR(T) grew at 20-40 °C (optimally at 37 °C), at pH 6.5-7.4 (optimally at pH 7.0) and in the presence of 0-25 g NaCl l(-1) (optimally at 0 g NaCl l(-1)). The strain utilized H(2)/CO(2) and formate for growth and produced methane. The G+C content of the genomic DNA was 56.4 mol%. Based on sequences of both the 16S rRNA gene and the methanogen-specific marker gene mcrA, strain TNR(T) was related most closely to Methanolinea tarda NOBI-1(T); levels of sequence similarities were 94.8 and 86.4 %, respectively. The 16S rRNA gene sequence similarity indicates that strain TNR(T) and M. tarda NOBI-1(T) represent different species within the same genus. This is supported by shared phenotypic properties, including substrate usage and cell morphology, and differences in growth temperature. Based on these genetic and phenotypic properties, strain TNR(T) is considered to represent a novel species of the genus Methanolinea, for which the name Methanolinea mesophila sp. nov. is proposed; the type strain is TNR(T) ( = NBRC 105659(T) = DSM 23604(T)). In addition, we also suggest family status for the E1/E2 group within the order Methanomicrobiales, for which the name Methanoregulaceae fam. nov. is proposed; the type genus of family is Methanoregula.

Two molecular methods, denaturing gradient gel electrophoresis (DGGE) and quantitative real-time polymerase chain reaction (qPCR) with the Universal ProbeLibrary (UPL) probe, were developed and used for the characterization and quantification of several microcystin producers in Moo-Tan Reservoir (MTR), Taiwan and its associated water treatment plant (Shih-Men Water Treatment Plant, SMWTP). Internal transcribed spacer (ITS) sequence, a highly diversified region between the 16S rRNA and 23S rRNA genes, was used to further identify the isolated strains from MTR and also used in DGGE for the detection of the specific DNA fragments and biomarkers for 11 strains observed in MTR. These ITS-DGGE biomarkers were successfully applied to monitor the community changes of potential toxigenic Microcystis sp. over a period of five years. Two highly specific primers were combined with UPL probes to measure microcystins synthesis gene (mcyB) and phycocyanin intergenic spacer region (cpcB) concentrations in water samples. The copy concentrations of UPL-mcyB and UPL-cpcB correlated well with MC-RR concentrations/water temperature and Microcystis sp. cell numbers in the water samples, respectively. For SMWTP, toxin concentrations were low, but the DGGE bands clearly demonstrated the presence of potential microcystin producers in both water treatment plants and finished water samples. It was demonstrated that toxigenic Microcystis sp. may penetrate through the treatment processes and pose a potential risk to human health in the drinking water systems.

Matriptase proteolytic activity must be tightly controlled for normal placental development, epidermal function, and epithelial integrity. Although hepatocyte growth factor activator inhibitor-1 (HAI-1) represents the predominant endogenous inhibitor for matriptase and the protein molar ratio of HAI-1 to matriptase is determined to be >10 in epithelial cells and the majority of carcinoma cells, an inverse HAI-1-to-matriptase ratio is seen in some ovarian and hematopoietic cancer cells. In the current study, cells with insufficient HAI-1 are investigated for the mechanisms through which the activity of matriptase is regulated. When matriptase activation is robustly induced in these cells, activated matriptase rapidly forms two complexes of 100- and 140-kDa in addition to the canonical 120-kDa matriptase-HAI-1 complex already described. Both 100- and 140-kDa complexes contain two-chain, cleaved matriptase but are devoid of gelatinolytic activity. Further biochemical characterization shows that the 140-kDa complex is a matriptase homodimer and that the 100-kDa complexes appear to contain reversible, tight binding serine protease inhibitor(s). The formation of the 140-kDa matriptase dimer is strongly associated with matriptase activation, and its levels are inversely correlated with the ratio of HAI-1 to matriptase. Given these observations and the likelihood that autoactivation requires the interaction of two matriptase molecules, it seems plausible that this activated matriptase homodimer may represent a matriptase autoactivation intermediate and that its accumulation may serve as a mechanism to control matriptase activity when protease inhibitor levels are limiting. These data suggest that matriptase activity can be rapidly inhibited by HAI-1 and other HAI-1-like protease inhibitors and "locked" in an inactive autoactivation intermediate, all of which places matriptase under very tight control.

Matrix metalloproteinases (Mmps) stimulate tumor invasion and metastasis by degrading the extracellular matrix. Here we reveal an unexpected role for Mmp10 (stromelysin 2) in the maintenance and tumorigenicity of mouse lung cancer stem-like cells (CSC). Mmp10 is highly expressed in oncosphere cultures enriched in CSCs and RNAi-mediated knockdown of Mmp10 leads to a loss of stem cell marker gene expression and inhibition of oncosphere growth, clonal expansion, and transformed growth in vitro. Interestingly, clonal expansion of Mmp10 deficient oncospheres can be restored by addition of exogenous Mmp10 protein to the culture medium, demonstrating a direct role for Mmp10 in the proliferation of these cells. Oncospheres exhibit enhanced tumor-initiating and metastatic activity when injected orthotopically into syngeneic mice, whereas Mmp10-deficient cultures show a severe defect in tumor initiation. Conversely, oncospheres implanted into syngeneic non-transgenic or Mmp10(-/-) mice show no significant difference in tumor initiation, growth or metastasis, demonstrating the importance of Mmp10 produced by cancer cells rather than the tumor microenvironment in lung tumor initiation and maintenance. Analysis of gene expression data from human cancers reveals a strong positive correlation between tumor Mmp10 expression and metastatic behavior in many human tumor types. Thus, Mmp10 is required for maintenance of a highly tumorigenic, cancer-initiating, metastatic stem-like cell population in lung cancer. Our data demonstrate for the first time that Mmp10 is a critical lung cancer stem cell gene and novel therapeutic target for lung cancer stem cells.

Purpose: To verify that low-frequency planar ultrasound can be used to disrupt the BBB in large animals, and the usefulness of MRI to quantitatively monitor the delivery of superparamagnetic iron oxide (SPIO) nanoparticles into the disrupted regions., Materials and Methods: Two groups of swine subjected to craniotomy were sonicated with burst lengths of 30 or 100 ms, and one group of experiment was also performed to confirm the ability of 28-kHz sonication to open the BBB transcranially. SPIO nanoparticles were administered to the animals after BBB disruption. Procedures were monitored by MRI; SPIO concentrations were estimated by relaxivity mapping., Results: Sonication for 30 ms created shallow disruptions near the probe tip; 100-ms sonications after craniotomy can create larger and more penetrating openings, increasing SPIO leakage ∼3.6-fold than 30-ms sonications. However, this was accompanied by off-target effects possibly caused by ultrasonic wave reflection. SPIO concentrations estimated from transverse relaxation rate maps correlated well with direct measurements of SPIO concentration by optical emission spectrometry. We have also shown that transcranial low-frequency 28-kHz sonication can induce secure BBB opening from longitudinal MR image follow up to 7 days., Conclusion: This study provides valuable information regarding the use low-frequency ultrasound for BBB disruption and suggest that SPIO nanoparticles has the potential to serve as a thernostic agent in MRI-guided ultrasound-enhanced brain drug delivery., (Copyright © 2011 Wiley Periodicals, Inc.)

The kitchen waste was chosen as a high solid (42 gL(-1) of volatile suspended solid, VSS) and high organic (107 gL(-1) of chemical oxygen demand) feedstock for operating a 3-L mesophilic fermentor. The greatest specific hydrogen production rate ( r(H2) was observed in Stage 3 as 3.4 L-H2 L(-1) day(-1) with a volumetric loading rate (VLR) of 100 g-CODL(-1) day(-1); the highest hydrogen yield was observed in Stage 2 as 96 mL-H2 g(-1) of influent VSS with a VLR of 46 g-COD L(-1) day(-1). In Stages 1 (with a VLR of 27 g-COD L(-1)) and 2, the sum of Butyrivibrio fibrisolvens and Clostridium proteoclasticum is dominant, but in Stage 3, Olsenella genomosp, became dominant and constituted 44% of the entire population. The dependence of VLR and r(H2)could be regressed as a linear equation of r(H2) = (2.83 VLR + 40.5) x 10(-2) ., (Copyright © 2011. Published by Elsevier Ltd.)

Background: To overcome the complexity of acetabular fractures, several techniques, such as extensive surgical exposure, transtrochanteric osteotomy, and columnar screw fixation, were reported. However, all these techniques have their disadvantages and limitations. We report the surgical results of a modified technique with posterior columnar screw insertion and neutralization plate in a single Kocher-Langenbeck approach for complex acetabular fractures., Methods: We identified 30 patients with 30 acetabular fractures who had been treated by this technique between 1995 and 2004. Demographic data, perioperative results, and complications were all recorded. The detail of surgical procedure was described and illustrated., Results: There were 13 men and 17 women with mean age of 36.4 years (range, 19-66 years). Mean follow-up duration was 49.2 months (range, 24-112 months). All fractures achieved union, and there was no loss reduction and fixation during the follow-up period. There were five complications during hospital stay, including superficial and deep infection and transient sciatic nerve palsy. There was no loss of reduction during follow-up period. Five patients underwent total hip arthroplasty caused by posttraumatic osteoarthritis and preexisting osteoarthritis. The mean Harris Hip Score at 24-month follow-up was 79.7 (median, 92; range, 33-99)., Conclusion: This study provided a modified surgical technique of percutaneous insertion of posterior columnar screw that appeared to be safe and reliably hold the column in place for healing.

Fifty-two consecutive adult patients with syndesmotic diastasis (SD) were treated with closed anatomical reduction and stable fixation by a trans-syndesmotic cancellous screw. A short leg splint was prescribed for a six week postoperative period. Treatment outcomes of syndesmotic screw removal at various time points were studied and compared (group 1 at six weeks, group 2 at three months and group 3 at an average of nine months). Recurrence of SD, incidence of syndesmotic screw breakage and ankle function were compared among the three groups. Recurrence of SD occurred in 15.8% (3/19) of patients in group 1, 15.0% (3/20) in group 2 and 0% (0/13) in group 3 (p = 0.054). Breakage of the syndesmotic screw occurred in three patients within three months (group 2, 15.0%) and in two patients beyond three months (group 3, each at six and 12 months, 15.4%). None of the group 1 patients experienced screw breakage (p = 0.034). Forty-three patients (82.7%) were classified as having satisfactory outcomes. Ankle function did not significantly differ among the three groups (p = 0.191), with or without syndesmotic screw breakage (p = 0.343) and with or without SD recurrence (p = 0.218). In conclusion, restriction of daily activity for at least three months is required to prevent recurrence. Removal of the syndesmotic screw at six weeks may prevent its breakage but increases the risk of recurrence. Over an average follow-up of 19 months, SD recurrence does not lead to deterioration in ankle function.

This study describes the creation and characterization of drug carriers prepared using the polymer poly[aniline-co-N-(1-one-butyric acid) aniline] (SPAnH) coated on Fe(3)O(4) cores to form three types of magnetic nanoparticles (MNPs); these particles were used to enhance the therapeutic capacity and improve the thermal stability of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), a compound used to treat brain tumors. The average hydrodynamic diameter of the MNPs was 89.2 ± 8.5 nm and all the MNPs displayed superparamagnetic properties. A maximum effective dose of 379.34 μg BCNU could be immobilized on 1 mg of MNP-3 (bound-BCNU-3). Bound-BCNU-3 was more stable than free-BCNU when stored at 4 °C, 25 °C or 37 °C. Bound-BCNU-3 could be concentrated at targeted sites in vitro and in vivo using an externally applied magnet. When applied to brain tumors, magnetic targeting increased the concentration and retention of bound-BCNU-3. This drug delivery system promises to provide more effective tumor treatment using lower therapeutic doses and potentially reducing the side effects of chemotherapy., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Malignant glioma is a common and severe primary brain tumor with a high recurrence rate and an extremely high mortality rate within 2 years of diagnosis, even when surgical, radiological, and chemotherapeutic interventions are applied. Intravenously administered drugs have limited use because of their adverse systemic effects and poor blood-brain barrier penetration. Here, we combine 2 methods to increase drug delivery to brain tumors. Focused ultrasound transiently permeabilizes the blood-brain barrier, increasing passive diffusion. Subsequent application of an external magnetic field then actively enhances localization of a chemotherapeutic agent immobilized on a novel magnetic nanoparticle. Combining these techniques significantly improved the delivery of 1,3-bis(2-chloroethyl)-1-nitrosourea to rodent gliomas. Furthermore, the physicochemical properties of the nanoparticles allowed their delivery to be monitored by magnetic resonance imaging (MRI). The resulting suppression of tumor progression without damaging the normal regions of the brain was verified by MRI and histological examination. This noninvasive, reversible technique promises to provide a more effective and tolerable means of tumor treatment, with lower therapeutic doses and concurrent clinical monitoring.

The superparamagnetic properties of magnetic nanoparticles (MNPs) allow them to be guided by an externally positioned magnet and also provide contrast for MRI. However, their therapeutic use in treating CNS pathologies in vivo is limited by insufficient local accumulation and retention resulting from their inability to traverse biological barriers. The combined use of focused ultrasound and magnetic targeting synergistically delivers therapeutic MNPs across the blood-brain barrier to enter the brain both passively and actively. Therapeutic MNPs were characterized and evaluated both in vitro and in vivo, and MRI was used to monitor and quantify their distribution in vivo. The technique could be used in normal brains or in those with tumors, and significantly increased the deposition of therapeutic MNPs in brains with intact or compromised blood-brain barriers. Synergistic targeting and image monitoring are powerful techniques for the delivery of macromolecular chemotherapeutic agents into the CNS under the guidance of MRI.

Extracellular acidosis often rapidly causes intracellular acidification, alters ion channel activities, and activates G protein-coupled receptors. In this report, we demonstrated a novel cellular response to acidosis: induction of the zymogen activation of matriptase. Acid-induced matriptase activation is ubiquitous among epithelial and carcinoma cells and is characterized by rapid onset, fast kinetics, and the magnitude of activation seen. Trace amounts of activated matriptase can be detected 1 min after cells are exposed to pH 6.0 buffer, and the vast majority of latent matriptase within the cells is converted to activated matriptase within 20 min. Matriptase activation may be a direct response to proton exposure because acid-induced matriptase activation also occurs in an in vitro, cell-free setting in which intracellular signaling molecules and ion channel activities are largely absent. Acid-induced matriptase activation takes place both on the cell surface and inside the cells, likely due to the parallel intracellular acidification that activates intracellular matriptase. Following matriptase activation, the active enzyme is immediately inhibited by binding to hepatocyte growth factor activator inhibitor 1, resulting in stable matriptase-hepatocyte growth factor activator inhibitor 1 complexes that are rapidly secreted. As an early response to acidosis, matriptase activation can also be induced by perturbation of intracellular pH homeostasis by 5-(N-methyl-N-isobutyl)-amiloride and 5-(N-ethyl-N-isopropyl)-amiloride, both of which inhibit Na(+)/H(+) exchangers, and diisothiocyanostilbene-2,2'-disulfonic acid, which can inhibit other acid-base ion channels. This study uncovers a novel mechanism regulating proteolysis in epithelial and carcinoma cells, and also demonstrates that a likely function of matriptase is as an early response to acidosis.

A newly-developed molecular method, hierarchical oligonucleotide primer extension (HOPE), was used to analyze various groups within the species Cylindrospermopsis raciborskii. PCR-amplified internally transcribed spacer sequences of 16S-23S from C. raciborskii in reservoir samples of Taiwan and Kinmen were examined. One of eight sequevars in the clone libraries was closely related to strains obtained from the European continent, while the others, designated of Taiwan (TW) type, belonged to a novel group. Optimized HOPE analyses showed that C. raciborskii distributed in different reservoirs with a relative abundance of 0.5% to 76.4% in the cyanobacterial communities. They further detected the concurrence of three C. raciborskii subpopulations, in which European and TW groups were predominant. The TW sequevars accounted for greater than 87.5% of C. raciborskii in the reservoirs Taihu, Yangmin, Jinsha, and Mudan, while this decreased to 55.4-58.1%, accompanied by a proportional increase of the European group, in reservoirs Lantan and Renyi. These findings revealed the complex subspecies structure within C. raciborskii and the subspecies dynamics associated with geographic locations.

Background: To assess clinical and functional outcomes as well as the relative stability of various configurations of tension band wiring approaches for treating olecranon fractures, a retrospective cohort study was conducted., Methods: Seventy-seven consecutive adult patients with 78 olecranon fractures were treated using tension band wiring techniques in three different configurations. The configurations differed in the location of the ends of Kirschner wires with the following locations being used: in the proximal ulnar canal, through the anterior ulnar cortex, and in the distal ulnar canal., Results: Based on average follow-up of 2.76 years (range, 1.1-5.5 years), all three techniques achieved high union rates and low complication rates. However, the Kirschner wires in the first technique allowed proximal pin migration with elbow irritation as compared with the second and the third techniques (p = 0.001, 0.03, respectively)., Conclusions: Placement of the ends of Kirschner wires in the proximal ulnar canal should be avoided whenever possible. Because placement of the ends of Kirschner wires through the anterior ulnar cortex may produce serious complications as reported in medical literature, placement of the ends of Kirschner wires in the distal ulnar canal may be the most effective approach.

Matriptase, a transmembrane serine protease, is broadly expressed by, and crucial for the integrity of, the epithelium. Matriptase is synthesized as a zymogen and undergoes autoactivation to become an active protease that is immediately inhibited by, and forms complexes with, hepatocyte growth factor activator inhibitor (HAI-1). To investigate where matriptase is activated and how it is secreted in vivo, we determined the expression and activation status of matriptase in seminal fluid and urine and the distribution and subcellular localization of the protease in the prostate and kidney. The in vivo studies revealed that while the latent matriptase is localized at the basolateral surface of the ductal epithelial cells of both organs, only matriptase-HAI-1 complexes and not latent matriptase are detected in the body fluids, suggesting that activation, inhibition, and transcytosis of matriptase would have to occur for the secretion of matriptase. These complicated processes involved in the in vivo secretion were also observed in polarized Caco-2 intestinal epithelial cells. The cells target latent matriptase to the basolateral plasma membrane where activation, inhibition, and secretion of matriptase appear to take place. However, a proportion of matriptase-HAI-1 complexes, but not the latent matriptase, appears to undergo transcytosis to the apical plasma membrane for secretion. When epithelial cells lose their polarity, they secrete both latent and activated matriptase. Although most epithelial cells retain very low levels of matriptase-HAI-1 complex by rapidly secreting the complex, gastric chief cells may activate matriptase and store matriptase-HAI-1 complexes in the pepsinogen-secretory granules, suggesting an intracellular activation and regulated secretion in these cells. Taken together, while zymogen activation and closely coupled HAI-1-mediated inhibition are common features for matriptase regulation, the cellular location of matriptase activation and inhibition, and the secretory route for matriptase-HAI-1 complex may vary along with the functional divergence of different epithelial cells.

We previously reported the isolation of novel methanogens by using a new cultivation method, referred to as the coculture method. Here, we extended our coculture method to various anaerobic environmental samples. As a result, we successfully cultivated some uncharacterized methanogens in coculture enrichments and eventually isolated a new methanogen, within the order Methanomicrobiales.

Salmonella enterica serovar Choleraesuis (SC) is an important enteric pathogen that causes serious systemic infections in swine and humans. To identify the genes required for resistance to antimicrobial peptides, we constructed a bank of SC transposon mutants and screened them for hypersensitivity to the cationic peptide polymyxin B. Here we report one isolated polymyxin B-susceptible mutant that also exhibited increased sensitivity toward human neutrophil peptide alpha-defensin 1 (HNP-1) and hydrophobic antibiotics including erythromycin and novobiocin. The mutant had a mutation in an ORF identified as outer membrane beta-barrel protein gene omb. The purified recombinant Omb protein was characterized as a ferrous iron-binding protein. The constructed omb isogenic mutant grew more slowly in iron-limiting conditions than the wild-type (WT) parent strain. In addition, compared with the WT strain, the omb mutant exhibited an increase in net negative charge upon the cell surface and was more easily killed by polymyxin B, HNP-1 and hydrophobic antibiotics. The omb gene was transcribed, regardless of the iron content within the growth medium, and the Omb protein appeared exclusively in the outer membrane fraction. Infection experiments demonstrated virulence attenuation when the mutant was administered orally or intraperitoneally to mice. This study indicates that Omb is a previously unrecognized ferrous iron-binding protein. In vivo, Omb may be involved in the acquisition of ferrous iron during the initial stages of SC infection and appears to be an important virulence factor for SC in mice.

Both pilot and laboratory scale experiments are conducted to compare the effect of ozone and permanganate preoxidation on algae removal by alum coagulation. Both appropriately dosed preoxidants are shown to be beneficial to algae coagulation removal. This may be attributed to a decrease in cell stability; however, overdosing may cause cell lysis and the release of organics, which could interfere with algae cell coagulation. The presence of calcium further enhances the beneficial effect of preoxidation on algae coagulation; however, this phenomenon is more significant for using permanganate than ozone. It is speculated that this is due to the fact that the positively charged calcium ions can serve as bridges to hold the negatively charged MnO(2) and algal cells together. Further, this behavior also explains the superior performance of permanganate preoxidation compared to that obtained using ozone for algae coagulation removal in pilot testing, as the source water contains high calcium content.

This study investigated the active microbial community in a full-scale granular activated carbon-anaerobic fluidized bed (GAC-AFB) reactor treating wastewater from the manufacturing of phenolic resin, using 16S rRNA-based molecular analyses. The results of cDNA from 16S rRNA revealed that Methanosaeta-related (83.9% of archaeal clones) and Syntrophorhabdaceae (formerly named Deltaproteobacteria group TA)-related (68.9% of bacterial clones) microorganisms were as the most predominant populations in the phenol-degrading GAC-AFB reactor. The high abundance of Syntrophorhabdaceae was supported by a terminal restriction fragment length polymorphism (T-RFLP) analysis, which showed that a Syntrophorhabdaceae-like fragment of 119 bp (~80% of total fragments) was the most predominant phylotype. Furthermore, fluorescence in situ hybridization (FISH) analyses suggested that Syntrophus- and Chloroflexi-like cells were also in high abundance in the GAC biofilm. A non-layered structure of microorganisms was found in the GAC biofilm, where Methanosaeta (thick filamentous), Syntrophorhabdaceae (oval-shaped), Syntrophus (small rods) and Chloroflexi (thin-filamentous) were randomly distributed with high abundance. These findings greatly improve our understanding of the diversity and distribution of microbial populations in a full-scale mesophilic bioreactor treating an actual phenol-containing waste stream.

Matriptase, a type 2 transmembrane serine protease, is predominately expressed by epithelial and carcinoma cells in which hepatocyte growth factor activator inhibitor 1 (HAI-1), a membrane-bound, Kunitz-type serine protease inhibitor, is also expressed. HAI-1 plays dual roles in the regulation of matriptase, as a conventional protease inhibitor and as a factor required for zymogen activation of matriptase. As a consequence, activation of matriptase is immediately followed by HAI-1-mediated inhibition, with the activated matriptase being sequestered into HAI-1 complexes. Matriptase is also expressed by peripheral blood leukocytes, such as monocytes and macrophages; however, in contrast to epithelial cells, monocytes and macrophages were reported not to express HAI-1, suggesting that these leukocytes possess alternate, HAI-1-independent mechanisms regulating the zymogen activation and protease inhibition of matriptase. In the present study, we characterized matriptase complexes of 110 kDa in human milk, which contained no HAI-1 and resisted dissociation in boiling SDS in the absence of reducing agents. These complexes were further purified and dissociated into 80-kDa and 45-kDa fragments by treatment with reducing agents. Proteomic and immunological methods identified the 45-kDa fragment as the noncatalytic domains of matriptase and the 80-kDa fragment as the matriptase serine protease domain covalently linked to one of three different secreted serpin inhibitors: antithrombin III, alpha1-antitrypsin, and alpha2-antiplasmin. Identification of matriptase-serpin inhibitor complexes provides evidence for the first time that the proteolytic activity of matriptase, from those cells that express no or low levels of HAI-1, may be controlled by secreted serpins.