Effectiveness of tumor­treating fields to reduce the proliferation and migration of liposarcoma cell lines.

Liposarcoma (LPS) is a rare type of soft tissue sarcoma that constitutes 20% of all sarcoma cases in adults. Effective therapeutic protocols for human LPS are not well-defined. Tumor-treating fields (TTFields) are a novel and upcoming field for antitumor therapy. TTFields combined with chemoradiotherapy have proven to be more effective than TTFields combined with radiotherapy or chemotherapy alone. The present study aimed to assess the effectiveness of TTFields in inhibiting cell proliferation and viability for the anticancer treatment of LPS. The present study used TTFields (frequency, 150 kHz; intensity, 1.0 V/cm) to treat two LPS cell lines (94T778 and SW872) and analyzed the antitumor effects. According to trypan blue and MTT assay results, TTFields markedly reduced the viability and proliferation of LPS cell lines along with the formation of colonies in three-dimensional culture. Based on the Transwell chamber assay, TTFields treatment also markedly reduced the migration of LPS cells. Furthermore, as shown by the higher activation of caspase-3 in the Caspase-3 activity assay and the results of the reactive oxygen species (ROS) assay, TTFields increased the formation of ROS in the cells and enhanced the proportion of apoptotic cells. The present study also investigated the inhibitory effect of TTFields in combination with doxorubicin (DOX) on the migratory capacity of tumor cells. The results demonstrated that TTFields treatment synergistically induced the ROS-induced apoptosis of LPS cancer cell lines and inhibited their migratory behavior. In conclusion, the present study demonstrated the potential of TTFields in improving the sensitivity of LPS cancer cells, which may lay the foundation for future clinical trials of this combination treatment strategy.

Capacitive Electrode-Based Electric Field Treatments on Redox-Toxic Iron Deposits in Transgenic AD Mouse Models: The Electroceutical Targeting of Alzheimer's Disease Feasibility Study.

Iron accumulation in the brain accelerates Alzheimer's disease progression. To cure iron toxicity, we assessed the therapeutic effects of noncontact transcranial electric field stimulation to the brain on toxic iron deposits in either the Aß fibril structure or the Aß plaque in a mouse model of Alzheimer's disease (AD) as a pilot study. A capacitive electrode-based alternating electric field (AEF) was applied to a suspension of magnetite (Fe3O4) to measure field-sensitized reactive oxygen species (ROS) generation. The increase in ROS generation compared to the untreated control was both exposure-time and AEF-frequency dependent. The frequency-specific exposure of AEF to 0.7-1.4 V/cm on a magnetite-bound Aß-fibril or a transgenic Alzheimer's disease (AD) mouse model revealed the degradation of the Aß fibril or the removal of the Aß-plaque burden and ferrous magnetite compared to the untreated control. The results of the behavioral tests show an improvement in impaired cognitive function following AEF treatment on the AD mouse model. Tissue clearing and 3D-imaging analysis revealed no induced damage to the neuronal structures of normal brain tissue following AEF treatment. In conclusion, our results suggest that the effective degradation of magnetite-bound amyloid fibrils or plaques in the AD brain by the electro-Fenton effect from electric field-sensitized magnetite offers a potential electroceutical treatment option for AD.

Location of Ulnar Nerve Branches to the Flexor Carpi Ulnaris during Surgery for Cubital Tunnel Syndrome.

OBJECTIVE: Cubital tunnel syndrome, the most common ulnar nerve entrapment neuropathy, is usually managed by simple decompression or anterior transposition. One of the concerns in transposition is damage to the nerve branches around the elbow. In this study, the location of ulnar nerve branches to the flexor carpi ulnaris (FCU) was assessed during operations for cubital tunnel syndrome to provide information to reduce operation-related complications. METHODS: A personal series (HJY) of cases operated for cubital tunnel syndrome was reviewed. Cases managed by transposition and location of branches to the FCU were selected for analysis. The function of the branches was confirmed by intraoperative nerve stimulation and the location of the branches was assessed by the distance from the center of medial epicondyle. RESULTS: There was a total of 61 cases of cubital tunnel syndrome, among which 31 were treated by transposition. Twenty-one cases with information on the location of branches were analyzed. The average number of ulnar nerve branches around the elbow was 1.8 (0 to 3), only one case showed no branches. Most of the cases had one branch to the medial head, and one other to the lateral head of the FCU. There were two cases having branches without FCU responses (one branch in one case, three branches in another). The location of the branches to the medial head was 16.3±8.6 mm distal to the medial epicondyle (16 branches; range, 0 to 35 mm), to the lateral head was 19.5±9.5 mm distal to the medial epicondyle (19 branches; range, -5 to 30 mm). Branches without FCU responses were found from 20 mm proximal to the medial condyle to 15 mm distal to the medial epicondyle (five branches). Most of the branches to the medial head were 15 to 20 mm (50% of cases), and most to the lateral head were 15 to 25 mm (58% of cases). There were no cases of discernable weakness of the FCU after operation. CONCLUSION: In most cases of cubital tunnel syndrome, there are ulnar nerve branches around the elbow. Although there might be some cases with branches without FCU responses, most branches are to the FCU, and are to be saved. The operator should be watchful for branches about 15 to 25 mm distal to the medial epicondyle, where most branches come out.

Relationship Between Feeding to Sleep During Infancy and Subsequent Childhood Disease Burden.

OBJECTIVE: To investigate the association of feeding to sleep during infancy and subsequent childhood health burdens. STUDY DESIGN: Information was collected from the parents of children who participated in the national health screening survey when the child was 9-12 months old. The exposure group included participants who were fed to sleep. The primary outcome was all-cause hospital admission (inpatient care, intensive care unit [ICU] admission, or general anesthesia) after age 24 months. Secondary outcomes were subsequent childhood diseases (ie, adenoidectomy and/or tonsillectomy, nasal polyps, allergic rhinitis, acute otitis media, asthma, pneumonia, and aspiration pneumonia), and growth status, as measured by weight-to-age and height-to-age z-scores. RESULTS: The study cohort consisted of 224 075 children who participated in the health screening program, 29 392 of whom (13.1%; 51% males) were fed to sleep. Exposure was associated with an increased risk of all-cause hospitalization after age 24 months (hazard ratio [HR], 1.05; 95% CI, 1.03-1.07), but not with admission to an ICU or receipt of general anesthesia. This also was related to adenoidectomy and/or tonsillectomy (HR, 1.08; 95% CI, 1.01-1.15), dental caries (HR, 1.32; 95% CI, 1.23-1.40), asthma (HR, 1.14; 95% CI, 1.14-1.24), pneumonia (HR, 1.10; 95% CI, 1.07-1.13), overweight (HR, 1.06; 95% CI, 1.03-1.09), and obesity (HR, 1.11; 95% CI, 1.06-1.16). CONCLUSIONS: Several adverse health outcomes are related to feeding to sleep during early childhood.

Emodin coupled with high LET neutron beam-a novel approach to treat on glioblastoma.

The primary motivation of this investigative study is trying to find an alternative treatment that can be used to slow down or treat glioblastoma due to the witnessed toxic side effects of the current drugs coupled with limited effectiveness in overall treatment. Consequently, a Chinese plant extract emodin proves to play a critical role in this investigative study since results from the Western blot and the other accompanying assays for anti-cancer effects indicate that it cannot work a lot to suppress cell migration and possible invasion, but rather emodin can be combined with radiation to give desired outcomes. Our result shows that the kind of radiation which acts well with emodin is neutron radiation rather than gamma radiation. Emodin significantly enhanced the radiosensitivity of LN18 and LN428 cells to γ-rays through MTT assay and cell counting. Accordingly, exposure to neutron radiation in the presence of emodin induced apoptotic cell death and autophagic cell death to a significantly higher extent, and suppressed cell migration and invasiveness more robustly. These effects are presumably due to the ability of emodin to amplify the effective dose from neutron radiation more efficiently. Thus, the study below is one such trial towards new interventional discovery and development in relation to glioblastoma treatment.

Effects of gold nanoparticles on normal hepatocytes in radiation therapy.

Background: Gold nanoparticles (GNP, AuNPs) have received much attention as a tool to improve the therapeutic index of radiation therapy. This study aimed to evaluate the normal in vitro toxicity of AuNPs at kilovoltage energies on hepatocytes to provide scientific support for using AuNPs with radiotherapy. Methods: Using the same treatment protocol applied to tumor cell lines, hepatocytes were exposed to AuNPs and/or radiation at various time points. Results: The combination of X-ray irradiation and AuNPs did not have any significant effect on cell survival and apoptosis in normal hepatocytes. Furthermore, the combination treatment resulted in no or little change in the level of gamma-H2A histone family member X (γ-H2AX), a marker for DNA double-strand breaks (DSB), nor on the proportion of cells in the G2/M phase. Additionally, interleukin-8 (IL-8) secretion was measured using an enzyme-linked immunosorbent assay (ELISA) to assess its role in tumor progression and angiogenesis. The combination of irradiation and AuNP treatment revealed no significant reduction in hepatocyte viability, proliferation, or secretory capacity compared to cells receiving either treatment alone. According to this study, AuNPs in combination with radiation do have potentially in the treatment of hepatocellular carcinoma (HCC) with no critical cytotoxicity on normal tissue. Conclusions: Therefore, it is postulated that radiation and AuNPs are an effective combination therapy against HCC with no little cytotoxic effects on normal tissue, a hypothesis which warrants further investigation in in vivo, as well as in in vitro.

Tumor-treating fields in combination with sorafenib curtails the growth of colorectal carcinoma by inactivating AKT/STAT3 signaling.

Background: Tumor-treating fields (TTFields) have been extensively used to treat various cancers as well as glioblastoma multiforme (GBM), owing to their antimitotic effects. Furthermore, sorafenib is also extensively used to treat hepatocellular carcinoma (HCC) and renal cell carcinoma (RCC) and is under phase II/III clinical trials for other solid tumors. Hence, this investigation aimed to assess the efficacy of combination therapy with TTFields and sorafenib for colorectal carcinoma (CRC). Methods: Human CRC HCT116 and SW480 cells were subjected to cell viability assay, followed by the assessment of their cell death using fluorescence-activated cell sorting (FACS) analysis. Furthermore, the expression of proteins involved in AKT/STAT3 signaling and apoptosis was assessed via western blotting. Results: Combination treatment inhibited cell proliferation and induced apoptosis via Reactive oxygen species (ROS) generation, evident from caspase-3 cleavage in CRC cells and suppressed the AKT/STAT3 signaling pathway, as evident from downregulation of BCL-2 after post-treatment. The present results indicate that combination treatment with TTFields and sorafenib inactivates AKT/STAT3 signaling pathway, thus altering the expression of BCL-2, thus inducing apoptosis and inhibiting the growth of CRC cells. Conclusions: Thus, combination treatment with TTFields and sorafenib is clinically applicable for treating metastatic CRC, although safety examination in patients with CRC will required to be achieved before this protocol can be implemented clinically for TTFields-sensitizer.

Tumor-treating fields in combination with sorafenib restrain the proliferation of liver cancer in vitro.

Liver cancer is a common malignancy worldwide, with a poor prognosis and a high recurrence rate despite the available treatment methodologies. Tumor-treating fields (TTFields) have shown good preclinical and clinical results for improving the prognosis of patients with glioblastoma and malignant pleural mesothelioma. However, there is minimal evidence for the effect of TTFields on other cancer types. Thus, the present study aimed to investigate the therapeutic efficacy of TTFields in an in vitro model, and to further elucidate the underlying mechanisms. In the present study, two hepatocellular carcinoma (HCC) cell lines (Hep3B and HepG2) were treated with TTFields (intensity, 1.0 V/cm; frequency, 150 kHz) in order to determine the potential antitumor effects of this approach. TTFields significantly inhibited the proliferation and viability of HCC cell lines, as measured using Trypan blue and MTT assays, as well as colony formation in three-dimensional cultures. The TTFields also significantly inhibited the migration and invasion of HCC cells in Transwell chamber and wound-healing assays. Moreover, TTFields enhanced the production of reactive oxygen species in the cells and increased the proportion of apoptotic cells, as evidenced by increased caspase-3 activity, as well as PARP cleavage in western blotting experiments. All of these effects were increased following the application of TTFields in combination with the multi-kinase inhibitor sorafenib, which demonstrated a synergistic effect. Thus, to the best of our knowledge, these results demonstrate for the first time the potential of TTFields in improving the sensitivity of HCC cells to sorafenib, which may lay the foundation for future clinical trials for this combination treatment strategy.

Combination therapy of Doxorubicin with TTFields and radiation: newer approaches to combat lung cancer.

BACKGROUND: Tumor-treating fields (TTFields) have been used singly or with chemoradiation for treating glioblastoma and mesothelioma but not yet for lung cancer. Survival rates in lung cancer remain abysmal despite advances in early diagnosis and targeted therapies. AIMS AND OBJECTIVES: We aimed to investigate the effectiveness of TTFields in inhibiting lung cancer growth and metastasis, as well as the therapeutic effectiveness of TTFields alongside radiation and chemosensitivity-enhancing agents in an in vitro model. METHODS: We generated TTFields yielding 0-800 V sine-wave signals, 0.9 V/cm applied electric field intensity, and 150 kHz frequency. The human lung cancer cell lines A549 and H460 were used in this study. Cell viability, colony formation, cell death detection, and cell invasion assays were performed to assess the therapeutic effectiveness of TTFields; sensitization of lung cancer cells to TTFields by doxorubicin (DOX); and the combined effect of TTFields, DOX, and irradiation (IR). RESULTS: Lung cancer cells showed a nearly 20% decrease in cell viability at 1 V/cm and 150 kHz. In A549 and H460 cells, TTFields increased apoptosis through increased cleaved caspase3, hindered cell migration and invasion, and improved chemosensitivity to DOX. The combination of DOX and TTFields showed better antitumor results than those of each individually. However, the DOX/TTFields/IR combination was most effective in reducing the viability and migration of lung cancer cells. CONCLUSION: TTFields as an adjuvant therapy offers probability for improving lung cancer patient outcomes.

Clinical differences between delayed and acute onset postoperative spinal infection.

ABSTRACT: Spine surgeons often encounter cases of delayed postoperative spinal infection (PSI). Delayed-onset PSI is a common clinical problem. However, since many studies have investigated acute PSIs, reports of delayed PSI are rare. The purpose of this study was to compare the clinical features, treatment course, and prognosis of delayed PSI with acute PSI.Ninety-six patients diagnosed with postoperative spinal infection were enrolled in this study. Patients were classified into 2 groups: acute onset (AO) within 90 days (n = 73) and delayed onset (DO) after 90 days (n = 23). The baseline data, clinical manifestations, specific treatments, and treatment outcomes were compared between the 2 groups.The history of diabetes mellitus (DM) and metallic instrumentation at index surgery were more DO than the AO group. The causative organisms did not differ between the 2 groups. Redness or heat sensation around the surgical wound was more frequent in the AO group (47.9%) than in the DO group (21.7%) (P = .02). The mean C-reactive protein levels during infection diagnosis was 8.9 mg/dL in the AO and 4.0 mg/dL in the DO group (P = .02). All patients in the DO group had deep-layer infection. In the DO group, revision surgery and additional instrumentation were required, and the duration of parenteral antibiotic use and total antibiotic use was significantly longer than that in the AO group. Screw loosening, disc space collapse, and instability were higher in the DO group (65.2%) than in the AO group (41.1%) (P = .04). However, the length of hospital stay did not differ between the groups.Delayed-onset PSI requires more extensive and longer treatment than acute-onset surgical site infection. Clinicians should try to detect the surgical site infection as early as possible.

Cross-species genetic screens identify transglutaminase 5 as a regulator of polyglutamine-expanded ataxin-1.

Many neurodegenerative disorders are caused by abnormal accumulation of misfolded proteins. In spinocerebellar ataxia type 1 (SCA1), accumulation of polyglutamine-expanded (polyQ-expanded) ataxin-1 (ATXN1) causes neuronal toxicity. Lowering total ATXN1, especially the polyQ-expanded form, alleviates disease phenotypes in mice, but the molecular mechanism by which the mutant ATXN1 is specifically modulated is not understood. Here, we identified 22 mutant ATXN1 regulators by performing a cross-species screen of 7787 and 2144 genes in human cells and Drosophila eyes, respectively. Among them, transglutaminase 5 (TG5) preferentially regulated mutant ATXN1 over the WT protein. TG enzymes catalyzed cross-linking of ATXN1 in a polyQ-length-dependent manner, thereby preferentially modulating mutant ATXN1 stability and oligomerization. Perturbing Tg in Drosophila SCA1 models modulated mutant ATXN1 toxicity. Moreover, TG5 was enriched in the nuclei of SCA1-affected neurons and colocalized with nuclear ATXN1 inclusions in brain tissue from patients with SCA1. Our work provides a molecular insight into SCA1 pathogenesis and an opportunity for allele-specific targeting for neurodegenerative disorders.

Interaction of curcumin with glioblastoma cells via high and low linear energy transfer radiation therapy inducing radiosensitization effects.

Glioblastoma is a deadly cancer tumor in the brain and has a survival rate of about 15 months. Despite the high mortality rate, temozolomide has proven to increase the survival rate of patients when combined with radiotherapy. However, its effects may be limited because some patients develop therapeutic resistance. Curcumin has proven to be a cancer treatment due to its broad anticancer spectrum, high efficiency and low toxic level. Additionally, curcumin significantly enhanced radiation efficacy under high and low Linear Energy Transfer (LET) radiation conditions in vitro. In combination with radiation, curcumin increased the cell population in the sub-G1 phase and the reactive oxygen species (ROS) level, ultimately increasing GBM cellular apoptosis. The radiosensitizing effects of curcumin are much higher in neutron (high LET)-irradiated cell lines than in γ (low LET)-irradiated cell lines. Curcumin plus neutron combination significantly inhibited cell invasion compared with that of single treatment or curcumin combined γ-ray treatment. Curcumin enhances the radiosensitivity of Glioblastoma (GBM), suggesting it may have clinical utility in combination cancer treatment with neutron high-LET radiation.

Enhanced proton treatment with a LDLR-ligand peptide-conjugated gold nanoparticles targeting the tumor microenvironment in an infiltrative brain tumor model.

The tumor microenvironment (TME) of glioblastoma malforms (GBMs) contains tumor invasiveness factors, microvascular proliferation, migratory cancer stem cells and infiltrative tumor cells, which leads to tumor recurrence in the absence of effective drug delivery in a Blood Brain Barrier (BBB)-intact TME and radiological invisibility. Low-density lipoprotein receptor (LDLR) is abundant in the blood brain barrier and overexpressed in malignant glioma cells. This study aimed to treat the TME with transmitted proton sensitization of LDLR ligand-functionalized gold nanoparticles (ApoB@AuNPs) in an infiltrative F98 glioma rat model. BBB-crossing ApoB@AuNPs were selectively taken up in microvascular endothelial cells proliferation and pericyte invasion, which are therapeutic targets in the glioma TME. Proton sensitization treated the TME and bulk tumor volume with enhanced therapeutic efficacy by 67-75% compared to that with protons alone. Immunohistochemistry demonstrated efficient treatment of endothelial cell proliferation and migratory tumor cells of invasive microvessels in the TME with saving normal tissues. Taken together, these data indicate that the use of LDLR ligand-functionalized gold nanoparticles is a promising strategy to treat infiltrative malignant glioma while overcoming BBB crossing.

Tumor-treating fields as a proton beam-sensitizer for glioblastoma therapy.

Few advances in GBM treatment have been made since the initiation of the Stupp trials in 2005. Experimental studies on immunotherapy drugs, molecular inhibitors, radiation dosage escalation and vascular growth factor blockers have all failed to provide satisfactory outcomes. TTFields therapy, on the other hand, have emerged as a viable substitute to therapies like radiation in GBM patients having a highly immunosuppressive tumor microenvironment. To enhance the biofunctional impacts, we explored the combination events with TTFields and proton treatment in this study. We conducted a cell viability test, a cell death detection evaluation, a ROS analysis, a three-dimensional (3D) culture system, and a migration assay. The combination of proton radiation and TTFields therapy laid a substantial anticancer impact on the F98 and U373 as compared to the consequences of either of these therapies used separately. The combination proton beam therapy used by TTFields was very successful in curbing GBM from migrating. GBM cell metastasis is restricted by TTFields combined proton by downregulating the MAPK, NF-κB, and PI3K/AKT indicating pathways, caused by reduced EMT marker expression. These findings furnish biological proof for the molecular grounds of TTFields in combination with proton used for GBM therapy.

Dual targeting of brain region-specific kinases potentiates neurological rescue in Spinocerebellar ataxia type 1.

A critical question in neurodegeneration is why the accumulation of disease-driving proteins causes selective neuronal loss despite their brain-wide expression. In Spinocerebellar ataxia type 1 (SCA1), accumulation of polyglutamine-expanded Ataxin-1 (ATXN1) causes selective degeneration of cerebellar and brainstem neurons. Previous studies revealed that inhibiting Msk1 reduces phosphorylation of ATXN1 at S776 as well as its levels leading to improved cerebellar function. However, there are no regulators that modulate ATXN1 in the brainstem-the brain region whose pathology is most closely linked to premature death. To identify new regulators of ATXN1, we performed genetic screens and identified a transcription factor-kinase axis (ZBTB7B-RSK3) that regulates ATXN1 levels. Unlike MSK1, RSK3 is highly expressed in the human and mouse brainstems where it regulates Atxn1 by phosphorylating S776. Reducing Rsk3 rescues brainstem-associated pathologies and deficits, and lowering Rsk3 and Msk1 together improves cerebellar and brainstem function in an SCA1 mouse model. Our results demonstrate that selective vulnerability of brain regions in SCA1 is governed by region-specific regulators of ATXN1, and targeting multiple regulators could rescue multiple degenerating brain areas.

Measurement and analysis of biomass content using gas emissions from solid refuse fuel incineration.

In this study, we compared the results of biomass and biocarbon content analysis of Solid Refuse Fuels using 14C method and selective dissolution method. Solid Refuse fuel Samples for biomass and biocarbon contents analysis were each collected from the silos and stack of the respective three facilities. Samples collected for 1, 10, 20, and 30 days for each method were analyzed. The analysis data were grouped into sample period, type and method and the optimum method for the detection of the biomass and biocarbon content was estimated. The biomass and biocarbon content showed a partially normal distribution. However, it does not satisfy equal variance. Therefore, we applied the parametric statistics Welch's ANOVA test and the nonparametric statistics Kruskal-Wallis test to compare the means of each sample group. The results of the Kruskal-Wallis test showed that sapmles collected over 20 days at Facility A had the same mean value. Therefore, when analyzing biocarbon content using the 14C method, conducting analyses by collecting exhaust gases for more than 20 days reduces errors in the results.

Tarsal tunnel syndrome caused by posterior facet talocalcaneal coalition: A case report.

RATIONALE: Tarsal tunnel syndrome (TTS) is a compressive neuropathy of the posterior tibial nerve and its branches. Tarsal coalition is defined as a fibrous, cartilaginous, or osseous bridging of 2 or more tarsal bones. TTS with tarsal coalition is uncommon. Here, we present a rare example of successful surgical management of TTS with posterior facet talocalcaneal coalition. PATIENT CONCERNS: A 74-year-old woman presented with hypoesthesia, numbness, and an intermittent tingling sensation on the plantar area over the right forefoot to the middle foot area. The hypoesthesia and paresthesia of the right foot began 6 years previously and were severe along the lateral plantar aspect. The symptoms were mild at rest and increased during daily activities. Tinel sign was positive along the posteroinferior aspect of the medial malleolus. DIAGNOSIS: Lateral ankle radiography showed joint-space narrowing and sclerotic bony changes with a deformed C-sign and humpback sign. Oblique coronal and sagittal computed tomography revealed an irregular medial posterior facet, partial coalition, narrowing, and subcortical cyst formation of the posterior subtalar joint. Magnetic resonance imaging showed an abnormal posterior talocalcaneal coalition compressing the posterior tibia nerve. Electromyography and nerve conduction velocity studies were performed, and the findings indicated that there was an incomplete lesion of the right plantar nerve, especially of the lateral plantar nerve, around the ankle level. INTERVENTIONS: Surgical decompression was performed. Intraoperatively, the lateral plantar nerve exhibited fibrotic changes and tightening below the posterior facet talocalcaneal coalition. The coalition was excised, and the lateral plantar nerve was released with soft-tissue dissection. OUTCOMES: The patient's symptoms of tingling sensation and hypoesthesia were almost relieved at 4 months postoperatively, but she complained of paresthesia with an itching sensation when the skin of the plantar area was touched. The paresthesia had disappeared almost completely at 8 months after surgery. She had no recurrence of symptoms at the 1-year follow-up. LESSONS: The TTS with tarsal coalition is rare. Supportive history and physical examination are essential for diagnosis. Plain radiographs and computed tomography or magnetic resonance imaging are helpful to determine the cause of TTS and verify the tarsal coalition. After diagnosis, surgical excision of the coalition may be appropriate for management with a good outcome.

Removal of bent intramedullary nail: Two case reports.

INTRODUCTION: The removal of bent intramedullary (IM) nail can become a challenge. Therefore, various methods have been reported for the extraction of nails after femoral refracture. We want to share our successful treatment. PATIENT CONCERNS: Case 1. A 44-year-old man was admitted to our clinic after falling while playing soccer. He complained severe right thigh pain with a visible deformity of the femur. His medical history revealed a right femoral shaft fracture caused in a traffic accident which had been treated with intramedullary nailing. Case 2. A 27-year-old man, who had suffered a right femur fracture after a motorcycle accident and been treated with an IM nail, presented after falling down the stairs. He had severe right thigh pain without any open wound or neurologic deficit. DIAGNOSIS: Case 1. Plain radiographs revealed a refracture of the right femoral shaft and a bent IM nail. The initial varus deformity of the nail was 60.1° in the coronal plane. Case 2. The valgus deformity of the nail was 16.1° with an apex-posterior angulation of 34.8° in the sagittal image of plain radiographs. INTERVENTIONS: Case 1. Initial manual reduction was tried in emergency room. Then, under general anesthesia closed reduction of the fracture and bent IM nail was done. After closed reduction, the nail was straightened and extracted smoothly. Case 2. Closed manipulation was attempted initially. But no difference in the deformity was achieved. Therefore, via skin incision, the bent nail was progressively sectioned with high-speed cutting burr until the nail could be straightened. OUTCOMES: Case 1. The patient was mobilized with partial-weight bearing assisted with a crutch on postoperative day two. One year after surgery, the fracture union was complete and the patient was pain-free. Case 2. Six months after surgery, the fracture union was complete with sufficient callus formation around the fracture site. CONCLUSION: There is no gold standard method to remove a bent IM nail. However, since manual reduction to straighten the bent nail causes minimal soft tissue damage, it should be considered first. If it fails, other methods should be attempted, progressing from the minimally invasive technique to more invasive methods.

Ultraviolet Photoactivated Room Temperature NO2 Gas Sensor of ZnO Hemitubes and Nanotubes Covered with TiO2 Nanoparticles.

Prolonged exposure to NO2 can cause lung tissue inflammation, bronchiolitis fibrosa obliterans, and silo filler's disease. In recent years, nanostructured semiconducting metal oxides have been widely used to fabricate gas sensors because of their unique structure and surface-to-volume ratio compared to layered materials. In particular, the different morphologies of ZnO-based nanostructures significantly affect the detection property of NO2 gas sensors. However, because of the large interaction energy of chemisorption (1-10 eV), metal oxide-based gas sensors are typically operated above 100 °C, overcoming the energy limits to attain high sensitivity and fast reaction. High operating temperature negatively affects the reliability and durability of semiconductor-based sensors; at high temperature, the diffusion and sintering effects at the metal oxide grain boundaries are major factors causing undesirable long-term drift problems and preventing stability improvements. Therefore, we demonstrate NO2 gas sensors consisting of ZnO hemitubes (HTs) and nanotubes (NTs) covered with TiO2 nanoparticles (NPs). To operate the gas sensor at room temperature (RT), we measured the gas-sensing properties with ultraviolet illumination onto the active region of the gas sensor for photoactivation instead of conventional thermal activation by heating. The performance of these gas sensors was enhanced by the change of barrier potential at the ZnO/TiO2 interfaces, and their depletion layer was expanded by the NPs formation. The gas sensor based on ZnO HTs showed 1.2 times higher detection property than those consisting of ZnO NTs at the 25 ppm NO2 gas.

Discovery of 2-((4-resorcinolyl)-5-aryl-1,2,3-triazol-1-yl)acetates as potent Hsp90 inhibitors with selectivity over TRAP1.

As the most abundant heat shock protein (HSP), Hsp90 is actively involved in tumor cell growth and various responses to anti-carcinogenic stress. Hsp90 has thus emerged as a potential drug target. A structure-based drug design approach was applied to develop novel resorcinolyltriazole derivatives as Hsp90 inhibitors. Structure-activity relationships (SARs) and molecular docking were investigated to provide a rationale for binding affinity and paralog selectivity. Click chemistry between iodoethynylresorcinol and an azido derivative was used to synthesize a new family of 2-((4-resorcinolyl)-5-aryl-1,2,3-triazol-1-yl) acetates that exhibited Hsp90 binding affinities of 40-100 nM (IC50). Among the synthesized molecules, the triazole alkyl acetates displayed the highest Hsp90 binding affinities. Their potency against Hsp90 was over 100-fold stronger than against TRAP1 and 1-3-fold stronger than against Grp94. In particular, compounds 18, 19, and 30 had Hsp90 inhibitory activities of ~45 nM (IC50) and they displayed over 350-fold selectivity for Hsp90 over TRAP1.