Outcomes of Patients With Spinal Metastases From Prostate Cancer Treated With Conventionally-Fractionated External Beam Radiation Therapy.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To evaluate the outcomes of conventionally-fractionated external beam radiation therapy (cEBRT) in the treatment of prostate cancer spinal metastases (PCSM). METHODS: Patients who received palliative cEBRT for PCSM in our institution between 2008 and 2018 were included. Our outcomes were local progression-free survival (LPFS), overall survival (OS), pain response and toxicities graded using CTCAE version 4.03. Univariable and multivariable Cox proportional hazard regressions were performed to identify predictors for LPFS and OS. RESULTS: A total of 100 patients with 132 sites of PCSM were identified, with a median follow-up of 54 months. Fourteen-percent of patients underwent surgical intervention before receiving cEBRT. Eighteen spinal segments (13.6%) had local progression, with a median time to local progression of 8 months. The median LPFS and OS were 7.8 and 9.0 months, respectively. The complete and partial pain response rates were 57% and 39% respectively. The incidence of grade ≥3 acute toxicities was 11%. Better ECOG performance status (0 to 1), castration-sensitive disease, spinal surgery and use of novel antiandrogen agent were identified as significant predictors for improved OS on multivariable analysis. CONCLUSIONS: In our prostate cancer cohort, cEBRT is an effective treatment modality for local palliation of spinal metastases. More aggressive treatment approach should be considered for patients with excellent performance status and castration-sensitive disease in light of their expected longer survival. Further studies are warranted to identify the predictors for radiotherapy response in this population.

Stereotactic body radiation therapy versus conventional external beam radiation therapy for painful bone metastases: A systematic review and meta-analysis of randomized trials.

PURPOSE: To compare the efficacy and safety of stereotactic body radiation therapy (SBRT) and conventional external beam radiation therapy (cEBRT) in patients with previously unirradiated painful bone metastases (BM). METHODS: We searched biomedical databases for eligible randomized controlled trials (RCTs). The outcomes of interest were pain response, local progression, overall survival (OS) and adverse events. We used established tools to assess the quality of the individual trials and certainty of the pooled evidence. We performed meta-analyses using random effects models. RESULTS: Six RCTs were identified. SBRT improved complete pain response rates at 3 months (OR, 3.38; 95% CI, 1.88-6.07; high certainty), reduced local progression rates (OR, 0.19; 95% CI, 0.06-0.62; high certainty) and increased pain flare rates. There were no differences for other outcomes. CONCLUSION: Among patients with previously unirradiated painful BM, SBRT significantly improved complete pain response rates at 3 months, delayed local progression and increased pain flare rates.

Survival rates and safety associated with chemoradiotherapy followed by surgery and chemoradiotherapy alone for patients with T4 esophageal cancer: a systematic review and meta-analysis.

BACKGROUND: The optimal treatment approach for T4 esophageal cancer is not well established. We aimed to perform a systematic review and meta-analysis to determine the survival rates and safety of chemoradiotherapy followed by surgery (CRT-S) and chemoradiotherapy alone (CRT) in patients with T4 Nany M0 esophageal cancer. MATERIALS AND METHODS: We searched databases for eligible prospective or retrospective studies. The outcomes of interest were overall survival (OS) at 1, 3 and 5 years, treatment-related fistula formation and mortality rates. Meta-analyses were performed using the random effects models separately for studies evaluating CRT-S and CRT. Subgroup analyses were performed based on histology, radiation dose, chemotherapy regimen and duration of the interval between CRT and surgery. RESULTS: We identified 23 studies including 1,119 patients with predominantly squamous cell carcinoma (93%) and adenocarcinoma (3%) histology. The OS rates of patients receiving CRT-S were 65%, 36% and 20% at 1, 3 and 5 years, respectively. The OS rates of patients receiving CRT were 30%, 11% and 10% at 1, 3 and 5 years, respectively. Treatment-related fistula formation rates were 4% for CRT-S and 9% for CRT. Treatment-related mortality rates were 3% for both groups. Subgroup analyses showed that the interval of >2 months between CRT and surgery was associated with significantly improved OS rates at 1, 3 and 5 years. CONCLUSION: Chemoradiotherapy is an efficacious treatment approach for T4 esophageal cancer, with clinically acceptable rates of treatment-related fistula formation and mortality. Tri-modality approach with surgery can be considered in carefully selected patients. Our study findings should be interpreted with caution due to the lack of high-quality evidence. Randomized controlled trials are warranted to confirm these findings.

Prevalence of thyroid malignancy and hormonal dysfunction following radiation exposure in childhood.

INTRODUCTION: Childhood radiation exposure is a known risk factor for thyroid malignancy and dysfunction. However, local data are limited and there is no consensus on the modality and frequency of screening in this high-risk group. METHODS: Retrospective analysis study evaluating patients with childhood radiation exposure in 2006-2016 and minimum of 1-year follow-up. RESULTS: Of the 132 childhood cancer survivors in the study, thyroid malignancy was detected in 2 cases (1.5%) and thyroid nodules in 13 (9.8%). The earliest thyroid malignancy was detected 5 years post-radiotherapy via ultrasound. Of the 84 patients who had screening thyroid function test, 26 (31.0%) were detected with abnormal test results post-radiation, majority being subclinical hypothyroidism. CONCLUSION: Regular screening via clinical examination for thyroid nodules should be performed at least annually. Where feasible and if resources permit, consideration should be given to using ultrasound for thyroid nodule(s) and malignancy screening at 5 years post-radiation therapy. Screening for thyroid dysfunction can be considered from 6-12 months post-radiotherapy.

Prophylactic irradiation of tracts in patients with malignant pleural mesothelioma: A systematic review and meta-analysis of randomized trials.

INTRODUCTION: The role of prophylactic irradiation of tracts (PIT) to prevent tumor seeding at the site of a diagnostic or therapeutic intervention in patients with malignant pleural mesothelioma (MPM) is controversial. This study aimed to determine the efficacy of PITs in preventing procedure tract metastases (PTM) after a chest wall procedure in MPM. MATERIALS AND METHODS: We searched various databases from inception date to April 2020 for randomized controlled trials (RCTs) comparing PIT with no PIT in patients who had a chest wall procedure for MPM. We assessed the risk of bias of individual RCT using the RoB2 tool. The primary outcome was the occurrence of PTM. Meta-analysis was performed using random-effects model. We employed the GRADE approach to assess the certainty of the evidence. RESULTS: We identified five RCTs including 737 patients. Two RCTs had a low risk of bias. PIT was associated with a significant reduction in the odds of PTM (odd ratio, 0.55; 95 % confidence interval, 0.32 to 0.95; P-value = 0.03; I2 = 13 %; GRADE: moderate certainty). One RCT reported no difference in overall survival outcome with the use of PIT. None of the RCTs performed subgroup analyses. Sensitivity analyses showed similar results when limited to RCTs with low risk of bias. CONCLUSION: PIT significantly reduces the occurrence of PTM in patients with MPM who had a diagnostic or therapeutic chest wall procedure.

Impact of programmed death-ligand 1 expression on the patients of stage IV non-small cell lung cancer harboring epidermal growth factor receptor mutation: a systematic review and meta-analysis.

BACKGROUND: To determine the impact of programed death-ligand 1 (PD-L1) expression on progression-free survival (PFS) outcomes in stage IV epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) treated with first-line EGFR tyrosine kinase inhibitors (TKIs). MATERIAL AND METHODS: We searched biomedical databases for studies comparing PFS outcomes of PD-L1-positive versus (vs) PD-L1-negative tumors. We assessed the methodological quality of eligible studies using ROBINS-I tool. We employed a two-staged meta-analysis approach by reconstructing individual patient data of each study from the published Kaplan-Meier curves and then pooling the individual hazard ratios (HRs) and weighted mean differences (WMDs) for restricted mean PFS time at 6 (RMPFST6) and 12 (RMPFST12) months using random-effect models. We assessed the quality of summarized evidence using GRADE approach. RESULTS: We identified five non-randomized comparative studies including 435 patients. The overall risk of bias in the methodological quality of included studies was moderate. PD-L1-positive tumors were associated with significantly worse PFS outcomes compared to PD-L1-negative tumors (HR: 2.41, 95% confidence interval (CI): 1.59-3.66, p < .001; WMD in RMPFST6: -1.01, 95% CI: -1.65 to -0.37, p = .002; WMD in RMPFST12: -2.64, 95% CI: -4.40 to -0.88, p = .003). Subgroup analysis showed that the effect of PD-L1 expression on PFS outcomes was greater for studies using older-generation rather than third-generation TKIs (HR: 2.69 vs 1.22, p = .069; WMD in RMPFST6: -1.23 vs -0.07, p = .005; WMD in RMPFST12: -3.29 vs -0.12, p = .003). The quality of summarized evidence was judged to be low. CONCLUSION: There is low certainty in the evidence to suggest that positive PD-L1 expression is associated with inferior disease control and survival outcomes in patients with stage IV EGFR-mutated NSCLC treated with first-line EGFR TKIs.

T4 cervical esophageal cancer cured with modern chemoradiotherapy: A case report.

BACKGROUND: T4 esophageal cancer portends a poor prognosis, particularly when it is complicated by a tracheoesophageal fistula (TEF) either resulting from disease or occurring as a complication of treatment. Patients with TEF that occurs during treatment are commonly treated with palliative intent because fistula-associated treatment complications such as aspiration pneumonia and mediastinitis are associated with high morbidity and mortality. To date, there is no clear evidence on the optimal treatment of T4 esophageal cancer, particularly when a TEF formation occurs. CASE SUMMARY: A 67-year-old gentleman who presented with dysphagia and weight loss. Endoscopy and imaging revealed a T4N1M0 cervical esophageal squamous cell carcinoma. He received image-guided intensity-modulated radiation therapy, with concurrent weekly carboplatin (area under curve 2 mg/mL per minute) and paclitaxel (50 mg/m2 of body surface area). One week after treatment initiation (16.2 Gy thus far), he developed cough on swallowing. A TEF was detected on image-guided radiation therapy using cone-beam computed tomography during the treatment course, for which a tracheal stent was inserted. After discussing the risks and morbidity of continuing treatment, he resumed chemoradiotherapy with an additional radiation dose of 45 Gy in 25 fractions. Three months after completion of chemoradiotherapy, he developed an esophageal stricture that required esophageal stenting and dilatation. The patient remains cancer-free at two year on follow-up. Complete response of esophageal cancer was evident on post-treatment endoscopy and computed tomography imaging, with successful closure of TEF. CONCLUSION: This case highlights that successful curative treatment for esophageal cancer complicated by a TEF is possible using novel chemotherapeutic regimens and modern radiation technologies.

Outcomes of patients with spinal metastases from renal cell carcinoma treated with conventionally-fractionated external beam radiation therapy.

Renal cell carcinoma (RCC) has been traditionally thought to be radioresistant. This retrospective cohort study aims to assess the outcomes of patients with spinal metastases from RCC treated with conventionally-fractionated external beam radiation therapy (cEBRT) in our institution.Patients diagnosed with histologically or radiologically-proven RCC who received palliative cEBRT to spinal metastases, using 3-dimensional conformal technique between 2009 and 2018 were reviewed. Local progression-free survival (PFS), overall survival (OS) and common terminology criteria for adverse events version 4.0-graded toxicity were assessed. Univariable and multivariable Cox proportional hazards regression analyses were performed to evaluate for predictors associated with survivals.Thirty-five eligible patients with forty spinal segments were identified, with a median follow-up of 7 months (range, 0-47). The median equivalent dose in 2 Gy fractions (EQD2) was 32.5 Gy 10 (range, 12-39). Thirty-seven percent of patients underwent surgical intervention. At the time of last follow-up, all but 1 patient had died. Seven patients developed local progression, with the median time to local progression of 10.2 months. The median local PFS and OS were 3.3 and 4.8 months. There was no grade 3 or higher toxicity. A higher radiation dose (equivalent dose to 2 Gy fraction <32.5 Gy 10 vs ≥32.5Gy 10) (hazard ratio [HR], 0.47; 95% confidence interval [CI], 0.17-3.18; P-value (P) = .68) and spinal surgery (HR, 2.35; 95% CI, 0.53-10.29; P = .26) were not significantly associated with local PFS on univariable analysis. Multivariable analysis showed that higher Tokuhashi score (HR, 0.41; 95% CI, 0.19-0.88; P = .02), lower number of spinal segments irradiated (HR, 1.18; 95% CI, 1.01-1.37; P = .04) and use of targeted therapy (HR, 0.41; 95% CI, 0.18-0.96; P = .04) were independent predictors for improved OS.For an unselected group of patients with RCC, there is no significant association between higher radiation dose and improved local control following cEBRT. This may be due to their short survivals. With the use of more effective systemic therapy, including targeted therapy and immunotherapy, survival will likely be prolonged. A tailored-approach is needed to identify patients with good prognosis who may still benefit from aggressive local treatments.

Frequency of discordance in programmed death-ligand 1 (PD-L1) expression between primary tumors and paired distant metastases in advanced cancers: a systematic review and meta-analysis.

Background: To determine the frequency of discordance in programmed death-ligand 1(PD-L1) expression between primary tumors and paired distant metastases in advanced cancers.Methods: We searched MEDLINE and EMBASE for eligible studies and assessed their methodologic quality using QUADAS-2 tool. We estimated the discordant rates (positive to negative or vice versa) of PD-L1 expression in primary tumors and paired distant metastases using logistic-normal random effects model. We performed subgroup analyses based on the PD-L1 status of primary tumors (positive or negative), location of primary tumors (lung or others) and distant metastases (central nervous system or others), timing of distant metastases (synchronous or metachronous), positivity thresholds of PD-L1 expression (1% or 5%) and types of antibody clones used (E1L3N or SP142).Results: Thirteen eligible studies including 451 cases were identified. The included studies were judged to have low to unclear risk of bias. The pooled estimate of discordant rates in PD-L1 expression was 31% (95% CI= 19-47%), with high heterogeneity across the studies (I2 = 75%). There was no significant effect modification in the discordant rates according to the predefined subgroups.Conclusion: Approximately one-third of advanced cancer cases have discordance in PD-L1 expression between primary tumors and paired distant metastases. A more liberal testing of PD-L1 expression in both primary and metastatic tumors is recommended in order to identify patients who may benefit from immune checkpoint blockade treatment. Further research exploring the mechanisms and its impact are warranted.

Clinical Outcomes of Dose-escalated Radiotherapy for Localised Prostate Cancer: A Single-institution Experience.

BACKGROUND/AIM: To report the outcomes of patients with prostate cancer treated with dose-escalated radiotherapy over a 15-year period at our Institution. PATIENTS AND METHODS: Patients with biopsy-proven cT1-4N0M0 disease who received radical external beam radiotherapy (EBRT) were reviewed. The endpoints were 5-year overall survival (OS), freedom from biochemical failure (FFBF) and late treatment toxicities. RESULTS: A total of 236 patients were eligible. Median follow-up was 70 months. Low-, intermediate- and high-risk disease was found in 9%; 29% and 62% of patients, respectively. The median radiation dose was 73.8 Gy. Overall 42% of patients had dose escalation to >74 Gy. Five-year OS and FFBF were 95.2%/81.6%/75.4% and 95.0%/98.0%/82.0% for low-/intermediate-/high-risk patients, respectively. Dose escalation to >74 Gy did not improve FFBF (hazard ratio=0.97, 95% confidence intervaI=0.43-2.19, p=0.93) and was associated with a 4.3-fold increase in the odds of grade 3 or more rectal bleeding (p<0.01). CONCLUSION: Dose escalation to >74 Gy did not improve OS or FFBF but was associated with a higher rate of grade 3 or more rectal haemorrhage.

Are heart doses associated with survival in patients with non-small cell lung cancer who received post-operative thoracic radiotherapy?: A national population-based study.

The aim of this retrospective national cohort study is to assess the association between various radiation heart dosimetric parameters (RHDPs), acute myocardial infarct (AMI) and overall survival (OS) outcomes in non-small cell lung cancer (NSCLC) patients treated with post-operative thoracic radiotherapy (PORT) using contemporary radiation techniques.We identified patients with stage I to III NSCLC treated with PORT at the 2 national cancer institutions from 2007 to 2014. We linked their electronic medical records to the national AMI and death registries. Univariable Cox regression was performed to assess the association between various RHDPs, AMI, and OS.We included 43 eligible patients with median follow-up of 36.6 months. Median age was 64 years. Majority of the patients had pathological stage III disease (72%). Median prescription dose was 60Gy. Median mean heart dose (MHD) was 9.4Gy. There were no AMI events. The 5-year OS was 34%. Univariable Cox regression showed that age was significantly associated with OS (hazard ratio, 1.06; 95% confidence interval, 1.01 to 1.10; P = .008). Radiation heart doses, including MHD, volume of heart receiving at least 5, 25, 30, 40, 50Gy and dose to 30% of heart volume, were not significantly associated with OS.There is insufficient evidence to conclude that RHDPs are associated with OS for patients with NSCLC treated with PORT in this study. Studies with larger sample size and longer term follow-up are needed to assess AMI outcome.

Clinical outcomes of external beam radiotherapy in patients with localized prostate cancer: Does dose escalation matter?

BACKGROUND: To report outcomes of localized prostate cancer treated with radical external beam radiation therapy (EBRT) in our institution over a 14-year period, and to determine the impact of dose escalation of prostate cancer outcomes. METHODS: Patients with T1-T4 N0 M0 prostate cancer who received radical EBRT between January 2002 and December 2015 were reviewed retrospectively. Clinical data were obtained via the institutional electronic medical records. The primary endpoint was 5-year overall survival (OS). The secondary endpoints were 5-year freedom from biochemical failure (FFBF) and treatment toxicities. RESULTS: A total of 200 eligible patients were identified. Median follow-up duration was 48 months. 13%, 36% and 51% of patients had low-, intermediate- and high-risk disease. Median dose was 79.2 Gy. The 5-year OS were 90%, 87% and 78% and FFBF were 94%, 100% and 81% for low-, intermediate- and high-risk patients, respectively. Multivariable analysis showed that Eastern Cooperate Oncology Group performance status 2 and Gleason grade group 5 were independent predictors of worse OS. The incidence of grade ≥2 proctitis was 24.5%. Dose escalation was significantly associated with increased incidence of grade ≥2 proctitis (odd ratio, 4.42; 95% confidence interval, 1.95-10.08; P < 0.01). CONCLUSION: Men with localized prostate cancer treated with EBRT in our population had excellent 5-year OS and biochemical outcomes. Dose escalation did not significantly improve these outcomes but was associated with significantly increased risk of grade ≥2 proctitis in our population. Future studies should be performed to identify patients who will benefit the most from dose-escalated EBRT.

Discordance of epidermal growth factor receptor mutation between primary lung tumor and paired distant metastases in non-small cell lung cancer: A systematic review and meta-analysis.

PURPOSE: To evaluate the rate of discordance of epidermal growth factor receptor (EGFR) mutation between primary lung tumor and paired distant metastases in non-small-cell lung cancer (NSCLC). METHODS: We performed a meta-analysis of 17 studies (518 cases) assessing discordance rates of EGFR mutation in primary tumors and paired distant metastases. We performed subgroup analyses based on EGFR mutation status in primary tumor (mutant or wildtype), site of distant metastasis (bone, central nervous system (CNS) or lung/ pleural), methods of testing (direct sequencing or allele-specific testing) and timing of metastasis (synchronous or metachronous). RESULTS: The overall discordance rate in EGFR mutation was low at 10.36% (95% CI = 4.23% to 18.79%) and varied widely between studies (I2 = 83.18%). The EGFR discordance rate was statistically significantly higher in bone metastases (45.49%, 95% CI = 14.13 to 79.02) than CNS (17.26%, 95% CI = 7.64 to 29.74; P = 0.002) and lung/ pleural metastases (8.17%, 95% CI = 3.35 to 14.85; P < 0.001). Subgroup analyses did not demonstrate any significant effect modification on the discordance rates by the EGFR mutation status in primary lung tumor, methods of testing and timing of metastasis. CONCLUSION: The overall discordance rate in EGFR mutation between primary lung tumor and paired distant metastases in NSCLC is low, although higher discordance rates were observed in bone metastases compared with CNS and lung/pleural metastases. Future studies assessing the impact of EGFR mutation discordance on treatment outcomes are required.

Association between radiation heart dosimetric parameters, myocardial infarct and overall survival in stage 3 non-small cell lung cancer treated with definitive thoracic radiotherapy.

OBJECTIVES: The aim of this retrospective observational study is to assess the association between various radiation heart dosimetric parameters (RHDPs) and acute myocardial infarct (AMI) and overall survival (OS) outcomes in stage III non-small cell lung cancer (NSCLC) treated with definitive radiotherapy with or without chemotherapy. MATERIALS AND METHODS: We identified eligible patients treated at two institutions from 2007 to 2014. We linked their electronic medical records to the national AMI and death registries. We performed univariable and multivariable Cox regressions analysis to assess the association between various RHDPs, AMI and OS. RESULTS: 120 eligible patients were included with a median follow-up of 17.6 months. Median age was 65.5 years. Median prescription dose was 60 Gy. Median mean heart dose (MHD) was 12.6 Gy. Univariable analysis showed that higher MHD (hazard ratio (HR), 1.03; 95% confidence interval (CI), 1.01-1.06; P = .008) and volume of heart receiving at least 5 Gy (V5) (HR, 1.01; 95% CI, 1.00-1.03; P = .042) were associated with increased hazards for AMI. Univariable analysis showed that higher MHD, V5, V25, V30, V40, V50 and dose to 30% of heart volume were associated with increased hazards for death. Multivariable analysis showed that there was no statistically significant association between various RHDPs and OS. CONCLUSION: The incidence of AMI is low among stage III NSCLC treated with definitive radiotherapy with or without chemotherapy. There is insufficient evidence to conclude that RHDPs are associated with AMI or OS in our study.

Correlation of the experimental and numerical results for the holding power of dental, traumatic, and spinal screws.

The holding power of the bone-screw interfaces is one of the key factors in the clinical performance of screw design. The value of the holding power can be experimentally measured by pullout tests. Historically, some researchers have used the finite-element method to simulate the holding power of the different screws. Among them, however, the assumed displacement of the screw withdrawal is unreasonably small (about 0.005-1.0 mm). In addition, the chosen numerical indices are quite different, including maximum stress, strain energy, and reaction force. This study systematically uses dental, traumatic, and spinal screws to experimentally measure and numerically simulate their bone-purchasing ability within the synthetic bone. The testing results (pullout displacement and holding power) and numerical indices (maximum stress, total strain energy, and reaction forces) are chosen to calculate their correlation coefficients. The pullout displacement is divided into five regions from initial to final withdrawal. The experimental results demonstrate that the pullout displacement consistently occurs at the final region (0.6-1.6 mm) and is significantly higher than the assumed value of the literature studies. For all screw groups, the measured holding power within the initial region is not highly or even negatively correlated with the experimental and numerical results within the final region. The observation from the simulative results shows the maximum stress only reflects the loads concentrated at some local site(s) and is the least correlated to the measured holding power. Comparatively, both energy and force are more global indices to correlate with the gross failure at the bone-screw interfaces. However, the energy index is not suitable for the screw groups with rather tiny threads compared with the other specifications. In conclusion, the underestimated displacement leads to erroneous results in the screw-pullout simulation. Among three numerical indices the reaction-force is the optimal index for the screw-pullout problem.

The effects of flute shape and thread profile on the insertion torque and primary stability of dental implants.

Easy insertion of the implant and stable bone purchase is essential for an ideal dental implantation. At the implant tip, the cutting flutes and conical profile are respectively designed to reduce insertion resistance and facilitate the initial insertion. However, the tapered tip might reduce the self-tapping and bone-purchasing abilities of the flutes and the tip threads. Using sawbone blocks as standard specimens, this study experimentally measures the insertion torque, holding power, and bending strength of eight varieties of implant (4 shapes×2 profiles). The bony contact, interfacial mechanism, and the altered shape of the flutes, at different section planes, are used to explain the experimental results. The results reveal that the bone-implant gaps at the tip region significantly suppress both the self-tapping and bone-purchasing abilities of the flutes and the tip threads. This makes initial insertion of the conical implant easier. However, the conical implant eventually requires a higher insertion torque and holding power, due to tighter bony contact, at the tail threads. The bowl-fluted design has the least flute space to store the squeezed bone chips, so both insertion torque and bending strength are significantly higher. For the conical group, the holding powers of three flute designs are nearly comparable. Overall, the conical implant with bowl flutes is the optimal design, with a lower resistance to initial insertion and higher stability, for final instrumentation.

Synthesis of BiFeO3/ZnO core-shell hetero-structures using ZnO nanorod positive templates.

We report the synthesis, morphology, and magnetization characteristics of BiFeO(3) (BFO)-covered ZnO nanorod arrays (ZNAs). High quality and well-aligned ZNAs were grown by a hydrothermal method. BFO shells were deposited by sputtering at ambient temperature and then annealing in an oxygen atmosphere. The BFO shells crystallized to form a perovskite structure at 450 °C. Scanning electron microscopy and high resolution transmission electron microscopy demonstrated that the BFO shell was polycrystalline and randomly oriented, covering the ZnO nanorods well. The magnetization-magnetic field loops measured at 5 and 300 K indicate that the BFO/ZNA hetero-structure exhibits ferromagnetic order. The BFO/ZNA displays enhanced coercivity and saturated magnetization as compared with BFO thin films.

Influence of muscular contractions on the stress analysis of distal femoral interlocking nailing.

BACKGROUND: In the literature, the commonly assumed loading conditions on the proximal femur are hip compression and/or gluteus contractions. However, no study has discussed the influence of muscle forces on failure of distal nail holes and locking screws. METHODS: This finite-element study analyzed the influence of muscular contractions on stress analysis of distal nail holes and locking screws. Three loading conditions were used for comparison, comprised of either hip compression alone or with muscle contractions. The head displacement of intact and fractured femur, the nail and screw stresses vs. fixation depth, and the stress distribution at the distal nail-screw interfaces were chosen as the comparison indices. FINDINGS: The addition of trochanteric and diaphysial muscles showed the more physiologically reasonable displacement of the femoral head. However, all loading conditions consistently showed the hole and screw stresses increase as the nail was inserted deeper. The stress distribution at the distal nail-screw interfaces was remarkably different under the condition of with or without the muscular contractions. The exertion of muscles predicted the fatigue cracking originated at the edge of the nail holes on the medial rather than lateral side. INTERPRETATION: Only hip compression and/or gluteus contraction generated a characteristic bending stress pattern and medially deflected nail curvature. Comparatively, the trochanteric and diaphysial muscles stabilized the femoral head and resulted in the higher stress concentration at the distally medial nail-screw interfaces. However, further experimental and clinical studies, focusing on the failure sites of the distal femoral hardware, should be undertaken to validate such findings.

Activation of group II metabotropic glutamate receptors induces depotentiation in amygdala slices and reduces fear-potentiated startle in rats.

There is a close correlation between long-term potentiation (LTP) in the synapses of lateral amygdala (LA) and fear conditioning in animals. We predict that reversal of LTP (depotentiation) in this area of the brain may ameliorate conditioned fear. Activation of group II metabotropic glutamate receptors (mGluR II) with DCG-IV induces depotentiation in the LA. The induction of depotentiation is independent of NMDA receptors, L-type Ca++ channels, and calcineurin activity, but requires presynaptic activity and extracellular Ca++. (2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG-IV) depotentiation is accompanied by a decrease in the frequency but not the amplitude of miniature excitatory post-synaptic currents (mEPSCs) and could be mimicked by endogenously released glutamate. DCG-IV inhibited the release of glutamate evoked by 4-AP but not that evoked by ionomycin, suggesting that the effect of DCG-IV is not mediated by an action downstream of Ca++ entry. Intra-amygdala infusion of mGluR II agonist blocks the consolidation of fear memory measured with fear-potentiated startle. Taken together, the present results characterize the properties of DCG-IV depotentiation and reveal a close parallel between depotentiation in the amygdala slice and the reduction of conditioned fear in animals.

Involvement of a calcineurin cascade in amygdala depotentiation and quenching of fear memory.

If fear memory is expressed by a long-term potentiation (LTP) of synaptic transmission in the amygdala, then reversal of LTP (depotentiation) in this area of the brain may provide an important mechanism for amelioration of anxiety and post-traumatic stress disorder. Herein, we show that low-frequency stimulation (LFS) of the external capsule elicits a depotentiation in the lateral nucleus of the amygdala. The induction of depotentiation requires activation of N-methyl-D-aspartate receptors and voltage-dependent calcium channels but is independent of adenosine A(1) and metabotropic glutamate group II receptors. Extracellular perfusion or loading cells with protein phosphatase (PP) 2B (calcineurin) inhibitors prevents depotentiation. The same stimulating protocol applied to the amygdala in vivo attenuates the expression of fear memory measured with fear-potentiated startle and reduces conditioning-elicited phosphorylation of Akt and mitogen-activated protein kinase (MAPK). This is paralleled by an increase in the activity of calcineurin. In addition, application of calcineurin inhibitor blocks LFS-induced extinction of fear memory and MAPK dephosphorylation. Taken together, this study characterizes the properties of LFS-induced depotentiation in the amygdala and suggests an involvement of calcineurin cascade in synaptic plasticity and memory storage.