A cross-national investigation of CT, MRI, PET, mammography, and radiation therapy resources and utilization.

PURPOSE: This study aimed to analyze the domestic and international landscape of imaging diagnostics and treatments, focusing on Japan, to provide current insights for policymaking, clinical practice enhancement, and international collaboration. METHODS: Data from 1996 to 2021 were collected from Japan's Ministry of Health, Labor and Welfare database for medical device counts of CT, MRI, PET, mammography, and radiotherapy. The National Database of Health Insurance Claims and Specific Health Checkups of Japan was utilized for examination numbers. An international comparison was made with data from 41 countries using the Organization for Economic Cooperation and Development (OECD) database. RESULTS: The data included a total of 108,596 CT devices, 47,233 MRI devices, 2998 PET devices, 20,641 MMG devices, and 8023 RT devices during the survey period. Upon international comparison, Japan ranked first in CT and MRI devices per million people and second in examination numbers per 1000 people. The number of PET devices per million people exceeded OECD averages; however, the number of examinations per 1000 people was below the OECD average in 2020 (Japan: 4.0, OECD: 4.9). Although Japan exceeded OECD averages in mammography device counts (Japan: 33.8, OECD: 24.5 in 2020), radiotherapy device counts were similar to OECD averages (Japan: 8.3, OECD: 7.9 in 2020). CONCLUSION: We have analyzed the utilization of equipment in the context of diagnostic imaging and radiotherapy in Japan. Since the initial survey year, all devices have shown an upward trend. However, it is essential not only to increase the number of devices and examinations but also to address the chronic shortage of radiologists and allied health professionals. Based on the insights gained from this study, understanding the actual status of diagnostic imaging and radiation therapy equipment is critical for grasping the domestic situation and may contribute to improving the quality of healthcare in Japan.

Adsorption of Prochiral Solvent Molecules by Surface-Confined Chiral Supramolecular Assemblies: How Solvent Impacts On-Surface Chirality.

The understanding of supramolecular chirality in self-assembled molecular networks (SAMNs) on surfaces generates a lot of interest because of its relation to the production of chiral sensors, reactors, and catalysts. We herein report the adsorption of a prochiral solvent molecule in porous SAMNs formed by a chiral dehydrobenzo[12]annulene (cDBA) derivative. Through the prochirality recognition of a solvent molecule, the supramolecular chirality of the SAMN is switched: the cDBA exclusively forms a counter-clockwise pore through co-adsorption of the solvent molecule in prochiral 1,2,4-trichlorobenzene, while in 1-phenyloctane it produces the opposite chiral, clockwise pore. The prochirality recognition of the solvent molecule in the chiral SAMN pores is attributed to the adaptable conformational changes of the chiral chains of the cDBA molecule.

Rotating Hinge Knee Arthroplasty for Charcot Joints of the Knees in Patients With Charcot-Marie-Tooth Disease: A Report of Two Cases.

We report two cases wherein rotating hinge knee (RHK) arthroplasty was performed for Charcot joints that developed secondary to Charcot-Marie-Tooth disease (CMT).  Case 1 was of a 74-year-old woman with CMT. She presented with muscle weakness and sensory disturbances of the distal lower limbs, deformity, and significant medial instability of the bilateral knees. She was then diagnosed with Charcot joints of the knees secondary to CMT, which were treated with RHK arthroplasty. Five years postoperatively, there was no instability, and she was able to stand unassisted without pain. Case 2 was a 90-year-old woman with CMT who presented with muscle weakness and sensory disturbances of the distal lower limbs, deformity, and significant medial instability of the bilateral knees. She was then diagnosed with Charcot joints of the knees secondary to CMT, which were also treated with RHK arthroplasty. One year postoperatively, there was no instability, and she was able to walk smoothly using a walker. These clinical cases indicate that RHK arthroplasty can be a good therapeutic option for Charcot joints of the knees in patients with CMT.

Frequency of and risk factors associated with local recurrence after spinal stereotactic body radiation therapy without surgery.

PURPOSE: This study aimed to identify factors associated with local recurrence after spinal stereotactic body radiation therapy (SBRT), focusing on patient movement during treatment and tumor characteristics. METHODS: A total of 48 patients who underwent spinal SBRT alone without surgery from August 2017 to October 2022 were evaluated. Logistic regression analysis was conducted to identify factors associated with local recurrence, including patient movement and tumor characteristics such as soft tissue involvement and tumor volume. Patient movement during treatment was measured using cone beam computed tomography before and after irradiation. RESULTS: Among the included cases, 68.7% and 42.6% had soft tissue involvement and movement exceeding 1 mm, respectively. The median follow-up duration for local recurrence was 11.6 (range: 0.7-44.9) months, whereas the median duration to local recurrence was 6.3 months. Within 12 months, 29.3% of the patients experienced local recurrence, among whom 43.9% moved ≥ 1 mm during treatment, whereas 15.8% did not move. Univariable analysis found that both soft tissue involvement (OR = 10.3, 1.21-87.9; p = 0.033) and patient movement ≥ 1 mm (OR = 5.75, 1.45-22.8; p = 0.013) were associated with local recurrence. Multivariable analysis identified patient movement as an independent prognostic factor for local recurrence (OR = 5.15, 1.06-25.0; p = 0.042). CONCLUSION: Our results suggest that patient movement during spinal SBRT was associated with local recurrence, emphasizing the need for better immobilization techniques and shorter delivery times to improve tumor control.

Long-term survival outcomes and quality of life of image-guided proton therapy for operable stage I non-small cell lung cancer: A phase 2 study.

BACKGROUND AND PURPOSE: This study evaluated long-term efficacy, safety, and changes in quality of life (QOL) of patients after image-guided proton therapy (IGPT) for operable stage I non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: This single-institutional prospective phase 2 study enrolled patients with operable histologically confirmed stage IA or IB NSCLC (7th edition of UICC). The prescribed dose was 66 Gy relative biological effectiveness equivalents (GyRBE) in 10 fractions for peripheral lesions, or 72.6 GyRBE in 22 fractions for central lesions. The primary endpoint was the 3-year overall survival (OS). The secondary endpoints included disease control, toxicity, and changes in QOL score. RESULTS: We enrolled 43 patients (median age: 68 years; range, 47-79 years) between July 2013 to January 2021, of whom 41 (95 %) had peripheral lesions and 27 (63 %) were stage IA. OS, local control, and progression-free survival rates were 95 % (95 % CI: 83-99), 95 % (82-99), and 86 % (72-94), respectively, at 3 years, and 83 % (66-92), 95 % (82-99), and 77 % (60-88), respectively, at 7 years. Four patients (9 %) developed grade 2, and one patient (2 %) developed grade 3 radiation pneumonitis. No other grade 3 or higher adverse events were observed. In the QOL analysis, global QOL remained favorable; however, approximately 40 % of patients reported dyspnea at 3 and 24 months. CONCLUSION: Our findings suggest that IGPT provides effective disease control and survival in operable stage I NSCLC, particularly for peripheral lesions. Moreover, toxicity associated with IGPT was minimal, and patients reported favorable QOL.

Trends and distribution of external radiation therapy facilities in Japan based on Survey of Medical Institutions from the Ministry of Health, Labour and Welfare.

This study aimed to explore the distribution of external radiation therapy (RT) facilities, the status of related device installations and the adoption of high-precision RT using Survey of Medical Institutions from the Ministry of Health, Labour and Welfare in Japan. Analysis, categorized by the hospital size and prefecture, provides specific insights into the trends in treatment facility healthcare capabilities. Data on the number of RT facilities, high-precision RT facilities, RT devices and treatment planning systems (TPS) categorized by the number of beds and prefecture from 1996 to 2020 were analyzed. In addition, the study examined the correlation between the high-precision implementation rate and the number of TPSs or radiation oncologists and other medical staff. High-precision RT exceeded 95% in large facilities (800+ beds) but remained <50% in medium-sized facilities (300-499 beds). In a prefecture-by-prefecture analysis, calculation of the maximum-minimum ratio of RT facilities per million population and per 30 km2 revealed a disparity of 3.7 and 73.1 times in the population ratio and the density ratio, respectively. Although a correlation was found between the number of TPSs per RT device or the number of medical physicists per million population and the rate of high-precision RT implementation, no correlation was found among other professions. Detailed analysis based on the hospital size and prefecture provided more specific information on the medical functions of RT facilities in Japan. These findings can potentially contribute to the future development of RT, including the standardization of treatment techniques and optimal resource allocation.

Impact of concurrent antibody-drug conjugates and radiotherapy on symptomatic radiation necrosis in breast cancer patients with brain metastases: a multicenter retrospective study.

AIM: We aimed to investigate the impact of concurrent antibody-drug conjugates (ADC) and radiotherapy on symptomatic radiation necrosis (SRN) in breast cancer patients with brain metastases (BM). METHODS: This multicenter retrospective study uses four institutional data. Eligibility criteria were histologically proven breast cancer, diagnosed BM with gadolinium-enhanced MRI, a Karnofsky performance status of 60 or higher, and radiotherapy for all BM lesions between 2017 and 2022. Patients with leptomeningeal dissemination were excluded. Concurrent ADC was defined as using ADC within four weeks before or after radiotherapy. The cumulative incidence of SRN until December 2023 with death as a competing event was compared between the groups with and without concurrent ADC. Multivariable analysis was performed using the Fine-Gray model. RESULTS: Among the 168 patients enrolled, 48 (29%) received ADC, and 19 (11%) had concurrent ADC. Of all, 36% were HER2-positive, 62% had symptomatic BM, and 33% had previous BM radiation histories. In a median follow-up of 31 months, 18 SRNs (11%) were registered (11 in grade 2 and 7 in grade 3). The groups with and without concurrent ADC had 5 SRNs in 19 patients and 13 SRNs in 149, and the two-year cumulative incidence of SRN was 27% vs. 7% (P = 0.014). Concurrent ADC was associated with a higher risk of SRN on multivariable analysis (subdistribution hazard ratio, 3.0 [95% confidence interval: 1.1-8.3], P = 0.030). CONCLUSIONS: This study suggests that concurrent ADC and radiotherapy are associated with a higher risk of SRN in HER2-positive breast cancer patients.

Classification of Patients With Painful Tumors to Predict Response to Palliative Radiation Therapy.

PURPOSE: This study aimed to identify factors affecting pain response to develop a patient classification system for palliative radiation therapy (RT). METHODS AND MATERIALS: Our prospective observational study (UMIN000044984) provided data on patients who received palliative RT for painful tumors. The eligibility criteria were having a numerical rating scale (NRS) score of 2 or more before treatment and receiving palliative RT between August 2021 and September 2022. Post-RT follow-up was scheduled prospectively at 2, 4, 12, 24, 36, and 52 weeks. Pain response was assessed using the International Consensus Pain Response Endpoints criteria, with the primary outcome being the response rate within 12 weeks. Multivariable logistic regression was performed to identify factors affecting pain response and develop the classification system. Each class evaluated the differences in response rate, time to response, and progression. RESULTS: Of the 488 registered lesions, 366 from 261 patients met the criteria. Most patients had bone metastases (75%), of whom 72% were using opioids and 22% underwent reirradiation. Conventional RT (eg, 8-Gy single fraction, 20 Gy in 5 fractions) was administered to 93% of patients. Over a median of 6.8 months of follow-up, the average NRS decreased from 6.1 to 3.4 at 12 weeks for 273 evaluable lesions, with a 60% response rate. Opioid use and reirradiation negatively affected the response rate in multivariate analysis (P < .01). Lesions were categorized into class 1 (no opioid use and no reirradiation; 89 lesions), class 2 (neither class 1 nor 3; 211 lesions), and class 3 (opioid use and reirradiation; 66 lesions), with respective response rates of 75%, 61%, and 36% (P < .001). Time to response was similar across the classes (P = .91), but the progression rates at 24 weeks differed (11%, 27%, and 63%, respectively; P < .001). CONCLUSIONS: Opioid use and reirradiation are factors leading to significant variations in pain response rates and time to progression.

Palliative radiotherapy for painful non-bone lesions in patients with advanced cancer: a single center retrospective study.

PURPOSE: This retrospective study aimed to assess the efficacy and safety of palliative radiotherapy for painful non-bone lesions in patients with advanced cancer. MATERIALS AND METHODS: We enrolled patients with painful non-bone lesions who underwent conventional palliative radiotherapy between September 2018 and September 2022. The treatment targets included primary tumor lesions, lymph node metastases, non-bone hematogenous metastases, and other lesions. The primary endpoint was the overall pain response rate in evaluable patients, determined based on the International Consensus Pain Response Endpoint criteria. The secondary endpoints included overall survival, pain recurrence, and adverse events. RESULTS: Of the 420 screened patients, 142 received palliative radiotherapy for painful non-bone lesions, and 112 were evaluable. A pain response was achieved in 67 patients (60%) of the 112 evaluable patients within a median of 1.2 months. Among these patients, 25 exhibited complete response, 42 partial response, 18 indeterminate response, and 27 pain progression. The median survival time was 5.5 months, recorded at a median follow-up of 6.0 months, during which 67 patients died. Multivariate analysis identified poor performance status scores of 2-4, opioid use, and re-irradiation as independent factors associated with a reduced likelihood of achieving a pain response. Pain recurrence occurred in 18 patients over a median of 4.1 months. Seventeen patients had grade 1-2 adverse events, while none experienced grade 3 or higher toxicity. CONCLUSION: Palliative radiotherapy can potentially be a safe and well-tolerated modality for managing painful non-bone lesions, with a low rate of adverse events.

Re-irradiation spine stereotactic body radiotherapy following high-dose conventional radiotherapy for metastatic epidural spinal cord compression: a retrospective study.

PURPOSE:  We aimed to evaluate the efficacy and safety of re-irradiation stereotactic body radiation therapy (SBRT) in patients with metastatic epidural spinal cord compression (MESCC) following high-dose conventional radiotherapy. MATERIALS AND METHODS:  Twenty-one patients met the following eligibility criteria: with an irradiation history of 50 Gy2 equivalent dose in 2-Gy fractions (EQD2) or more, diagnosed MESCC in the cervical or thoracic spines, and treated with re-irradiation SBRT of 24 Gy in 2 fractions between April 2018 and March 2023. Prior treatment was radiotherapy alone, not including surgery. The primary endpoint was a 1-year local failure rate. Overall survival (OS) and treatment-related adverse events were assessed as the secondary endpoints. Since our cohort includes one treatment-related death (TRD) of esophageal perforation, the cumulative esophageal dose was evaluated to find the dose constraints related to severe toxicities. RESULTS:  The median age was 68, and 14 males were included. The primary tumor sites (esophagus/lung/head and neck/others) were 6/6/7/2, and the median initial radiotherapy dose was 60 Gy2 EQD2 (range: 50-105 Gy2, 60-70/ > 70 Gy2 were 11/4). Ten patients underwent surgery followed by SBRT and 11 SBRT alone. At the median follow-up time of 10.4 months, 17 patients died of systemic disease progression including one TRD. No radiation-induced myelopathy or nerve root injuries occurred. Local failure occurred in six patients, with a 1-year local failure rate of 29.3% and a 1-year OS of 55.0%. Other toxicities included five cases of vertebral compression fractures (23.8%) and one radiation pneumonitis. The cumulative esophageal dose was recommended as follows: Dmax < 203, D0.035 cc < 187, and D1cc < 167 (Gy3 in biological effective dose). CONCLUSION:  Re-irradiation spine SBRT may be effective for selected patients with cervical or thoracic MESCC, even with high-dose irradiation histories. The cumulative dose assessment across the original and re-irradiated esophagus was recommended to decrease the risk of severe esophageal toxicities.

Changing trends in gamma knife surgery to linear accelerator brain stereotactic radiotherapy in Japan: a survey based on the nationwide claims database.

PURPOSE: This study evaluated the trends in the platform for stereotactic radiotherapy to the brain (SRT), utilizing the open data of the National Database published by the Ministry of Health, Labour, and Welfare. MATERIALS AND METHODS: This study analyzed data from FY2014 to FY2021. The practices included in the study were gamma knife surgery (GKS) and SRT with a linear accelerator (LINAC). The total number of outpatient and inpatient cases in each SRT system was evaluated annually. RESULTS: From April 2014 to March 2022, the study included 212,016 cases (102,691 GKS and 109,325 LINAC) of the registered 1,996,540 radiotherapy cases. In the first year, 13,117 (54.1%) cases were GKS, and 11,128 (45.9%) were LINAC; after that, GKS decreased, and LINAC increased, reaching the same rate in FY2017. Compared to the first year, the final year showed 11,702 GKS (- 1415 or - 10.8%) and 17,169 LINAC (+ 6041 or + 54.3%), with an increase of 4626 total SRT cases to 28,871 (+ 19.1%). The percentage of outpatient treatment also increased from 4.6 to 11.8% for GKS and from 44.7 to 57.9% for LINAC. CONCLUSION: The study found a gradual decrease in the selection of GKS, an increasing trend in the selection of LINAC, and an increase in the overall number of stereotactic irradiations. In particular, the proportion of outpatient treatment increased, indicating that more than half of LINAC was selected for outpatient treatment.

Pseudarthrosis of Pelvic Fracture With Charcot Arthropathy Successfully Treated With Constrained Total Hip Arthroplasty.

Charcot arthropathy is a rapidly progressive and destructive form of arthropathy caused by various neurological diseases. Total hip arthroplasty (THA) is usually contraindicated in patients with Charcot arthropathy; however, recent studies have reported good results following THA in this patient population. Herein, we report a case of Charcot arthropathy secondary to syphilis in a patient who was successfully treated with constrained THA, a new type of THA. A 56-year-old man was injured in a car accident, and a displaced acetabular fracture was revealed three weeks later. He was treated conservatively but soon developed greater displacement of the fracture and femoral head destruction. The patient was referred to our hospital for further treatment. The patient had pelvic pseudarthrosis secondary to Charcot arthropathy at the time of the first visit to our hospital. First, THA was performed with the acetabular reconstruction of the deficient bone. However, the acetabular implant was displaced one week postoperatively. THA revision was performed using a constrained cup. Postoperatively, the patient exhibited good hip stability without dislocation. However, displacement of the acetabular cup occurred one year after the second surgery. We performed a re-revision of THA using a new type of constrained cup that offers a high level of constraint to maintain range of motion (ROM) and prevent dislocations. The patient was able to walk with a T-cane one year postoperatively. Herein, we report a difficult case of revision THA in a patient with Charcot arthropathy concomitant with syphilis. THA is usually contraindicated in patients with Charcot arthropathy; however, we propose that THA using constrained cups that offer a wider ROM may be a useful therapeutic strategy for the treatment of Charcot arthropathy.

Jugular Venous Pressure and Kussmaul's Sign as Predictors of Outcome in Heart Failure.

Simplifying the estimation of internal jugular venous pressure (JVP) as visible or not visible above the right clavicle in the sitting position has attracted attention for risk assessment in patients with heart failure (HF). It remains unclear whether this simple assessment, combined with its inspiration response known as Kussmaul's sign, is useful in patients with HF who vary in features such as HF with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF).This study consisted of 246 patients who were admitted for the management of HF. JVP was assessed before discharge and considered high if visible at rest. The inspiration response was also examined. The primary outcome was a composite of all-cause death and hospitalization for worsening HF.One year after discharge, primary outcome events occurred in 91 patients (37%). The incidence of primary outcome was higher in patients with a high JVP at rest (odds ratio, 5.06; 95% confidence interval, 2.31-11.1; P = 0.0001) or with inspiration (odds ratio, 5.93; 95% confidence interval, 2.14-16.4; P < 0.01) than in patients without high JVP conditions. These findings were similarly observed among patients with HFrEF and HFpEF (odds ratios, 3.53 and 6.76; 95% confidence intervals, 1.68-8.68 and 2.19-15.5; P = 0.01 and < 0.01, respectively) and in subgroup analysis stratified by baseline characteristics of the patients.A high JVP at rest and with inspiration as assessed by this simple, practical method may be useful for risk assessment in patients with HF, independent of baseline characteristics.

Retrospective non-inferiority study of stereotactic radiosurgery for more than ten brain metastases.

AIM: This study aimed to investigate the clinical benefits of stereotactic radiosurgery (SRS) in patients with > 10 brain metastases (BM) compared to patients with 2-10 BM. METHODS: The study included multiple BM patients who underwent SRS between 2014 and 2022, excluding patients who underwent whole brain radiotherapy, had a Karnofsky Performance Status score < 60, suspected leptomeningeal disease, or a single BM lesion. Patients were divided into two groups (2-10 and > 10 BM groups) and matched 2:1 based on propensity scores. The primary endpoint was overall survival (OS) in the matched dataset, with intracranial progression-free survival (PFS) as the secondary endpoint. Non-inferiority was established if the upper limit of the 95% confidence interval (CI) of the adjusted hazard ratio was below 1.3. RESULTS: Of the 1042 patients identified, 434 met eligibility criteria. After propensity score matching, 240 patients were analyzed (160 in the BM 2-10 group and 80 in the > 10 BM group). The median OS was 18.2 months in the 2-10 BM group and 19.4 months in the > 10 BM group (P = 0.60). The adjusted hazard ratio was 0.86 (95% CI: 0.59-1.24), indicating non-inferiority. PFS was not significantly different between the groups (4.8 months vs. 4.8 months, P = 0.94). The number of BM did not significantly impact OS or PFS. CONCLUSIONS: SRS for selected patients with > 10 BM was non-inferior in terms of OS compared to those with 2-10 BM in a propensity score-matched dataset.

Recent trends of characteristics and treatments in adults with newly diagnosed brain metastases.

OBJECTIVE: We aimed to evaluate recent trends in characteristics and treatments among patients with brain metastases in clinical practice. METHODS: All newly diagnosed patients with brain metastases during 2016-2021 at a single cancer center were enrolled. We collected the detailed features of each patient and estimated the number of candidates considered to meet the following criteria used in common clinical trials: Karnofsky performance status ≥ 70 and mutated non-small cell lung cancer, breast cancer or melanoma. The brain metastases treatments were classified as follows: (i) stereotactic radiosurgery, (ii) stereotactic radiosurgery and systemic therapy, (iii) whole-brain radiotherapy, (iv) whole-brain radiotherapy and systemic therapy, (v) surgery, (vi) immune checkpoint inhibitor or targeted therapy, (vii) cytotoxic agents and (ix) palliative care. Overall survival and intracranial progression-free survival were estimated from brain metastases diagnosis to death or intracranial progression. RESULTS: A total of 800 brain metastases patients were analyzed; 597 (74.6%) underwent radiotherapy, and 422 (52.7%) underwent systemic therapy. In addition, 250 (31.3%) patients were considered candidates for common clinical trials. Compared to 2016, the later years tended to shift from whole-brain radiotherapy to stereotactic radiosurgery (whole-brain radiotherapy: 35.7-29.1% and stereotactic radiosurgery: 33.4-42.8%) and from cytotoxic agents to immune checkpoint inhibitor/targeted therapy (cytotoxic agents: 10.1-5.0 and immune checkpoint inhibitor/targeted therapy: 7.8-10.9%). There was also an increase in the proportion of systemic therapy combined with radiation therapy (from 26.4 to 36.5%). The median overall survival and progression-free survival were 12.7 and 5.3 months, respectively. CONCLUSIONS: This study revealed the diversity of brain metastases patient characteristics, recent changes in treatment selection and the percentage of candidates in clinical trials.

Linear π-conjugated polycyclic compounds consisting of four-, five-, and six-membered rings: benzo[1'',2'':3,4;4'',5'':3',4']bis(cyclobuta[1,2-c]thiophene).

Linear π-conjugated polycyclic compounds, BBCTs, containing linearly annulated 5-, 4-, 6-, 4-, and 5-membered rings were produced via copper-mediated double intramolecular coupling reactions. The absorption spectra and electrochemical results confirmed their moderate optical energy gaps and high HOMO energy levels, respectively. In a crystalline state, the BBCT molecules adopt a herringbone structure, while the methylated molecules form slipped one-dimensional columns. The local and global aromaticity of the new polycyclic compounds is discussed based on the experimental results and theoretical predictions. The present fundamental findings are useful for the further design and synthesis of novel π-conjugated polycyclic compounds containing four-membered rings with potential applications in electronic materials.

Optimal timing of a γH2AX analysis to predict cellular lethal damage in cultured tumor cell lines after exposure to diagnostic and therapeutic radiation doses.

Phosphorylated H2AX (γH2AX) is a sensitive biomarker of DNA double-strand breaks (DSBs). To assess the adverse effects of low-dose radiation (<50 mGy), γH2AX levels have typically been measured in human lymphocytes within 30 min of computed tomography (CT) examinations. However, in the presence of DSB repair, it remains unclear whether γH2AX levels within 30 min of irradiation completely reflect biological effects. Therefore, we investigated the optimal timing of a γH2AX analysis to predict the cell-surviving fraction (SF). Three tumor cell lines were irradiated at different X-ray doses (10-4000 mGy), and the relationships between SF and relative γH2AX levels were investigated 15 min and 2, 6, 12 and 24 h after irradiation. Data were analyzed for high-dose (0-4000 mGy) and low-dose (0-500 mGy) ranges. Correlations were observed between SF and the relative number of γH2AX foci/nucleus at 12 h only (R2 = 0.68, P = 0.001 after high doses; R2 = 0.37, P = 0.016 after low doses). The relative intensity of γH2AX correlated with SF 15 min to 12 h after high doses and 2 to 12 h after low doses, with the maximum R2 values being observed 2 h after high doses (R2 = 0.89, P < 0.001) and 12 h after low doses (R2 = 0.65, P < 0.001). Collectively, cellular lethal damage in tumor cells was more accurately estimated with residual DSBs 12 h after low-dose (10-500 mGy) irradiation. These results may contribute to determination of the optimal timing of biodosimetric analyses using γH2AX in future studies.

The influence of stem alignment on the bone mineral density around the Polarstem following total hip arthroplasty.

INTRODUCTION: Bone mineral density is important in detecting implant loosening after total hip arthroplasty. The Polarstem can improve postoperative bone mineral density changes, but no information exists on the influence of postoperative stem alignment. Therefore, we investigated the relationship between bone mineral density change and stem alignment following total hip arthroplasty using a cementless Polarstem. MATERIALS AND METHODS: This retrospective study included 42 patients (50 hips) who underwent total hip arthroplasty using a cementless Polarstem. Bone mineral density around the stem was measured according to the established Gruen zone classification using dual-energy X-ray absorptiometry. Measurements were performed 2 months postoperatively (baseline) and 6, 12, 18, and 24 months postoperatively. Bone mineral density changes at each follow-up were calculated as (bone mineral density at follow-up/at 2 weeks) × 100 (%). The stem varus, anterior tilt, and anteversion angles were measured using computed tomography. The correlation coefficient between bone mineral density changes and stem alignment were investigated. RESULTS: The 24-month postoperative bone mineral density increased in zones 4 (106.0%) and 5 (107.3%) and decreased in zones 1 (89.6%) and 7 (90.6%). The mean stem varus angle, anterior tilt, and anteversion error were - 0.3° ± 1.8°, 1.9° ± 2.2°, and 6.8° ± 5.4°. Negative correlations were observed between the stem varus angle and 24-month postoperative bone mineral density change in zone 1 (r = - 0.34, p = 0.02), and the stem anteversion error and 24-month postoperative bone mineral density change in zone 1 (r = - 0.48, p < 0.01) and zone 7 (r = - 0.31, p = 0.03). CONCLUSIONS: The cementless Polarstem may have a positive effect on postoperative bone mineral density in the distal femur. However, varus malalignment and anteversion error of the stem could have a negative influence on the bone mineral density changes in the proximal femur.

Symmetry and spacing controls in periodic covalent functionalization of graphite surfaces templated by self-assembled molecular networks.

We herein present the periodic covalent functionalization of graphite surfaces, creating a range of patterns of different symmetries and pitches at the nanoscale. Self-assembled molecular networks (SAMNs) of rhombic-shaped bis(dehydrobenzo[12]annulene) (bisDBA) derivatives having alkyl chain substituents of different lengths were used as templates for covalent grafting of electrochemically generated aryl radicals. Scanning tunneling microscopy (STM) observations at the 1,2,4-trichlorobenzene/graphite interface revealed that these molecules form a variety of networks that contain pores of different shapes and sizes. The covalently functionalized surfaces show hexagonal, oblique, and quasi-rectangular periodicities. This is attributed to the favorable aryl radical addition at the pore(s). We also confirmed the successful transmission of chirality information from the SAMNs to the alignment of the grafted aryls. In one case, the addition of a guest molecule was used to switch the SAMN symmetry and periodicity, leading to a change in the functionalized surface periodicity from oblique to hexagonal in the presence of the guest molecule. This contribution highlights the potential of SAMNs as templates for the controlled formation of nanopatterned carbon materials.

Paracrine effect of the stromal vascular fraction containing M2 macrophages on human chondrocytes through the Smad2/3 signaling pathway.

The adipose-derived stromal vascular fraction (SVF) is composed of a heterogeneous mix of adipose-derived stem cells (ADSCs), macrophages, pericytes, fibroblasts, blood, and other cells. Previous studies have found that the paracrine effects of SVF cells may be therapeutic, but their role in osteoarthritis treatment remains unclear. This study aimed to investigate the therapeutic effect of SVF cells on chondrocytes. Chondrocytes were seeded on culture plates alone (control) or cocultured with SVF or ADSCs on cell culture inserts. After 48 h of coculture, chondrocyte collagen II, tissue inhibitors of metalloproteinases-3 (TIMP-3), and matrix metalloproteinases-13 (MMP-13) messenger RNA (mRNA) expression levels were evaluated using reverse-transcription polymerase chain reaction, and the transforming growth factor-ß (TGF-ß) levels in the supernatant were measured using ELISA. Immunohistochemical staining and flow cytometry were used to evaluate the macrophages in the SVF. These macrophages were characterized according to phenotype using the F4/80, CD86, and CD163 markers. To determine whether the Smad2/3 signaling pathways were involved, the chondrocytes were pre-treated with a Smad2/3 phosphorylation inhibitor and stimulated with the SVF, and then Smad2/3 phosphorylation levels were analyzed using western blot. The mRNA expression levels of various paracrine factors and chondrocyte pellet size were also assessed. Collagen II and TIMP-3 expression were higher in the SVF group than in the ADSC group and controls, while MMP-13 expression was the highest in the ADSC group and the lowest in the controls. TGF-ß levels in the SVF group were also elevated. Immunohistochemical staining and flow cytometry revealed that the macrophages in the SVF were of the anti-inflammatory phenotype. Western blot analysis showed that the SVF increased Smad2/3 phosphorylation, while Smad2/3 inhibitors decreased phosphorylation. Smad2/3 inhibitors also reduced the expression of various other paracrine factors and decreased chondrocyte pellet size. These findings suggested that the paracrine effect of heterogeneous cells, such as anti-inflammatory macrophages, in the SVF partly supports chondrocyte regeneration through TGF-ß-induced Smad2/3 phosphorylation.