Radiographic Assessment of Transverse Tarsometatarsal Instability Complicated by Metatarsus Adductus in Hallux Valgus Patients.

Objective evaluations of transverse tarsometatarsal (TMT) hypermobility/instability are lacking. This study aims to radiographically explore the relationship between transverse TMT instability and metatarsus adductus (MA) in hallux valgus (HV). This study retrospectively analyzed 207 feet with varying degrees of HV, employing the distance between the first and second metatarsals (M1-2 distance) to assess transverse TMT instability of the first ray. Participants were categorized into MA and non-MA groups. It was found that the M1-2 distance significantly increased with the hallux valgus angle (HVA) and metatarsus adductus angle (MAA), demonstrating significant differences between the MA and non-MA groups. The measurement of M1-2 distance showed high reliability, and its cutoff value was determined to be 4.05 mm. Additionally, the results suggest that the widening of the M1-2 distance may be a predisposing factor for MA in HV patients, highlighting its role in the pathogenesis of this foot condition. These findings highlight the need for a comprehensive assessment of TMT instability on both the axial and sagittal planes for the surgical planning of HV, particularly when complicated by a large MAA. Based on these insights, reoriented first-TMT arthrodesis might be recommended for HV with significant MA to address potential multiplanar instability.

Segmentation of In vitro Fertilization with High-intensity Focused Ultrasound in Repeated Implantation Failure with Adenomyosis.

Adenomyosis is a complex issue in reproductive-age women not only on worsening of quality of life due to severe dysmenorrhea or heavy menstrual bleeding but also on the impact of infertility. A 39-year-old female, gravida 0 para 0, with a history of bilateral ovarian endometrioma post laparoscopic surgery presented to our hospital due to suspected deep infiltrative endometriosis (DIE), adenomyosis, and repeated implantation failure. Initially, gonadotropin-releasing hormone analog treatment for DIE with progestin-primed ovarian stimulation protocol was arranged. Four D5 blastocysts were obtained and freezed. Two frozen embryo transfer were performed after ultrasound-guided high-intensity focused ultrasound (USgHIFU) treatment of adenomyosis. She later had a dichorionic diamniotic twin pregnancy, and two healthy newborns were delivered by Cesarean section at gestational age of 35 weeks due to antepartum hemorrhage with placenta previa and preeclampsia. In conclusion, USgHIFU can be a potential treatment option in segmented in vitro fertilization in future.

Long-Term Exposure to Fine Particulate Matter and the Deterioration of Estimated Glomerular Filtration Rate: A Cohort Study in Patients With Pre-End-Stage Renal Disease.

Limited literature has explored the effect of air pollutants on chronic kidney disease (CKD) progression, especially for patients with pre-end-stage renal disease (pre-ESRD). In this study, we reported the linear and nonlinear relationships of air pollutants of particles with diameter <2.5 µm (PM2.5) and nitrogen dioxide (NO2) with estimated glomerular filtration rate (eGFR) deterioration after adjusting for smoking status and other traditional clinical factors. This study adopted a retrospective cohort of patients with stage 3b to stage 5 CKD (N = 11,479) from Taichung Veterans General Hospital during January 2006 to December 2020. The eGFR deterioration was defined as a decline in eGFR > 5 ml/min/1.73 m2/year. Hybrid kriging/land-use regression models were used to estimate the individual exposure levels of PM2.5 and NO2. The relationships of air pollutants with eGFR deterioration were evaluated using Cox proportional hazard models. After adjusting for smoking status, baseline eGFR stages, and other traditional clinical factors, the risk of eGFR deterioration was found to increase with increasing PM2.5 and NO2 level (p < 0.0001 and p = 0.041, respectively), especially for those exposed to PM2.5 ≥ 31.44 µg/m3 or NO2 ≥ 15.00 ppb. Similar results were also found in the two-pollutant models. Nonlinear dose-response relationships of eGFR deterioration were observed for concentrations of 26.11 µg/m3 for PM2.5 and 15.06 ppb for NO2. In conclusion, linear and nonlinear associations between PM2.5 and NO2 levels and the incidence risk of eGFR deterioration were observed in patients with pre-ESRD.

Severe hyperbilirubinemia is associated with higher risk of contrast-related acute kidney injury following contrast-enhanced computed tomography.

INTRODUCTION: Contrast-induced acute kidney injury (CI-AKI) is associated with high risks of morbidity and mortality. Hyperbilirubinemia might have some renal protection but with no clear cutoff value for protection. Related studies are typically on limited numbers of patients and only in conditions of vascular intervention. METHODS: We performed this study to elucidate CI-AKI in patients after contrast-enhanced computed tomography (CCT). The outcomes were CI-AKI, dialysis and mortality. Patients were divided to three groups based on their serum levels of total bilirubin: ≤1.2 mg/dl, 1.3-2.0 mg/dl, and >2.0 mg/dl. RESULTS: We enrolled a total of 9,496 patients who had received CCT. Patients with serum total bilirubin >2.0 mg/dl were associated with CI-AKI. Those undergoing dialysis had the highest incidence of PC-AKI (p<0.001). No difference was found between the two groups of total bilirubin ≤1.2 and 1.3-2.0 mg/dl. Patients with total bilirubin >2mg/dl were associated with CI-AKI (OR = 1.89, 1.53-2.33 of 95% CI), dialysis (OR = 1.40, 1.01-1.95 of 95% CI) and mortality (OR = 1.63, 1.38-1.93 of 95% CI) after adjusting for laboratory data and all comorbidities (i.e., cerebrovascular disease, coronary artery disease, peripheral arterial disease, and acute myocardial infarction, diabetes mellitus, hypertension, gastrointestinal bleeding, cirrhosis, peritonitis, ascites, hepatoma, shock lung and colon cancer). We concluded that total bilirubin level >2 mg/dl is an independent risk factor for CI-AKI, dialysis and mortality after CCT. These patients also had high risks for cirrhosis or hepatoma. CONCLUSION: This is the first study providing evidence that hyperbilirubinemia (total bilirubin >2.0 mg/dl) being an independent risk factor for CI-AKI, dialysis and mortality after receiving CCT. Most patients with total bilirubin >2.0mg/dl had cirrhosis or hepatoma.

Mechanochemical synthesis of Si/Cu3Si-based composite as negative electrode materials for lithium ion battery.

Mechanochemical synthesis of Si/Cu3Si-based composite as negative electrode materials for lithium ion battery is investigated. Results indicate that CuO is decomposed and alloyed with Si forming amorphous Cu-Si solid solution due to high energy impacting during high energy mechanical milling (HEMM). Upon carbonization at 800 °C, heating energy induces Cu3Si to crystallize in nanocrystalline/amorphous Si-rich matrix enhancing composite rigidity and conductivity. In addition, residual carbon formed on outside surface of composite powder as a buff space further alleviates volume change upon lithiation/delithiation. Thus, coin cell made of C-coated Si/Cu3Si-based composite as negative electrode (active materials loading, 2.3 mg cm-2) conducted at 100 mA g-1 performs the initial charge capacity of 1812 mAh g-1 (4.08 mAh cm-2) columbic efficiency of 83.7% and retained charge capacity of 1470 mAh g-1 (3.31 mAh cm-2) at the end of the 100th cycle, opening a promised window as negative electrode materials for lithium ion batteries.

High Mobility of Graphene-Based Flexible Transparent Field Effect Transistors Doped with TiO2 and Nitrogen-Doped TiO2.

Graphene with carbon atoms bonded in a honeycomb lattice can be tailored by doping various species to alter the electrical properties of the graphene for fabricating p-type or n-type field-effect transistors (FETs). In this study, large-area and single-layer graphene was grown on electropolished Cu foil using the thermal chemical vapor deposition method; the graphene was then transferred onto a poly(ethylene terephthalate) (PET) substrate to produce flexible, transparent FETs. TiO2 and nitrogen-doped TiO2 (N-TiO2) nanoparticles were doped on the graphene to alter its electrical properties, thereby enhancing the carrier mobility and enabling the transistors to sense UV and visible light optically. The results indicated that the electron mobility of the graphene was 1900 cm(2)/(V·s). Dopings of TiO2 and N-doped TiO2 (1.4 at. % N) lead to n-type doping effects demonstrating extremely high carrier mobilities of 53000 and 31000 cm(2)/(V·s), respectively. Through UV and visible light irradiation, TiO2 and N-TiO2 generated electrons and holes; the generated electrons transferred to graphene channels, causing the FETs to exhibit n-type electric behavior. In addition, the Dirac points of the graphene recovered to their original state within 5 min, confirming that the graphene-based FETs were photosensitive to UV and visible light. In a bending state with a radius of curvature greater than 2.0 cm, the carrier mobilities of the FETs did not substantially change, demonstrating the application possibility of the fabricated graphene-based FETs in photosensors.

Pharmacokinetics, dosimetry and comparative efficacy of 188Re-liposome and 5-FU in a CT26-luc lung-metastatic mice model.

The biodistribution, pharmacokinetics, dosimetry and comparative therapeutic efficacy of intravenously administrated (188)Re-N,N-bis(2-mercaptoethyl)-N',N'-diethylethylenediamine (BMEDA)-labeled pegylated liposome ((188)Re-liposome) and 5-FU were investigated in a CT26-luc lung-metastatic model. After intravenous administration of (188)Re-liposome, tumor accumulation from the radioactivity was observed. Levels of radioactivity in tumors were maintained at steady levels (from 5.40 to 5.67 %ID/g) after 4 to 24 h. In pharmacokinetics, the AUC((0→∞)), MRT((0→∞)) and Cl of (188)Re-liposome in blood via intravenous route were 998 h %ID/ml, 28.7 h and 0.1 ml/h, respectively. The total excreted fractions of feces and urine were 0.61 and 0.26, respectively. Absorbed doses for (188)Re-liposome in the liver and red marrow were 0.31 and 0.08 mSv/MBq, respectively. Tumor-absorbed doses for (188)Re-liposome ranged from 48.4 to 1.73 mGy/MBq at 10 to 300 g tumor spheres. In therapeutic efficacy, the survival times of mice after (188)Re-liposome [80% maximum tolerated dose (MTD); 29.6 MBq], 5-FU (80% MTD; 144 mg/kg), liposome or normal saline treatments were evaluated. Consequently, radiotherapeutics of (188)Re-liposome attained a longer lifespan (increase of 34.9%; P=.005) in mice than in the normal saline group. The increase in lifespan of the (188)Re-liposome group was 2.5-fold greater than that of the 5-FU group. Therefore, intravenous administration of (188)Re-liposome could provide a benefit and it is a promising strategy for delivery of passive nanotargeted radiotherapeutics in oncology applications.

Biodistribution and pharmacokinetics of 188Re-liposomes and their comparative therapeutic efficacy with 5-fluorouracil in C26 colonic peritoneal carcinomatosis mice.

BACKGROUND: Nanoliposomes are designed as carriers capable of packaging drugs through passive targeting tumor sites by enhanced permeability and retention (EPR) effects. In the present study the biodistribution, pharmacokinetics, micro single-photon emission computed tomography (micro-SPECT/CT) image, dosimetry, and therapeutic efficacy of (188)Re-labeled nanoliposomes ((188)Re-liposomes) in a C26 colonic peritoneal carcinomatosis mouse model were evaluated. METHODS: Colon carcinoma peritoneal metastatic BALB/c mice were intravenously administered (188)Re-liposomes. Biodistribution and micro-SPECT/CT imaging were performed to determine the drug profile and targeting efficiency of (188)Re-liposomes. Pharmacokinetics study was described by a noncompartmental model. The OLINDA|EXM computer program was used for the dosimetry evaluation. For therapeutic efficacy, the survival, tumor, and ascites inhibition of mice after treatment with (188)Re-liposomes and 5-fluorouracil (5-FU), respectively, were evaluated and compared. RESULTS: In biodistribution, the highest uptake of (188)Re-liposomes in tumor tissues (7.91% ± 2.02% of the injected dose per gram of tissue [%ID/g]) and a high tumor to muscle ratio (25.8 ± 6.1) were observed at 24 hours after intravenous administration. The pharmacokinetics of (188)Re-liposomes showed high circulation time and high bioavailability (mean residence time [MRT] = 19.2 hours, area under the curve [AUC] = 820.4%ID/g*h). Micro-SPECT/CT imaging of (188)Re-liposomes showed a high uptake and targeting in ascites, liver, spleen, and tumor. The results were correlated with images from autoradiography and biodistribution data. Dosimetry study revealed that the (188)Re-liposomes did not cause high absorbed doses in normal tissue but did in small tumors. Radiotherapeutics with (188)Re-liposomes provided better survival time (increased by 34.6% of life span; P < 0.05), tumor and ascites inhibition (decreased by 63.4% and 83.3% at 7 days after treatment; P < 0.05) in mice compared with chemotherapeutics of 5-fluorouracil (5-FU). CONCLUSION: The use of (188)Re-liposomes for passively targeted tumor therapy had greater therapeutic effect than the currently clinically applied chemotherapeutics drug 5-FU in a colonic peritoneal carcinomatosis mouse model. This result suggests that (188)Re-liposomes have potential benefit and are safe in treating peritoneal carcinomatasis of colon cancer.

Early detection of tumor response by FLT/microPET Imaging in a C26 murine colon carcinoma solid tumor animal model.

Fluorine-18 fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) imaging demonstrated the change of glucose consumption of tumor cells, but problems with specificity and difficulties in early detection of tumor response to chemotherapy have led to the development of new PET tracers. Fluorine-18-fluorothymidine ((18)F-FLT) images cellular proliferation by entering the salvage pathway of DNA synthesis. In this study, we evaluate the early response of colon carcinoma to the chemotherapeutic drug, lipo-Dox, in C26 murine colorectal carcinoma-bearing mice by (18)F-FDG and (18)F-FLT. The male BALB/c mice were bilaterally inoculated with 1 × 10(5) and 1 × 10(6) C26 tumor cells per flank. Mice were intravenously treated with 10 mg/kg lipo-Dox at day 8 after (18)F-FDG and (18)F-FLT imaging. The biodistribution of (18)F-FDG and (18)F-FLT were followed by the microPET imaging at day 9. For the quantitative measurement of microPET imaging at day 9, (18)F-FLT was superior to (18)F-FDG for early detection of tumor response to Lipo-DOX at various tumor sizes (P < 0.05). The data of biodistribution showed similar results with those from the quantification of SUV (standard uptake value) by microPET imaging. The study indicates that (18)F-FLT/microPET is a useful imaging modality for early detection of chemotherapy in the colorectal mouse model.

Molecular imaging, pharmacokinetics, and dosimetry of In-AMBA in human prostate tumor-bearing mice.

Molecular imaging with promise of personalized medicine can provide patient-specific information noninvasively, thus enabling treatment to be tailored to the specific biological attributes of both the disease and the patient. This study was to investigate the characterization of DO3A-CH(2)CO-G-4-aminobenzoyl-Q-W-A-V-G-H-L-M-NH(2) (AMBA) in vitro, MicroSPECT/CT imaging, and biological activities of (111)In-AMBA in PC-3 prostate tumor-bearing SCID mice. The uptake of (111)In-AMBA reached highest with 3.87 ± 0.65% ID/g at 8 h. MicroSPECT/CT imaging studies suggested that the uptake of (111)In-AMBA was clearly visualized between 8 and 48 h postinjection. The distribution half-life (t(1/2α)) and the elimination half-life (t(1/2ß)) of (111)In-AMBA in mice were 1.53 h and 30.7 h, respectively. The C(max) and AUC of (111)In-AMBA were 7.57% ID/g and 66.39 h % ID/g, respectively. The effective dose appeared to be 0.11 mSv/MBq(-1). We demonstrated a good uptake of (111)In-AMBA in the GRPR-overexpressed PC-3 tumor-bearing SCID mice. (111)In-AMBA is a safe, potential molecular image-guided diagnostic agent for human GRPR-positive tumors, ranging from simple and straightforward biodistribution studies to improve the efficacy of combined modality anticancer therapy.

Multimodality imaging and preclinical evaluation of 177Lu-AMBA for human prostate tumours in a murine model.

AMBA (DO3A-CH(2)CO-G-(4-aminobenzoyl)-QWAVGHLM-NH(2)) is a bombesin (BN)-like peptide having high affinity with gastrin-releasing peptide receptors (GRPr).(177)Lu-AMBA is currently undergoing clinical trial as a systemic radiotherapy for hormone refractory prostate cancer (HRPC) patients. This study evaluated the biodistribution, pharmacokinetics, bioluminescent imaging (BLI) and microSPECT/CT imaging of (177)Lu-AMBA in PC-3M-luc-C6 luciferase-expressing human prostate tumour-bearing mice. Plasma stability of (177)Lu-AMBA could be maintained up to 55.67±6.07% at 24 h in a protection buffer. High positive correlations of PC-3M luc-C6 tumour growth in SCID mice between caliper measurement and BLI were observed (R(2)=0.999). Both the biodistribution and microSPECT/CT imaging in PC-3M-luc-C6 bearing-tumour mice showed that (177)Lu-AMBA in tumour uptake could be retained for 24 h. The distribution half-life (t(1/2α)) and the elimination half-life (t(1/2ß)) of (177) Lu-AMBA in mice were 0.52 h and 26.6 h, respectively. These results indicated that BLI could be used to monitor the growth of tumour. High uptake of (177)Lu-AMBA in PC-3M-luc-C6 tumour-bearing mice by microSPECT/CT imaging can further evaluate the potential of (177)Lu-AMBA therapy for PC-3M-luc-C6 tumours.

MicroSPECT/CT imaging and pharmacokinetics of 188Re-(DXR)-liposome in human colorectal adenocarcinoma-bearing mice.

Nanoliposome can be designed as a drug delivery carrier to improve the pharmacological and therapeutic properties of drug administration. (188)Re-labeled nanoliposomes are useful for diagnostic imaging as well as for targeted radionuclide therapy. In this study, the in vivo nuclear imaging, pharmacokinetics and biodistribution of administered nanoliposomes were investigated as drug and radionuclide carriers for targeting solid tumor via intravenous (i.v.) administration. The radiotherapeutics ((188)Re-liposome) and radiochemotherapeutics ((188)Re-DXR-liposome) were i.v. administered to nude mice bearing human HT-29 colorectal adenocarcinoma xenografts. (188)Re-liposome and (188)Re-DXR-liposomes show similar biodistribution profile; both have higher tumor uptake, higher blood retention time, and lower excretion rate than (188)Re-N,N-bis(2-mercaptoethyl)-N',N'-diethylenediamine (BMEDA). In contrast to tumor uptake, the area under the curve (AUC) value of tumor for (188)Re-liposome and (188)Re-DXR-liposome was 16.5- and 11.5-fold higher than that of free (188)Re-BMEDA, respectively. Additionally, (188)Re-liposome and (188)Re-DXR-liposome had a higher tumor-to-muscle ratio at 24 h (14.4+/-2 .7 and 17.14+/-4.1, respectively) than (188)Re-BMEDA (1.6+/-0.1). The tumor targeting and distribution of (188)Re-(DXR)-liposome (representing (188)Re-DXR-liposome and (188)Re-liposome) can also be acquired by signal photon-emission computed tomography/computed tomography images as well as whole body autoradiograph. These results suggest that (188)Re-(DXR)-liposomes are potentially promising agents for passive targeting treatment of malignant disease.

Receptor-binding, biodistribution, dosimetry, and micro-SPECT/CT imaging of 111In-[DTPA(1), Lys(3), Tyr(4)]-bombesin analog in human prostate tumor-bearing mice.

Gastrin-releasing peptide receptors (GRPRs) are overexpressed on a variety of human tumors, such as prostate, breast, and lung cancer. Bombesin (BN) is a 14-amino-acid peptide with high affinity for these GRPRs. We synthesized DTPA-Q-K-Y-G-N-Q-W-A-V-G-H-L-M, a 13-amino-acid peptide chelated with diethylenetriaminepentaacetic acid (DTPA), and radiolabeled this BN analog with 111InCl(3). Biologic activity of 111In-[DTPA(1), Lys(3), Tyr(4)]-BN was evaluated in PC-3 prostate tumor-bearing severely compromised immunodeficient (SCID) mice. The purity of synthesized [DTPA(1), Lys(3), Tyr(4)]-BN was greater than 95%. The radiolabeling efficiency of 111In-[DTPA(1), Lys(3), Tyr(4)]-BN was 96.9% +/- 2.46%. The IC(50) and K(i) of [DTPA(1), Lys(3), Tyr(4)]-BN in the human bombesin 2 receptor were 1.05 +/- 0.46 and 0.83 +/- 0.36 nM, respectively. The K(d) of 111In-[DTPA(1), Lys(3), Tyr(4)]-BN in GRPR-expressing PC-3 tumor cells was 22.9 +/- 6.81 nM. Both biodistribution and micro-SPECT/CT (single-photon emission computed tomography/computed tomography) imaging studies with 111In-[DTPA(1), Lys(3), Tyr(4)]-BN demonstrated the highest uptake at 8 hours postinjection. The Pearson correlation analysis showed a positive correlation of tumor uptake between biodistribution and micro-SPECT/CT semiquantification imaging analysis (r = 0.832). Our results revealed 111In-[DTPA(1), Lys(3), Tyr(4)]-BN has high affinity with BN type 2 receptor. The results demonstrated a good uptake in the GRPR-overexpression of PC-3 tumor-bearing SCID mice. 111In-[DTPA(1), Lys(3), Tyr(4)]-BN is a potential agent for imaging GRPR-positive tumors in humans.

Pharmacokinetics, micro-SPECT/CT imaging and therapeutic efficacy of (188)Re-DXR-liposome in C26 colon carcinoma ascites mice model.

The pharmacokinetics and internal radionuclide therapy of intraperitoneally administrated (188)Re-N,N-bis(2-mercaptoethyl)-N',N'-diethylethylenediamine (BMEDA)-labeled pegylated liposomal doxorubicin ((188)Re-DXR-liposome) were investigated in the C26 murine colon carcinoma ascites mouse model. After intraperitoneal administration of the nanotargeted bimodality (188)Re-DXR-liposome, the ascites and tumor accumulation of the radioactivity were observed, the levels of radioactivity within the ascites were maintained at relatively higher levels before 48 h and the levels of radioactivity in the tumor were maintained at steady levels after 4 h. The AUC((o-->infinity)) of (188)Re-DXR-liposome in blood, ascites and tumor was 9.3-, 4.2- and 4.7-fold larger than that of (188)Re-BMEDA, respectively. The maximum tolerated dose of intraperitoneally administrated (188)Re-DXR-liposome was determined in normal BALB/c mice. The survival, tumor and ascites inhibition of mice after (188)Re-DXR-liposome (22.2 MBq of (188)Re, 5 mg/kg of DXR) treatment were evaluated. Consequently, radiochemotherapeutics of (188)Re-DXR-liposome attained better survival time, tumor and ascites inhibition (decreased by 49% and 91% at 4 days after treatment; P<.05) in mice than radiotherapeutics of (188)Re-liposome or chemotherapeutics of Lipo-Dox did. Therefore, intraperitoneal administration of novel (188)Re-DXR-liposome could provide a benefit and promising strategy for delivery of passive nanotargeted bimodality radiochemotherapeutics in oncology applications.

Biodistribution and pharmacokinetics of transgenic pig-produced recombinant human factor IX (rhFIX) in rats.

BACKGROUND: Recombinant human factor IX (rhFIX) is a 56 kDa glycoprotein with full biological activity providing a guarantee of freedom from blood-borne viral contamination in the therapy of hemophilia B, but no data are available on the distribution of transgenic pig-produced rhFIX post injection (p.i.). Therefore, an 131I-radiolabeled rhFIX was developed to evaluate the distribution of rhFIX in rats. MATERIALS AND METHODS: rhFIX was labeled with the lodogen method. 131I-rhFIX (25 microCi/25 microg/200 microl/rat) was intravenously injected through the tail vein in normal Sprague-Dawley (SD) rats and the biodistribution was examined from 5 min to 72 h p.i.. The pharmacokinetics were also evaluated from 5 min to 96 h p.i. RESULTS: The radiolabeled efficiency and radiochemical purity of 131I-rhFIX was over 96% and 98%, respectively. The biodistribution study showed that the rhFIX chiefly accumulated in the liver. The distribution and elimination half-life (t(1/2alpha) and t(1/2beta)) of 131I-rhFIX were 0.82 and 9.34 h, respectively. The maximum concentration in the plasma (Cmax) and the area under the concentration versus time curve (AUC(INF)) of 131I-rhFIX in rats were 3.09% injected dose (ID)/g and 15.3 h x % ID/g. CONCLUSION: The transgenic pig-produced rhFIX is mostly retained in the liver and the preclinical biodistribution and pharmacokinetic studies of 131I radiolabeled rhFIX are helpful for researching its biological effect in vivo.