SPECT/CT imaging of radiolabeled cubosomes and hexosomes for potential theranostic applications

We have developed a highly efficient method for the radiolabeling of phytantriol (PHYT)/oleic acid (OA)-based hexosomes based on the surface chelation of technetium-99m (^99mTc) to preformed hexosomes using the polyamine 1, 12-diamino-3, 6, 9-triazododecane (SpmTrien) as chelating agent. We also report on the unsuccessful labeling of cubosomes using the well-known chelating agent hexamethylpropyleneamine oxime (HMPAO). The ^99mTc-labeled SpmTrien-hexosomes (^99mTc-SpmTrien-hexosomes) were synthesized with good radiolabeling (84%) and high radiochemical purity (>90%). The effect of radiolabeling on the internal nanostructure and the overall size of these aqueous dispersions was investigated by using synchrotron small angle X-ray scattering (SAXS), dynamic light scattering (DLS), and transmission electron cryo microscopy (cryo-TEM). Further, we show the utility of ^99mTc-SpmTrien-hexosomes for the in vivo imaging of healthy mice using single photon emission computed tomography (SPECT) in combination with computed tomography (CT), i.e. SPECT/CT. SPECT/CT experiments of subcutaneously administered ^99mTc-SpmTrien-hexosomes to the flank of mice showed a high stability in vivo allowing imaging of the distribution of the radiolabeled hexosomes for up to 24 h. These injected ^99mTc-SpmTrien-hexosomes formed a deposit within the subcutaneous adipose tissue, displaying a high biodistribution of ∼343% injected dose/g tissue (%ID/g), with negligible uptake in other organs and tissues. The developed ^99mTc labeling method for PHYT/OA-based hexosomes could further serve as a useful tool for investigating and imaging the in vivo performance of cubosomal and hexosomal drug nanocarriers.     

A serine-to-asparagine mutation at position 314 of H5N1 avian influenza virus NP is a temperature-sensitive mutation that interferes with nuclear localization of NP

We have generated a temperature-sensitive (ts) mutant from a human isolate of the H5N1 avian influenza virus by classical adaptation in cell culture. After 20 passages at low temperature, the virus showed a ts phenotype. The ts mutant also showed an attenuated phenotype after nasal inoculation in mice. Using reverse genetics, we generated reassortants carrying individual genomic segments of the wild-type and mutant viruses in an A/Puerto Rico/8/34 background, and found that the nucleoprotein (NP) gene could confer the ts phenotype. This mutant NP contains a serine-to-asparagine mutation at position 314 (S314N). The mutant NP protein showed a defect in nuclear localization at high temperature in mammalian cells.     

人体日常健康管理可穿戴设备研究进展

随着大众对便携地获得个体健康信息的需求不断扩大,可穿戴设备不仅被广泛应用于临床,还由于其智能化、微型化、便携化等特点,被逐渐应用到普通家庭日常健康管理中.本文通过PubMed及CNKI数据库对可穿戴设备的文献进行搜索,依据可穿戴设备实现的不同功能对其进行分类,简述了其应用的算法及具体分析方法,并对其在人体健康领域的发展趋势做出了展望.     

Fluorescent nanoparticle-mediated semiquantitative MYC protein expression analysis in morphologically diffuse large B-cell lymphoma

The current World Health Organization (WHO) classification defines a new disease entity of high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, making fluorescence in situ hybridization (FISH) screening for these genes mandatory. In addition, the prognostic significance of MYC expression was reported, with a cut-off value of 40%. However, interobserver discrepancies arise due to the heterogeneous intensity of MYC expression by immunohistochemistry. Moreover, a cut-off value of positivity for MYC protein in diffuse large B-cell lymphoma (DLBCL) varies among studies at present. Here, we applied a high-sensitivity semiquantitative immunohistochemical technique using fluorescent nanoparticles called phosphor-integrated dots (PID) to evaluate the MYC expression in 50 de novo DLBCL cases, and compared it with the conventional diaminobenzidine (DAB)-developing system. The high MYC expression detected by the PID-mediated system predicted poor overall survival in DLBCL patients. However, we found no prognostic value of MYC protein expression for any cut-off value by the DAB-developing system, even if the intensity was considered. These results indicate that the precise evaluation of MYC protein expression can clarify the prognostic values in DLBCL, irrespective of MYC rearrangement.     

Facile synthesis of multi-functional elastic polyaniline/polyvinyl alcohol composite gels by a solution assembly method

Polyaniline gels with a three-dimensional network structure are attractive for their broad application prospects in flexible and stretchable electric devices. In this paper, we develop a facile solution assembly method to prepare an elastic polyaniline/poly(vinyl alcohol) composite organogel and a hydrogel. The polyaniline and poly(vinyl alcohol) chains gelate from the homogeneous mixed solution in N-methyl-2-pyrrolidone via crystallization of poly(vinyl alcohol), producing a uniform organogel with hydrogen bonds between two polymers, and the organogel can be further converted into a hydrogel by solvent exchange. The composite gels exhibit excellent mechanical properties, which make them one of the best materials for additive manufacture, such as molding and 3D printing. This study develops an efficient method to fabricate polyaniline gels with good processability and multifunctions.

Polyaniline/polyvinyl alcohol composite organogels and hydrogels were prepared by a solution assembly method and used in stretchable electrochemical capacitors and press sensors.     

Pharmaceutical care for adult asthma patients: A controlled intervention one‐year follow‐up study

Asthma is a clinical problem with social, psychological and economic burdens. To improve patient disease management, different education programmes have been developed. Challenges in asthma management may be partially attributed to non‐adherence or improper use of inhalers. This study aimed to implement and assess hospital‐based pharmaceutical care services for asthmatic patients. A 12‐month, single‐centre, randomized, controlled study was initiated in asthmatic adult patients who had been divided into either a control or intervention group. Patients in the control group received the usual care, and patients in the intervention group received patient counselling per study protocol that covered asthma knowledge, control, adherence to treatment and inhalation techniques. The main variables compared measurements at baseline with those at 6 and 12 months. A total of 192 patients completed the study protocol: 90 in the control group and 102 in the intervention group. The control group included 90 patients, and the intervention group included 102 patients. Over the course of the 12‐month follow‐up period, a significant difference was observed between intervention and control groups with respect to asthma control (38.2% vs 10.0%; P < .001), mean correct inhalation technique (confidence interval [CI]: 8.1, 7.8‐8.5 vs CI: 6.1; 5.6‐6.6; P = .01) and good medication adherence (60.7% vs 50.0%, P = .02). There were 34% and 25% decreases in emergency room visits and hospital admissions, respectively, in the intervention group compared to the control group. This study emphasizes the importance of patient counselling in asthma management and the significant contribution that the pharmacist's intervention can have on asthma control.     

Laparoscopic radical nephrectomy for a right renal tumor with renal vein tumor thrombus in a patient with situs inversus totalis

Situs inversus totalis (SIT) is a rare congenital anomaly characterized by complete inversion of the thoracic and abdominal organs. Many intra‐abdominal and vessel anomalies have been reported in association with SIT. However, there have been no reports on the use of laparoscopic radical nephrectomy with thrombectomy for renal vein thrombus, which is considered as a safe and feasible procedure, in patients with SIT. We herein present the case of an 80‐year‐old man with SIT who was preoperatively diagnosed with a right renal tumor and renal vein tumor thrombus. The patient underwent laparoscopic right nephrectomy and tumor thrombectomy with no intraoperative complications. To ensure a safe procedure, the anatomy and vessels were carefully evaluated preoperatively using 3‐D multiplanar reconstructed CT imaging. Assessing anatomical structures leads to safer laparoscopic radical nephrectomy for renal cell carcinoma with venous tumor thrombus in patients with SIT.     

Effects of mild and global cognitive impairment on the prevalence of fear of falling in community-dwelling older adults

Objectives

Few studies have reported the relationship between fear of falling (FoF) and mild and global cognitive impairment in community-dwelling older adults. We aimed to determine whether the status of cognitive impairment affects the prevalence of FoF in community-dwelling older adults.

Study design

Cross-sectional study among 4474 community-dwelling older adults who participated in the Obu Study of Health Promotion for the Elderly.

Main outcome measures

Participants underwent cognitive tests and were divided into three groups: cognitive healthy, mild cognitive impairment (MCI), and global cognitive impairment (GCI). FoF and related variables, such as fall history, physical function, and depression, were also investigated.

Results

The prevalence of FoF was significantly different by group (p < 0.001; healthy: 43.6%, MCI: 50.6%, GCI: 40.6%). Logistic regression analysis showed that GCI (odds ratio = 0.63; 95% confidence interval = 0.526–0.76) was independently associated with FoF, after controlling for confounding factors. Older adults with GCI showed the lowest prevalence of FoF, although they had the lowest physical function comparing with the other groups (p < 0.001).

Conclusion

MCI and GCI in community-dwelling older adults affect the prevalence of FoF in a completely different manner. Further study is required to determine whether insensitivity to FoF with GCI increases the risk of falling in older adults.     

Visceral fat accumulation is a significant risk factor for white matter lesions in Japanese type 2 diabetic patients

Background The presence of white matter lesions (WML) is an important prognostic factor for the development of stroke. The elevated visceral fat accumulation (VFA) has been reported to be closely related to the development of atherosclerosis. This preliminary study was therefore designed to test the hypothesis that the presence of WML correlates with VFA and insulin resistance in type 2 diabetic patients not receiving insulin treatment. Material and methods Based on brain magnetic resonance imaging (MRI), 95 type 2 diabetic patients were divided into two groups: WML‐positive group (aged 59 ± 7 years, mean ± SD n = 37) and WML‐negative group (aged 58 ± 5, years, n = 58). The level of blood glucose was assessed by fasting plasma glucose (FPG), fasting immunoreactive insulin, homeostasis model assessment (HOMA) index, and haemoglobin A1c. The fat distribution was evaluated by measuring the visceral fat accumulation by abdominal computerized tomography at the umbilical level. Results The body mass index was higher in the WML‐positive group than in the WML‐negative group (P < 0·005). Plasma levels of triglycerides were higher while high‐density lipoprotein cholesterol was lower in the WML‐positive group than in the WML‐negative group (P < 0·05 and P < 0·01, respectively). FPG (P < 0·01), insulin concentrations (P < 0·0001), HOMA index (P < 0·0001) and VFA (<0·0001) levels were higher in the WML‐positive group than in the WML‐negative group. Multivariate logistic analysis revealed that WML was independently predicted by the high VFA and insulin resistance (P < 0·001, P < 0·0001, respectively). Conclusions The results of this preliminary study indicate that the presence of WML was associated with the high VFA and insulin resistance in Japanese patients with type 2 diabetes mellitus. Further larger cohort studies are warranted to confirm these findings.     

Functional motor recovery of an infant after a huge ependymoma resection

Huge supratentorial ependymomas are rarely encountered tumors, even in the infant population. A recovery from complete hemiplegia following a tumor resection including the primary motor cortex was observed.A 5-month-old girl presented with a conjugate deviation to the right and a head circumference that had gradually expanded since birth. Magnetic resonance imaging (MRI) demonstrated a well-enhanced huge mass extending into the right hemisphere. A subtotal removal with the primary motor cortex was performed. However, a regrowth of the residual tumor was observed and, thereafter, the patient underwent a subsequent surgical intervention 5 months later. The histological findings demonstrated an ependymoma. Her motor function was dramatically improved after rehabilitation and no tumor recurrence was detected for 10 years. A diffusion tensor imaging study showed that the motor fibers arose from the residual frontal lobe.The successful surgical management of ependymoma may depend on a total microscopic resection. In a case demonstrating a huge ependymoma, we had to remove a very thin motor cortex with the tumor. However, the motor function recovered completely. The motor damage inflicted at an early developmental age may be fully compensated due to the neuroplasticity of the residual brain.