Preparation and Characterization of Cellulose Ether Liposomes for the Inhibition of Prion Formation in Prion-Infected Cells

Prion accumulation in the brain and lymphoreticular system causes fatal neurodegenerative diseases. Our previous study revealed that cellulose ethers (CE) have anti-prion activities in vivo and in prion-infected cells when administered at high doses. This study aims to improve the bioavailability of a representative CE using a liposomal formulation and characterized CE-loaded liposomes in cultured cells. The liposomal formulation reduced the EC₅₀ dose of CE by <1/200-fold in prion-infected cells. Compared to empty liposomes, CE-loaded liposomes were taken up much more highly by prion-infected cells and less by macrophage-like cells. Phosphatidylserine modification reduced the uptake of CE-loaded liposomes in prion-infected cells and did not change the anti-prion activity, whereas increased the uptake in macrophage-like cells. Polyethylene glycol modification reduced the uptake of CE-loaded liposomes in both types of cells and reduced the anti-prion activity in prion-infected cells. These results suggest that a liposomal formulation of CE is more practical than unformulated CE and showed that the CE-loaded liposome uptake levels in prion-infected cells were not associated with anti-prion activity. Although further improvement of the stealth function against phagocytic cells is needed, the liposomal formulation is useful to improve CE efficacy and elucidate the mechanism of CE action.     

Rehabilitation pharmacotherapy: A scoping review

Many patients in rehabilitation facilities are affected by polypharmacy. Polypharmacy is associated with rehabilitation outcomes and functional recovery. Consequently, a combination of rehabilitation and pharmacotherapy may improve the outcomes of older people undergoing rehabilitation. A recent report described the concept of rehabilitation pharmacotherapy. The concept envisages helping frail older people and people with disabilities to achieve the highest possible body function, activity level and quality of life. There are two key tenets of rehabilitation pharmacotherapy: “pharmacotherapy in consideration of rehabilitation” and “rehabilitation in consideration of pharmacotherapy.” “Pharmacotherapy in consideration of rehabilitation” includes use of drugs to treat impairment, activity limitation and participation restriction based on the International Classification of Functioning, Disability, and Health. “Rehabilitation in consideration of pharmacotherapy” refers to tailoring of rehabilitation considering the content of pharmacotherapy. With respect to drugs and motor dysfunction, anticholinergic drugs are associated with dysphagia and fractures. Increased use of potentially inappropriate medications may adversely affect the nutritional status. With respect to activities of daily living, polypharmacy and use of potentially inappropriate medications negatively affect the improvement in motor function during rehabilitation. Potent anticholinergic drugs are more likely to impede the improvement in cognitive function. In this review, we address the concept of rehabilitation pharmacotherapy and discuss its importance from the perspective of polypharmacy, the effect of drugs on disability and disease, nutritional status and activities of daily living. Geriatr Gerontol Int 2020; 20: – .     

Usefulness of prominently projected aortic arch on chest radiograph to predict severe tortuosity of the right subclavian or brachiocephalic artery in patients aged >44 years undergoing coronary angiography with a right radial artery approach

Although it is well known that certain characteristics, such as older age, female gender, hypertension, and high body mass index, are closely associated with severe arterial tortuosity among patients undergoing transradial coronary angiography, few data are available regarding useful predictors of severe arterial tortuosity among geriatric patients. The purpose of the present study was to evaluate the characteristics of geriatric patients with severe tortuosity of the right subclavian artery or brachiocephalic artery. The coronary angiographic reports of patients with severe tortuosity of the right subclavian artery or brachiocephalic artery and age- and gender-matched control patients were retrospectively evaluated. A total of 847 consecutive patients underwent right transradial coronary angiography. Of these patients, 48 (5.7%) had severe tortuosity (29 women, age 73.4 ± 8.6 years). The factors associated with severe arterial tortuosity were greater body mass index (odds ratio 1.17, p = 0.02), the presence of a prominently projected aortic arch on a chest radiograph (odds ratio 5.62, p <0.01), and lower serum creatinine value (odds ratio 0.05, p <0.01). In conclusion, the presence of a prominently projected aortic arch on the chest radiograph is a useful predictor of severe arterial tortuosity.     

Long-term follow-up of adalimumab monotherapy for rheumatoid arthritis in Japanese patients: a report of six cases

We present six cases of patients with Japanese rheumatoid arthritis (RA) treated with a tumor necrosis factor (TNF)-alpha blocking agent, adalimumab as monotherapy for 220?weeks. All six patients were women, and the median age was 54.0?±?7.07?years old. The median duration of the disease was 7.43?±?11.1?years, and the median disease activity score (DAS28-CRP) was 5.35?±?0.69. Three of six patients were able to continue to receive this treatment for 220?weeks successfully, and the DAS28-CRP decreased to 1.89?±?0.75. Two patients withdrew because of lack of efficacy, and one patient withdrew because of adverse events (non-Hodgkin lymphoma). Adalimumab resulted in a sustained clinical response in RA patients during 220-week follow-up.     

Epidemiological and microbiological analysis of community-associated methicillin-resistant Staphylococcus aureus strains isolated from a Japanese hospital

Reports of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections have recently increased in Japan; however, these studies contain limited information on their epidemiology. We performed a single-center study in the Tokyo Medical University Hospital located in Shinjuku, a central area of Tokyo, Japan. From 2,099 MRSA isolates obtained during July 2007 to March 2009, we selected 44 MRSA isolates with a MIC of <2 μg/mL for imipenem. Among 44 isolates, 28 strains had type IV or type V SCCmec, and we classified them as CA-MRSA. We identified only 1 Panton-Valentine leukocidin (PVL)-positive MRSA strain, which belonged to SCCmec type V. The PVL-positive CA-MRSA strain was isolated from a patient with multiple subcutaneous abscesses. The patient had returned to Japan from India; thus, the strain may have been contracted from outside of Japan. Thirteen (46.4%) and 15 strains (53.6%) were isolated from outpatients and inpatients, respectively. The major sites of infection included the respiratory tract (8 strains, 28.6%), skin/soft tissue (4 strains, 14.3%), and nasal cavity (4 strains, 14.3%). It is important to note that the most common site of CA-MRSA infection in inpatients was the respiratory tract; respiratory infections with CA-MRSA frequently cause severe infectious diseases.     

Magnetic resonance imaging (MRI) detection of synovitis and bone lesions of the wrists and finger joints in early-stage rheumatoid arthritis: comparison of the accuracy of plain MRI-based findings and gadolinium-diethylenetriamine pentaacetic acid-enhanced MRI-based findings

Objective

To explore whether synovitis and bone lesions in the wrists and finger joints visualized by plain magnetic resonance imaging (MRI)-based findings correspond exactly or not to those judged by gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA)-enhanced MRI-based findings.

Methods

Magnetic resonance imaging of the wrists and finger joints of both hands were examined in 51 early-stage rheumatoid arthritis (RA) patients whose median disease duration from the onset of articular manifestations to entry was 5?months, by both plain (T1 and short-time inversion recovery images) and Gd-DTPA-enhanced MRI (post-contrast fat-suppressed T1-weighted images) simultaneously. We focused on 15 sites per hand, to examine the presence of synovitis and bone lesions (bone edema and bone erosion). Gd-DTPA-enhanced MRI-based findings were considered “true” lesions, and we evaluated the accuracy of plain MRI-based findings in comparison to Gd-DTPA-enhanced MRI-based findings.

Results

Synovitis, judged by plain MRI-based findings, appeared as false-positive at pretty frequency; thus, the specificity, positive predictive value and accuracy of the findings were low. The rate of enhancement (E-rate) in false-positive synovitis sites was significantly low compared with true-positive synovitis sites where Gd-DTPA enhancement appears. In contrast to synovitis, the false-positivity of bone lesions, judged by plain MRI-based findings, was very low compared with Gd-DTPA-enhanced MRI-based findings.

Conclusion

Synovitis judged by plain MRI-based findings is sometimes considered false-positive especially in sites where synovitis is mild. However, plain MRI is effective in identifying bone lesions in the wrist and finger joints in early-stage RA.     

Is there a relationship between attention deficit/hyperactivity disorder and Osgood–Schlatter disease?

Purpose

The purpose of this prospective study is to investigate the relationship between Osgood–Schlatter disease (OSD) and attention deficit/hyperactivity disorder (ADHD).

Methods

Seventy-four children with a diagnosis of OSD were referred to child and adolescent psychiatry department for the evaluation of ADHD. Diagnostic and Statistical Manual of Mental Disorders was used for diagnostic criteria.

Results

Diagnosis of ADHD was made in 56 (75.6 %) out of 74 children.

Conclusions

Results of this study suggest that ADHD is a significant risk factor for OSD. During the evaluation of a patient with OSD, a thorough history should be obtained about the behavioral symptoms that indicate underlying ADHD. In case of suspicion, these patients should be referred for an additional evaluation by a child psychiatrist.

Level of evidence

II.     

A neonate with an anomalous bone attached to the cervical spine

Background contextA digit/rib-like ectopic bone is a rare congenital anomaly that is most commonly seen in the thorax or pelvis. There is a single report of an adult possessing a phalanx-like bone in the cervical region; however, whether the abnormal bone was congenital or acquired remains elusive.PurposeTo elucidate that a phalanx-like bone in the cervical region represents a congenital anomaly.Study designCase report.MethodsReport of the imaging findings in a neonate with a palpable bone projection in the posterior neck.ResultsPlain radiographs demonstrated an ectopic bone posterior to the spinous process of the C5 vertebra. Three-dimensional computed tomography demonstrated that the anomalous bone was attached to the left lamina of the C5 vertebra and that there was abnormal segmentation of the left side of the cervical spine.ConclusionsThe anomalous bone in the neck is a congenital malformation that is accompanied by the maldevelopment of the cervical spine.