Activity

Due to their stable fluorescence, biocompatibility, and amenability to functionalization, fluorescent nanodiamonds (FND) are promising materials for long term cell labeling and tracking. However, transporting them to the cytosol remains a major challenge, due to low internalization efficiencies and endosomal entrapment. Here, nanostraws in combination with low voltage electroporation pulses are used to achieve direct delivery of FND to the cytosol. The nanostraw delivery leads to efficient and rapid FND transport into cells compared to when incubating cells in a FND-containing medium. Moreover, whereas all internalized FND delivered by incubation end up in lysosomes, a significantly larger proportion of nanostraw-injected FND are in the cytosol, which opens up for using FND as cellular probes. Furthermore, in order to answer the long-standing question in the field of nano-biology regarding the state of the cell membrane on hollow nanostructures, live cell stimulated emission depletion (STED) microscopy is performed to image directly the state of the membrane on nanostraws. CID-1067700 purchase The time-lapse STED images reveal that the cell membrane opens entirely on top of nanostraws upon application of gentle electrical pulses, which supports the hypothesis that many FND are delivered directly to the cytosol, avoiding endocytosis and lysosomal entrapment.

To determine the relationship between polyvascular disease and risk of hospitalization for heart failure (HHF) and cardiovascular (CV) death in the EMPA-REG OUTCOME population, and the relationship of kidney dysfunction co-existent with polyvascular disease on CV/heart failure (HF) outcomes.

Patients with type 2 diabetes and atherosclerotic CV (ASCVD) received empagliflozin 10, 25 mg or placebo. Post hoc, subgroups were analyzed by one versus two or more vascular beds, and the estimated glomerular filtration rate ([eGFR] < vs. ≥60 mL/min/1.73 m

) at baseline. The empagliflozin arms were pooled. Time to CV death, HHF, CV death (excluding fatal stroke) or HHF, all-cause mortality (ACM) and 3-point major adverse CV events (3P-MACE) were assessed using multivariable Cox regression models.

Baseline characteristics (N = 6959) within subgroups were balanced between treatment groups. In the placebo group, two or more versus one vascular bed increased HHF risk (1.59 [95% confidence interval 1.02, 2.49]), CV death (2.17 [1.52, 3.09]), CV death/HHF (1.79 [1.32, 2.43]), ACM (1.95 [1.44, 2.64]) and 3P-MACE (1.76 [1.36, 2.27]). Hazard ratios for those with polyvascular disease/kidney dysfunction (vs. 1 vascular bed/eGFR ≥60 mL/min/1.73 m

) were HHF 2.80 (1.46, 5.36), CV death 3.10 (1.87, 5.13), CV death/HHF 2.71 (1.74, 4.23), ACM 2.59 (1.67, 4.02) and 3P-MACE 2.62 (1.82, 3.77). Empagliflozin reduced the risk of all outcomes across subgroups.

Polyvascular disease with/without kidney dysfunction markedly increases the risk of HF/CV events. Empagliflozin consistently reduces risk, regardless of vascular bed and kidney function status.

Polyvascular disease with/without kidney dysfunction markedly increases the risk of HF/CV events. Empagliflozin consistently reduces risk, regardless of vascular bed and kidney function status.

This study was performed to clarify the treatment outcome of patients with primary mediastinal germ cell tumors (PMGCTs), focusing on the clinical manifestations and management during definitive therapy and long-term follow-up.

In this study, we retrospectively reviewed the medical records of patients with PMGCTs treated at Shinshu University School of Medicine, and examined the clinical profiles and treatment outcomes of 22 patients (mean age of 29 years) with primary mediastinal GCTs treated at our hospital between 1983 and 2019.

Five patients were diagnosed with pure seminoma and 17 had nonseminomatous GCT. A total of 21 patients were treated with cisplatin-based chemotherapy and 15 patients (68.2%) underwent thoracic surgery after chemotherapy. Although all cases of nonseminomatous GCT were negative for tumor markers after cisplatin-based chemotherapy, two cases showed variable GCT cells and two had somatic components (angiosarcoma and rhabdomyosarcoma) in resected specimens. Three relapsed soon aft the various clinical features and secondary malignancies in primary mediastinal GCTs.

Our experiences demonstrated that long-term survival and/or cure can be achieved with adequate chemotherapy followed by local surgical treatment even in patients with mediastinal GCTs. However, the clinical manifestations and biological behaviors during and/or after chemotherapy were complex and varied. In addition, the development of secondary malignancies should be taken into consideration for long-term follow-up. Clinicians should be aware of the various clinical features and secondary malignancies in primary mediastinal GCTs.

This study used ecological momentary assessment (EMA) to empirically test the theoretical propositions that habit for and level of physical activity (PA) and sedentary behaviour (SB) should be associated with degree of context stability of those behaviours.

Older adults (N=104) completed a 10-day EMA protocol and continuous accelerometer monitoring.

As part of the EMA protocol older adults answered 6 EMA prompts per day to assess current behaviour as well as social and physical contexts of behaviour. Temporal context was determined via time stamps of EMA questionnaires. Context stability was calculated as the reversed entropy scores of the contexts (physical, social, temporal, behavioural [i.e., type]) of PA and SB weighted for total frequency of context prompts. Habit for PA and SB (operationalized as self-reported behavioural automaticity) was assessed via baseline questionnaire. An ActivPAL monitor was worn to assess average daily time spent in moderate-vigorous PA (MVPA), light PA, and SB, and number of sit-to-stand transitions.

More stable physical contexts for physical activity predicted more MVPA (β=10.22) and more stable social contexts for sitting predicted more SB (β=1.36). More variety of time people tended to report engaging in SB, the more SB engaged in (β=-13.76). No context stability scores predicted light PA, sit-to-stand transitions, or habit.

Although context stability was related to behaviour, this did not appear to be explained by habit, as habit did not differ by the degree of context stability surrounding bouts of PA or SB.

Although context stability was related to behaviour, this did not appear to be explained by habit, as habit did not differ by the degree of context stability surrounding bouts of PA or SB.