The silaboration of 1.1.1propellane enables direct introduction of B and Si functional groups onto the bicyclo1.1.1pentane (BCP) scaffold in high yield under mild, additive‐free conditions. The ...silaborated BCP can be obtained on a gram‐scale in a single step without the need for column‐chromatographic purification, and is storable and easy to handle, providing a versatile synthetic intermediate for BCP derivatives. We also describe various conversions of the C−B/C−Si bonds on the BCP scaffold, including development of a modified Suzuki–Miyaura cross‐coupling reaction at the highly sterically hindered bridgehead sp3 carbon center of the BCP skeleton using a combination of highly activated BCP boronic esters, copper(I) oxide, and a PdCl2(dppf) catalyst system.
Silaboration of 1.1.1propellane enabled direct introduction of B and Si functional groups onto the bicyclo1.1.1pentane (BCP) scaffold in high yield under mild, additive‐free conditions. The silaborated BCP can be obtained on a gram scale in a single step without the need for column chromatography purification, and is storable and easy to handle, providing a versatile synthetic intermediate for BCP derivatives.
There is still a substantial unmet need for less invasive and lower-cost blood-based biomarkers to detect brain Alzheimer's disease (AD) pathology. This study is aimed to determine whether ...quantification of plasma tau phosphorylated at threonine 181 (p-tau181) is informative in the diagnosis of AD.
We have developed a novel ultrasensitive immunoassay to quantify plasma p-tau181, and measured the levels of plasma p-tau181 in three cohorts.
In the first cohort composed of 20 AD patients and 15 age-matched controls, the plasma levels of p-tau181 were significantly higher in the AD patients than those in the controls (0.171 ± 0.166 pg/ml in AD versus 0.0405 ± 0.0756 pg/ml in controls, p = 0.0039). The percentage of the subjects whose levels of plasma p-tau181 exceeded the cut-off value (0.0921 pg/ml) was significantly higher in the AD group compared with the control group (60% in AD versus 16.7% in controls, p = 0.0090). In the second cohort composed of 20 patients with Down syndrome (DS) and 22 age-matched controls, the plasma concentrations of p-tau181 were significantly higher in the DS group (0.767 ± 1.26 pg/ml in DS versus 0.0415 ± 0.0710 pg/ml in controls, p = 0.0313). There was a significant correlation between the plasma levels of p-tau181 and age in the DS group (R
= 0.4451, p = 0.0013). All of the DS individuals showing an extremely high concentration of plasma p-tau181 (> 1.0 pg/ml) were older than the age of 40. In the third cohort composed of 8 AD patients and 3 patients with other neurological diseases, the levels of plasma p-tau181 significantly correlated with those of CSF p-tau181 (R
= 0.4525, p = 0.023).
We report for the first time quantitative data on the plasma levels of p-tau181 in controls and patients with AD and DS, and these data suggest that the plasma p-tau181 is a promising blood biomarker for brain AD pathology. This exploratory pilot study warrants further large-scale and well-controlled studies to validate the usefulness of plasma p-tau181 as an urgently needed surrogate marker for the diagnosis and disease progression of AD.
The abilities of plasmons to generate local heat at the nanoscale cannot be underestimated, and this heat becomes valuable as a reliable resource for energy devices. In this paper, we report a ...photoelectric conversion triggered only by plasmonic local heat. Periodic silver nanorods covered with an organic thermoelectric thin film were fabricated; the nanorods were then irradiated with monochromatic light. A flow of electric current was detected through the thermoelectric film when plasmons of the silver nanorods were excited. The intensity of the electric current was found to be strongly dependent on the irradiation wavelength and the direction of polarization. The direction of polarization could be used to excite the short-axis plasmon resonance and maximize the electric current intensity, which implies that plasmons are the dominant driving force for generating electric currents. The photoelectric conversion efficiency, where the wavelength of the radiated light was that of the short-axis plasmon resonance of the silver nanorods, was observed to be approximately 0.001%.
Additive manufacturing has been utilized recently for prototyping and mass production of parts especially in the aerospace and medical industries. Most of the parts are processed by the powder bed ...fusion (PBF) method. On the other hand, the directed energy deposition (DED) method is attractive due to the high deposition speed. However, various parameters must be set for deposition processes and how these parameter settings affect the quality of products in terms of pores and machine properties have not been clarified. This paper studies factors contributing to pore generation in the deposition processes of Inconel 625 by the DED method. First, tests for deposition processes in single layer and multiple layers were conducted under various depositing conditions by changing the laser output and the amount of powder. The test results have clarified depositing conditions where less pores are generated, differences in hardness by deposited position, and the factors for those differences.
•Recurrent short-term hypo- and hyper-glycemia reduced Schwann cells viabilities.•Cleaved caspase-3 and CHOP levels increased and Bcl-2 decreased in hypo- and hyper-glycemic groups.•TBARS levels ...increased by hypo- and hyperglycemia.•Recurrent short-term hypoglycemia induced apoptosis and oxidative stress in Schwann cells.•4-PBA treatment ameliorated cell death and oxidative stress in both groups.
Hypoglycemia and fluctuating high or low glucose conditions are under-appreciated sources of oxidative stress contributing to diabetic neuropathy. We investigated the effects of recurrent short-term hypoglycemia and hyperglycemia, on apoptosis and oxidative stress in Schwann cells. Immortalized adult mouse Schwann (IMS32) cells were exposed to five different glucose treatments over 3 days: 1) normal glucose (NG), 2) constant low glucose (LG), 3) constant high glucose (HG), 4) intermittent low glucose (ILG; 1 h three times per day), 5) intermittent high glucose (IHG; 1 h three times per day). Cell viability was decreased by all treatment variants, in comparison to NG. Thiobarbituric acid reactive substance (TBARS) levels were increased by HG, LG, IHG, and ILG. High glucose (HG and IHG) and low glucose (LG and ILG) increased the expression of cleaved caspase-3 and reduced that of Bcl-2. In addition, endoplasmic reticulum (ER) stress-responsive transcription factor C/EBP homologous protein (CHOP) expression was increased under low and high glucose conditions. Cell death and oxidative stress induced by HG, LG, IHG, and ILG were significantly reduced by 4-phenyl butyric acid (4-PBA), an ER stress inhibitor. These findings indicate that recurrent short-term hypoglycemia and hyperglycemia induce apoptosis and oxidative stress via the ER stress response in Schwann cells.
Aims/Introduction
Recent studies advocate that omega‐3 polyunsaturated fatty acids (ω‐3 PUFAs) have direct anti‐oxidative and anti‐inflammatory effects in the vasculature; however, the role of ω‐3 ...PUFAs in Schwann cells remains undetermined.
Materials and methods
Immortalized mouse Schwann (IMS32) cells were incubated with the ω‐3 PUFAs docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). The messenger ribonucleic acid levels of several anti‐oxidant enzymes (heme oxygenase‐1 Ho‐1, nicotinamide adenine dinucleotide phosphate H quinone oxidoreductase 1, catalase, superoxide dismutase and glutathione peroxidase) were identified using real‐time reverse transcription polymerase chain reaction. Ho‐1 and nicotinamide adenine dinucleotide phosphate H quinone oxidoreductase 1 protein levels were evaluated using Western blotting. Nuclear factor (erythroid‐derived 2)‐related factor 2 (Nrf2) of the nuclear fraction was also quantified using western blotting. Catalase activity and glutathione content were determined by colorimetric assay kits. Nrf2 promoter‐luciferase activity was evaluated by a dual luciferase assay system.
Results
Treatment with tert‐butyl hydroperoxide decreased cell viability dose‐dependently. DHA or EPA pretreatment significantly alleviated tert‐butyl hydroperoxide‐induced cytotoxicity. DHA or EPA increased the messenger ribonucleic acid levels of Ho‐1, nicotinamide adenine dinucleotide (phosphate) H quinone oxidoreductase 1 and catalase dose‐dependently. Ho‐1 protein level, catalase activity, Nrf2 promoter‐luciferase activity and intracellular glutathione content were significantly increased by DHA and EPA.
Conclusions
These findings show that DHA and EPA can induce Ho‐1 and catalase through Nrf2, thus protecting Schwann cells against oxidative stress. ω‐3 PUFAs appear to exert their neuroprotective effect by increasing defense mechanisms against oxidative stress in diabetic neuropathies.
We demonstrated that both DHA and EPA could prevent cell death by inducing numerous antioxidants in IMS32 cells. Our findings suggest that enhancements of antioxidative defenses might have therapeutic value in the treatment of diabetic neuropathy.
This research deals with the oscillation frequency of a classical and simple flip-flop jet nozzle with one feed-back loop based on the measurements of pressure and velocity. From these measurements, ...the traces of pressure difference between both ends of a connecting tube are modeled by a triangular wave, and the flow velocities in the connecting tube are calculated numerically. The resulting accumulated flow work, which consists of the time integral of mass flux into the re-circulation region on the low pressure side wall from the re-circulation region on the opposite high-pressure side wall through the connecting tube, is more adequate to determine jet-oscillation frequency than any other time integrals. This includes those of momentum flux and kinetic-energy flux. It is confirmed that jet-oscillation frequency predicted on the basis of this accumulated flow work agrees well with experiment.
In cases of adolescent and early adulthood eating disorders, despite the importance of the patients' relationship with their parents, conflict and confusion frequently occur among them. Interpersonal ...psychotherapy (IPT) is a present-focused psychotherapy that emphasizes the interpersonal context of symptoms. We developed a remote family education and support program exclusively for parents of patients with eating disorders, based on the principle of IPT. The use of IPT is expected to reduce conflicts in the patient-parent relationship. Consequently, parents will be better able to listen to patients, and patients will be better able to express their thoughts and desires. In this study, we describe the protocol for a randomized controlled trial designed to examine the effectiveness of this program in promoting effective communication in their home based on active listening skills of parents of patients with adolescent and early adulthood eating disorders.
Participants will be parents of patients aged 12-29 years with adolescent and early adulthood eating disorders. Individually randomized, parallel-group trial design will be employed. Seventy participants will be allocated to one of two treatment conditions: (1) remote family education and support program (four, 150 min weekly group sessions) for parents plus treatment-as-usual for patients (consultation by physicians or no treatment), or (2) waiting for the control condition (parents will wait to start the program for 8 weeks) plus treatment-as-usual for patients. The primary outcome measure will be parents' active listening ability as measured by the Active Listening Attitude Scale at 8 weeks after randomization. Additionally, perception of social support (Social Provision Scale-10 item), loneliness (UCLA Loneliness Scale), mental health status (K6), family function (Family Assessment Device), and parent-evaluated eating disorder symptoms (Anorectic Behavior Observation Scale) will be assessed. Data from the intention-to-treat sample will be analyzed 8 weeks after randomization.
This is the first study to evaluate the effectiveness of a family education and support program for parents of patients with adolescent and early adulthood eating disorders based on IPT. If this type of intervention is effective, although indirect, it could be a new support method for this patient population.
Clinical Trials. gov ID NCT05840614.
We have exploited a compact and facile microfluidic droplet creation device consisting of a poly(dimethylsiloxane) microfluidic chip possessing T‐junction channel geometry, two inlet reservoirs, and ...one outlet reservoir, and a piezoelectric (PZT) diaphragm micropump with controller. Air was evacuated from the outlet reservoir using the PZT pump, reducing the pressure inside. The reduced pressure within the outlet reservoir pulled oil and aqueous solution preloaded in the inlet reservoirs into the microchannels, which then merged at the T‐junction, successfully forming water‐in‐oil emulsion droplets at a rate of ∼1000 per second with minimal sample loss. We confirmed that the onset of droplet formation occurred immediately after turning on the pump (<1 s). Over repeated runs, droplet formation was highly reproducible, with droplet size purity (polydispersity, <4%) comparable to that achieved using other microfluidic droplet preparation techniques. We also demonstrated single‐molecule PCR amplification in the created droplets, suggesting that the device could be used for effective droplet digital PCR platforms in most laboratories without requiring great expense, space, or time for acquiring technical skills.
Aims
We investigated the impact of actual waiting time and perceived waiting time on treatment satisfaction in patients with diabetes receiving outpatient care.
Methods
Three hundred and thirty-six ...outpatients diagnosed with diabetes mellitus or impaired glucose tolerance were selected and the time they spent in reception, blood collection, consultation, and accounting were recorded to measure the time they spent waiting in the hospital (actual waiting time). Simultaneously, we conducted a questionnaire survey that included questions on their perceptions of the waiting time (perceived waiting time) and satisfaction with treatment (DTSQ).
Results
No significant relationship was found between actual waiting time and DTSQ score, although associations were observed with perceived waiting time. The patients who felt the overall waiting time was long scored 23.0, those who felt it was short scored 26.0, and those who felt it was very short scored 34.0, with those who felt the waiting time was long having a significantly lower score (
p
= 0.004,
p
< 0.001, respectively) and those who felt it was short having a significantly lower score than those who felt it was very short (
p
= 0.008). In addition, more patients who felt the waiting time was long expressed dissatisfaction with the responses of doctors and staff than those who felt the waiting time was short.
Conclusions
These results suggest that in addition to reducing actual waiting times, shortening perceived waiting times by improving the responses of medical staff could help to increase patient satisfaction.
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