Perfusion quantification using dynamic contrast-enhanced ultrasound: The impact of dynamic range and gain on time-intensity curves

The objective of this study was to assess the impact of dynamic range and gain on perfusion quantification using linearized log-compressed data. An indicator-dilution experiment was developed with an in vitro flow phantom setup used with SonoVue contrast agent (Bracco SpA, Milan, Italy). Imaging was performed with a Philips iU22 scanner and a C5-1 curvilinear transducer using a contrast-specific nonlinear pulse sequence (power modulation) at 1.7 MHz. Clinical dynamic contrast-enhanced ultrasound image loops of liver tumors were also collected for preliminary validation of the in vitro findings. Time-intensity curves were extracted from image loops with two different approaches: from linearized log-compressed data and from linear (uncompressed) data. The error of time-intensity curve parameters derived from linearized log-compressed data (deviation from linear data) was found to be less than 2.1% and 5.4% for all studied parameters in the in vitro experiment and in the clinical study, respectively, when a high dynamic range setting (at least 50 dB on the iU22) is used. The gain must be carefully adjusted to ensure a high signal-to-noise ratio and to avoid signal saturation. From the time-intensity curve analysis it was also found that rise time of the bolus time-intensity curve is the least variable of all the studied time-intensity curve parameters.     

Effects of Massage Therapy and Occlusal Splint Usage on Quality of Life and Pain in Individuals with Sleep Bruxism: A Randomized Controlled Trial

Purpose: The aim of the present study was to investigate the effects of massage therapy on the masticatory muscles and occlusal splint usage on quality of life and pain in individuals with sleep bruxism. Method: A randomized, controlled, blinded, clinical trial was conducted involving 78 volunteers aged 18 to 40 years with sleep bruxism. Quality of life and pain assessments were performed. Results: Significant differences (p < 0.05) were found on the physical functioning, general health state, vitality, role emotional and mental health subscales. A large effect size was found for all treatment protocols with regard to pain. The largest effect was found in the combined treatment group. Conclusions: The findings of the present study reveal that the occlusal splint usage alone led to improvements in components of quality of life among individuals with sleep bruxism. Moreover, both treatments (occlusal splint usage and massage therapy on the masticatory muscles) led to a reduction in pain.     

Recent progress in the detection and treatment of atherosclerosis by nanoparticles

Cardiovascular diseases (CVDs) have high mortality and morbidity in the US and presently rank as one of the leading causes of death. Atherosclerosis (AS) acts as one of the CVDs, playing an important role in mortality because of many lethal complications. The common cause of AS is that low-density lipoprotein (LDL) in the blood circulation enters the intima through endothelial cells that have been broken for various reasons. Under the action of inflammatory factors secreted by damaged endothelial cells, monocytes also enter the inner membrane and differentiate into macrophages. Macrophages engulf the oxidized LDL and become foam cells which eventually become apoptotic. However, recent studies have shown that LDL entry into the intima, an important step in AS, may be associated with endothelial cells actively inhaling LDL through the receptor. Nanotechnology is a promising technology that can be applied in the noninvasive imaging and therapy of AS. Nanoparticles (NPs) have the ability to passively target AS because of their inherent small diameter. They can also be loaded with chemicals for targeting lesions, contrast agents for imaging, and drugs for treatment to achieve accurate diagnosis and treatment of AS. This review consequently highlights the recent progress in the detection and treatment of AS by NPs.     

Etiology and treatment of psychogenic voice disorder:Results of a follow-up study of thirty patients

It is generally accepted that psychogenic voice disorder (PVD) is aresult of psychosocial stress; however, systematic studies of etiological factors in this condition are few. Furthermore, although immediate effects of therapy are estimated to be good, relapses are frequent, and the long-term effects of therapy are not known. The present prospective and longitudinal study on 30 patients was thus focused on possible etiological factors, the course of therapy, and the long-term results of therapy for PVD. The results indicate that interpersonal conflicts related to family and work are of basic importance in precipitating this condition. PVD is interpreted as a specific disorder of verbal emotional expression. Our therapy model in which vocal exercises are performed, together with training of communicative skills, seems rewarding. Relapses were not reported in 88% of the patients during the followup period of 1.9-8.4 years after therapy.     

Use of micellar liquid chromatography to analyze darunavir,ritonavir, emtricitabine,and tenofovir in plasma

Danuravir, ritonavir, emtricitabine, and tenofovir are together prescribed against AIDS as a highly active antiretroviral therapy regimen. Micellar liquid chromatography has been applied to determine these four antiretroviral drugs in plasma. The sample preparation is shortened to the dilution of the sample in a micellar solution, filtration, and injection. Clean‐up steps are avoided, due to the solubilization of plasma matrix in micellar media. The drugs were analyzed in <20 min using a mobile phase of 0.06 M sodium dodecyl sulfate/2.5% 1‐pentanol (pH 7) running under isocratic mode through a C₁₈ column at 1 mL/min at room temperature. Absorbance wavelength detection was set at 214 nm. The method was successfully validated following the ICH Harmonized Tripartite Guideline in terms of selectivity, limit of detection (0.080–0.110 μg/mL), limit of quantification (0.240–0.270 μg/mL), linearity between 0.25 and 25 μg/mL (r² > 0.995), accuracy (89.3–103.2%), precision (<8.2%) and robustness (<7.5%). Real plasma sample from patients taking this therapy were analyzed. This is the first paper showing the simultaneous detection of this four drugs. Therefore, the methodology was proven useful for the routine analysis of these samples in a hospital laboratory for clinical purposes.     

Aerodynamic, laryngoscopic, and perceptual-acoustic characteristics in dysphonic females with posterior glottal chinks: A retrospective study

The relationships of posterior glottal chink magnitude and nodule size with phonatory flow rate, resistance, and breathiness were investigated in 70 women in a retrospective study. Results demonstrated a strong relationship between chink size airflow, but no relationship between nodule size and airflow. Resistance and nodule size were moderately correlated. Breathiness was not explained by airflow, nodule size, or chink magnitude. Subjects in therapy demonstrated concurrent reductions in airflow and chink size. For the laryngeal magnitude measures, visual-perceptual ratings were compared with computer-based measurements. The discussion includes a critical analysis of measurement methods and directions for future research.     

The value of diffusion-weighted MRI to evaluate the response to radiochemotherapy for cervical cancer

Purpose

To investigate the value of apparent diffusion coefficient (ADC) to predict and monitor the therapy response for cervical cancer patients receiving concurrent radiochemotherapy, and to analyze the influence of different b-value combinations on ADC-based evaluation of treatment response.

Material and Methods

Seventy-five cervical cancer patients treated with radiochemotherapy received conventional MRI and DWI prior to therapy, after 2 weeks of therapy, after four weeks of therapy and after therapy completion. Treatment response was classified as complete response (CR, n = 35), partial response (PR, n = 22) and stable disease (SD, n = 18), which was determined according to final tumor size after 6 months of therapy completion. Dynamic changes of apparent diffusion coefficients (ADC) and tumor size in the three tumor groups were observed and compared. All the ADCs were calculated from b = 0, 600 s/mm² and b = 0, 1000 s/mm².

Results

The ADC increased percentage was higher in CR group than those in PR and SD groups after two weeks and four weeks of therapy, with significant differences in absolute ADCs between CR and PR, SD groups after therapy completion; the overall discriminatory capability for differentiation of CR and PR, SD groups was higher for high b-value combination (0, 1000 s/mm²) than for low b-value combination (0, 600 s/mm²).

Conclusion

DWI can be used as a predictive and monitoring biomarker of treatment response to radiochemotherapy in patients with cervical cancer. High b-value combination may be more reliable to evaluate the treatment response for cervical cancer.     

Dendronized DNA Chimeras Harness Scavenger Receptors To Degrade Cell Membrane Proteins

Bispecific chimeras bridging cell membrane proteins with lysosome-trafficking receptors (LTRs) provide an effective therapeutic approach through lysosomal degradation of disease-relevant targets. Here, we report a novel dendronized DNA chimera (DENTAC) strategy that uses a dendritic DNA to engage cell surface scavenger receptors (SRs) as LTR. Using bioorthogonal strain-promoted alkyne-azide cycloaddition to conjugate the dendritic DNA with protein binder, the resulting DENTAC is able to traffic the protein target into the lysosome for elimination. We demonstrated the utility of DENTAC by degrading oncogenic membrane nucleolin (NCL) and epidermal growth factor receptor (EGFR). The anti-cancer application of NCL-targeting DENTAC was validated in a mouse xenograft model of lung cancer. This work thus presents a new avenue for rapid development of potent degraders against membrane proteins, with also broad research and therapeutic prospects.     

Using Biological Photophysics to Map the Excited-State Topology of Molecular Photosensitizers for Photodynamic Therapy

This study employs TLD1433, a Ru^II-based photodynamic therapy (PDT) agent in human clinical trials, as a benchmark to establish protocols for studying the excited-state dynamics of photosensitizers (PSs) in cellulo, in the local environment provided by human cancer cells. Very little is known about the excited-state properties of any PS in live cells, and for TLD1433, it is terra incognita. This contribution targets a general problem in phototherapy, which is how to interrogate the light-triggered, function-determining processes of the PSs in the relevant biological environment, and establishes methodological advances to study the ultrafast photoinduced processes for TLD1433 when taken up by MCF7 cells. We generalize the methodological developments and results in terms of molecular physics by applying them to TLD1433’s analogue TLD1633, making this study a benchmark to investigate the excited-state dynamics of phototoxic compounds in the complex biological environment.     

A DNA-Gated and Self-Protected Bioorthogonal Catalyst for Nanozyme-Assisted Safe Cancer Therapy

Transition metal catalysts (TMCs) mediated bioorthogonal uncaging catalysis has sparked increasing interest in prodrug activation. However, due to their “always-on” catalytic activity as well as the complex and catalytic-detrimental intracellular environment, the biosafety and therapeutic efficiency of TMCs are unsatisfactory. Herein, a DNA-gated and self-protected bioorthogonal catalyst has been designed by modifying nanozyme-Pd⁰ with highly programmable nucleic acid (DNA) molecules to achieve efficient intracellular drug synthesis for cancer therapy. Monolayer DNA molecules could endow the catalyst with targeting and perform as a gatekeeper to achieve selective prodrug activation within cancer cells. Meanwhile, the prepared graphitic nitrogen-doped carbon nanozyme with glutathione peroxidase (GPx) and catalase (CAT)-like activities could improve the catalytic-detrimental intracellular environment to prevent the catalyst from being inactivated and sensitize the subsequent chemotherapy. Overall, we believe that our work will promote the development of secure and efficient bioorthogonal catalytic systems and provide new insights into novel antineoplastic platforms.