Shaving Papillary Thyroid Carcinoma Involving Functioning Recurrent Laryngeal Nerve: Safety of Incomplete Tumor Resection and Nerve Sparing.

BACKGROUND: Whether to sacrifice or spare the recurrent laryngeal nerve (RLN) when papillary thyroid carcinoma (PTC) involves a functioning RLN remains controversial. Oncological outcomes after shaving PTC with gross remnant on the RLN have been rarely reported. The objective of this study was to evaluate the oncological outcomes of patients who underwent shaving of a PTC from the RLN, leaving a gross residual tumor with the intent of vocal function preservation. METHODS: A retrospective, cohort study was conducted in 47 patients who were determined to have PTC invasion of the RLN via intraoperative inspection and underwent tumor shaving with macroscopic remnant (R2 resection) less than 1 cm in length and 4 mm in thickness. Median follow-up period was 93 (range, 60-215) months. The primary endpoint was the recurrence-free survival and the progression-free survival. Secondary endpoints were biochemical outcomes (serum thyroglobulin) and vocal cord function. RESULTS: Of the 47 patients, five (10.6%) patients showed recurrence (central neck, 3; lateral neck, 2) without death or distant metastasis. The RLN was resected along with the tumor in one (2.1%) patient who presented with progression of the residual tumor. Postoperative temporary vocal cord paralysis occurred in six (12.8%) patients without permanent cases. The final nonstimulated serum thyroglobulin was 0.7 ± 1.8 ng/ml. CONCLUSIONS: Shaving a tumor from a RLN with gross residual disease may be considered an alternative strategy to preserve vocal function when complete tumor resection with nerve preservation is impossible in patients with PTC invading a functioning RLN.

Characteristics of plaque lipid-associated macrophages and their possible roles in the pathogenesis of atherosclerosis.

PURPOSE OF REVIEW: Recent findings from single-cell transcriptomic studies prompted us to revisit the role of plaque foamy macrophages in the pathogenesis of atherosclerosis. In this review, we compared the gene expression profile of plaque foamy macrophages with those of other disease-associated macrophages and discussed their functions in the pathogenesis of atherosclerosis. RECENT FINDINGS: To understand the phenotypes of macrophages in atherosclerotic aorta, many research groups performed single-cell RNA sequencing analysis and found that there are distinct phenotypic differences among intimal foamy, nonfoamy and adventitial macrophages. Especially, the plaque foamy macrophages express triggering receptor expressed on myeloid cells 2 (TREM2), a key common feature of disease-associated macrophages in Alzheimer's disease, obesity, cirrhosis and nonalcoholic steatohepatitis. These TREM2 + macrophages seem to be protective against chronic inflammation. SUMMARY: As the gene expression profile of plaque foamy macrophages is highly comparable to that of lipid-associated macrophages from obesity, we named the plaque foamy macrophages as plaque lipid-associated macrophages (PLAMs). PLAMs have a high level of gene expression related to phago/endocytosis, lysosome, lipid metabolism and oxidative phosphorylation. Considering the protective function of lipid-associated macrophages against adipose tissue inflammation, PLAMs may suppress atherosclerotic inflammation by removing modified lipids and cell debris in the plaque.

Structure-based inhibitor design for reshaping bacterial morphology.

The spiral shape of intestinal pathogen Campylobacter jejuni is critical for invasion of intestinal mucosa epithelial cells. Insofar as this cell morphology plays a role in the pathology of C. jejuni infection, its restructuring by pharmacological intervention could be an unexplored means to prevention of infection. We recently described that peptidoglycan hydrolase 3 (Pgp3) is involved in the spiral-shape formation of C. jejuni. We report herein the design and synthesis of the hydroxamate-based inhibitors targeting Pgp3. C. jejuni cells exposed to these inhibitors changed from the helical- to rod-shaped morphology, comparable to the case of the pgp3-deletion mutant. Evidence for the mechanism of action was provided by crystal structures of Pgp3 in complex with inhibitors, shedding light into the binding modes of inhibitors within the active site, supported by kinetics and molecular-dynamics simulations. C. jejuni exposed to these inhibitors underwent the morphological change from helical- to rod-shaped bacteria, an event that reduce the ability for invasion of the host cells. This proof of concept suggests that alteration of morphology affects the interference with the bacterial infection.

Radiation Safety in Videofluoroscopic Swallowing Study: Systematic Review.

Videofluoroscopic swallowing study (VFSS) is generally used to diagnose dysphagia and oropharyngeal aspiration during swallowing movement. Patients and bolus-feeding operators (such as occupational therapist and speech language pathologist) may undergo multiple VFSS procedure, placing them at risk for more radiation exposure due to increased scan time. The present study investigated the dose-area product, effective dose of various protocols, and summarized dose reports from various studies of VFSS. The PubMed database searched for relevant publications reporting radiation dose in the VFSS procedure. 13 articles were selected to be reviewed. This systematic review involved 13 peer-reviewed articles that reported the specific dose of the VFSS procedure. The articles were categorized into three types: operator radiation dose, adult patient radiation dose, and pediatric radiation dose. The operator dose reports showed that the operators' scattering exposure, equivalent dose (across the whole body, eyes, and hands), and annual effective dose were significantly lower than the annual dose limit of 20 mSv. Both adult and pediatric patient dose reports showed that the effective dose, which was estimated from recorded dose-area product, was significantly lower than the annual background exposure of 2.4 mSv in various protocols. The present literature review suggested that the radiation dose of VFSS by modified barium swallowing is acceptable in both operators and patients. However, various radiation protection strategies should be conducted during the procedure to reduce the risk of stochastic effect.

Information and Communications Technology-Based Telehealth Approach for Occupational Therapy Interventions for Cancer Survivors: A Systematic Review.

(1) Background: Occupational therapy (OT) practice has a unique perspective that addresses the complex needs of cancer survivors. Despite the expanded research and application of OT services using telehealth (TH) to promote clients' health and well-being, studies on OT services using TH for cancer survivors are rare. This study aimed to review the TH approaches in the scope of OT and the outcome of factors affecting occupational engagement in adult cancer survivors. (2) Materials and Methods: This systematic review performed a literature search of five databases (Medline Complete, PubMed, CINAHL, PsycINFO, Web of Science) using a combination of keywords and cross-referencing. Studies were included if they described a TH intervention within the scope of OT practice to improve occupational engagement. (3) Results: Fifteen studies (12 randomized controlled trials, three quasiexperimental studies) were reviewed. Physical activity had a positive effect on physical and cognitive function. Symptom self-management showed positive effects on the relief of symptom burden. Psychosocial interventions, which included cognitive behavioral therapy, problem-solving, cognitive behavioral therapy for insomnia, mind-body training, reduced sleep disturbance, and improved physical activity. Lifestyle behavior change interventions improved participation in moderate-intensity physical activity and diet quality. In addition, these interventions reduced cancer-related symptoms such as pain, depression, fatigue, distress, and improved quality of life. There were no direct outcomes of occupational engagement, excluding sleep, that could be confirmed through this review. (4) Conclusion: This review explored and confirmed the usefulness of TH approaches in the scope of OT practice in adult cancer survivors. It also supports the notion that OT-specific research using TH interventions for cancer survivors will be needed in the future.

Development of a dried blood spot sampling method towards therapeutic monitoring of radotinib in the treatment of chronic myeloid leukaemia.

WHAT IS KNOWN AND OBJECTIVE: Dried blood spot (DBS) sampling is a minimally invasive method of blood sampling that enables monitoring of drug concentrations to be more convenient. This study aimed at developing a DBS sampling method for an accurate and precise prediction of radotinib plasma concentrations (Cp ) in patients with chronic myeloid leukaemia (CML). METHODS: Dried blood spot and venous blood samples were simultaneously collected from fifty CML patients who had been receiving radotinib for at least a week. Radotinib concentrations were measured using a high-performance liquid chromatographic method with tandem mass spectrometric detection. Unmeasured Cp was predicted directly based on a Deming regression between DBS concentrations (CDBS ) and Cp . Unmeasured Cp was also predicted from CDBS corrected by each patient's haematocrit (Hct). Both prediction methods were evaluated for their accuracy and precision using Deming regression and Bland-Altman analysis. RESULTS AND DISCUSSION: The Deming regression equation between CDBS and Cp was obtained as follows: Cp  = 1.34∙CDBS  + 4.26 (r2  = .97). Cp was directly predictable using Cp,pred1  = 1.34∙CDBS  + 4.26. With Hct correction, Cp was alternatively predictable using Cp,pred2  = CDBS / (1-Hct + Hct2 ). The slopes of Deming regression line between predicted and measured Cp were 0.99 and 1.02 for the direct and Hct-corrected method, respectively. The mean biases (accuracy) were -0.44% and 1.6% with the 95% limits of agreement (precision) of -22.4% to 21.5% and -20.5% to 23.7%, respectively. More than 93% of predicted and measured Cp pairs had their differences within 20% of the mean of each pair in both methods. WHAT IS NEW AND CONCLUSIONS: Radotinib CDBS are highly correlated with radotinib Cp. Radotinib Cp can be accurately and precisely predicted from CDBS using direct or Hct-corrected prediction methods. Both appear to be appropriate for the therapeutic monitoring of radotinib in patients with CML.

Tyrosinase inhibitory components from the seeds of Cassia tora.

Ten compounds (1-10) isolated from the seeds of Cassia tora were evaluated for tyrosinase inhibition. Compounds 3, 4, and 7 inhibited tyrosinase enzymatic activity in a dose-dependent manner, with IC50 values of 3.0 ± 0.8, 7.0 ± 0.4, and 9.2 ± 3.4 µM, respectively. Kinetic analyses revealed a mechanism consistent with competitive inhibition. In silico molecular docking showed that compounds 3 and 4 docked in the active site of tyrosinase, whereas 7 interacted with Ala246 and Val248 at outside of the active site, and His244 and Glu256 at inside. Additionally, compounds 3, 4, and 7 suppressed melanogenesis in α-MSH-treated B16F10 melanoma cells at a concentration of 10 µM.

Asymmetric dumbbell-shaped silver nanoparticles and spherical gold nanoparticles green-synthesized by mangosteen (Garcinia mangostana) pericarp waste extracts.

Mangosteen (Garcinia mangostana) pericarp waste extract was used to synthesize gold and silver nanoparticles by a green strategy. The extract was both a reducing and stabilizing agent during synthesis. Phytochemical screening of the extract was conducted to obtain information regarding the presence/absence of primary and secondary metabolites in the extract. The in vitro antioxidant activity results demonstrated that the extract had excellent antioxidant activity, which was comparable to a standard (butylated hydroxy toluene). Spherical gold nanoparticles (gold nanoparticles green synthesized by mangosteen pericarp extract [GM-AuNPs]) with an average size of 15.37±3.99 to 44.20±16.99 nm were observed in high-resolution transmission electron microscopy (HR-TEM) images. Most interestingly, the silver nanoparticles (silver nanoparticles green synthesized by mangosteen pericarp extract [GM-AgNPs]) had asymmetric nanodumbbell shapes where one tail grew from a spherical head. The average head size was measured to be 13.65±5.07 to 31.08±3.99 nm from HR-TEM images. The hydrodynamic size of both nanoparticles tended to increase with increasing extract concentration. Large negative zeta potentials (-18.92 to -34.77 mV) suggested that each nanoparticle solution possessed excellent colloidal stability. The reaction yields were 99.7% for GM-AuNPs and 82.8% for GM-AgNPs, which were assessed by inductively coupled plasma optical emission spectroscopy. A high-resolution X-ray diffraction pattern confirmed the face-centered cubic structure of both nanoparticles. Based on phytochemical screening and Fourier transform infrared spectra, the hydroxyl functional groups of carbohydrates, flavonoids, glycosides, and phenolic compounds were most likely involved in a reduction reaction of gold or silver salts to their corresponding nanoparticles. The in vitro cytotoxicity (based on a water-soluble tetrazolium assay) demonstrated that GM-AgNPs were toxic to both A549 (a human lung cancer cell) and NIH3T3 (a mouse fibroblast cell). The cytotoxicity of GM-AgNPs on A549 cells was related to apoptotic cell death. However, GM-AuNPs did not show any significant cytotoxicity to either cell. These results suggest that GM-AuNPs have the potential to be drug delivery vehicles or carriers for pharmaceutical and biomedical applications.

Clinical implications of microscopic extrathyroidal extension in patients with papillary thyroid carcinoma.

BACKGROUND: Extrathyroidal extension (ETE) is a poor prognostic factor in papillary thyroid carcinoma (PTC). However, the impact of the degree of ETE, especially microscopic ETE, has not been well established. The purpose of present study was to compare differences in clinicopathological characteristics and clinical outcomes according to the presence or extent of ETE. METHODS: Data from 381 patients who underwent total thyroidectomy with/without lymph node (LN) dissection for PTC between 2004 and 2010 were analyzed. Clinicopathological features such as age, gender, LN metastasis, capsular invasion, lymphovascular invasion, and recurrence were compared among three groups divided according to degree of ETE: no ETE (n=144), microscopic ETE (n=191), and macroscopic ETE (n=46). RESULTS: Tumor size, LN metastasis, lymphovascular invasion, extent of surgery, and administration of postoperative radioactive iodine (RAI) were significantly correlated with degree of ETE. Especially, among the patients with a primary tumor size ≤4cm, the patients with microscopic ETE showed more LN metastasis and lymphovascular invasion than those without ETE, whereas less LN metastasis and lymphovascular invasion than those with macroscopic ETE. In addition, the microscopic ETE group had a significantly lower 5-year recurrence free survival (RFS) than the no-ETE group (92.1% vs. 99.3%, p<0.001) and a significantly higher 5-year RFS than the macroscopic ETE group (92.1% vs. 65.2%, p<0.001). CONCLUSIONS: The degree of ETE is correlated with clinicopathologic features and tumor recurrence. Patients with microscopic ETE have a poorer clinical outcome than those without ETE, but they showed a better outcome than patients with macroscopic ETE.

Headspace-solid phase microextraction-gas chromatography-tandem mass spectrometry (HS-SPME-GC-MS2) method for the determination of pyrazines in perilla seed oils: impact of roasting on the pyrazines in perilla seed oils.

A new headspace (HS)-solid phase microextraction (SPME)-gas chromatography-tandem quadrupole mass spectrometry (GC-MS(2)) was established for the simultaneous characterization and quantitation of pyrazines in perilla seed oils. HS-SPME conditions such as fiber choice, extraction temperature, and adsorption times were tested. The established GC-MS(2) showed low detection limit (LOD) and high specificity, recovery, and precision for analysis of pyrazines in perilla seed oils. The LODs for the pyrazines were in the range of 0.07-22.22 ng/g oil. The relative standard deviations (RSDs) for the intra- and interday repeated analyses of pyrazines were less than 9.49 and 9.76%, respectively. The mean recoveries for spiked pyrazines in perilla seed oil were in the range of 94.6-107.92%. Perilla seed oils were obtained by mechanical pressing from perilla seeds roasted to different degrees of roasting (mild, medium, medium dark, and dark roasting). Fourteen pyrazine compounds in perilla seed oils were isolated, identified, and quantitated. Among them, 2-methyl-3-propylpyrazine, tetramethylpyrazine, and 2,3-diethyl-5-methylpyrazine were the first identified in perilla seed oils. Degree of roasting influenced greatly the composition and contents of pyrazines in perilla seed oils. In light-roasted perilla seed oil, 2,5-dimethylpyrazine was the most predominant pyrazine. However, in dark-roasted perilla seed oil, 2-methylpyrazine was the most abundant pyrazine in the oil, representing 38.3% of its total pyrazine content. Dark-roasted perilla seed oil contains 16.78 times higher quantity of pyrazines than light-roasted perilla seed oil. This represents the first report on the quantity of pyrazines in perilla seed oils.