Impact of Low Skeletal Muscle Mass on the Prognosis of Patients with Head and Neck Cancer Treated Nonsurgically.

INTRODUCTION: Sarcopenia, characterized by low skeletal muscle mass, and the outcome of cancer therapy are closely related based on recent research. This study aimed to evaluate the correlation between skeletal muscle mass and prognosis in head and neck cancer (HNC) patients. METHODS: In this study, 51 male patients with HNC treated nonsurgically between January 2016 and April 2018 at Shinshu University Hospital were evaluated. Skeletal muscle mass was assessed using bioelectrical impedance analysis, and the skeletal mass index (SMI) was calculated to classify the patients. RESULTS: The low-SMI group had a significantly worse overall survival (OS) than the normal-SMI group (3-year OS: 72.0% vs. 93.0%, p = 0.014), and there was a trend toward worse progression-free survival (PFS) in the low-SMI group (3-year PFS: 49.6% vs. 79.3%, p = 0.064). Multivariate analysis also showed that low SMI (p = 0.04) and severe N stage (p = 0.009) were significantly associated with poorer OS. CONCLUSION: The pretreatment assessment of SMI using bioelectrical impedance analysis is useful for identifying patients with poor prognoses. To improve the treatment outcome in HNC, we need to think of the intervention, such as cancer rehabilitation and nutritional support, during or before treatment, especially for patients with low SMI.

Human deafness-associated variants alter the dynamics of key molecules in hair cell stereocilia F-actin cores.

Stereocilia protrude up to 100 µm from the apical surface of vertebrate inner ear hair cells and are packed with cross-linked filamentous actin (F-actin). They function as mechanical switches to convert sound vibration into electrochemical neuronal signals transmitted to the brain. Several genes encode molecular components of stereocilia including actin monomers, actin regulatory and bundling proteins, motor proteins and the proteins of the mechanotransduction complex. A stereocilium F-actin core is a dynamic system, which is continuously being remodeled while maintaining an outwardly stable architecture under the regulation of F-actin barbed-end cappers, severing proteins and crosslinkers. The F-actin cores of stereocilia also provide a pathway for motor proteins to transport cargos including components of tip-link densities, scaffolding proteins and actin regulatory proteins. Deficiencies and mutations of stereocilia components that disturb this "dynamic equilibrium" in stereocilia can induce morphological changes and disrupt mechanotransduction causing sensorineural hearing loss, best studied in mouse and zebrafish models. Currently, at least 23 genes, associated with human syndromic and nonsyndromic hearing loss, encode proteins involved in the development and maintenance of stereocilia F-actin cores. However, it is challenging to predict how variants associated with sensorineural hearing loss segregating in families affect protein function. Here, we review the functions of several molecular components of stereocilia F-actin cores and provide new data from our experimental approach to directly evaluate the pathogenicity and functional impact of reported and novel variants of DIAPH1 in autosomal-dominant DFNA1 hearing loss using single-molecule fluorescence microscopy.

Microfabrication of Gelatin Methacrylate/Hydroxyapatite Composites by Utilizing Alternate Soaking Process.

To construct a complex three-dimensional (3D) structure mimicking bone microstructure, hydrogel models of polymerized gelatin methacrylate (pGelMA) were fabricated by using stereolithography and modified with hydroxyapatite (HAp) via an alternate soaking process (ASP) using a solution of calcium and phosphate ions. Fabricated pGelMA line models whose widths were designed as 100, 300, and 600 µm were modified with HAp by ASP by changing the immersion time and number of cycles. After ASP, all of the line models with widths of 100, 300, and 600 µm were successfully modified with HAp, and large amounts of HAp were covered with the fabricated models by increasing both the immersion time and the number of cycles in ASP. HAp was observed near the surface of the line model with a width of 600 µm after ASP at an immersion time of 10 s, while the entire model was modified with HAp using ASPs for longer immersion times. The adhesion and spread of mesenchymal stem cells (MSCs) on the pGelMA-HAp discs depended on the ASP conditions. Moreover, the HAp modification of 3D pyramid models without alteration of the microstructure was also conducted. This two-step fabrication method of first fabricating frameworks of hydrogel models by stereolithography and subsequently modifying the fabricated models with HAp will lead to the development of 3D cell culture systems to support bone grafts or to create biological niches, such as artificial bone marrow.

Hydroxyapatite Particles from Simulated Body Fluids with Different pH and Their Effects on Mesenchymal Stem Cells.

Bone-like hydroxyapatite (HAp) has been prepared by biomimetic synthesis using simulated body fluid (SBF), mimicking inorganic ion concentrations in human plasma, or 1.5SBF that has 1.5-times higher ion concentrations than SBF. In this study, the controllable preparations of HAp particles from 1.5SBF with different pH values were examined. The particles obtained as precipitates from 1.5SBF showed different morphologies and crystallinities depending on the pH of 1.5SBF. Micro-sized particles at pH 7.4 of 1.5SBF had a higher Ca/P ratio and crystallinity as compared with nano-sized particles at pH 8.0 and pH 8.4 of 1.5SBF. However, a mixture of micro-sized and nano-sized particles was obtained from pH 7.7 of 1.5SBF. When Ca2+ concentrations in 1.5SBF during mineralization were monitored, the concentration at pH 7.4 drastically decreased from 12 to 24 h. At higher pH, such as 8.0 and 8.4, the Ca2+ concentrations decreased during pH adjustment and slightly decreased even after 48 h. In this investigation at pH 7.7, the Ca2+ concentrations were higher than pH 8.0 and 8.4.Additionally, cytotoxicity of the obtained precipitates to mesenchymal stem cells was lower than that of synthetic HAp. Controllable preparation HAp particles from SBF has potential applications in the construction of building components of cell scaffolds.

Genetic testing has the potential to impact hearing preservation following cochlear implantation.

Background: Recent advances in less-invasive surgery and electrode design allow for a high degree of hearing preservation (HP) after cochlear implantation (CI), although residual hearing still deteriorates in some patients. To date, the factors predictive of preserving residual hearing remain a controversial topic.Objective: The aim of this study was to investigate the predictive factors, including the etiology of hearing loss (HL) as a patient-related factor, influencing residual HP after CI.Methods: Forty-four patients (50 ears, 41 families) with residual acoustic hearing who underwent CI were included. Auditory thresholds before and at 6 months after initial activation were measured. Genetic testing was performed to identify the responsible genes for HL.Results: We identified the cause of HL in 21 families (51.2%). HP was marginally correlated with age at implantation, while it was independent of pre-operative low-frequency hearing thresholds, cochlear duct length, and electrode length. We found that patients who had pathogenic variants in the CDH23, MYO7A, or MYO15A gene showed statistically better HP scores compared with patients with HL due to other causes (p = .002).Conclusions: Identification of the etiology of HL using genetic testing is likely to facilitate the prediction of HP after implant surgery.

Novel ACTG1 mutations in patients identified by massively parallel DNA sequencing cause progressive hearing loss.

Human ACTG1 mutations are associated with high-frequency hearing loss, and patients with mutations in this gene are good candidates for electric acoustic stimulation. To better understand the genetic etiology of hearing loss cases, massively parallel DNA sequencing was performed on 7,048 unrelated Japanese hearing loss probands. Among 1,336 autosomal dominant hearing loss patients, we identified 15 probands (1.1%) with 13 potentially pathogenic ACTG1 variants. Six variants were novel and seven were previously reported. We collected and analyzed the detailed clinical features of these patients. The average progression rate of hearing deterioration in pure-tone average for four frequencies was 1.7 dB/year from 0 to 50 years age, and all individuals over 60 years of age had severe hearing loss. To better understand the underlying disease-causing mechanism, intracellular localization of wild-type and mutant gamma-actins were examined using the NIH/3T3 fibroblast cell line. ACTG1 mutants p.I34M p.M82I, p.K118M and p.I165V formed small aggregates while p.R37H, p.G48R, p.E241K and p.H275Y mutant gamma-actins were distributed in a similar manner to the WT. From these results, we believe that some part of the pathogenesis of ACTG1 mutations may be driven by the inability of defective gamma-actin to be polymerized into F-actin.

Adhesion properties of a putative polymorphic fimbrial subunit protein from Bifidobacterium longum subsp. longum.

In our previous study, we found that the open reading frame bl0675 in the genome of Bifidobacterium longum subsp. longum isolated from human feces encoded a novel putative fimbrial protein, was highly polymorphic, and had five variants (A, B, C, D, and E types). The aim of this study was to evaluate the affinity of these variants to porcine colonic mucins (PCMs). Protein-binding properties were examined using the recombinant BL0675 protein containing a C-terminal 6 × His tag (His-BL0675). Surface plasmon resonance analysis demonstrated that the His-BL0675 A type had strong affinity to PCMs (KD = 9.82 × 10(-8) M), whereas the B, C, D, and E types exhibited little or no binding. In a competitive enzyme-linked immunosorbent assay, His-BL0675 A type binding was reduced by addition of mucin oligosaccharides, suggesting that the binding occurs via carbohydrate chains of PCMs. The localization of BL0675 to the B. longum subsp. longum cell surface was confirmed by western blot analysis using A type polyclonal antibodies. Bacterial adhesion of B. longum subsp. longum to PCMs was also blocked by A type-specific antibodies; however, its adhesion properties were strain specific. Our results suggest that the BL0675 variants significantly contribute to the adhesion of B. longum subsp. longum strains. The expression and the adhesive properties of this protein are affected by genetic polymorphisms and are specific for B. longum subsp. longum strains. However, further studies are required on the properties of binding of these putative fimbrial proteins to the human gastrointestinal tract.

Ferromagnetic Interaction between Aminium Radical Centers through m-Phenylene and m-1,3,5-Triazinediyl.

Ab initio MO study (at the ROHF, GVB, and CASSCF levels) of m-phenylenediamine (1) and 2,4-diamino-1,3,5-triazine (2) dication diradicals, which are model molecules of two possible high-spin polymers, poly(m-aniline) and poly(imino-1,3,5-triazinediyl) cation radicals, is presented. On the basis of qualitative MO considerations, it was seen that the electronic structures of 1(2+) and 2(2+) differed considerably. The singlet-triplet splittings (DeltaE(S)(-)(T)) of 1(2+) and 2(2+) were calculated to be 0.7 and 12.5 kcal/mol, respectively, at the CASPT2 level. m-1,3,5-Triazinediyl is shown to be a strong ferromagnetic coupler for aza-substituted systems.