Surveys of full–coverage restorations made of titanium at Matsumoto Dental University Hospital

Considering the presence of metal allergies and the sharp rise in the prices of precious metals, full–coverage restorations made of titanium have been covered by Japanese insurance since June 1, 2020. The clinical application of these restorations is expected to increase in the future. However, due to its high melting point and high affinity to oxygen at high temperatures, titanium has not been widely used in prosthetic clinical practice. This study aimed to survey the actual use of full–coverage metal restorations at Matsumoto Dental University Hospital. Patients who had full–coverage metal restorations placed on their molars from June 1 to December 28, 2020, were consecutively enrolled, and data on the type of metal, placement site, and time were recorded. Besides, the dentists who used titanium restorations (Ti–Rs) were given a questionnaire. We asked them to rate their impressions of Ti–Rs in comparison with full–coverage restorations made of Ag–Pd–Cu–Au alloy (Pd–R) in six categories, including occlusal adjustment, polishing, and luting operations. In all, 338 molars received full–coverage metal restorations. Ti–R was used in 33 cases and Pd–R in 305 cases; 14 upper and 19 lower, 12 first molars, 18 second molars, and 3 third molars received Ti–Rs, while 137 upper and 168 lower, 174 first molars, 174 second molars, and 3 third molars received Pd–Rs. Seven dentists responded to the questionnaire survey. Many dentists stated that Ti–R was more challenging to use than Pd–R for occlusal adjustment, polishing, and adjustment time. On the other hand, most of them stated that the luting process was similar for both. Besides, Ti–R was favorably evaluated in terms of metal allergy. The number of patients who received Ti–Rs increased during the study period, suggesting that Ti–Rs will be a commonly used metal allergy–friendly prosthetic in the future. We plan to continue the survey and study the prognosis

CTが診断契機となったディスジャーミノーマIA期の再発症例

　ディスジャーミノーマの術後経過観察において、腫瘍マーカーや内診による身体診察が推奨される一方、CT検査での全身検索については一定の見解が得られていない。今回、ディスジャーミノーマIA期術後に、CTが診断契機となったディスジャーミノーマIA期の傍大動脈リンパ節への単独再発症例を経験したので報告する。　症例は17歳、未妊。下腹部痛を主訴に来院した。MRIで臍高に達する右卵巣の充実性腫瘍を認めた。血液検査にてLDH、ALP、CA125、β-human chorionic gonadotropin(β-hCG)は高値を示したが、α-fetoprotein(AFP)は正常値であった。ディスジャーミノーマを疑い、右付属器切除および大網切除を施行した。術前のCTおよび腹腔内検索でリンパ節腫大や播種性病変を認めなかったため、リンパ節生検は省略した。術後病理でディスジャーミノーマIA期と診断され、術後化学療法は行わず、1ヵ月間隔で経過観察した。術後いずれの腫瘍マーカーも陰性化し、身体診察でも異常を認めず経過したが、術後6ヵ月で虫垂炎を発症。その際に撮影されたCTで、偶発的に傍大動脈リンパ節腫大を認めた。腹腔鏡下傍大動脈リンパ節摘出および虫垂切除術を施行し、ディスジャーミノーマの傍大動脈リンパ節への遠隔再発と診断された。術後BEP療法を3コース行い、現在再発なく経過している。　リンパ節郭清および術後補助化学療法が省略されたディスジャーミノーマIA期は再発のリスクが高いことを認識し、CT検査を含む厳重な経過観察が必要であることが示唆された。(著者抄録

WDR55 Is a Nucleolar Modulator of Ribosomal RNA Synthesis, Cell Cycle Progression, and Teleost Organ Development

The thymus is a vertebrate-specific organ where T lymphocytes are generated. Genetic programs that lead to thymus development are incompletely understood. We previously screened ethylnitrosourea-induced medaka mutants for recessive defects in thymus development. Here we report that one of those mutants is caused by a missense mutation in a gene encoding the previously uncharacterized protein WDR55 carrying the tryptophan-aspartate-repeat motif. We find that WDR55 is a novel nucleolar protein involved in the production of ribosomal RNA (rRNA). Defects in WDR55 cause aberrant accumulation of rRNA intermediates and cell cycle arrest. A mutation in WDR55 in zebrafish also leads to analogous defects in thymus development, whereas WDR55-null mice are lethal before implantation. These results indicate that WDR55 is a nuclear modulator of rRNA synthesis, cell cycle progression, and embryonic organogenesis including teleost thymus development

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Endocrine, inflammatory and immune responses and individual differences in acute hypobaric hypoxia in lowlanders

Abstract When lowlanders are exposed to environments inducing hypobaric hypoxia (HH) such as high mountains, hemodynamic changes occur to maintain oxygen levels in the body. However, changes to other physiological functions under such conditions have yet to be clarified. This study investigated changes in endocrine, inflammatory and immune parameters and individual differences during acute HH exposure using a climatic chamber (75 min of exposure to conditions mimicking 3500 m) in healthy lowlanders. Aldosterone and cortisol were significantly decreased and interleukin (IL)-6, IL-8 and white blood cell (WBC) counts were significantly increased after HH. Lower peripheral oxygen saturation (SpO2) was associated with higher IL-6 and WBC counts, and higher IL-8 was associated with higher cortisol. These findings suggest that endocrine, inflammatory and immune responses are evoked even with a short 75-min exposure to HH and individuals with lower SpO2 seemed to show more pronounced responses. Our results provide basic data for understanding the physiological responses and interactions of homeostatic systems during acute HH

Efficacy of a Novel Augmented Reality Navigation System Using 3D Computer Graphic Modeling in Endoscopic Transsphenoidal Surgery for Sellar and Parasellar Tumors

In endoscopic transsphenoidal skull base surgery, knowledge of tumor location on imaging and the anatomic structures is required simultaneously. However, it is often difficult to accurately reconstruct the endoscopic vision of the surgical field from the pre-surgical radiographic images because the lesion remarkably displaces the geography of normal anatomic structures. We created a precise three-dimensional computer graphic model from preoperative radiographic data that was then superimposed on a visual image of the actual surgical field and displayed on a video monitor during endoscopic transsphenoidal surgery. We evaluated the efficacy of this augmented reality (AR) navigation system in 15 consecutive patients with sellar and parasellar tumors. The average score overall was 4.7 [95% confidence interval: 4.58–4.82], which indicates that the AR navigation system was as useful as or more useful than conventional navigation in certain patients. In two patients, AR navigation was assessed as less useful than conventional navigation because perception of the depth of the lesion was more difficult. The developed system was more useful than conventional navigation for facilitating an immediate three-dimensional understanding of the lesion and surrounding structures

Observation of Vertically Ejected Plumes Generated by the Impact of Hollow Projectiles at Various Velocities

Recently, impact experiments in space have been conducted in planetary exploration using hollow or internally structured projectiles. In laboratory experiments using hollow projectiles to investigate the differences in crater and ejecta from the case of solid projectiles, a plume perpendicular to the target surface has been observed, which has not been seen in conventional cratering experiments using solid projectiles. In this study, we conducted crater-formation experiments using hollow resin projectiles to understand the mechanism through which vertical plumes form in the case of hollow projectiles. We examined the generation of a vertical plume as a function of the impact velocity, v _imp . We found that (i) no vertical plume occurs at v _imp < 200 m s ^−1 , (ii) the cases with or without a vertical plume are mixed at 200 < v _imp < 350 m s ^−1 , (iii) no vertical plume occurs at 350 < v _imp < 800 m s ^−1 , and (iv) a vertical plume occurs at 2 < v _imp < 3 km s ^−1 . We qualitatively discussed the generation mechanism of the vertical plume using the results of recovered projectiles. Depending on v _imp , an empty hole in which there is no projectile materials can be opened along the central axis, resulting in the generation of a vertical plume