Investigation of emission plane control in GaInN/GaN multiple-quantum shells for efficient nanowire-based LEDs.

Significant attention has been directed toward core-shell GaInN/GaN multiple-quantum shell (MQS) nanowires (NWs) in the context of high-efficiency micro light-emitting diodes (micro-LEDs). These independent three-dimensional NWs offer the advantage of reducing the impact of sidewall etching regions. Furthermore, the emitting plane on the sidewalls demonstrates either nonpolar or semipolar orientation, while the dislocation density is exceptionally low. In this study, we assessed how changes in the NW morphology are affected by GaInN/GaN superlattice (SL) structures grown at varying growth temperatures, as well as control of the emission plane via the p-GaN shell and emission sizes. The SL growth rate was enhanced at elevated growth temperatures, accompanied by the shrinkage of the (0001)-plane and expansion of the (11̄01)-plane on the NWs. The samples exhibited a higher light output when the SLs were grown at elevated temperatures compared to those grown with lower temperatures. A similar trend was observed for the samples with a gradual temperature transition during the growth. These findings indicate that the dimensions of the (0001)-plane can be controlled through SL growth, which in turn influences the emission properties of NW-LEDs. In addition, the emission properties of NW-LEDs with different growth time p-GaN shells and different emission sizes were investigated. Based on the NW-LED characteristics, it was revealed that the weak emission of the (0001)-plane was the dominant factor for the limited light output, and the most effective way to realize high efficiency devices is to suppress current injection into the apex or minimize the grown (0001)-plane region. Overall, it is one promising way to control the emission planes of NWs, which holds significant relevance for the potential application of NW-LEDs in the realm of micro-LEDs.

Utility of prognostic nutritional index and systemic immune-inflammation index in oral cancer treatment.

PURPOSE: This study aimed to evaluate the utility of inflammation-based prognostic scores (IBPS) and systemic immune-inflammation index (SII) in the treatment of oral cancer patients. METHODS: For the 183 patients enrolled in this study, IBPS and SII were calculated from peripheral blood samples obtained before and after treatment and at the time of relapse. We examined overall survival (OS) and disease-free survival (DFS) using previously reported cut-off values for IBPS. Cut-off values of neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), and prognostic nutritional index (PNI) were analyzed as NLR 1.79, PLR 114.97, LMR 5, and PNI 52.44. The cut-off value for SII was set at 569. OS and DFS were analyzed by Kaplan-Meier methods using the cutoff of each IBPS and SII. Univariate analysis and multivariate analysis using Cox proportional hazards were performed for OS and DFS. RESULTS: Kaplan-Meier methods showed the high-PNI group showed good prognosis including OS and DFS, while the high-SII group displayed poor DFS. Univariate analysis showed that pre-treatment high PNI and low SII were significantly associated with better prognosis. Multivariate analysis identified pre-treatment PNI as independently associated with OS. For DFS, univariate analysis using Cox proportional hazards modeling showed that pre-treatment high NLR and high SII were significantly associated with worse prognosis, while high PNI was significantly associated with better prognosis. Multivariate analysis identified pre-treatment PNI and SII as independently associated with DFS. Parameters of PNI and SII components were compared between pre-treatment, post-treatment and at relapse in the high- and low-PNI groups. PNI was predominantly decreased in both high- and low-PNI groups at post-treatment and at relapse compared to pre-treatment. This trend was also observed for albumin. CONCLUSIONS: Higher pre-treatment PNI was associated with better OS, while lower pre-treatment PNI and higher treatment SII were associated with poorer DFS in oral cancer patients. Our data indicated that PNI and SII might offer useful biomarkers for gauging prognosis and the efficacy of conventional therapies.

[Pharmaceutical Intervention According to Strict Management System Can Normalize Decreased Serum Calcium Level by Denosumab and Prevent Its Aggravation].

Denosumab is a fully monoclonal antibody against the receptor activator of nuclear factor kappa-B ligand (RANKL), and prevents skeletal-related events by bone metastasis. Hypocalcemia is the most typical adverse effect of denosumab use. We have developed a management system for the more efficient and safer management of denosumab administration, and evaluated pharmaceutical interventions for the better control of hypocalcemia. All pharmaceutical interventions in the system from April 2016 to March 2020 were retrospectively evaluated. We have also assessed the incidence of hypocalcemia in 158 patients who were administered denosumab for six months or more in the period. A total of 282 pharmaceutical interventions (7.0% of the total administration) were conducted. The most conducted intervention was regarding hypocalcemia, which involved the suspension of the injection and/or the increase of calcium and vitamin D supplement with 65% adoption and 17% temporary treatment suspensions. Other interventions were about hypercalcemia, request of laboratory examination and ordering supplements, dental consultation, and poor renal function. A total of 199 interventions (70.6%) were adopted, with 33 administrations suspended. The frequency of hypocalcemia was 27.8% with just one patient having grade 2 hypocalcemia, suggesting that there were no severe cases. Moreover, hypocalcemia was significantly normalized following pharmaceutical intervention and/or handling by physicians (p=0.02) according to the system. Conversely, the normalization rate in hypercalcemia did not differ according to the countermeasures. In conclusion, pharmaceutical interventions according to our management system benefit safe denosumab treatment, especially in severe hypocalcemia prevention.

Evaluation of Chemotherapy Regimen Management Practice by Oncology-Specialized and Non-specialized Pharmacists Collaboration.

Chemotherapy regimen management is one of the most important oncology pharmacy practices, because chemotherapy is conducted according to the registered regimens. In this study, we evaluated the pharmaceutical practice that assumes the initial confirmation of chemotherapy regimens and the quality of practice sharing between oncology-specialized and non-specialized pharmacists in regimen management committee. Pharmacists initially confirmed the applied regimen prescribed by physicians regarding chemotherapeutic agents and prophylactic supportive care medicines. Following confirmation, the regimens were reviewed by the Hokkaido University Hospital Regimen Management Committee. A total of 233 regimens were reviewed by the committee over three years. In total, 110 pharmaceutical inquiries were conducted, 45% of inquiries were concerning chemotherapeutic agents, of which approximately half were regarding supportive care medicines. Most inquiries were regarding premedication, followed by those on administration time, solvent of infusion medicines, and dosage. Correction was performed for 84.5% of inquiries. There was no significant difference in inquiry rates between practice and trial regimens. We have entrusted the first basic regimen review according to the checklist, creation of the chemotherapy plan document, and registry of the adopted regimens in the ordering system from oncology-certified pharmacists to non-certified pharmacists. Basic regimen review was well conducted by a non-certified pharmacist, and a more advanced review was additionally performed by certified pharmacists. In conclusion, we demonstrated the utility of pharmaceutical confirmation in a chemotherapeutic regimen review, suitable review coverage, and quality practice sharing between oncology-certified and non-certified pharmacists, which is one of the recommended methods in chemotherapy regimen review.

Pharmaceutical Care Contributes to the Advanced Management of Patients Receiving Immune Checkpoint Inhibitors.

We previously reported that successive pharmaceutical care by oncology pharmacy specialists contributes to quality outpatient chemotherapy. However, there are a few reports regarding such care during immune checkpoint inhibitors (ICIs) treatment, despite increasing patients being treated with ICIs and the profile of immune-related adverse events being quite different from that of the adverse effects of cytotoxic agents. We retrospectively evaluated the effectiveness of continuous pharmaceutical care in outpatient ICI treatment, focusing especially on the period of providing pharmaceutical recommendations. The adoption rate, efficacy, and period of pharmaceutical interventions, such as prescription questions and pharmaceutical recommendations, were evaluated. A total of 3597 ICI administrations (366 patients) were evaluated. We performed 2625 face-to-face medication counseling. A total of 282 prescription questions and 147 pharmaceutical recommendations were conducted. Approximately 70% of the questions were regarding ordering of laboratory examination, and 86.5% of these questions were adopted. Pharmaceutical recommendations were categorized into medication recommendations (81.1%), examination recommendations (10.8%), and recommendation of expert consultation (8.1%). The adoption rate of pharmaceutical recommendations was 96.0, and 70% of the medication recommendations attenuated the symptoms. Finally, the provision rate of pharmaceutical recommendations was significantly higher in the first 3 months after ICI treatment initiation. We found that pharmaceutical care contributes to an improved quality of outpatient ICI treatment, and face-to-face pharmaceutical counseling up to 3 months after ICI treatment initiation is the most important.

Falls Due to Loss of Consciousness are Associated With Maxillofacial Fracture Severity.

PURPOSE: Falls are a common cause of the maxillofacial fractures, and falls associated with loss of consciousness might have special characteristics. The purpose of the present study was to measure the association between the types of falls and maxillofacial injury severity. PATIENTS AND METHODS: The present retrospective cross-sectional study focused on patients with maxillofacial fractures resulting from falls who had been treated at the Hirosaki University Hospital from 1990 to 2016. The falls were divided into 2 categories according to the reason for their occurrence: 1) falls from slipping, tripping, or stumbling (STSFs); and 2) falls from loss of consciousness (LOCFs). The primary outcome measure of the present study was the severity of the maxillofacial fractures. The secondary outcomes were the pattern of maxillofacial fractures, pattern of concomitant injuries, and treatment modality. Multiple linear regression analysis was performed to evaluate the independent predictors for fracture severity. RESULTS: A total of 148 patients had been admitted for maxillofacial fractures resulting from falls. The sample included 107 STSFs (72.3%) and 41 LOCFs (27.7%). The cause of the LOCFs was orthostatic-hypotension syncope in 13 patients, neurally mediated syncope in 10, cardiogenic syncope in 9, epilepsy in 5, and other in 4 patients. The proportion of mandibular fractures and the mean facial injury severity scale score were significantly greater in the LOCF group (2.20 ± 1.19) than in the STSF group (1.65 ± 1.15; P = .0067). The incidence of concomitant injuries was significantly greater in the STSF group than in the LOCF group (P = .023), and the distribution of sites was significantly different between the 2 groups (P = .039). CONCLUSIONS: Our results have shown that maxillofacial fractures secondary to LOCFs tend to be more severe and to have a lower incidence of concomitant injuries compared with STSFs. We believe these features originate from the absence of protective reflexes resulting from the loss of consciousness.

[Evaluation of the Stability of Indomethacin Oral Spray in Two Different Formulation Conditions].

　Indomethacin (IM) oral spray is a hospital preparation that is used to reduce pain from oral mucositis induced by radiotherapy and chemotherapy. IM oral spray consists of IM (0.25%) dissolved in KH2PO4-NaOH buffer (Formulation A) or Formulation A containing xylitol (Xyl) and glycerin (Gly) (Formulation B). To clarify the stability of IM oral spray in two different formulation conditions, we evaluated the residual rates of IM in these formulations to determine the optimal storage temperature and shelf-life. IM oral spray was stored at freezer temperature (-20°C), refrigerator temperature (4°C) and room temperature (25°C) for up to 16 weeks after preparation. The residual rate of IM was determined by using HPLC. The residual rates of IM in Formulation A and Formulation B after storage for 16 weeks at freezer temperature were ≥95%. When stored at refrigerator temperature, the residual rate of IM in Formulation A was 96.1% after 12 weeks, and the residual rates of IM in Formulation B were 95.8% after 2 weeks, 90.1% after 4 weeks and 72.7% after 12 weeks. These results suggested that Formulation A is stable for at least 12 weeks when stored at 4°C. However, degradation of IM seemed to be accelerated in the formulation containing Xyl and Gly, suggesting that the expiration date should be shortened to 2 weeks at 4°C. In addition, both formulations were stable for at least 16 weeks in a freezer, indicating that long-term preservation is possible.

Oral-maxillofacial trauma of a geriatric population in a super-ageing country.

BACKGROUND/AIM: World population has been ageing, and oral-maxillofacial trauma of geriatric population is expected to increase. The aim of this study was to analyse the characteristic features of oral-maxillofacial trauma in the geriatric population. MATERIALS AND METHODS: Data from 127 patients aged 65 years old or older, who were treated for oral-maxillofacial trauma at the Department of Oral and Maxillofacial Surgery, Hirosaki University, from 2000 to 2014, were retrospectively analysed. The data from 292 patients aged 20-64 years were used as a comparison. RESULTS: Oral-maxillofacial trauma in the geriatric population had been increasing over 15-year period. The male to female ratio was 1.05:1 in the older group and 2.3:1 in the younger group. In the older group, 117 patients (92.1%) had one or more underlying systemic diseases, and 16 (12.6%) had suffered injuries in association with acute medical disorders. The most common injuries in the older group were bone fractures (46.5%). The ratio of fractures in the older group was lower than in the younger group (69.2%). Trauma in the older group most frequently occurred because of falls from a standing height or lower (52.0%), and the mandible was the most common site of fracture (74.6%). A conservative form of treatment for maxillofacial fractures was most commonly (86.4%) chosen for the older group, whilst surgical treatment was most commonly in the younger group (55.0%). CONCLUSION: Oral-maxillofacial trauma in the geriatric population shows characteristic features in terms of aetiology, patterns and treatment modalities.

Impalement of an unusual foreign body on the temporomandibular joint causing severe trismus.

A penetrating injury by a foreign body is comparatively common in the oral and maxillofacial region. On the other hand, injury to the temporomandibular joint (TMJ) by a foreign object is very rare. The TMJ is an anatomically narrow space surrounded by hard bony processes. An unusual case of trauma with severe trismus caused by a foreign body that impaled the TMJ is reported. A 55-year-old man presented with a 5 × 1-cm laceration to the right cheek caused by a flying object propelled during the use of a lawn mower. The edge of the foreign body had a metallic wire, which became imbedded in the wound. His jaw opening was severely limited. Computed tomography revealed that the foreign body was 3 mm in diameter and was impaled on the articular capsule. The object was successfully removed, and the wound and interior of the TMJ were irrigated. Rehabilitation of mouth opening was started on postoperative day 3. On day 9, mouth opening had improved to 35 mm, and he was discharged. After 1 year, mouth opening was 45 mm with no sign of any TMJ disorders.

Professional oral health care reduces oral mucositis pain in patients treated by superselective intra-arterial chemotherapy concurrent with radiotherapy for oral cancer.

PURPOSE: Oral mucositis (OM) is a painful complication of radiation therapy (RT) for head and neck cancer. OM can compromise nutrition, require opioid analgesics and hospitalization for pain control, and lead to interruption of treatment. Severe oral mucositis appears inevitable in superselective intra-arterial chemotherapy concurrent with radiotherapy (SSIACRT), requiring management of OM for the patient. The objective of this study was to assess the utility of professional oral health care (POHC) for the management of OM in patients undergoing SSIACRT. METHODS: Thirty-three patients were enrolled in this study. The first 17 patients underwent SSIACRT before we created an oral management team, and thus did not receive POHC. The remaining 16 patients received POHC. Fever duration, duration of oral feeding difficulty, opioid usage, duration of opioid administration, duration of hospitalization, and number of hospital days from the end of irradiation to discharge were compared between these two groups. RESULTS: Median total dose of morphine during SSIACRT, median number of hospital days from end of irradiation to discharge, and duration of hospitalization all differed significantly between groups (P < 0.05). Duration of opioid administration, fever duration, and duration of oral feeding difficulty did not differ significantly between groups. CONCLUSIONS: These findings indicate that POHC may reduce opioid use and shorten the hospital stay. Such results might be obtained through infection control by POHC. This report appears to be the first study to evaluate the efficiency of POHC in SSIACRT for oral cancer from the perspective of mucositis pain and opioid use.

Role of type I- and type II-interferon in expression of melanoma differentiation-associated gene-5 in HSC-3 oral squamous carcinoma cells.

Melanoma differentiation-associated gene 5 (MDA-5) and retinoic acid-inducible gene-I (RIG-I)are members of DExH family of proteins, and known to play important roles in antiviral responses to induce type I interferons (IFNs). MDA-5 has been thought to sense RNA virus with long(>1 kb) double-stranded RNA. However, MDA-5 is also induced by type II IFN that is involved in acquired immunity, suggesting that role of MDA-5 remains to be elucidated. In addition, no study regarding MDA-5 in oral region has been performed. Here we investigated the role of MDA-5 in HCS-3 squamous carcinoma cells derived from oral epithelial cells. Treatment of HCS-3 cells with IFN-α2b or IFN-γ significantly induced MDA-5 as well as RIG-I. IFN-α2b exerted anti-proliferative effect in HSC-3 cells while no such effect was observed in the cells treated with IFN-γ. MDA-5 is known to be associated with tumor cell growth in melanoma. However, overexpression of MDA-5 did not alter the proliferation in HSC-3 cells, indicating that MDA-5 is unrelated to the cell growth in this type of cells. We conclude that MDA-5 is induced by both type I- and type II-IFNs in HSC-3 cells, and this suggests MDA-5 may play a role in immune responses in oral cavity.

Periosteum-derived cells respond to mechanical stretch and activate Wnt and BMP signaling pathways.

The periosteum supplies osteoblasts and nutrients for bone metabolism and is important for osteoblast differentiation and osteogenesis. Recently, periosteum-derived cells have been used for orofacial bone regeneration therapy. However, little is known about the function of the periosteum in physiological bone remodeling. On our hypothesis that the periosteum senses a mechanical stress to induce bone remodeling, we subjected human jaw bone periosteum cells (HJBPCs) to uniaxial stretching for 24 h and characterized their gene expression profiles by microarray analysis. Of62,976 genes detected, 550 genes related to bone metabolism were extracted, and 76 of these genes with large changes in gene expression were short-listed. The results indicated that mechanical stretch in HJBPCs regulated the expression levels of genes involved in the Wingless-type MMTV integration (Wnt) site, bone morphogenetic protein (BMP) signaling pathways, and inflammatory cytokines. We propose that periosteum-derived cells sense mechanical stress and then activate and regulate signals for osteoblast differentiation and osteogenesis.

[A case of submandibular gland cancer in elderly patients showed significant effect by S-1 and intravenous docetaxel chemotherapy concurrent with radiotherapy].

An elderly case of with advanced head and neck cancer treated by intravenous infusion chemotherapy with weekly docetaxel( DOC)and concurrent radiotherapy was reported. The patient was a 77-year-old man. Clinical diagnosis was submandibular gland carcinoma. He was treated by intravenous infusion chemotherapy with weekly DOC and concurrent radiotherapy (total dose 66 Gy). Two months after irradiation, PET-CT showed a partial response (PR). Therefore, chemotherapy of S-1 (80 mg/day) for 2 weeks every 3 weeks was performed. Two months after the end of chemotherapy, PET-CT showed a complete response(CR). This therapy is effective for the treatment of advanced head and neck cancers for elderly inoperable patients.

Expression of interferon-stimulated gene 20 in vascular endothelial cells.

ISG20 is an ribonuclease specific for single-stranded RNA and considered to play a role in innate immunity against virus infections. We herein show that both poly IC, an authentic double-stranded RNA, and IFN-gamma induced ISG20 expression in cultured HUVEC. Poly IC-induced ISG20 expression was inhibited by LY294002, an inhibitor of PI3K, or by RNA interference against IFN regulatory factor three. ISG20 expression was not induced by IFN-beta, loxoribine or CpG oligonucleotide. These results suggest that ISG20 induction by poly IC may not be dependent on the IRF-3-mediated type I IFN induction pathway in HUVEC. ISG20 may be involved in innate immunity against viral infection in vascular endothelial cells.

Expression of retinoic acid-inducible gene-I (RIG-I) in macrophages: possible involvement of RIG-I in atherosclerosis.

AIM: Retinoic acid-inducible gene-I (RIG-I) is one of the genes induced by interferon (IFN)-gamma which plays an important role in atherosclerosis. The aim of this study is to examine if RIG-I is involved in atherosclerosis. METHODS: The expression of RIG-I in atherosclerotic lesions in human aorta was examined by immunohistochemical analysis. The expression of RIG-I in THP-1 monocytic cell line or human monocyte-derived macrophages was studied by western blot and RT-PCR analyses. RESULTS: Intense immunoreactivity for RIG-I was detected in intimal macrophages in atherosclerotic lesions. IFN-gamma slightly enhanced the RIG-I expression in THP-1 cells. Treatment of the cells with phorbol 12-myristate 13-acetate, which induces the differentiation of the cells into macrophage-like cells, significantly enhanced the IFN-gamma -induced RIG-I expression. IFN-gamma also stimulated the expression of RIG-I in monocyte-derived macrophages. CONCLUSION: These results suggest that RIG-I may be involved in differentiation and activation of macrophages, playing a role in atherosclerosis.