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Background: According to scientific literature, some 99% of patients affected by Alzheimer’s disease (AD) suffer from behavioral and psychological symptoms of dementia (BPSD), also known as neuropsychiatric symptoms (NPSs). In particular, agitation is one of the most difficult disorders to treat. States of agitation represent a very serious problem as they make these subjects dangerous for themselves and others and worsen as the disease advances. To date, there are no specific solutions for treating agitation. The only authorized drug is risperidone (as well as brexpiprazole, approved by the FDA on 11 May 2023), which can be used for no longer than 6–12 weeks because it increases the risk of death—owing to cardiocerebrovascular accidents—by 1.6–1.7 times. Methods: In order to address the latter noteworthy unmet medical need, NanoBEO was produced. The aim of the present work is to generate the health technology assessment (HTA) of this nanotechnological device. The latter consists of a controlled release system, based on solid lipid nanoparticles loaded with bergamot essential oil (BEO). Results: The results of the present research assessed the current evidence in the field of non-pharmacological treatments for this condition, including relevant primary preclinical and clinical data studies supporting the use of this device and the production of the operative plan for its launch on the market. The findings offer recommendations for decision-making on its implementation in dementia. Conclusions: NanoBEO represents a public-worth innovation in this neglected area, marking a significant advancement in the history of dementia, moving from academic research to product development.

Abstract Background Masticatory muscle tendon-aponeurosis hyperplasia (MMTAH) is a relatively newly identified clinical condition that manifests as trismus with a square-shaped mandible. Herein, we report a case of MMATH that was initially misdiagnosed for polymyositis due to trismus and simultaneous lower limb pain, with literature review. Case presentation A 30-year-old woman had a history of lower limb pain after exertion for 2 years. Initial physical examination had been performed at the Department of General Medicine in our hospital. There was also redness in the hands and fingers. Although polymyositis was suspected, it was denied. The patient visited our department for right maxillary wisdom tooth extraction. Clinical examination revealed that the patient had a square-shaped mandible. The maximal mouth opening was 22 mm. There was no temporomandibular joint pain at the time of opening. Furthermore, there was awareness of clenching while working. Panoramic radiography revealed developed square mandibular angles with flattened condyles. Computed tomography showed enlarged masseter muscles with high-density areas around the anterior and lateral fascia. Magnetic resonance imaging also showed thickened tendons and aponeuroses on the anterior surface and inside bilateral masseter muscles. Finally, the patient was diagnosed with MMTAH. Bilateral aponeurectomy of the masseter muscles with coronoidectomy and masseter muscle myotomy was performed under general anesthesia. The maximum opening during surgery was 48 mm. Mouth opening training was started on day 3 after surgery. Histopathological examination of the surgical specimen showed that the muscle fibers were enlarged to 60 μm. Immunohistochemistry testing for calcineurin, which was associated with muscle hypertrophy due to overload in some case reports, showed positive results. Twelve months after surgery, the mouth self-opening and forced opening were over 35 mm and 44 mm, respectively. Conclusions Herein, we report a case of MMATH. Lower limb pain due to prolonged standing at work and overload due to clenching were considered risk factors for symptoms onset of MMATH.

A complication of diabetes is neuropathic pain, which is difficult to control with medication. We have confirmed that neuropathic pain due to mechanical allodynia in diabetic mice is mediated by a characteristic neuropeptide in the spinal cord. We evaluated the strength of mechanical allodynia in mice using von Frey filaments. When mice were intravenously injected with streptozotocin, mechanical allodynia appeared 3 days later. Antibodies of representative neuropeptides were intrathecally (i.t.) administered to allodynia-induced mice 7 days after the intravenous administration of streptozotocin, and allodynia was reduced by anti-cholecystokinin octapeptide antibodies, anti-nociceptin/orphanin FQ antibodies, and anti-hemokinin-1 antibodies. In contrast, i.t.-administered anti-substance P antibodies, anti-somatostatin antibodies, and anti-angiotensin II antibodies did not affect streptozotocin-induced diabetic allodynia mice. Mechanical allodynia was attenuated by the i.t. administration of CCK-B receptor antagonists and ORL-1 receptor antagonists. The mRNA level of CCK-B receptors in streptozotocin-induced diabetic allodynia mice increased in the spinal cord, but not in the dorsal root ganglion. These results indicate that diabetic allodynia is caused by cholecystokinin octapeptide, nociceptin/orphanin FQ, and hemokinin-1 released from primary afferent neurons in the spinal cord that transmit pain to the brain via the spinal dorsal horn.

The histological grade of oral squamous cell carcinoma affects the prognosis. In the present study, we performed a radiomics analysis to extract features from 18F-FDG PET image data, created machine learning models from the features, and verified the accuracy of the prediction of the histological grade of oral squamous cell carcinoma. The subjects were 191 patients in whom an 18F-FDG-PET examination was performed preoperatively and a histopathological grade was confirmed after surgery, and their tumor sizes were sufficient for a radiomics analysis. These patients were split in a 70%/30% ratio for use as training data and testing data, respectively. We extracted 2993 radiomics features from the PET images of each patient. Logistic Regression (LR), Support Vector Machine (SVM), Random Forest (RF), Naïve Bayes (NB), and K-Nearest Neighbor (KNN) machine learning models were created. The areas under the curve obtained from receiver operating characteristic curves for the prediction of the histological grade of oral squamous cell carcinoma were 0.72, 0.71, 0.84, 0.74, and 0.73 for LR, SVM, RF, NB, and KNN, respectively. We confirmed that a PET radiomics analysis is useful for the preoperative prediction of the histological grade of oral squamous cell carcinoma.

(1) Background: The impacts of metal artifacts (MAs) on the contouring workload for head and neck radiotherapy have not yet been clarified. Therefore, this study evaluated the relationship between the contouring time of the MAs area and MAs on head and neck radiotherapy treatment planning. (2) Methods: We used treatment planning computed tomography (CT) images for head and neck radiotherapy. MAs were classified into three severities by the percentage of CT images containing MAs: mild (75%). We randomly selected nine patients to evaluate the relationship between MAs and the contouring time of the MAs area. (3) Results: The contouring time of MAs showed moderate positive correlations with the MAs volume and the number of CT images containing MAs. Interobserver reliability of the extracted MAs volume and contouring time were excellent and poor, respectively. (4) Conclusions: Our study suggests that the contouring time of MAs areas is related to individual commitment rather than clinical experience. Therefore, the development of software combining metal artifact reduction methods with automatic contouring methods is necessary to reducing interobserver variability and contouring workload.

(1) Background: In oral cancer staging, ultrasonography (US), computed tomography (CT), magnetic resonance imaging (MRI), and 2-deoxy-2-[fluorine-18]fluoro-D-glucose (FDG) with positron emission tomography/computed tomography (PET/CT) are routinely used in clinical practice. The present study is a retrospective examination of the diagnostic accuracy of cervical lymph node metastasis using US, CT, MRI, and PET/CT, with histopathological diagnosis as a reference, to compare the different diagnostic imaging modalities. (2) Methods: The participants included 16 patients with oral squamous cell carcinoma who underwent US-, CT-, MRI-, and PET/CT-based preoperative diagnostic imaging and simultaneous primary lesion resection and neck dissection, including 82 level regions and 424 lymph nodes. We compared the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of each imaging modality based on the imaging results and the pathology results of metastasis. (3) Results: Of the four diagnostic imaging modalities, PET/CT exhibited the highest sensitivity but the lowest specificity and accuracy. US, CT, and MRI had high specificities. Comparing each level region and lymph node showed that differences were observed in PET/CT. (4) Conclusions: PET/CT to diagnose lymph node metastasis requires a comprehensive evaluation because it produces more false positives than other diagnostic imaging modalities. Using US, CT, and MRI, which have excellent spatial resolution, improves diagnostic accuracy at the lymph node level.

Abstract Background Spindle cell squamous cell carcinoma is an uncommon variant of squamous cell carcinoma; its diagnosis is sometimes challenging because it histopathologically resembles neoplastic or reactive spindle cell lesions of mesenchymal origins. Here, we report a rare case of spindle cell squamous cell carcinoma exhibiting prominent neutrophil phagocytosis. Case presentation A 69-year-old Japanese man presented with pain and a polypoid mass on the lower left gingiva. He had received chemoradiotherapy for squamous cell carcinoma of the buccal mucosa 15 years prior to this consultation. In addition, he was treated for mandibular osteonecrosis 6 years after chemoradiotherapy without evidence of cancer recurrence. A biopsy revealed atypical spindle or pleomorphic cells scattered in the edematous and fibrin-rich stroma; however, no malignant squamous components were apparent. These atypical cells frequently contained neutrophils within their cytoplasm that formed cell-in-cell figures. Immunohistochemically, the atypical cells were negative for cytokeratins, epithelial membrane antigen, and E-cadherin, but positive for p63, vimentin, and p53. Although these findings suggested spindle cell squamous cell carcinoma, it was difficult to reach a definitive diagnosis. Based on a clinical diagnosis of a malignant tumor, the patient underwent a hemimandibulectomy. The surgically resected specimen had a typical spindle cell squamous cell carcinoma histology consisting of biphasic spindle cells and conventional squamous cell carcinoma components. Moreover, the surgical specimen also exhibited spindle tumor cells that frequently included neutrophils, around which intense staining for lysosomal-associated membrane protein 1 and cathepsin B was observed. This suggested that the cell-in-cell figures represent active neutrophil phagocytosis by tumor cells, and not emperipolesis. Conclusion The presence of neutrophil phagocytosis may be a potent indicator of malignancy.

Primary chronic osteomyelitis (PCO) of the jaw is a rare condition of unknown etiology with severe pain and/or facial swelling. In this article, a 63-year-old man whose severe pain caused by PCO of the mandible was treated with intravenous administration of lidocaine and magnesium is described. At the first visit, paresthesia on the right lower lip and chin was noted in an extraoral examination, and the results of an intraoral examination and laboratory examination were normal. Radiographic findings showed a ground glass-like opaque image and a bone resorption image on the right mandible. The patient was clinically diagnosed as having PCO. Pain control was difficult with conventional treatment, but successful pain control was achieved with intravenous administration of lidocaine and magnesium. The results suggested that intravenous administration of lidocaine and magnesium could be a new therapy for refractory PCO of the jaw.

Long-Term Evolution cellular networks are the main enabler for the massive Machine-Type Communications service and therefore must handle a large number of Machine-Type Devices (MTDs). To control the number of devices allowed to contend on the Physical Random Access Channel (PRACH), the group paging scheme that divides the MTDs into smaller groups and lets the network sequentially trigger the groups has been studied. However, as the number of PRACH preambles is limited, a group’s size must be kept relatively small compared to the MTD population. This paper exploits the possibility that a significant portion of the MTDs is also covered by densely deployed small-cells such that a Small-cell Base Station (SBS) may act as a representative for its MTDs during the preamble transmission step to reduce the load on PRACH. Once the SBS succeeds, its MTDs then contend locally to send their own signaling messages on the corresponding reserved uplink resources. Computer simulations show that the manageable group size can be significantly increased at a reasonable cost on the Physical Uplink Shared Channel. A theoretical model to quickly predict the effect of the ratio of MTDs that are under the coverage of the SBSs is also derived and verified.

Chronic pain is one of the most common causes of the need for clinical evaluation, acquiring more importance in the elderly with cognitive impairment. Reduced self-reporting capabilities cause unrelieved pain contributing to the development of agitation. Safe and effective pain treatment can afford the management of agitation without the serious increase in death risk associated with neuroleptics. To this aim, the essential oil of bergamot (BEO), proven by rigorous evidence to have strong preclinical anti-nociceptive and anti-allodynic properties, has been engineered (NanoBEO, patent EP 4003294) to allow randomized, double-blind, placebo-controlled trials (BRAINAID, NCT04321889). The present study: (1) assesses the analgesic effects of a single therapeutic dose of NanoBEO, as supplied by an airless dispenser for clinical translation, in models of inflammatory, neuropathic, and sensitization types of pain relevant to clinic; (2) provides a dose–response analysis of the efficacy of NanoBEO on scratching behavior, a typical behavioral disturbance occurring in dementia. A single therapeutic dose of NanoBEO confirms efficacy following thirty minutes pre-treatment with capsaicin and on the central sensitization phase induced by formalin. Moreover, it has an ID50 of 0.6312 mg and it is efficacious on static and dynamic mechanical allodynia. Altogether, the gathered results strengthen the potential of NanoBEO for clinical management of pain and agitation.

The involvement of spinal release of histamine in the nociceptive behaviors induced by cholecystokinin-8 (CCK-8) was investigated in mice. Intrathecal (i.t.) injection of CCK-8 elicited the nociceptive behaviors consisting of biting and licking. The nociceptive behaviors induced by i.t. treatment with CCK-8 showed two bell-shaped patterns. The histamine H3 receptor antagonist significantly promoted the nociceptive behaviors induced by CCK-8 at doses of 1–100 fmol and 100 pmol. The nociceptive behaviors elicited by CCK-8 was inhibited by i.t. administration of the CCK-B receptor antagonist in a dose-dependent manner, but not by the CCK-A receptor antagonist. The nociceptive behaviors induced by CCK-8 were markedly suppressed by i.t. pretreatment with antiserum against histamine and were abolished in histidine decarboxylase-deleted gene mice. In histamine H1 receptor-deleted gene mice, the nociceptive behaviors induced at both 10 amol and 10 pmol of CCK-8 were not affected. The tachykinin neurokinin-1 (NK1) receptor antagonists inhibited CCK-8 (10 pmol)-induced nociceptive behaviors in a dose-dependent manner. CCK-8 (10 amol)-induced nociceptive behaviors was not antagonized by co-administration with the tachykinin NK1 receptor antagonists. The nociceptive behaviors elicited by CCK-8 were inhibited by i.t. administration of the antagonist for the N-methyl-D-aspartate (NMDA) receptor in a dose-dependent manner. Our results suggest that the nociceptive behaviors induced by i.t. administration of CCK-8 (10 pmol) are mediated through the spinal release of histamine and are elicited via activation of the tachykinin NK1 and NMDA receptors, whereas the nociceptive behaviors induced by i.t. administration of CCK-8 (10 amol) are mediated through the spinal release of histamine and elicited via NMDA receptor activation.

Recent developments in visible light communications (VLC) have focused on enhancing its security and privacy. This paper studies the physical layer security in VLC networks with multiple users when there is a single wiretap eavesdropper. In particular, our aim is to design the optimal artificial noise (AN)-aided precoding scheme to improve the secrecy performance in terms of legitimate users and eavesdropper’s signal-to-interference-plus-noise ratios (SINRs). The purpose of our AN-aided precoding design is to ensure a fairness of the legitimate users’ SINRs while impairing the quality of eavesdropper’s channel as much as possible. Depending on the availability of the eavesdropper’s channel state information (CSI) at the transmitters, there are generally two design strategies. When the eavesdropper’s CSI is unknown to the transmitters (i.e., passive eavesdropper), the AN is constructed to be orthogonal to the users’ aggregate channel matrix. In case the eavesdropper’s CSI is available (i.e., active eavesdropper), the AN design strategy is to keep the SINR of the eavesdropper below a certain predefined threshold. Aside from the general design, we also study a specific design with the zero-forcing (ZF) technique and compare its performance with that of the general design. In both designs, numerical results show that significant gaps between users’ and eavesdropper’s SINR can always be achieved, thus guaranteeing a high secrecy performance. It is also observed that while the general design outperforms the ZF one in terms of the users’ SINRs, it does not result in lower eavesdropper’s SINRs compared to the ZF design, especially in the low transmit power region.

Abstract This study investigated electron beam laser excitation in the UV region using a GaN/AlGaN multiquantum well (MQW) active layer. Laser emission was observed when the GaN/AlGaN MQW was excited by an electron beam, with a wavelength of approximately 353 nm and a threshold power density of 230 kW/cm2. A comparison of optical pumping and electron beam pumping demonstrated that the rate of generation of electron-hole pairs when using electron beam excitation was approximately one quarter that of light excitation.

Recent development of the ultrasonography (US) equipments enables the visualization of fine detail of the surface structure of the face and neck soft tissue. In this article, some studies referring to the clinical usefulness of the US in dentistry in the diagnosis of lymph node metastases, tongue carcinomas, periapical lesions and temporomandibular joint disorders are reviewed. For the early detection of lymph node metastases, follow-up US is recommended at an interval of no more than 1 month if a “wait-and-see” policy is adopted. US-elastography has a potential to be a promising method offering complementary information to conventional US. In order to determine the appropriate treatment planning of tongue carcinoma (including the prediction of subsequent lymph node metastases), intraoral US should be routinely used as one of the standard technique for the evaluation of the depth of tumor invasion. In the diagnosis of periapical lesions, US can provide useful information about the extent of the lesions and the location of the tooth root apices once the surface cortical bone around the lesion is eroded. Moreover, US is reported to be useful as an alternative imaging technique for visualization of disk position, joint effusion and bone abnormalities for the evaluation of temporomandibular joint disorders.

Most cases of hypophosphatasia (HPP) exhibit early loss of primary teeth. Results of microcomputed tomography (micro-CT) analysis of teeth with HPP have rarely been reported. The purpose of the present study was to describe the mineral density distribution and mapping of exfoliated teeth from an HPP patient using micro-CT. Four exfoliated teeth were obtained from a patient with HPP. Enamel and dentin mineral densities of exfoliated teeth were measured on micro-CT. The mean values of enamel and dentin mineral densities in mandibular primary central incisors with HPP were 1.61 and 0.98 g/cm3, respectively. The corresponding values in the mandibular primary lateral incisors were 1.60 and 0.98 g/cm3, respectively. Enamel hypoplasia was seen in the remaining teeth, both maxillary and mandibular primary canines and first and second molars. Micro-CT enables nondestructive, noninvasive evaluation and is useful for studying human hard tissues obtained from patients.