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Advances in fluorescence imaging technology have been crucial to the progress of neuroscience. Whether it was specific expression of indicator proteins, detection of neurotransmitters, or miniaturization of fluorescence microscopes, fluorescence imaging has improved upon electrophysiology, the gold standard for monitoring brain activity, and enabled novel methods to sense activity in the brain. Hence, we developed a lightweight and compact implantable CMOS-based lensless Ca2+ imaging device for freely moving transgenic G-CaMP mouse experiments. However, without a lens system, determination of regions of interest (ROI) has proven challenging. Localization of fluorescence activity and separation of signal from noise are difficult. In this study, we report an ROI selection method using a series of adaptive binarizations with a gaussian method and morphological image processing. The parameters for each operation such as the kernel size, sigma and footprint size were optimized. We then validated the utility of the algorithm with simulated data and freely moving nociception experiments using the lensless devices. The device was implanted in the dorsal raphe nucleus to observe pain-related brain activity following a formalin test to stimulate pain. We observed significant increases in fluorescence activity after formalin injection compared to the control group when using the ROI determination algorithm., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Castillo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: There have been few reports of patients for whom a cancer gene panel test for solid tumors revealed the simultaneous presence of BRCA mutation and microsatellite instability (MSI)-high status. BRCA mutations have been reported in 13% of castration-resistant prostate cancer (CRPC) patients, and 3.1% of prostate cancer cases are MSI-high/mismatch repair deficient., Case Presentation: A 71-year-old man with a history of urinary retention was referred to our department for clinically suspected prostate cancer and a high prostate-specific antigen (PSA) level (141 ng/mL). MRI revealed features of prostate cancer invading the bladder, seminal vesicles, and rectum. A histopathological examination of a transperineal needle biopsy specimen obtained from the prostate revealed adenocarcinoma. Bone scintigraphy revealed multiple metastases. The patient was treated with abiraterone acetate combined with androgen deprivation therapy followed by local radiation. Rectal wall thickening and lymph node metastasis were also observed, and docetaxel was administered. A cancer gene panel test was positive results for BRCA2 mutation with a MSI-high. After six courses of docetaxel, lymph node enlargement was observed and olaparib was initiated. Two months later, the metastatic lesions showed enlargement and the PSA level increased. Subsequently, pembrolizumab was administered. At 2 to the patient months after the initiation of pembrolizumab administration, PSA levels decreased to <0.025 ng/mL and the rectal lesions and lymph node metastases disappeared. The patient was continuing to receive pembrolizumab without any apparent adverse events or exacerbations, 9 months after initiation., Conclusion: We herein report a case in which pembrolizumab treatment resulted in a complete response in a CRPC patient with both a BRCA2 mutation and an MSI-high status., Competing Interests: The authors declare no conflicts of interest in association with the present study., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Objective : Current neuronal imaging methods mostly use bulky lenses that either impede animal behavior or prohibit multi-depth imaging. To overcome these limitations, we developed a lightweight lensless biophotonic system for neuronal imaging, enabling compact and simultaneous visualization of multiple brain layers. Approach : Our developed 'CIS-NAIST' device integrates a micro-CMOS image sensor, thin-film fluorescence filter, micro-LEDs, and a needle-shaped flexible printed circuit. With this device, we monitored neuronal calcium dynamics during seizures across the different layers of the hippocampus and employed machine learning techniques for seizure classification and prediction. Main results : The CIS-NAIST device revealed distinct calcium activity patterns across the CA1, molecular interlayer, and dentate gyrus. Our findings indicated an elevated calcium amplitude activity specifically in the dentate gyrus compared to other layers. Then, leveraging the multi-layer data obtained from the device, we successfully classified seizure calcium activity and predicted seizure behavior using Long Short-Term Memory and Hidden Markov models. Significance : Taken together, our 'CIS-NAIST' device offers an effective and minimally invasive method of seizure monitoring that can help elucidate the mechanisms of temporal lobe epilepsy., (Creative Commons Attribution license.)

In this study, we developed and demonstrated a millimeter-wave electric field imaging system using an electro-optic crystal and a highly sensitive polarization measurement technique using a polarization image sensor, which was fabricated using a 0.35-µm standard CMOS process. The polarization image sensor was equipped with differential amplifiers that amplified the difference between the 0° and 90° pixels. With the amplifier, the signal-to-noise ratio at low incident light levels was improved. Also, an optical modulator and a semiconductor optical amplifier were used to generate an optical local oscillator (LO) signal with a high modulation accuracy and sufficient optical intensity. By combining the amplified LO signal and a highly sensitive polarization imaging system, we successfully performed millimeter-wave electric field imaging with a spatial resolution of 30×60 µm at a rate of 1 FPS, corresponding to 2400 pixels/s.

Acetylcholine (ACh) plays a pivotal role as a neurotransmitter, influencing nerve cell communication and overall nervous system health. Imbalances in ACh levels are linked to neurodegenerative diseases, such as Alzheimer's and Parkinson's. This study focused on developing electrochemical sensors for ACh detection, utilizing graphene oxide (GO) and a composite of reduced graphene oxide and zinc oxide (rGO/ZnO). The synthesis involved modified Hummers' and hydrothermal methods, unveiling the formation of rGO through deoxygenation and the integration of nano-sized ZnO particles onto rGO, as demonstrated by XPS and TEM. EIS analysis also revealed the enhancement of electron transfer efficiency in rGO/ZnO. Cyclic voltammograms of the electrode, comprising the rGO/ZnO composite in ACh solutions, demonstrated prominent oxidation and reduction reactions. Notably, the composite exhibited promise for ACh detection due to its sensitivity, low detection threshold, reusability, and selectivity against interfering compounds, specifically glutamate and gamma-aminobutyric acid. The unique properties of rGO, such as high specific surface area and electron mobility, coupled with ZnO's stability and catalytic efficiency, contributed to the composite's potential in electrochemical sensor applications. This research, emphasizing the synthesis, fabrication, and characterization of the rGO/ZnO composite, established itself as a reliable platform for detecting the acetylcholine neurotransmitter., (© 2024. The Author(s).)

Previous human and rodent studies indicated that nociceptive stimuli activate many brain regions that is involved in the somatosensory and emotional sensation. Although these studies have identified several important brain regions involved in pain perception, it has been a challenge to observe neural activity directly and simultaneously in these multiple brain regions during pain perception. Using a transgenic mouse expressing G-CaMP7 in majority of astrocytes and a subpopulation of excitatory neurons, we recorded the brain activity in the mouse cerebral cortex during acute pain stimulation. Both of hind paw pinch and intraplantar administration of formalin caused strong transient increase of the fluorescence in several cortical regions, including primary somatosensory, motor and retrosplenial cortex. This increase of the fluorescence intensity was attenuated by the pretreatment with morphine. The present study provides important insight into the cortico-cortical network during pain perception., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

We propose and demonstrate a method for equivalent time sampling using image sensors to selectively detect only the target frequency. Shortening the exposure time of the image sensor and using equivalent time sampling allows for the detection of frequency components that are higher than the frame rate. However, the imaging system in our previous work was also sensitive to the frequency component at 1/4 of the frame rate. In this study, we control the phase relationship between the exposure time and observed signal by inserting an additional interval once every four frames to detect the target frequency selectively. With this technique, we conducted electric field imaging based on the electro-optic effect under high noise conditions in the low-frequency band to which the conventional method is sensitive. The results demonstrated that the proposed method improved the signal-to-noise ratio.

Goreisan is a Kampo medicine used to treat headaches associated with climate change. Here, by using an implantable complementary metal-oxide-semiconductor (CMOS) device, we evaluated the effects of Goreisan and loxoprofen on cerebral blood flow (CBF) dynamics associated with barometric pressure fluctuations in freely moving mice. In the vehicle group, decreasing barometric pressure increased CBF that was prevented by Goreisan and loxoprofen. Notably, Goreisan, but not loxoprofen, reduced CBF after returning to atmospheric pressure. These results indicate that, unlike the mechanism of action of antipyretic analgesics, Goreisan normalizes CBF abnormalities associated with barometric pressure fluctuations by actively reducing CBF increase., Competing Interests: Declaration of competing interest The authors declare no potential conflicts of interest regarding this research and/or publication., (Copyright © 2023 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

Decision-making is always coupled with some level of risk, with more pathological forms of risk-taking decisions manifesting as gambling disorders. In macaque monkeys trained in a high risk-high return (HH) versus low risk-low return (LL) choice task, we found that the reversible pharmacological inactivation of ventral Brodmann area 6 (area 6V) impaired the risk dependency of decision-making. Selective optogenetic activation of the mesofrontal pathway from the ventral tegmental area (VTA) to the ventral aspect of 6V resulted in stronger preference for HH, whereas activation of the pathway from the VTA to the dorsal aspect of 6V led to LL preference. Finally, computational decoding captured the modulations of behavioral preference. Our results suggest that VTA inputs to area 6V determine the decision balance between HH and LL.

Dopamine (DA)'s relationship with addiction is complex, and the related pathways in the mesocorticolimbic system are used to deliver DA, regulating both behavioral and perceptual actions. Specifically, the mesolimbic pathway connecting the ventral tegmental area (VTA) and the nucleus accumbens (NAc) is crucial in regulating memory, emotion, motivation, and behavior due to its responsibility to modulate dopamine. To better investigate the relationship between DA and addiction, more advanced mapping methods are necessary to monitor its production and propagation accurately and efficiently. In this study, we incorporate dLight1.2 adeno-associated virus (AAV) into our latest CMOS (complementary metal-oxide semiconductor) imaging platform to investigate the effects of two pharmacological substances, morphine and cocaine, in the NAc using adult mice. By implanting our self-fabricated CMOS imaging device into the deep brain, fluorescence imaging of the NAc using the dLight1.2 AAV allows for the visualization of DA molecules delivered from the VTA in real time. Our results suggest that changes in extracellular DA can be observed with this adapted system, showing potential for new applications and methods for approaching addiction studies. Additionally, we can identify the unique characteristic trend of DA release for both morphine and cocaine, further validating the underlying biochemical mechanisms used to modulate dopaminergic activation.

Introduction: Early detection of dysphagia risk, initiating rehabilitation, and resumption of appropriate diet based on swallowing function is important during deep neck infection (DNI) control. This study aimed to evaluate the extent of cervical abscess development, particularly in the deep neck space, and its relationship to postoperative swallowing function., Methods: A retrospective chart review was performed for all DNI cases treated between April 2015 and April 2021. Deep neck spaces were divided into categories based on computed tomography findings. Functional Oral Intake Scale (FOIS) scores of 4 or higher was defined as normal or slight swallowing disorder and 3 or lower as dysphagia., Results: Seventeen cases were included in the analysis. Based on FOIS, 14 cases were classified into the dysphagia group at 2 weeks after surgery, 11 cases at 4 weeks, and 8 cases at 8 weeks. There was no significant difference between the location of the abscess and dysphagia at 2 weeks after surgery. Patients with anterior cervical space abscess significantly increased dysphagia 4 weeks ( p = 0.018) and 8 weeks ( p = 0.036) after surgery., Conclusion: Abscess formation in the anterior cervical space may be associated with prolonged dysphagia after treatment due to inflammation and scarring of the muscles associated with swallowing., Competing Interests: The authors declare no financial relationships or conflict of interest., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Tracheobronchial foreign bodies (TFBs) are pediatric airway emergencies frequently seen. We aimed to examine the changes in the clinical characteristics of pediatric TFB patients in a single institution within the past 36 years. We retrospectively reviewed the data of 85 patients aged 0-10 years with TFBs lodged in the trachea or bronchus admitted at the Department of Otolaryngology-Head and Neck Surgery at Tohoku University Hospital between 1986 and 2021. We also compared the characteristics, diagnostic methods, and treatments of the previous 64 cases (1986-2005) with those of the recent 21 cases (2006-2021). The number of TFB patients decreased later in this study (3.2 vs. 1.3 patients per year). The proportion of TFB patients aged > 3 years was significantly higher in the later period (6.3% vs. 23.8%, p = 0.038). Peanut was the most common cause of TFBs in both periods, and the overall incidence of peanut aspiration significantly decreased in the later period (68.8% vs. 38.1%, p = 0.019). No patient had an undetected TFB for more than 1 month after the onset of symptoms in the later period. Foreign body extraction using rigid bronchoscopy was performed in all patients earlier, whereas flexible bronchoscopy was used in 14.3% later. Our study revealed a recent trend in the clinical characteristics of pediatric TFB patients in a single institution in Northeast Japan. The prevention and treatment of pediatric TFBs should be considered following the recent trends.

Background: Amyloidosis is a collection of disorders characterized by the extracellular deposition of amyloid, a specialized fibrous protein, in diverse tissues, leading to functional impairments., Case Presentation: A 70-year old Asian-Japanese female was referred to our department for further examination of her left hydronephrosis come from lower ureteral obstruction. Contrast enhanced CT and retrograde pyelo-nephrography revealed left ureteral tumor. Though ureteroscropic biopsy did not show malignant pathological findings, ureteroscopic image suspected malignant disease, thus nephroureterectomy was performed. Pathological findings revealed localized ureteral amyloidosis. Whole body examination including gastro endoscopy and cardio ultrasonography could not reveal amyloidosis except ureter. She was free from recurrence 9 months postoperatively., Conclusion: We herein report a rare case of localized ureteral amyloidosis., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Analyzing the way of deposition of saliva stains contributes to appropriate interpretation of saliva as evidence in court, particularly in sexual assault cases. In this proof-of-concept study, we aimed to confirm the difference between drooling-derived (non-contact) saliva and licking-derived (contact) saliva and clarify whether objectively distinguishing between the two saliva is possible. To allow discrimination between these two samples, an indicator was devised where the relative Streptococcus salivarius DNA quantity was calculated by dividing the S. salivarius DNA copies by the amount of stained saliva from the same saliva sample using quantitative polymerase chain reaction and salivary α-amylase activity assays. The study findings reveal that the value of the proposed indicator of licking-derived saliva was 100-fold significantly greater than that of drooling-derived saliva (P < 0.05, Welch's t-test). However, theoretical and technical challenges preclude the application of this indicator as a practical method. We believe that this saliva-specific bacterial DNA-based approach could allow estimation of the saliva stain deposition method., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The pink teeth phenomenon has occasionally been observed in forensic autopsies. This study aimed to establish an experimental pink tooth model and an objective color tone evaluation method in order to clarify changes in the color tone of teeth and the relationship with hemoglobin monoxide and its decomposition products and with red pigment-producing bacteria, under various external environmental factors. It was confirmed that the color tone evaluation with ΔE and the L*C*h color space was useful. The results of various examinations using this model showed that color development was suppressed under aerobic conditions, faded early under light, became bright red under a low temperature and showed a tendency to be reddish at 3 days under high humidity and in the presence of soft tissue. The biochemical analysis revealed a significant increase in carboxyhemoglobin at 7 days and a tendency toward increasing the total heme pigment and bilirubin levels over time. The bacteriological analysis revealed that red pigment-producing bacteria increased over time but that the color faded after 7 days. These results suggest that putrefaction greatly affects the pink teeth phenomenon, whereas red pigment-producing bacteria have little effect on the occurrence of pink teeth. However, further studies are needed to clarify bacteriological involvement.

Chronic pain and attention-deficit hyperactivity disorder (ADHD) frequently coexist. However, the common pathology is still unclear. Attenuated noradrenergic endogenous analgesia can produce acute pain chronification, and dysfunction of noradrenergic systems in the nervous system is relevant to ADHD symptoms. Noxious stimuli-induced analgesia (NSIA) is measured to estimate noradrenergic endogenous analgesia in spontaneously hypertensive rats (SHR) as an ADHD model and control. Recovery of pain-related behaviors after paw incision was assessed. Contributions of noradrenergic systems were examined by in vivo microdialysis and immunohistochemistry. The SHR showed attenuated NSIA and needed a more extended period for recovery from acute pain. These results suggest ADHD patients exhibit acute pain chronification due to pre-existing attenuated noradrenergic endogenous analgesia. Immunohistochemistry suggests abnormal noradrenaline turnover and downregulation of the target receptor (alpha2a adrenoceptor). Standard ADHD treatment with atomoxetine restored NSIA and shortened the duration of hypersensitivity after the surgery in the SHR. NSIA protocol activated the locus coeruleus, the origin of spinal noradrenaline, of both strains, but only the control exhibited an increase in spinal noradrenaline. This result suggests dysfunction in the noradrenaline-releasing process and can be recognized as a novel mechanism of attenuation of noradrenergic endogenous analgesia., (© 2023. The Author(s).)

In this research, we combined our ultralight micro-imaging device for calcium imaging with microdialysis to simultaneously visualize neural activity in the dorsal raphe nucleus (DRN) and measure serotonin release in the central nucleus of the amygdala (CeA) and the anterior cingulate cortex (ACC). Using this platform, we observed brain activity following nociception induced by formalin injection in the mouse's hind paw. Our device showed that DRN fluorescence intensity increased after formalin injection, and the increase was highly correlated with the elevation in serotonin release in both the CeA and ACC. The increase in calcium fluorescence intensity occurred during the acute and inflammatory phases, which suggests the biphasic response of nociceptive pain. Furthermore, we found that the increase in fluorescence intensity was positively correlated with mouse licking behavior. Lastly, we compared the laterality of pain stimulation and found that DRN fluorescence activity was higher for contralateral stimulation. Microdialysis showed that CeA serotonin concentration increased only after contralateral stimulation, while ACC serotonin release responded bilaterally. In conclusion, our study not only revealed the inter-regional serotonergic connection among the DRN, the CeA, and the ACC, but also demonstrated that our device is feasible for multi-site implantation in conjunction with a microdialysis system, allowing the simultaneous multi-modal observation of different regions in the brain.

Hybrid emission filters, comprising an interference filter and an absorption filter, exhibit high excitation light rejection performance and can act as lensless fluorescent devices. However, it has been challenging to produce them in large batches over a large area. In this study, we propose and demonstrate a method for transferring a Si substrate, on which the hybrid filter is deposited, onto an image sensor by attaching it to the sensor and removing the substrate via plasma etching. Through this method, we can transfer uniform filters onto fine micrometer-sized needle devices and millimeter-sized multisensor chips. Optical evaluation reveals that the hybrid filter emits light in the 500 to 560 nm range, close to the emission region of green fluorescent protein (GFP). Furthermore, by observing the fluorescence emission from the microbeads, a spatial resolution of 12.11 μm is calculated. In vitro experiments confirm that the fabricated device is able to discriminate GFP emission patterns from brain slices.

Objective: Aspiration pneumonia is one of the leading causes of death in patients with muscular dystrophy; therefore, it is important to predict its occurrence in the clincal setting. We aimed to examine the usefulness of repeated saliva swallowing test (RSST), modified water swallowing test (MWST), and flexible endoscopic evaluation of swallowing (FEES) for evaluating the Hyodo score at the bedside, to predict the risk of aspiration pneumonia in patients with Duchenne muscular dystrophy (DMD)., Methods: In this retrospective cohort study involving 43 patients, we evaluated the swallowing function using the RSST, MWST, and FEES, and predicted the likelihood of aspiration pneumonia within 2 years after the assessment. The Hyodo score, a scoring system for evaluating the swallowing function determined by the FEES, was used., Results: Pneumonia was observed in 14 patients (32.6%). The RSST was not significantly useful for predicting the onset of pneumonia. The MWST was reported to have a cutoff value of < 4 points. Significantly more patients in the pneumonia group had an MWST score of < 4 points. The results revealed that the occurrence of pneumonia could be predicted based on a Hyodo cutoff score of ≥ 6. Significantly more patients in the pneumonia group had an MWST score of < 4 or a Hyodo score of ≥ 6., Conclusions: Combining MWST and FEES is useful for evaluating the bedside swallowing function and predicting the onset of pneumonia., (Copyright © 2022. Published by Elsevier B.V.)

Pseudobulbar palsy and bulbar palsy cause dysphagia in patients with amyotrophic lateral sclerosis (ALS). Dysphagia in patients with ALS not only increases the risk of aspiration and pneumonia but also leads to malnutrition and weight loss, which are poor prognostic factors. Gastrostomy is the preferred route of feeding and nutritional support in patients with dysphagia. However, there are no established standards to determine the ideal timing of gastrostomy for patients with ALS. Therefore, we used the videofluoroscopic dysphagia scale (VDS), which objectively quantifies swallowing function, in videofluoroscopic swallowing study (VFSS) to investigate whether this scale at diagnosis can be a useful predictor for the timing of gastrostomy. We retrospectively evaluated 22 patients with ALS who were diagnosed at our hospital. We assessed the VDS scores in all patients within 3 months of diagnosis. A decline in the ALS functional rating scale revised (ALSFRS-R) scores was used as an indicator of disease progression. As a result, we found that the VDS score of the pharyngeal phase and the total VDS score were significantly correlated with the ΔALSFRS-R scores. These scores were also associated with the existing indicators for the timing of gastrostomy, i.e., decreased body weight and percent-predicted forced vital capacity. We demonstrated the noninferiority of the VDS scores relative to the existing indicators. In addition, the VDS score of the pharyngeal phase was significantly correlated with the time from diagnosis to gastrostomy. The VDS score could estimate the timing of gastrostomy in patients with ALS with dysphagia at diagnosis.

Amino acid racemization of dentin (AAR) is among the most precise methods for age estimation in unidentified adult cadavers. Although vital teeth are generally used for this technique, cases often have endodontically treated (Endo) teeth only. Therefore, the aim of this preliminary pilot study was to determine the applicability of Endo teeth by comparing AAR rates between vital and Endo teeth. Thirty-six dentin samples from vital teeth and 18 dentin samples from Endo teeth were analyzed, including the maxillary first premolar, maxillary second molar, and mandibular second premolar. Standard calibration curves for the mandibular second premolar and maxillary second molar were compared among vital teeth, Endo teeth, and mixed vital/Endo teeth. Discrepancies between estimated and actual ages were assessed by analyzing the AAR rates for the maxillary first premolar between vital and Endo teeth. The AAR rates for Endo teeth were higher than those for vital teeth in both the mandibular second premolar and maxillary second molar, and the correlation of the standard calibration curve for vital teeth only was highest (r = 0.982836; r = 0.92011467), followed by mixed (r = 0.949579; r = 0.76158) and Endo teeth only (r = 0.896082; r = 0.744991). In the maxillary first premolar, discrepancies were more than 10 years for all 5 Endo teeth, based on the standard calibration curve of vital teeth. The present study suggests that the AAR rates for Endo teeth might be affected by variation in dentin structure between vital and Endo teeth., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Advancing the understanding of the relationship between perinatal nicotine addiction and the reward mechanism of the brain is crucial for uncovering and implementing new treatments for addiction control and prevention. The mesolimbic pathway of the brain, also known as the reward pathway, consists of two main areas that regulate dopamine (DA) and addiction-related behaviors. The ventral tegmental area (VTA) releases DA when stimulated, causing the propagation of neuronal firing along the pathway. This ends in the release of DA into the extracellular space of the nucleus accumbens (NAc), which is directly modulated by the uptake of DA. Much research has been conducted on the effects of nicotine addiction, but little research has been conducted concerning nicotine addiction and the mesolimbic pathway regarding maturation due to the small brain size. In this study, we apply our novel microstimulation experimental system to rat pups that have been perinatally exposed to nicotine. By using our self-fabricated photo-stimulation (PS) device, we can stimulate the VTA and collect dialysate, which is then used to estimate DA released into the NAc. The proposed platform has demonstrated the potential to monitor neural pathways as the pups mature.

Background: This prospective, randomized, double-blinded, active controlled trial assessed whether a single preoperative administration of 40 mg of duloxetine could decrease postoperative pain and numbness after posterior lumbar interbody fusion surgery (PLIF)., Methods: Patients with an American Society of Anesthesiologists physical status I or II undergoing PLIF were included. At 2 hours before inducing anesthesia, patients were administered 40 mg duloxetine or 4 mg diazepam (control drug). Postoperative pain and other symptoms were evaluated on the basis of a visual analog scale, amount of fentanyl used, fentanyl dose request times, rate of use of adjunctive analgesics (diclofenac sodium or pentazocine), and lower limb numbness score (0-3) during the first 2 postoperative days., Results: Forty-six patients were randomly assigned to the duloxetine and diazepam groups (n = 23 each); 6 were lost to follow-up, and analysis was performed on data from 22 patients in the duloxetine group and 18 in the diazepam group. No significant differences were detected in the patient background, postoperative visual analog scale score at rest in the lumbar region and lower limbs, fentanyl use, rate of analgesic adjuvant use, or incidence of side effects. The numbness score in the lower limbs, however, was significantly lower in the duloxetine group., Conclusion: A single preoperative 40-mg dose of duloxetine did not improve postoperative pain after PLIF, but did improve lower limb numbness. Duloxetine may suppress neuropathic pain-like symptoms after PLIF surgery., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: The objectives of the study were to clarify the characteristics of dysphagia and the incidence of pneumonia in Myotonic dystrophy type 1 (DM1) patients, and to investigate the relationship between the development of pneumonia and the DM1 patient's background, especially concerning swallowing function evaluated by endoscopy., Methods: The subjects were 88 DM1 patients who underwent swallowing function evaluation. The severity of disease in DM1patients was assessed based on the muscular impairment rating scale (MIRS), and the number of CTG repeats. Patients were divided into two groups; those who developed aspiration pneumonia within two years after swallowing assessment and those who did not develop aspiration pneumonia. Swallowing function was assessed using the food intake level scale (FILS), repetitive saliva swallowing test (RSST), the modified water swallowing test (MWST), and the Hyodo score., Results: Onset of pneumonia within two years of assessment was observed in 22 cases (25%). Age, FILS, and Hyodo score were significantly different between pneumonia and non-pneumonia groups. There was a significant difference in swallowing function tests such as FILS, RSST, and Hyodo score between males and females. The Hyodo score cutoff value for predicting pneumonia within two years was determined by ROC analysis. A cutoff value of 6 was found to have a sensitivity of 0.545 and a specificity of 0.833 (area under the curve=0.722)., Conclusion: It is important to evaluate the swallowing function of DM1 patients by endoscopy to prevent aspiration pneumonia. In addition, male patients are more likely to deteriorate in swallowing function and should be carefully monitored., Competing Interests: Declaration of Competing Interest The authors declare no financial relationships or conflict of interest., (Copyright © 2022. Published by Elsevier B.V.)

This study sought to clarify the characteristics and trends of physical elder abuse and the status of collaboration between forensic medicine departments and related institutions in Japan. Questionnaires were sent to 82 forensic medicine departments and 2857 institutions randomly selected from hospitals, municipalities and public community general support centers. The survey period was February to June 2021, including an extension period for collection. Responses from 675 facilities were analyzed. The most common finding in cases of physical elder abuse at forensic medicine departments was subcutaneous hemorrhage on the head (85.7%), with mixed old and new injuries most commonly observed in the lower limbs (70%). There were few cases in which there was collaboration between forensic medicine departments and other institutions. Among the issues identified, there is a need to provide related institutions with information obtained in forensic medicine departments. A new collaboration system is needed to achieve this.

Abstract: Nasopharyngeal foreign bodies (FBs), which are generally caused by a strong, external force, are seldomly encountered. Removing these FBs is challenging for otorhinolaryngological surgeons because of the vital structures surrounding the nasopharynx, such as the skull base, cranial nerves, and internal carotid artery. Here, the authors report the case of a 69-year-old man referred to our hospital after accidentally cutting his face while using a grinder. Grinder fragments were deeply embedded in the face, thus becoming nasopharyngeal FBs. The authors evaluated three-dimensional volume rendering images and immediately removed these FBs using an endoscopic endonasal transseptal approach under general anesthesia. The postoperative course was uneventful. Using the endoscopic endonasal transseptal approach after evaluating preoperative three-dimensional volume rendering images may help eliminate nasopharyngeal FBs safely., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by Mutaz B. Habal, MD.)

Background: The palatal augmentation prosthesis (PAP) is an intraoral prosthesis used in the treatment of dysphagia., Aim: The objective of the study is to examine the effect of PAP using tongue pressure and the Videofluoroscopic Dysphagia Scale (VDS) to understand the precise mechanism for improvement in swallowing function with PAP for oral cancer at retrospective survey., Methods and Results: Fifteen patients were provided PAPs. Tongue pressure and VDS were evaluated with and without PAP. After intervention with PAP, tongue pressure significantly increased as compared to when without PAP (p < .05). The total mean VDS score with PAP was found to have significantly improved (p < .05). The mean VDS score of the oral phase also significantly improved with the PAP compared to without the PAP group (p < .05). Significant differences (p < .01) were found in each category, such as tongue to palate contact and pyriform sinus residue., Conclusion: PAP can improve tongue pressure, tongue to palate contact, and pyriform sinus residue., (© 2021 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

A readout device for a dual-functional neural observation system is presented. The authors separately developed the reading operation of an implantable CMOS image sensor and a setup for fast-scan cyclic voltammetry and implemented them together in a microcontroller-based device. The developed imaging readout device with a size of [Formula: see text] can reach the highest reading rate of 160 fps with a 120×268 pixel image sensor. The voltammetry function was verified through an experiment using commercial carbon fiber electrodes in phosphate-buffered saline. When the imaging is sequentially operated with 400 V/s-scan rate voltammetry from -0.4 to 1.3 V, the system can operate at up to 60 fps. With this system, calcium imaging and dopamine recording in a freely behaving mouse can be achieved together in a simpler manner. This study aims to be the basis for the development of an implantable multi-functional sensor.

Objectives: To describe cases of patulous Eustachian tube (PET) or patent ET conditions in oculopharyngeal muscular dystrophy (OPMD)., Patients: Four cases of PET or patent ET conditions with OPMD., Main Outcome Measures: Clinical case records, objective ET function tests (tubo-tympano-aerodynamic graphy and sonotubometry), and swallowing function (videoendoscopic examination and Food Intake Level Scale) were analyzed., Results: Two cases of definite PET, one case of possible PET, and one case lacking aural symptoms with findings of patent ET. All patients have ptosis, and three cases have dysphagia. Body mass index indicated that three cases were underweight. Magnetic resonance imaging in case 4 showed atrophy and fat replacement of palatine and masticatory muscles., Conclusions: It is important to consider PET or patent ET conditions when OPMD patients describe aural symptoms., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2022, Otology & Neurotology, Inc.)

Systemic administration of morphine increases serotonin (5-HT) in the spinal dorsal horn (SDH), which attenuates the analgesic effects of morphine on neuropathic pain through spinal 5-HT3 receptors. We hypothesized that dysfunction of the descending serotonergic system, including the periaqueductal gray (PAG), contributes to attenuate the efficacy of morphine on neuropathic pain through spinal 5-HT3 receptors and GABA neurons. Morphine (100 ng) injected into the PAG produced analgesic effects in normal rats, but not in spinal nerve ligation (SNL) rats. In vivo microdialysis showed that PAG morphine increased the SDH 5-HT concentration in both groups. Intrathecal injection of the 5-HT3 receptor antagonist ondansetron and the GABA A receptor antagonist bicuculline attenuated the analgesic effects of PAG morphine in normal rats, but increased the effects in SNL rats. The increased analgesic effect of PAG morphine induced by bicuculline was reversed by pretreatment with the tropomyosin receptor kinase B (TrkB) antagonist K252a. Activation of spinal 5-HT3 receptors by 2-methyl-5-HT increased the GABA concentration in both groups. Morphine activates GABAergic interneurons in the SDH by activating descending serotonergic neurons. Functional changes in GABA A receptors from inhibitory to facilitatory through the activation of TrkB receptors may contribute to the attenuated efficacy of morphine against neuropathic pain. PERSPECTIVE: Although morphine provides strong analgesia against acute pain, it has limited efficacy against neuropathic pain. This article demonstrates that functional changes in GABA A receptors in the spinal dorsal horn after nerve injury might strongly contribute to the attenuation of opioid-induced analgesia for neuropathic pain., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

The Calvin-Benson cycle (CB cycle) is quantitatively the most important metabolic pathway for CO 2 fixation. In the canonical CB cycle, fructose 6-phosphate (F6P), fructose 1,6-bisphosphate (FBP), sedoheptulose 7-phosphate (S7P), and sedoheptulose 1,7-bisphosphate (SBP) appear as essential intermediates, where F6P is formed from FBP by the fructose 1,6-bisphosphatase (FBPase) reaction, and S7P is formed from SBP by the sedoheptulose 1,7-bisphosphatase (SBPase) reaction. Although the involvement of SBP and SBPase in the canonical CB cycle is consistent with the reported dependency of photosynthetic carbon metabolism on SBPase, the involvement of FBP and FBPase is not completely consistent with the reported FBP- or FBPase-related findings such as, although with a diminished growth rate, an Arabidopsis mutant lacking FBPase grew photoautotrophically in soil. Here, we show a novel variant of the CB cycle involving SBP, SBPase, and transaldolase, but neither FBP nor FBPase. This novel variant, named the S7P-removing transaldolase variant, bypasses FBP. This variant explains the FBP- or FBPase-related findings more easily than the canonical CB cycle as well as the dependency of photosynthetic carbon metabolism on SBPase and further suggests that co-overexpression of SBPase and transaldolase can be a strategy for enhancing photosynthetic carbon metabolism, which is important for the global environment., (© 2022. The Author(s).)

Significance: Intrinsic optical signals (IOS) generated in the cortical tissue as a result of various interacting metabolic processes are used extensively to elucidate the underlying mechanisms that govern neurovascular coupling. However, current IOS measurements still often rely on bulky, tabletop imaging systems, and there remains a dearth of studies in freely moving subjects. Lightweight, miniature head-mounted imaging devices provide unique opportunities for investigating cortical dynamics in small animals under a variety of naturalistic behavioral settings., Aim: The aim of this work was to monitor IOS in the somatosensory cortex of wild-type mice by developing a lightweight, biocompatible imaging device that readily lends itself to animal experiments in freely moving conditions., Approach: Herein we describe a method for realizing long-term IOS imaging in mice using a 0.54-g, compact, CMOS-based, head-mounted imager. The two-part module, consisting of a tethered sensor plate and a base plate, allows facile assembly prior to imaging sessions and disassembly when the sensor is not in use. LEDs integrated into the device were chosen to illuminate the cortical mantle at two different wavelengths in the visible regime (λcenter: 535 and 625 nm) for monitoring volume- and oxygenation state-dependent changes in the IOS, respectively. To test whether the system can detect robust cortical responses, we recorded sensory-evoked IOS from mechanical stimulation of the hindlimbs (HL) of anesthetized mice in both acute and long-term implantation conditions., Results: Cortical IOS recordings in the primary somatosensory cortex hindlimb receptive field (S1HL) of anesthetized mice under green and red LED illumination revealed robust, multiphasic profiles that were time-locked to the mechanical stimulation of the contralateral plantar hindpaw. Similar intrinsic signal profiles observed in S1HL at 40 days postimplantation demonstrated the viability of the approach for long-term imaging. Immunohistochemical analysis showed that the brain tissue did not exhibit appreciable immune response due to the device implantation and operation. A proof-of-principle imaging session in a freely behaving mouse showed minimal locomotor impediment for the animal and also enabled estimation of blood flow speed., Conclusions: We demonstrate the utility of a miniature cortical imaging device for monitoring IOS and related hemodynamic processes in both anesthetized and freely moving mice, cueing potential for applications to some neuroscientific studies of sensation and naturalistic behavior.

Dopamine (DA) is the key regulator of reward behavior. The DA neurons in the ventral tegmental area (VTA) and their projection areas, which include the prefrontal cortex (PFC), nucleus accumbens (NAc), and amygdala, play a primary role in the process of reward-driven behavior induced by the drugs of addiction, including nicotine and alcohol. In our previous study, we developed a novel platform consisting of micro-LED array devices to stimulate a large area of the brain of rats and monkeys with photo-stimulation and a microdialysis probe to estimate the DA release in the PFC. Our results suggested that the platform was able to detect the increased level of dopamine in the PFC in response to the photo-stimulation of both the PFC and VTA. In this study, we used this platform to photo-stimulate the VTA neurons in both ChrimsonR-expressing (non-specific) wild and dopamine transporter (DAT)-Cre (dopamine specific) mice, and measured the dopamine release in the nucleus accumbens shell (NAcShell). We measured the DA release in the NAcShell in response to optogenetic stimulation of the VTA neurons and investigated the effect of GABAergic neurons on dopaminergic neurons by histochemical studies. Comparing the photo-stimulation frequency of 2 Hz with that of 20 Hz, the change in DA concentration at the NAcShell was greater at 20 Hz in both cases. When ChrimsonR was expressed specifically for DA, the release of DA at the NAcShell increased in response to photo-stimulation of the VTA. In contrast, when ChrimsonR was expressed non-specifically, the amount of DA released was almost unchanged upon photo-stimulation. However, for nonspecifically expressed ChrimsonR, intraperitoneal injection of bicuculline, a competitive antagonist at the GABA-binding site of the GABA A receptor, also significantly increased the release of DA at the NAcShell in response to photo-stimulation of the VTA. The results of immunochemical staining confirm that GABAergic neurons in the VTA suppress DA activation, and also indicate that alterations in GABAergic neurons may have serious downstream effects on DA activity, NAcShell release, and neural adaptation of the VTA. This study also confirms that optogenetics technology is crucial to study the relationship between the mesolimbic dopaminergic and GABAergic neurons in a neural-specific manner.

Objective: Noninvasive neural stimulation via temporally interferential (TI) electrical field is currently an area of interest as a noninvasive method of brain stimulation. The major limitation of TI stimulation is the difficulty of precise temporal control of the stimulation, due to the nature of the sinusoidal envelope generated by the interference. The purpose of this study was to investigate the possibility of improving interferential stimulation by introducing precise temporal control using phase modulation., Methods: In conventional TI, a sinusoidal current is applied to two electrode pairs with slightly different frequencies, to cause interference. In this paper we describe phase modulation interference (PMI). Instead of shifting frequency, the phase of a sinusoidal wave was partially modulated, causing a transient increase or decrease of the envelope. The spatial distribution of envelope modulation amplitude by TI and PMI was visualized using both electromagnetic simulation and actual measurement using tissue phantom., Results: The measured voltage transient in the tissue phantom produce a precise, temporally controlled pulse-like envelope using PMI. The spatial distributions of the amplitude of the envelope modulation by TI and PMI did not differ significantly, and were consistent with electromagnetic simulation., Conclusion: PMI allows precise temporal control of interferential stimulation, thus increasing the practical utility of interferential stimulation., Significance: PMI improves interferential stimulation, allowing more temporally precise stimulation to neural tissue located distantly from the stimulating electrodes.

Auditory-evoked responses can be affected by the sound presented to the contralateral ear. The different contra-sound effects between noise and music stimuli on N1m responses of auditory-evoked fields and those on psychophysical response were examined in 12 and 15 subjects, respectively. In the magnetoencephalographic study, the stimulus to elicit the N1m response was a tone burst of 500 ms duration at a frequency of 250 Hz, presented at a level of 70 dB, and white noise filtered with high-pass filter at 2000 Hz and music stimuli filtered with high-pass filter at 2000 Hz were used as contralateral noise. The contralateral stimuli (noise or music) were presented in 10 dB steps from 80 dB to 30 dB. Subjects were instructed to focus their attention to the left ear and to press the response button each time they heard burst stimuli presented to the left ear. In the psychophysical study, the effects of contralateral sound presentation on the response time for detection of the probe sound of a 250 Hz tone burst presented at a level of 70 dB were examined for the same contra-noise and contra-music used in the magnetoencephalographic study. The amplitude reduction and latency delay of N1m caused by contra-music stimuli were significantly larger than those by contra-noise stimuli in bilateral hemisphere, even for low level of contra-music near the psychophysical threshold. Moreover, this larger suppressive effect induced by contra-music effects was also observed psychophysically; i.e., the change in response time for detection of the probe sound was significantly longer by adding contralateral music stimuli than by adding contra-noise stimuli. Regarding differences in effect between contra-music and contra-noise, differences in the degree of saliency may be responsible for their different abilities to disturb auditory attention to the probe sound, but further investigation is required to confirm this hypothesis., Competing Interests: The authors have declared that no competing interests exist.

Objective: To analyze the outcomes of the underwater endoscopic ear surgery (UWEES) technique for closure of cholesteatomatous labyrinthine fistula (LF) with preservation of auditory function., Study Design: Retrospective case review study., Setting: Tertiary referral center., Patients: A total of 12 patients with cholesteatomatous LF., Intervention: Surgical method of closure using UWEES for cholesteatomatous LF to minimize inner ear damage. Artificial cerebrospinal fluid (CSF) was used as the perfusate, except for earlier cases when saline was employed., Main Outcome Measures: Comparison of bone conductance hearing level (BCHL) before and after surgery. A change of BCHL less than 10 dB was defined as successful preservation of bone conductance hearing., Results: All cases of LF were treated successfully by closure using the UWEES technique. Seven cases were type I, one was type IIa, and four were type III according to the Milewski and Dornhoffer classification of LF. The average LF size was 3.1 mm (1-7 mm). Eleven patients were evaluated and their bone conductance hearing was well preserved in all of them (11/11). One patient was too young for preoperative evaluation of BCHL, but hearing preservation was verified 2 years later at the age of 6 years. Remarkably, none of the patients complained of vertigo, except for only a slight manifestation on postoperative day 1., Conclusion: The UWEES technique was effective for closure of cholesteatomatous LF with preservation of auditory function., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2021, Otology & Neurotology, Inc.)

Significance: Gene expression analysis is an important fundamental area of biomedical research. However, live gene expression imaging has proven challenging due to constraints in conventional optical devices and fluorescent reporters., Aim: Our aim is to develop smaller, more cost-effective, and versatile imaging capabilities compared with conventional devices. Bioluminescence reporter-based gene expression analysis was targeted due to its advantages over fluorescence-based imaging., Approach: We created a small compact imaging system using micro-CMOS image sensors (μCIS). The μCIS model had an improved pixel design and a patterned absorption filter array to detect the low light intensity of bioluminescence., Results: The device demonstrated lower dark current, lower temporal noise, and higher sensitivity compared with previous designs. The filter array enabled us to subtract dark current drift and attain a clearer light signal. These improvements allowed us to measure bioluminescence reporter-based gene expression in living mammalian cells., Conclusion: Using our μCIS system for bioluminescence imaging in the future, the device can be implanted in vivo for simultaneous gene expression imaging, behavioral analysis, and optogenetic modulation.

Dysphasia is one of the complications which may cause functional disability after the surgical treatment of oral cancer. The loss of the function derived by tongue and other oral tissues impairs the retention and delivery of liquids and food masses as well as the swallowing motion into pharynx. As accumulation of liquids or food masses in the larynx can lead to pneumonia, therefore swallowing support to improve each coordination of the tongue, the epiglottis and the esophagus in the process of swallowing is highly desirable. In this study, we designed a new artificial tongue which was capable of contracting to deliver the bolus masses in the swallowing propulsion phase in the oral cavity. We designed a two-layered artificial tongue simulating the anatomical identical muscle structures with the longitudinal muscle, and the transverse muscle-genioglossus layer. A silicone rubber material was used for the surface layer, and the covalent shape memory alloy fibers (diameter: 150µm) were implemented in the secondary structure beneath of the silicone rubber material of the artificial tongue. Its contraction was driven by with shape memory alloy fibers shortage inside of the artificial tongue unit. The actuation was accurately controlled by the originally designed electrical current input with pulse width modulation. Firstly, we examined a prototype structure of the artificial tongue as well as the changes in unit thickness as it constricted by electric power supply switching. Secondly, we performed a feasibility study of the prototype into the head-neck medical training model with larynx-tracheal structure with esophagus. The results were as follows: a) the artificial tongue model showed a large contraction with a motion to increase upward pressure, b) the tongue unit expressed the capability of reducing shallow space between dorsal tongue surface and palate in the oral cavity model. Therefore, the first artificial tongue design with active contractile motion will be useful orally installable device for improving delivery function of bolus masses through swallowing procedure in dysphasia.Clinical Relevance- The active artificial tongue system designed for the first time exhibited an effective contractile motion to support bolus food masses propulsion in swallowing process in the oral cavity in the patients with dysphasia.