Targeting M-MDSCs enhances the therapeutic effect of BNCT in the 4-NQO-induced murine head and neck squamous cell carcinoma model.

Purpose: Malignant head and neck squamous cell carcinoma (HNSCC) is characterized by a poor prognosis and resistance to conventional radiotherapy. Infiltrating myeloid-derived suppressive cells (MDSCs) is prominent in HNSCC and is linked to immune suppression and tumor aggressiveness. This study aimed to investigate the impact of boron neutron capture therapy (BNCT) on the MDSCs in the tumor microenvironment and peripheral blood and to explore the potential for MDSCs depletion combined with BNCT to reactivate antitumor immunity. Methods and materials: Carcinogen, 4-NQO, -induced oral tumors were irradiated with a total physical dose of 2 Gy BNCT in Tsing Hua Open Reactor (THOR). Flow cytometry and immunohistochemistry accessed the dynamics of peripheral MDSCs and infiltrated MDSCs within the tumor microenvironment. Mice were injected with an inhibitor of CSF-1 receptor (CSF-1R), PLX3397, to determine whether modulating M-MDSCs could affect mice survival after BNCT. Results: Peripheral CD11b+Ly6ChighLy6G- monocytic-MDSCs (M-MDSCs), but not CD11b+Ly6CloLy6Ghigh polymorphonuclear-MDSCs (PMN-MDSCs), increased as tumor progression. After BNCT treatment, there were temporarily decreased and persistent increases of M-MDSCs thereafter, either in peripheral blood or in tumors. The administration of PLX-3397 hindered BNCT-caused M-MDSCs infiltration, prolonged mice survival, and activated tumor immunity by decreasing tumor-associated macrophages (TAMs) and increasing CD8+ T cells. Conclusion: M-MDSCs were recruited into 4-NQO-induced tumors after BNCT, and their number was also increased in peripheral blood. Assessment of M-MDSCs levels in peripheral blood could be an index to determine the optimal intervention window. Their temporal alteration suggests an association with tumor recurrence after BNCT, making M-MDSCs a potential intervention target. Our preliminary results showed that PLX-3397 had strong M-MDSCs, TAMs, and TIL (tumor-infiltrating lymphocyte) modulating effects that could synergize tumor control when combined with BNCT.

Nanodiamonds Doped with Manganese for Applications in Magnetic Resonance Imaging.

Nanodiamonds (NDs) are emerging with great potential in biomedical applications like biomarking through fluorescence and magnetic resonance imaging (MRI), targeted drug delivery, and cancer therapy. The magnetic and optical properties of NDs could be tuned by selective doping. Therefore, we report multifunctional manganese-incorporated NDs (Mn-NDs) fabricated by Mn ion implantation. The fluorescent properties of Mn-NDs were tuned by inducing the defects by ion implantation and enhancing the residual nitrogen vacancy density achieved by a two-step annealing process. The cytotoxicity of Mn-NDs was investigated using NCTC clone 929 cells, and the results revealed no cytotoxicity effect. Mn-NDs have demonstrated dual mode contrast enhancement for both T 1- and T 2-weighted in vitro MR imaging. Furthermore, Mn-NDs have illustrated a significant increase in longitudinal relaxivity (fivefold) and transversal relaxivity (17-fold) compared to the as-received NDs. Mn-NDs are employed to investigate their ability for in vivo MR imaging by intraperitoneal (ip) injection of Mn-NDs into mice with liver tumors. After 2.5 h of ip injection, the enhancement of contrast in T 1- and T 2-weighted images has been observed via the accumulation of Mn-NDs in liver tumors of mice. Therefore, Mn-NDs have great potential for in vivo imaging by MR imaging in cancer therapy.

WiFi-Based Detection of Human Subtle Motion for Health Applications.

Neurodegenerative diseases such as Parkinson's disease affect motor symptoms with abnormally increased or reduced movements. Symptoms such as tremor and hand movement disorders can be subtle and vary daily such that the actual condition of the disease may not fully present in clinical sessions. Health examination and monitoring, if available in the living space, can capture comprehensive and quantitative information about a patient's motor symptoms, allowing physicians to make a precise diagnosis and devise a more personalized treatment. WiFi-based sensing is a potential solution for passively detecting human motion in a contactless way that collects no personally identifiable information. This study proposed an approach for human micromotion detection using the WiFi channel state information, which can be realized in a regular-sized room for home health monitoring and examination. Three types of motion were tested to evaluate the proposed method in quantifying micromotion using single and multiple WiFi links. The results show that micromotion could be captured at all distributed locations in the experimental environment (4.2 m × 7.9 m). Our computer algorithm computed the frequency and duration of simulated hand tremors with an average accuracy of 90.9% (single WiFi link)-95.7% (multiple WiFi links).

Hyperviscosity-related retinopathy and serous macular detachment in Waldenström's macroglobulinemia: A mortal case in 5 years.

PURPOSE: To present a 5-year mortal case of Waldenström's macroglobulinemia-related retinopathy and serous macular detachment. CASE REPORT: A 63-year-old man, with unremarkable medical history, presented with bilateral decreased vision for 2 months. Fundus examination revealed bilateral scattered retinal hemorrhages, exudates, venous tortuosity, and serous macular detachment. Hematologic and biochemistry profiles showed pancytopenia with blood smear demonstrating erythrocyte rouleaux formation. Hyperviscosity syndrome was suspected and later Waldenström's macroglobulinemia was diagnosed by bone marrow biopsy and high concentration of serum IgM. Plasmapheresis and subsequent chemotherapy were arranged. In spite of resolution of most retinal abnormalities, his visual acuity still showed no improvement with a persistent bilateral macular detachment. The patient then died 5 years after the diagnosis of Waldenström's macroglobulinemia. CONCLUSIONS: Long-term toxicity of IgM to the retinal pigment epithelium may impede the resolution of the persistent serous macular detachment, resulting in an inability of recovery in his vision. Therefore, early diagnosis and timely reduction of serum paraproteins by plasmapheresis and chemotherapy is critical for preventing permanent damages to patients' health and vision.

Cervical lymphatic malformations amenable to transhairline robotic surgical excision in children: A case series.

ABSTRACT: Lymphatic malformations are rare benign malformations that predominantly occur in the head and neck region. The advent of surgical robots in head and neck surgery may provide beneficial outcomes for pediatric patients. Here, we describe our experiences with transhairline incisions for robot-assisted surgical resection of cervical lymphatic malformations in pediatric patients.In this prospective longitudinal cohort study, we recruited consecutive patients under 18 years of age who were diagnosed with congenital cervical lymphatic malformations and scheduled for transhairline approach robotic surgery at a single medical center. We documented the docking times, console times, surgical results, complications, and postoperative follow-up outcomes.The studied patients included 2 with mixed-type lymphatic malformations and 2 with macrocystic-type lymphatic malformations. In all 4 patients, the incision was hidden in the hairline; the incision length was <5 cm in 3 patients but was extended to 6 cm in 1 patient. Elevating the skin flap and securely positioning it with Yang retractor took <1 hour in all cases. The mean docking time was 5.5 minutes, and the mean console time was 1 hour and 46 minutes. All 4 surgeries were completed endoscopically with the robot. The average total drainage volume in the postoperative period was 21.75 mL. No patients required tracheotomy or nasogastric feeding tubes. Neither were adverse surgery-associated neurovascular sequelae observed. All 4 patients were successfully treated for their lymphatic malformations, primarily with robotic surgical excisions.Cervical lymphatic malformations in pediatric patients could be accessed, properly visualized, and safely resected with transhairline-approach robotic surgery. Transhairline-approach robotic surgery is an innovative method for meeting clinical needs and addressing esthetic concerns.

Kikuchi-Fujimoto Disease Associated With Mycoplasma Pneumoniae Infection.

Kikuchi-Fujimoto disease (KFD) is a self-limited disease that is more common in young Asian women. Typical presentations included fever and cervical lymphadenopathy. The etiology of KFD is unknown, and diagnosis is based mainly on lymph node biopsy. KFD has been reported to be associated with Mycoplasma pneumoniae infection. However, the role of antibiotic treatment is unclear. We reported 2 cases of KFD associated with Mycoplasma pneumoniae infection and were successfully treated with a macrolide.

Local Interleukin-12 Treatment Enhances the Efficacy of Radiation Therapy by Overcoming Radiation-Induced Immune Suppression.

Radiation therapy (RT) recruits myeloid cells, leading to an immunosuppressive microenvironment that impedes its efficacy against tumors. Combination of immunotherapy with RT is a potential approach to reversing the immunosuppressive condition and enhancing tumor control after RT. This study aimed to assess the effects of local interleukin-12 (IL-12) therapy on improving the efficacy of RT in a murine prostate cancer model. Combined treatment effectively shrunk the radioresistant tumors by inducing a T helper-1 immune response and influx of CD8+ T cells. It also delayed the radiation-induced vascular damage accompanied by increased α-smooth muscle actin-positive pericyte coverage and blood perfusion. Moreover, RT significantly reduced the IL-12-induced levels of alanine aminotransferase in blood. However, it did not further improve the IL-12-induced anti-tumor effect on distant tumors. Upregulated expression of T-cell exhaustion-associated genes was found in tumors treated with IL-12 only and combined treatment, suggesting that T-cell exhaustion is potentially correlated with tumor relapse in combined treatment. In conclusion, this study illustrated that combination of radiation and local IL-12 therapy enhanced the host immune response and promoted vascular maturation and function. Furthermore, combination treatment was associated with less systemic toxicity than IL-12 alone, providing a potential option for tumor therapy in clinical settings.

First report of leopard fossils from a limestone cave in Kenting area, southern Taiwan.

Longshia-dong Cave, a limestone cave located in the Kenting area within the Kenting National Park of southern Taiwan, yields numerous terrestrial mammalian fossils. Many of them were not reported in historical literature and are neither present in Taiwan. For instance, no historical literature mentioned leopards inhabited in Taiwan, and thus their existence remained unknown. This study describes three fossil leopard (Panthera pardus) teeth uncovered from Longshia-dong Cave. Two isolated lower premolars and one lower molar, respectively p3, p4 and m1, were discovered in a very small area (11 × 6 cm) and show a series of progressive increase in size. Thus, the three teeth should have been belonging to the same individual from the subfamily of Pantherinae. Traditional linear measurements and two-dimensional geometric morphometric analysis for the occlusal surface outlines were conducted on the fossil teeth and extant pantherines inhabited in Asia such as clouded leopards (Neofelis nebulosa), leopards (Panthera pardus), and tigers (Panthera tigiris). Results show that the fossil teeth are similar both in size and morphology to the teeth of extant leopards, suggesting the assignment of the fossil teeth to leopards. This study, for the first time, reported the presence of leopards in the Late Pleistocene of Taiwan. In addition, the smaller size of the fossil teeth in comparison with Chinese fossil leopards is putatively attributed to insular dwarfism or individual size variability, yet more studies are required.

Age and growth of Palaeoloxodon huaihoensis from Penghu Channel, Taiwan: significance of their age distribution based on fossils.

Dental material attributed to Palaeoloxodon huaihoensis from the Middle to Late Pleistocene were recovered over decades from the Penghu Channel during commercial fisheries activities. The National Museum of Nature Science (NMNS) has a collection of such dental material, which differs in size and morphology and likely represents ontogenetic variation and growth trajectory of various age groups of P. huaihoensis. However, little is known regarding age determination. By using length of dental material, enamel thickness (ET), and plate counts, we established the method to distinguish the age of the species, which is directly derived from the extant African forest elephant Loxodonta africana. When measuring signs of allometric growth, we found that in both the upper and lower jaws, tooth width was correlated negatively with lamellar frequency but positively with ET. In the same age group, the number of lamellae was higher in P. huaihoensis than in L. africana. The reconstructed age distribution indicated no difference in the upper or lower jaw. Notably, within our sample, P. huaihoensis is skewed towards adult and older individuals with median age between 33-34.5 years and differed significantly from that of Mammuthus primigenius in the European Kraków Spadzista site. This age distribution pattern is speculated to be related to the harsh environmental conditions and intense intraspecific competition among P. huaihoensis during the last ice age.

No evidence for widespread island extinctions after Pleistocene hominin arrival.

The arrival of modern humans into previously unoccupied island ecosystems is closely linked to widespread extinction, and a key reason cited for Pleistocene megafauna extinction is anthropogenic overhunting. A common assumption based on late Holocene records is that humans always negatively impact insular biotas, which requires an extrapolation of recent human behavior and technology into the archaeological past. Hominins have been on islands since at least the early Pleistocene and Homo sapiens for at least 50 thousand y (ka). Over such lengthy intervals it is scarcely surprising that significant evolutionary, behavioral, and cultural changes occurred. However, the deep-time link between human arrival and island extinctions has never been explored globally. Here, we examine archaeological and paleontological records of all Pleistocene islands with a documented hominin presence to examine whether humans have always been destructive agents. We show that extinctions at a global level cannot be associated with Pleistocene hominin arrival based on current data and are difficult to disentangle from records of environmental change. It is not until the Holocene that large-scale changes in technology, dispersal, demography, and human behavior visibly affect island ecosystems. The extinction acceleration we are currently experiencing is thus not inherent but rather part of a more recent cultural complex.

Lipemia retinalis with different therapeutic responses: A report of two cases.

Lipemia retinalis is characterized by retinal blood vessels that are creamy white in color and is considered to be directly correlated to serum triglyceride levels. It is a rare retinal manifestation, with typical serum triglyceride levels above 2500 mg/dL required for its expression. We report two cases of lipemia retinalis with hypertriglyceridemia who presented with different retinal pictures during a 5-year follow-up. One showed a normalization of retinal vessels even though the serum triglyceride level was still far more than 2500 mg/dL (4660 mg/dL), but the other had persistent creamy white discoloration despite decreases in serum triglyceride level to below 2500 mg/dL (1031 mg/dL). This suggests that the absolute serum triglyceride level may not be the sole determinant of the typical retinal manifestation. In spite of this, early detection that leads to timely treatment will assist in prevention of severe ocular and systemic vascular complications.

Prevalence and patterns of tongue deformation in obstructive sleep apnea: A whole-night simultaneous ultrasonographic and polysomnographic study.

Tongue deformation during whole-night natural sleep in adult patients with obstructive sleep apnea has not been well evaluated. Through simultaneous ultrasonography and polysomnography during whole-night sleep, we examined the prevalence and patterns of tongue depth changes and their relationship with the severity of obstructive sleep apnea. Sixty consecutive eligible adults presenting with symptoms suggesting obstructive sleep apnea were enrolled. We observed that 88.4% (38/43) of patients with obstructive sleep apnea exhibited a significant increase in the maximum ultrasonographic tongue depth when hypopnea or apnea occurred during sleep. A mixed-model analysis of variance demonstrated that compared with patients with primary snoring or mild obstructive sleep apnea, those with moderate to severe obstructive sleep apnea have significantly greater maximum ultrasonographic tongue depth during respiratory events (p = .0047). We identified three different ultrasonographic patterns of tongue deformation, namely en bloc, tongue body and tongue base. Approximately 82% (27/33) of patients with moderate to severe obstructive sleep apnea demonstrated an en bloc tongue deformation. By contrast, 70% (19/27) of primary snorers or patients with mild obstructive sleep apnea showed a tongue body obstruction. Recognizing the prevalence and patterns of tongue deformation during sleep may provide insights into pathogenesis and treatment decisions in patients with obstructive sleep apnea. Future studies are warranted to verify the treatment results of various tongue procedures by using this approach.

Magnet ingestion by children: A retrospective study in a medical center in Taiwan.

BACKGROUND: The ingestion of multiple magnets may lead to severe complications including bowel obstruction, perforation, fistula, peritonitis, short bowel syndrome, life-threatening injuries, and even death. The annual case number of high-powered neodymium magnets ingestion has been increasing in the western world and the dearth of available data demonstrates that this issue has been neglected in Taiwan. METHODS: We searched the electronic medical records of our institution for patients younger than 18 years old who were diagnosed with, who had ever visited our emergency department, or been hospitalized for magnetic foreign body ingestion between January 2009 and March 2018. Demographic data including the number, shape, and size of magnets ingested, the clinical presentation, type of intervention, and complications were reviewed. RESULTS: Thirteen patients who met the enrollment criteria were analyzed. One patient was documented between 2009 and 2013, and twelve were documented between January 2014 and March 2018. Five of the cases documented between 2014 and 2018 had ingested Buckyballs. The median age of the patients was 5 years. All of the patients with clinical symptoms had ingested more than one magnet and required endoscopic or surgical intervention. Bowel perforation or deep ulcer with impending perforation was found in three patients during surgery. CONCLUSION: The number of children who visited our emergency department or were hospitalized due to the ingestion of magnets has increased recently. The presence of high power of neodymium magnets in many products increases the risk of ingesting multiple magnets resulting in serious complications. Therefore, stricter policies are needed to prevent children from obtaining products that contain magnets.

Ultrasound Shear-Wave Elastography of the Tongue in Adults with Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) is a chronic breathing disorder characterized by intermittent sleep state-dependent upper airway (UA) collapse. The tongue comprises the primary UA dilator muscle and plays an essential role in the pathogenesis of OSA. We examined whether tongue stiffness measurement using ultrasound (US) shear wave elastography (SWE) is useful for predicting the existence of OSA. Forty-six participants (20 healthy controls and 26 patients with OSA) underwent transcutaneous submental SWE using a US system. Quantification with a shear modulus of 0-200 kPa was recorded during normal breathing and Müller's maneuver (MM). Polysomnography was used as the reference standard. Mid-sagittal tongue stiffness was significantly higher in awake patients with OSA than in controls during normal breathing and the MM (p < 0.0001). The posterior third of the tongue in patients with OSA had the highest value of shear modulus during the MM (p < 0.001). With cut-offs of 27.6 and 35.2 kPa for the whole tongue and posterior third during the MM, respectively, the sensitivity obtained was 69.2% and 76.9%, and the specificity was 85% and 95%, respectively, for detecting OSA. The corresponding areas under the receiver operating characteristic curve were 0.82 and 0.88, respectively. US SWE may have the potential for non-invasive tongue stiffness measurement in OSA.

Hypoxia, hypotension, and bradycardia induced by povidone-iodine ingestion: A pediatric case report and literature review.

Povidone-iodine (PI) is a disinfectant and antiseptic agent commonly used to sterilize skin, mucous membranes, and wounds. PI intoxication is very rare, but the complications may be severe. We report a pediatric patient who presented in the emergency department with hypoxia, hypotension, and bradycardia after unintentional PI ingestion.

Clinical and nutritional outcome of pediatric esophageal stenosis with endoscopic balloon dilatation.

AIM: The present study evaluates the long-term clinical and nutritional effect to endoscopic balloon dilatation (EBD) in pediatric esophageal stricture. METHODS: This was a 15-year retrospective study involving pediatric patients with esophageal stricture treated with EBD. Outcome parameters included the number of dilatations, procedural success rates, nutritional status, and complications. EBD was performed in patients with a dysphagia score greater than 2. The nutritional status was assessed by weight-for-age z-score. Clinical success was defined as no requirement for EBD for at least 1 year and/or increasing interval between dilatation and the numbers of EBD was fewer than 4 times per year. RESULTS: A total of 50 cases (mean age, 4.41 ± 4.9 years) were enrolled. During a mean follow-up of 3.2 ± 1.9 years, a total of 268 EBD sessions were performed, with an average of 5.36 sessions per patient (range, 1-33). Patients who had short segment stricture (<2 cm) were prone to achieve clinical success after EBD (p = 0.0094). Procedural perforation rate is 2.6% (7/268); subsequent tracheoesophageal fistula occurred in two patients. The clinical success rate of EBD therapy was 72% (36/50). All had increments of weight-for-age z-score after EBD therapy, and the increment was significantly greater in those patients with short segment stricture or stricture in the middle esophagus at 12 months (p = 0.01 and 0.008, respectively). CONCLUSIONS: EBD has good long-term clinical success and nutritional promotion in pediatric patients with esophageal stricture, especially in short segment stricture or stricture in the middle esophagus.

A right whale (Mysticeti, Balaenidae) from the Pleistocene of Taiwan.

Current patterns of biological distribution result from the deep past. Of particular interest, some closely related species appear at high latitudes of both hemispheres, but not in between, a pattern known as antitropical distribution. However, the timing, pathway, and drivers of antitropical distributions remain mostly unknown. Here we describe a new fossil, a left tympanic bulla (part of the ear bones), from the Middle/Late Pleistocene (0.78-0.01 mya, but not excluding the possibility of Holocene in age, as the specimen was dredged from the sea bottom and the geological horizon remains uncertain) of Taiwan. The tympanic bulla is diagnostic in baleen whales, and this specimen shows morphological features that are identical to extant Eubalaena, including: relatively large size (the anteroposterior length is 117 mm); rectangular outline in medial view; short anterior lobe, judging from the remaining of the lateral furrow; squared anterior margin; prominent transverse crease on the involucrum; transversely compressed in anterior view; well-developed and rounded outer lip; and parallel involucral and main ridges. Although incomplete, the morphological characters and overall similarity to extant Eubalaena allow a reliable taxonomic assignment to Eubalaena sp. The occurrence of a Pleistocene Eubalaena on the southern margin of the western North Pacific is the first balaenid fossil evidence indicative of the biotic interchange between two hemispheres leading to the origin of antitropical distribution in the Pleistocene; alternatively, this specimen might merely represent an extra-limital record of the North Pacific Eubalaena. Furthermore, this find suggests that the Eubalaena interchange, being one of the largest species displaying antitropical distribution pairs in the history of life, likely took place along the western Pacific. Notably, this does not preclude the Eubalaena interchange from other routes, such as the eastern Pacific or the Atlantic Ocean, and future finds should test the scenario for the biotic interchange between Northern and Southern Hemispheres of Eubalaena.