Increased nociceptive behaviors and spinal c-Fos expression in the formalin test in a rat repeated cold stress model.

Repeated cold stress (RCS) can trigger the development of fibromyalgia (FM)-like symptoms, including persistent deep-tissue pain, although nociceptive changes to the skin have not been fully characterized. Using a rat RCS model, we investigated nociceptive behaviors induced by noxious mechanical, thermal, and chemical stimuli applied to plantar skin. Neuronal activation in the spinal dorsal horn was examined using the formalin pain test. In rats exposed to RCS, nociceptive behavioral hypersensitivity was observed in all modalities of cutaneous noxious stimuli: the mechanical withdrawal threshold was decreased, and the heat withdrawal latency was shortened one day after the cessation of stress. The duration of nocifensive behaviors in the formalin test was prolonged in phase II but not in phase I. The number of c-Fos-positive neurons increased in the entire dorsal horn laminae I-VI, ipsilateral, but not contralateral, to formalin injection at the L3-L5 segments. The duration of nocifensive behavior in phase II was significantly and positively correlated with the number of c-Fos-positive neurons in laminae I-II. These results demonstrate that cutaneous nociception is facilitated in rats exposed to RCS for a short time and that the spinal dorsal horn neurons are hyperactivated by cutaneous formalin in the RCS model.

Nivolumab Therapy in Lung Cancer Associated with IgG4-related Disease.

A 75-year-old man with severe bilateral pleural thickening and dense soft tissue masses surrounding the abdominal aorta on computed tomography was diagnosed with IgG4-related disease (IgG4-RD) as a complication of lung cancer. He was started on nivolumab as second-line therapy along with low-dose prednisolone. Nivolumab was administered for 15 months until disease progression, during which time IgG4-RD did not relapse, and no problematic immune-related adverse events occurred. These results suggest that anti-programmed cell death protein-1 antibody may be used safely in lung cancer associated with IgG4-RD concomitantly with low-dose steroids.

Self-assembling bilayer wiring with highly conductive liquid metal and insulative ion gel layers.

Ga-based liquid metals (LMs) are expected to be suitable for wiring highly deformable devices because of their high electrical conductivity and stable resistance to extreme deformation. Injection and printed wiring, and wiring using LM-polymer composites are the most popular LM wiring approaches. However, additional processing is required to package the wiring after LM patterning, branch and interrupt wiring shape, and ensure adequate conductivity, which results in unnecessary wiring shape changes and increased complexity of the wiring methods. In this study, we propose an LM-polymer composite comprising LM particles and ion gel as a flexible matrix material with low viscosity and specific gravity before curing. Moreover, the casting method is used for wire patterning, and the material is cured at room temperature to ensure that the upper insulative layer of the ion gel self-assembles simultaneously with the formation of LM wiring in the lower layer. High conductivity and low resistance change rate of the formed wiring during deformation are achieved without an activation process. This ion gel-LM bilayer wiring can be used for three-dimensional wiring by stacking. Furthermore, circuits fabricated using ion gel-LM bilayer wiring exhibit stable operation. Therefore, the proposed method can significantly promote the development of flexible electronic devices.

Transbronchial cryobiopsy using an ultrathin cryoprobe with a guide sheath for the diagnosis of pulmonary mucosa-associated lymphoid tissue lymphoma.

Pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma is difficult to diagnose and relatively rare. Tissue sampling through transbronchial biopsy is often inadequate, necessitating surgical lung biopsy. However, a recently developed technique, transbronchial lung cryobiopsy (TBLC), has shown promise for obtaining larger specimens. A 1.1 mm cryoprobe has recently become available, and its usefulness has been increasingly reported. Use of a conventional cryoprobe for TBLC in diagnosing pulmonary MALT lymphoma has been previously reported; however, there are no reports on the use of a 1.1 mm ultrathin cryoprobe and guide sheath (GS). We aimed to assess the effectiveness and safety of using a 1.1 mm ultrathin cryoprobe in combination with a GS for diagnosing pulmonary MALT lymphoma using a simpler and safer method. We retrospectively analyzed the findings for four patients showing characteristic computed tomography (CT) findings of MALT lymphoma, including peripheral pulmonary lesions, air bronchogram nodules, and bronchiectasis, at our hospital. Each patient underwent endobronchial ultrasound (EBUS) with a GS, followed by TBLC using a 1.1 mm cryoprobe. Morphological diagnosis, immunohistochemical examination, and molecular testing were performed on the biopsy specimens to establish the diagnosis. Complications during the procedure were also monitored. We obtained 8-16 biopsy specimens in all four cases using a cryoprobe. Histopathological analysis of two cases revealed the infiltration of small lymphocytes with numerous lymphoepithelial lesions, confirming MALT lymphoma. Immunohistochemical examination further demonstrated B-cell lymphocyte proliferation and light-chain restriction, confirming monoclonality and providing a definitive diagnosis. In the remaining two cases, histopathological evidence of pulmonary MALT lymphoma was lacking. However, molecular testing using polymerase chain reaction to analyze immunoglobulin gene rearrangements revealed B-cell clonality, which supported the diagnosis. Molecular testing proved particularly useful when histopathological diagnosis alone was inconclusive. No complications such as pneumothorax or hemorrhage occurred during the procedure. The combination of a GS and EBUS facilitated specimen collection at the same location as EBUS, with the GS providing compression hemostasis and eliminating the need for an additional hemostatic device. Therefore, TBLC with a GS is a useful and safe method for diagnosing pulmonary MALT lymphomas and reproducibly yielded sufficient quantities of good-quality biopsy specimens.

Successful surgical treatment of epithelioid hemangioendothelioma involving multiple liver lesions and bilateral lung nodules.

Epithelioid hemangioendothelioma (EHE) affects many organs, particularly lung and liver, and typically presents as multiple lesions. Treatment for EHE is not yet standardized, but surgery is appropriate when lesions are resectable. In our patient, radiography revealed multiple bilateral pulmonary nodules, and CT showed several liver tumors. The liver masses and those in the right lung were removed during the initial surgery; pathology of hepatic specimens confirmed the diagnosis of EHE. During the second operation, the left lung nodules were excised, and all were EHEs. Surgical removal of multiorgan multinodular EHE is a viable treatment option, especially for young patients.

Stretchable Gas Barrier Films Using Liquid Metal toward a Highly Deformable Battery.

Highly deformable batteries that are flexible and stretchable are important for the next-generation wearable devices. Several studies have focused on the stable operation and life span of batteries. On the other hand, there has been less focus on the packaging of highly deformable batteries. In wearable devices, solid-state or pouch lithium-ion batteries (LIBs) packaged in aluminum (Al)-laminated films, which protect against moisture and gas permeation, are used. Stretchable elastomer materials are used as the packaging films of highly deformable batteries; however, they are extremely permeable to gas and moisture. Therefore, a packaging film that provides high deformability along with gas and moisture barrier functionalities is required for the stable operation of highly deformable batteries used in ambient conditions. In this study, a stretchable packaging film with high gas barrier functionality is developed successfully by coating a thin layer of liquid metal onto a gold (Au)-deposited thermoplastic polyurethane film using the layer-by-layer method. The film exhibits excellent oxygen gas impermeability under mechanical strain and extremely low moisture permeability. It shows high impermeability along with high mechanical robustness. Using the proposed stretchable gas barrier film, a highly deformable LIB is assembled, which offers reliable operation in air. The operation of the highly deformable battery is analyzed by powering LEDs under mechanical deformations in ambient conditions. The proposed stretchable packaging film can potentially be used for the development of packaging films in advanced wearable electronic devices.

Pressure pain threshold map of thoracolumbar paraspinal muscles after lengthening contractions in young male asymptomatic volunteers.

This study aimed to characterise topographic distribution of pressure pain thresholds (PPTs) of thoracolumbar paraspinal muscles and its change after lengthening contractions (LCs) of the back muscles. Using young male asymptomatic participants in Experiment 1, we systematically examined the distribution of PPTs bilaterally in the range of Th1-L5 at measurement points 2 and 4 cm from the midline. PPTs were found to be higher in the lumbar segments of the paraspinal muscles than in the thoracic segments, and in muscles closer to the vertebrae (2 vs. 4 cm from the midline). The PPTs did not differ between the left and right sides in each segment. In Experiment 2, LC was applied by asking a part of participants recruited in Experiment 1 to fall their trunk from a starting position (parallel to the floor) to 40° flexed position, and then made it back as quickly as possible to the starting position. This cycle was repeated until participants could not keep contractions (30 times/set, 25.4 ± 10.6 sets). PPTs of the LC group decreased prominently in the lower thoracic and lumbar segments, and the decrease was more evident 24 h after LC compared to that 48 h after. In contrast, PPTs in the control group without LC remained unchanged. These results provided broad topographic images of PPTs in the thoracolumbar paraspinal muscles of young male participants with and without LC, and the obtained PPT maps could be a useful guide for better treatment of exercise-induced myofascial pain in the lower back.

Nociceptive chemical hypersensitivity in the spinal cord of a rat reserpine-induced fibromyalgia model.

The pathological mechanisms of fibromyalgia (FM) are largely unknown. Recently, a rat reserpine-induced pain model showing exaggerated pain-related behaviors to mechanical and thermal stimuli has been used in FM research. However, the model has not been fully characterized. Here, we investigated nociceptive hypersensitivity to chemical stimuli and its spinal mechanisms to further characterize the model. The rat model was induced by administering reserpine to the nervous system. Nociceptive behaviors to chemical stimuli were quantified using the formalin pain test, and neuronal activation of the stimuli was examined using spinal c-Fos immunohistochemistry and electrophysiological recordings of superficial dorsal horn (SDH) neurons. The duration of pain-related behaviors was prolonged in both phases I (0-5 min) and II (10-60 min) and the interphase; and the number of c-Fos-immunoreactive nuclei increased in laminae I-II, III-IV, and V-VI at the spinal segments L3-L5 on the side ipsilateral to the formalin injection, and these factors were significantly and positively correlated. The action potentials of SDH neurons induced by formalin injection were markedly increased in rats treated with reserpine. These results demonstrate that pain-related behaviors are facilitated by noxious chemical stimuli in a rat reserpine-induced FM model, and that the behavioral hypersensitivity is associated with hyperactivation of SDH neurons.

Direct Wiring of Liquid Metal on an Ultrasoft Substrate Using a Polyvinyl Alcohol Lift-off Method.

In recent years, wiring and system construction on ultrasoft materials such as biological tissues and hydrogels have been proposed for advanced wearable devices, implantable devices, and soft robotics. Among the soft conductive materials, Ga-based liquid metals (LMs) are both biocompatible and ultrasoft, making them a good match for electrodes on the ultrasoft substrates. However, gels and tissues are softer and less wettable to the LMs than conventional soft substrates such as Ecoflex and polydimethylsiloxane. In this study, we demonstrated the transfer of LM paste composed of Ga-based LM and Ni nanoparticles onto ultrasoft substrates such as biological tissue and gels using sacrificial polyvinyl alcohol (PVA) films. The LM paste pattern fabricated on the PVA film adhered to the ultrasoft substrate along surface irregularities and was transferred without being destroyed by the PVA film before the PVA's dissolution in water. The minimum line width that could be wired was approximately 165 µm. Three-dimensional wiring, such as the helical structure on the gel fiber surface, is also possible. Application of this transfer method to tissues using LM paste wiring allowed the successful stimulation of the vagus nerve in rats. In addition, we succeeded in transferring a temperature measurement system fabricated on a PVA film onto the gel. The connection between the solid-state electrical element and the LM paste was stable and maintained the functionality of the temperature-sensing system. This fundamental study of wiring fabrication and system integration can contribute to the development of advanced electric devices based on ultrasoft substrates.

A case of pulmonary tuberculosis with hemoptysis from a peripheral pulmonary aneurysm.

An 88-year-old woman visited our hospital for hemoptysis due to ruptured peripheral pulmonary aneurysm diagnosed by contrast computed tomography (CT) and angiography. Her bleeding was stopped by interventional radiology vascular embolization. She was diagnosed with pulmonary tuberculosis due to a positive acid-fast bacillus (AFB) smear test following admission and the positive polymerase chain reaction for tuberculosis, despite no obvious cavity lesions or scatter shadows on CT. The causes of hemoptysis due to pulmonary tuberculosis are known to be Rasmussen aneurysm, in which the blood vessel wall adjacent to the lung cavity is thinned to form an aneurysm, or bleeding from the bronchial artery. In this case, it was considered that the inflammation caused by pulmonary tuberculosis spread directly to the pulmonary artery and formed a pulmonary aneurysm without forming a cavity. Similar cases have been rarely reported. Clinicians need to consider pulmonary tuberculosis as the cause of pulmonary aneurysm, even without cavity lesions in the lungs. It is important to perform AFB examination to diagnose pulmonary tuberculosis.

Responses of cutaneous C-fiber afferents and spinal microglia after hindlimb cast immobilization in rats.

Previous studies have shown that persistent limb immobilization using a cast increases nociceptive behavior to somatic stimuli in rats. However, the peripheral neural mechanisms of nociception remain unclear. Using single-fiber electrophysiological recordings in vitro, we examined the general characteristics of cutaneous C-fiber afferents in the saphenous nerve and their responsiveness to mechanical and heat stimuli in a rat model of immobilization-induced pain by subjecting the rats to hindlimb cast immobilization for 4 weeks. The mechanical response of C-fibers appeared to increase in the model; however, statistical analysis revealed that neither the response threshold nor the response magnitude was altered. The general characteristics and heat responses of the C-fibers were not altered. The number of microglia and cell diameters significantly increased in the superficial dorsal horn of the lumbar spinal cord. Thus, activated microglia-mediated spinal mechanisms are associated with the induction of nociceptive hypersensitivity in rats after persistent cast immobilization.

Effects of walking with a "draw-in maneuver" on the knee adduction moment and hip muscle activity.

[Purpose] To investigate the effect of performing a draw-in maneuver (DI) on knee adduction moment (KAM) and hip and trunk muscle activities while walking. [Participants and Methods] We included 30 healthy young adults (21.5 ± 0.6 years, 16 males and 14 females) in this study. We measured the KAM and lever arm while participants walked with either a normal gait or a DI gait. We also performed surface electromyography (EMG) of the hip and trunk muscles (i.e., internal oblique abdominal muscle [IO], external oblique abdominal muscle [EO], multifidus muscle [MF], and gluteus medius muscle [GM]). [Results] The 1st peak of the KAM was significantly lower when walking with a DI gait compared to when walking with a normal gait. The integrated EMG activity of the IO, EO, and GM during the 1st half of the stance phase, and of the IO and EO during the 2nd half of the stance phase was significantly higher during the DI than during normal gait. [Conclusion] Compared with a normal gait, a DI gait leads to a decrease in the 1st peak of the KAM as a result of the shorter lever arm, and an increase in the muscular activity of the GM, IO, and EO.

Neonatal wearable device for colorimetry-based real-time detection of jaundice with simultaneous sensing of vitals.

Neonatal jaundice occurs in >80% of newborns in the first week of life owing to physiological hyperbilirubinemia. Severe hyperbilirubinemia could cause brain damage owing to its neurotoxicity, a state commonly known as kernicterus. Therefore, periodic bilirubin monitoring is essential to identify infants at-risk and to initiate treatment including phototherapy. However, devices for continuous measurements of bilirubin have not been developed yet. Here, we established a wearable transcutaneous bilirubinometer that also has oxygen saturation (SpO2) and heart rate (HR) sensing functionalities. Clinical experiments with neonates demonstrated the possibility of simultaneous detection of bilirubin, SpO2, and HR. Moreover, our device could consistently measure bilirubin during phototherapy. These results demonstrate the potential for development of a combined treatment approach with an automatic link via the wearable bilirubinometer and phototherapy device for optimization of the treatment of neonatal jaundice.

Liquid metal-based nanocomposite materials: fabrication technology and applications.

Research on liquid metals has been steadily garnering more interest in recent times, especially in flexible electronics applications because of their properties like possessing high conductivity and being liquid state at room temperature. The unique properties afforded by such materials at low temperatures can compensate for the limitations of stretchable electronic devices, particularly robustness and their fluidic property, which can enhance the flexibility and deformation of these devices. Therefore, interest in liquid-metal nanoparticles and liquid metals with nanocomposites has enabled research into their fabrication technologies as well as utilisation in fields such as chemistry, polymer engineering, computational modelling, and nanotechnology. In particular, in flexible and stretchable electronic device applications, the research attention is focused on the fabrication methodologies of liquid-metal nanoparticles and liquid metals containing nanocomposites. This review attempts to summarise the available stretchable and flexible electronics applications that use liquid-metal nanoparticles as well as liquid metals with nanomaterial additives.

Spontaneously regressed granulomatosis with polyangiitis: A case report.

A 71-year-old woman presented with chest pain, cough, and back pain. A chest roentgenogram showed multiple nodular shadows in both lungs. She was diagnosed with granulomatosis with polyangiitis (GPA). The multiple nodular shadows in both lungs regressed spontaneously in a few months. There are few reports of spontaneous regression of GPA, and the underlying mechanism is unclear. Neutrophil extracellular traps (NETs) have been recently shown to be involved in GPA. NETs may also be related to the natural regression of GPA.

Transformable Electrocardiograph Using Robust Liquid-Solid Heteroconnector.

In this study, a highly transformable electrocardiograph that can considerably deform the position of stretchable electrodes based on the lead method for diagnosing heart disease was developed; these electrodes exhibited high resistance stability against considerable stretching and multiple stretching. To realize the large deformable functionality of the electrodes of a system, liquid metal electrodes and a heteroconnector composed of a liquid metal paste and carbon-based conductive rubber were employed. The developed device can achieve a 200% strain with only 6% resistance change and a high stability of resistances after the 100-time stretching test. In addition, the study demonstrated electrocardiograms in different lead methods of adult and child using the same device. The proposed combination of large deformable electrodes with high electric stability and a robust heteroconnector is an important technology, and it presents a considerable advancement in the application of stretchable electronic systems.

Highly stretchable sensing array for independent detection of pressure and strain exploiting structural and resistive control.

Stretchable physical sensors are crucial for the development of advanced electrical systems, particularly wearable devices and soft robotics. Currently available stretchable sensors that detect both pressure and strain are based on piezoelectric, piezoresistive, or piezocapacitive effects. The range of pressure sensing is 1-800 kPa with large deformations being within the range of deformations of parts of the human body, such as elbows and knees. However, these devices cannot easily allow simultaneous and independent detection of pressure and strain with sensor arrays at large tensions (> 50%) because strain affects the pressure signal. In this study, we propose a monolithic silicone-based array of pressure and strain sensors that can simultaneously and independently detect the in-plane biaxial tensile deformation and pressure. To realize these functionalities, the deformation of the device structure was optimized using a hetero-silicone substrate made of two types of silicone with different hardness characteristics and porous silicone bodies. In addition, the resistances of the sensors were controlled by adjusting a mixture based on carbon nanoparticles to improve the sensitivity and independence between the pressure and strain sensors. These concepts demonstrate the potential of this approach and its compatibility with the current architectures of stretchable physical sensors.

Retroperitoneal Metastasis, with Marked Fibrosis, of Lung Adenocarcinoma after Afatinib Treatment: An Autopsy Case Report.

A 73-year-old woman was admitted to our hospital for treatment of vomiting. Four months previously, she had been diagnosed with lung adenocarcinoma (cT3N3M1a stage IVA) and started receiving afatinib as first-line treatment. On admission, the primary tumor had shrunk, but abdominal computed tomography revealed a new retroperitoneal lesion causing duodenal obstruction and hydronephrosis. She underwent gastrojejunostomy, and a biopsy of the peritoneum revealed adenocarcinoma. She was treated with second-line chemotherapy but developed cerebral infarction and died 104 days after admission. An autopsy revealed marked fibrosis with scattered tumor cells in the retroperitoneum. The underlying mechanism of the metastasis is discussed.