Clinical activity of crizotinib in lung adenocarcinoma harboring a HLA_A­ROS1 rearrangement: A case report.

The benefits of crizotinib therapy in patients with tyrosine receptor kinase ROS proto-oncogene 1 (ROS1)-rearranged non-small cell lung cancer (NSCLC) have been demonstrated. The present study reports a 47-year-old woman with lung adenocarcinoma harboring a rare HLA_A-ROS1 rearrangement with clinical response to crizotinib. To the best of our knowledge there have been no reports of HLA_A-ROS1-rearranged lung cancer regarding clinical course and the efficacy of treatment with crizotinib. A good response to crizotinib therapy in the present case could be a reference for the treatment and prognosis of ROS1-rearranged NSCLC with the same fusion partner. The current report will remind oncologists and pulmonologists to consider the importance of accurate multigene panel assays for detecting driver oncogenes in treating patients with NSCLC.

[Liver metastasis from alpha-fetoprotein-producing gastric cancer 27 years postoperation:a case report].

A 75-year-old man with a history of distal gastrectomy for gastric cancer at 48 years of age underwent abdominal computed tomography, which revealed a left hepatic lobe tumor alongside direct gastric invasion. His blood test results revealed significant increase in serum alpha-fetoprotein (AFP) levels (32240.3ng/mL). A gastroscopy revealed that the histopathological findings of the biopsy specimens of the gastric invasion area were identical to those observed in the surgical specimens of gastric cancer, which was diagnosed 27 years earlier. The evaluation of the biopsy and surgical specimens revealed AFP positivity, which confirmed the diagnosis of the late recurrence of AFP-positive gastric cancer. Herein, we presented a rare clinical case of this malignancy. Additionally, a close, long-term postoperative follow-up is warranted in patients with AFP-producing gastric cancer.

A multicenter explanatory survey of patients' and clinicians' perceptions of motivational factors in rehabilitation.

BACKGROUND: Patient motivation is an important determinant of rehabilitation outcomes. Differences in patients' and clinicians' perceptions of motivational factors can potentially hinder patient-centered care. Therefore, we aimed to compare patients' and clinicians' perceptions of the most important factors in motivating patients for rehabilitation. METHODS: This multicenter explanatory survey research was conducted from January to March 2022. In 13 hospitals with an intensive inpatient rehabilitation ward, 479 patients with neurological or orthopedic disorders undergoing inpatient rehabilitation and 401 clinicians, including physicians, physical therapists, occupational therapists, and speech-language-hearing therapists, were purposively selected using inclusion criteria. The participants were asked to choose the most important factor motivating patients for rehabilitation from a list of potential motivational factors. RESULTS: Here we show that realization of recovery, goal setting, and practice related to the patient's experience and lifestyle are the three factors most frequently selected as most important by patients and clinicians. Only five factors are rated as most important by 5% of clinicians, whereas nine factors are selected by 5% of patients. Of these nine motivational factors, medical information (p < 0.001; phi = -0.14; 95% confidence interval = -0.20 to -0.07) and control of task difficulty (p = 0.011; phi = -0.09; 95% confidence interval = -0.16 to -0.02) are selected by a significantly higher proportion of patients than clinicians. CONCLUSIONS: These results suggest that when determining motivational strategies, rehabilitation clinicians should consider individual patient preferences in addition to using the core motivational factors supported by both parties.

Rehabilitation is the interventions needed to restore the abilities required for daily life following illness or injury. Patients and clinicians who provide these interventions may have different ideas about what encourages patients to engage in rehabilitation. It is important to understand what motivates patients and any differences in opinion between patients and clinicians. We asked patients and clinicians about the most important motivational factors. All agreed that realizing recovery is possible, setting goals or targets for the stages of recovery, and targeting interventions relevant to the patient's experience and lifestyle were the most important motivational factors. The patients also found access to medical information and being able to control the difficulty of tasks required during rehabilitation motivating. These findings could help clinicians provide rehabilitation care that is more specifically tailored to each patient's needs and preferences.

Lung Cancer Complicated by Relapsing Polychondritis.

A 77-year-old man presented with a 1-month history of cough, pharyngeal discomfort, and weight loss. Chest radiography revealed a mass shadow in the right upper lung field. Bronchoscopy showed multiple white nodules along the tracheal cartilage ring. Although adenocarcinoma cells were detected in the mass, several biopsy specimens of the tracheal lesions exhibited no malignancy. 18F-fluorodeoxyglucose positron emission tomography revealed an intense accumulation in the mass, nasal septum, and tracheal cartilage. Furthermore, anti-type II collagen antibody levels were elevated. We finally diagnosed him with lung cancer complicated by relapsing polychondritis. Treatment with oral prednisolone was initiated, followed by sequential chemoradiotherapy for lung cancer.

[A Case of Second Primary Small Cell Lung Carcinoma after Radiotherapy for Breast Cancer].

We report the case of a 72-year-old woman who underwent partial mastectomy due to left breast cancer(invasive ductal carcinoma)in March 20XX-4. This was followed by radiotherapy(50 Gy/25 Fr)and hormone therapy. In July 20XX, she was referred to our department because a chest computed tomography(CT)scan performed at the postoperative follow-up revealed a band-like consolidation adjacent to the pleura in the lingular segment, with enlarged ipsilateral hilar and mediastinal lymph nodes. CT-guided lung tumor biopsy was performed, and she was diagnosed with limited-stage small cell lung cancer. Chemotherapy with carboplatin, etoposide, and atezolizumab was initiated. Radiotherapy was not performed due to the overlap between the distribution of the lung tumor and the postoperative irradiation field of breast cancer. Due to the difference in the histopathological findings of the first and second primary tumors, and the location of the tumor in the postoperative irradiation field, the second cancer was considered to be radiation-induced cancer despite the short latency period.

A case of anisakiasis in the sigmoid colon.

Colonic anisakiasis is rare because most cases of anisakiasis occur in the stomach. An accurate diagnosis is sometimes difficult because of the rarity and symptom nonspecificity. We should consider the possibility of colonic anisakiasis when examining patients who have a history of consuming raw fish.

[Diagnosis of an ileal neuroendocrine tumor based on lymph node metastases: a case report].

A 72-year-old man was diagnosed with tumors outside of the stomach and mesentery of the small intestine on abdominal computed tomography. Histopathological examination of an endoscopic ultrasound-guided fine-needle aspiration biopsy specimen confirmed the diagnosis of lymph node metastasis of a neuroendocrine tumor (NET). Gastroscopy, colonoscopy, small bowel capsule endoscopy, somatostatin receptor scintigraphy, and 18F-fluorodeoxyglucose positron emission tomography were performed. However, the primary lesion could not be diagnosed. The patient underwent surgery, and an ileal submucosal tumor, which was not identified preoperatively in addition to the aforementioned abdominal tumors, was detected. All tumors were diagnosed as NET, and the ileal tumor was considered the primary lesion. The patient has shown no recurrence postoperatively. The current study presents a case of an ileal NET with lymph node metastases in a patient in whom the primary lesion remained preoperatively undiagnosed.

[Comparative Verification of DNA Extraction Methods for Bacterial Nucleic Acid Amplification Test].

Genetic testing is widely used as a rapid diagnostic method to identify microorganisms and detect antibiotic resistance genes. The nucleic acid to be analyzed is located inside the cell wall, the cell membrane or nuclear envelope. Therefore, it is essential to disassemble them in nucleic acid extraction operation. It is also necessary to remove or inactivate interfering substances by exposing cytoplasmic components accompanying cell disruption. Nucleic acid extraction is an indispensable task, but depending on the selected method, it may have a significant effect on the genetic test results. However, the DNA extraction method that is actually selected tends to emphasize work efficiency, and the appropriate evaluation of the extraction operation is neglected. In this study, we focused on the purity of the extracted DNA, and examined six existing extraction methods and original extraction methods using Gram-negative bacilli as a simple model. As a result, there was a large difference in DNA purity depending on the extraction method. When used in a qualitative gene amplification test, there was a difference in the shading of the bands. However, the detection of resistance genes all gave similar results. Furthermore, as a result of using the original extraction method, the extraction method using sodium decylbenzenesulfonate (SDBS) was the most excellent extraction method from the viewpoint of recovered DNA and operability.

[Development and Evaluation of Screening Culture Medium for Detection of Drug-Resistant Gram Negative Rods Containing Stealth Type CPE].

There is a report that an infection by medicine resistant bacteria will be the number one cause of death in 2050 according to the recommendation of WHO, and the CPE (carbapenem-producing Enterobacteriaceae) infection is regarded as a problem in particular. When detecting CPE, it is important how to detect stealth type CPE sensitive to carbapenem series medicines. So we used the 2 types of screening culture medium, "KBM" CRE-JU culture medium (CRE-JU culture medium) and the FRPM culture medium, and tried to detect drug-resistant gram-negative bacilli such as CPE, stealth type CPE, ESBL-producing bacteria, and excess AmpC-producing bacteria (AmpC-producing bacteria), etc. in combination of this culture mediums. As a result, CRE-JU culture medium showed a difference in the growth of CPE depending on the amount of inoculated bacteria while ß-lactamase non-producing strain and other strains except for high concentration ESBL-producing bacteria and AmpC-producing bacteria were un-growing. Most of the CRE, stealth type CPE, ESBL-producing bacteria and AmpC-producing bacteria grew in the FRPM culture medium while most of the ß-lactamase non-producing strains with a MIC value of meropenem (MEPM) of 2 µg/mL or less were un-growing. From these results, it was suggested that when a strain grown on CRE-JU and FRPM culture mediums, it could be distinguished as CPE, and when strains grown on FRPM culture medium which were un-grown on CRE-JU culture medium, it could be distinguished as drug-resistant bacteria such as stealth type CPE, ESBL-producing bacteria, and AmpC-producing bacteria. When strains not grown on CRE-JU and FRPM culture mediums, it could be distinguished as sensitive.

[A trial of simple and rapid carbapenemase big five gene analysis using LAMP method].

Reliable detection and typing of carbapenemase is important in the treatment of infectious diseases. In this study we newly designed LAMP primer based on the latest information, and established a detection method for Carbapenemase Big five gene. For DNA extraction from strains, alkaline boiling method and commercial kit were used. The reaction temperatures of the LAMP method was VIM: 65°C, NDM: 63°C, KPC: 65°C, OXA-48-like: 65°C, IMP: 61°C. And simultaneous LAMP method was at 63°C, for 60 min. It was possible to detect up to 103 copies/ml. The reactivity of LAMP using 36 strains verified by Multiplex-PCR was VIM (4/4: number of LAMP method positive strains/number of strains evaluated), NDM (2/2), KPC (4/4), OXA-48-like (4/4), IMP (17/17). The type of carbapenemase determined by the LAMP method were all consistent with multiplex PCR. All strains were detected within 30 min. In VIM, both VIM-1-like and VIM-2-like were able to detect. In this study, although the number and variation of the strains evaluated was limited, LAMP method was clinically useful as a simple and rapid carbapenemase detection method.

RsgA couples the maturation state of the 30S ribosomal decoding center to activation of its GTPase pocket.

During 30S ribosomal subunit biogenesis, assembly factors are believed to prevent accumulation of misfolded intermediate states of low free energy that slowly convert into mature 30S subunits, namely, kinetically trapped particles. Among the assembly factors, the circularly permuted GTPase, RsgA, plays a crucial role in the maturation of the 30S decoding center. Here, directed hydroxyl radical probing and single particle cryo-EM are employed to elucidate RsgA΄s mechanism of action. Our results show that RsgA destabilizes the 30S structure, including late binding r-proteins, providing a structural basis for avoiding kinetically trapped assembly intermediates. Moreover, RsgA exploits its distinct GTPase pocket and specific interactions with the 30S to coordinate GTPase activation with the maturation state of the 30S subunit. This coordination validates the architecture of the decoding center and facilitates the timely release of RsgA to control the progression of 30S biogenesis.

Ribosome-small-subunit-dependent GTPase interacts with tRNA-binding sites on the ribosome.

RsgA (ribosome-small-subunit-dependent GTPase A, also known as YjeQ) is a unique GTPase in that guanosine triphosphate hydrolytic activity is activated by the small subunit of the ribosome. Disruption of the gene for RsgA from the genome affects the growth of cells, the subunit association of the ribosome, and the maturation of 16S rRNA. To study the interaction of Escherichia coli RsgA with the ribosome, chemical modifications using dimethylsulfate and kethoxal were performed on the small subunit in the presence or in the absence of RsgA. The chemical reactivities at G530, A790, G925, G926, G966, C1054, G1339, G1405, A1413, and A1493 in 16S rRNA were reduced, while those at A532, A923, G1392, A1408, A1468, and A1483 were enhanced, by the addition of RsgA, together with 5'-guanylylimidodiphosphate. Among them, the chemical reactivities at A532, A790, A923, G925, G926, C1054, G1392, A1413, A1468, A1483, and A1493 were not changed when RsgA was added together with GDP. These results indicate that the binding of RsgA induces conformational changes around the A site, P site, and helix 44, and that guanosine triphosphate hydrolysis induces partial conformational restoration, especially in the head, to dissociate RsgA from the small subunit. RsgA has the capacity to coexist with mRNA in the ribosome while it promotes dissociation of tRNA from the ribosome.

The choroidal circulation assessed by laser-targeted angiography.

The choroid plays an important role in supplying nutrients to and removing waste products from the outer region of the retina. Abnormal choroidal blood flow can disrupt normal retinal function and lead to alterations in visual function. Visualization of the choriocapillaris in vivo is a great challenge to understanding its normal physiology and involvement in the disease process. Laser-targeted angiography (LTA) is a relatively new method used to visualize and analyze the choroidal circulation. Carboxyfluorescein (CF), encapsulated in heat-sensitive liposomes, is released locally in the choroid through the application of a heat beam provided by an infrared laser. Video angiograms are generated with excitation illumination provided by an argon laser. Obtained images are highly selective to the choriocapillaris and are sharply contrasted against underlying and overlying structures. The images can be obtained repetitively, during which period the circulating liposome concentration is sufficient to generate adequate angiograms. These high-quality images have revealed three distinct phases (filling, plateau, and draining) of the choriocapillaris. In the plateau phase, a cluster of lobules fed by a common arteriole has been uniformly illuminated. This defined cluster area does not change in size while an infrared laser is continuously applied to the same spot, which demonstrates that each cluster is functionally independent and no physiological communication exists between them. Only in posterior regions do the angiograms demonstrate during the filling and draining phases that each lobule is filled from a central spot and drained along a peripheral ring, showing honeycomb flow patterns. The regional differences in choriocapillaris flow patterns revealed by LTA suggests that the choriocapillaris provides a more highly efficient system of outflow in posterior regions than in peripheral regions. LTA is useful in analyzing choroidal circulation in vivo and has the potential for clinical application in the future. Additionally, LTA has a unique capability to image choroidal neovascularization in animal models and it promises potential application in age-related macular degeneration (AMD).

Analysis of choriocapillaris flow patterns by continuous laser-targeted angiography in monkeys.

PURPOSE: To investigate choriocapillaris flow patterns and its segmental distribution in monkeys by continuous laser-targeted angiography (LTA). METHODS: A slit lamp was modified to incorporate two kinds of lasers (argon and diode). Carboxyfluorescein (CF) was encapsulated in heat-sensitive liposomes and injected intravenously. Encapsulated CF was released locally by applying a continuous heat beam provided by the diode laser (810 nm). Video angiograms were generated with excitation illumination provided by the argon laser (488 and 514 nm), to observe selective images of the choriocapillaris. RESULTS: Continuous application of the diode laser disclosed three distinct phases (filling, plateau, and draining) of fluorescent images of the choriocapillaris. In the plateau phase, a cluster of lobules fed by a common arteriole was uniformly illuminated. This defined area did not change in size while a continuous diode laser was applied to the same spot. Only in posterior regions did the angiograms demonstrate that during the filling and draining phases each lobule was filled from a central spot and drained along a peripheral ring, showing honeycomb flow patterns. In peripheral regions, large choroidal vessels as well as choriocapillaris were observed. CONCLUSIONS: Continuous LTA demonstrated clusters of lobules fed by a common arteriole, and each cluster was found to be functionally independent. There were regional differences in choriocapillaris flow patterns, which suggests that the choriocapillaris provides a more highly efficient system of outflow in posterior regions than in peripheral regions. This modified LTA method appears to be useful in analyzing choroidal circulation in vivo.

In vivo analysis of choroidal circulation by continuous laser-targeted angiography in the rat.

PURPOSE: To obtain high-quality angiograms of the rat choriocapillaris with continuous laser-targeted angiography (LTA), for the purpose of assessing the choroidal circulation system in vivo by studying the patterns of the images. METHODS: A slit lamp was modified to incorporate two kinds of lasers (argon and diode). Carboxyfluorescein was encapsulated in heat-sensitive liposomes and injected intravenously. Encapsulated carboxyfluorescein was released locally by applying a continuous heat beam provided by diode laser (810 nm) with various powers. Video angiograms were generated with excitation illumination provided by argon laser (488 and 514 nm) to observe highly selective images of the choriocapillaris. RESULTS: Three distinct phases (filling, plateau, and draining) were observed in fluorescent images of choriocapillaris by applying the diode laser continuously. In the plateau phase, a lobe-shaped area of choriocapillaris peripheral to the laser site was illuminated, and this finite area did not change in size with continuous laser application to the same spot. When laser power was increased, a larger area of choriocapillaris was illuminated in the plateau phase. The filling and draining phases demonstrated the flow patterns in choriocapillaris lobules, which filled from a central spot and drained along a peripheral ring. CONCLUSIONS: This study showed that the rat choriocapillaris is divided into independent functional units and that the choroidal circulation is segmental under normal conditions. The results implied that in LTA, the diode laser warms up a choroidal artery and the released fluorescein flows downstream to an area of choriocapillaris fed by the same artery. LTA appeared to be a powerful method to analyze choroidal circulation in vivo.

Noninvasive technique for monitoring chorioretinal temperature during transpupillary thermotherapy, with a thermosensitive liposome.

PURPOSE: To develop a technique for noninvasive and real-time monitoring of chorioretinal temperature in transpupillary thermotherapy (TTT). METHOD: A modified slit lamp, which was equipped with two laser wavelengths (490 nm for illumination and fluorescein excitation and 810 nm for hyperthermia), was developed for TTT and temperature monitoring. Five types of liposomes were prepared, and their phase-transition temperatures were 40 degrees C, 46 degrees C, 47 degrees C, 48 degrees C, and 52 degrees C, respectively. Carboxyfluorescein was encapsulated in each liposome. After intravenous injection of each liposome, TTT with the modified slit lamp was performed on normal rat choroid or tissue with choroidal neovascularization (CNV). During TTT, chorioretinal temperature was monitored by observing release of fluorescein from circulating liposomes. RESULTS: Fluorescence from liposomes was initially observed around the heated lesion immediately after TTT began and disappeared rapidly when irradiation stopped. Choroidal and retinal temperatures were monitored separately. TTT for normal retina required higher power than that for normal choroid to observe fluorescence from a 40 degrees C, 46 degrees C, and 47 degrees C liposome. Retinal whitening was observed after TTT at a high-power setting. TTT for CNV required higher laser power than that for the normal choroid and retina. CONCLUSIONS: The results demonstrate the potential use of a noninvasive monitoring technique of chorioretinal temperature during TTT. The method should be useful to establish the TTT setting and achieve the optimal temperature increase in CNV.

Quantitative evaluation for blood-retinal barrier breakdown in experimental retinal vein occlusion produced by photodynamic thrombosis using a new photosensitizer.

Purpose. To establish a rat model of retinal vein occlusion (RVO), we applied photodynamic thrombosis using a new photosensitizer. By measuring the breakdown of the blood-retinal barrier (BRB), we evaluated the model quantitatively. We also investigated how hypertension and retinal pigment epithelium (RPE) influence the breakdown of BRB after RVO. Methods. We modified a slit lamp biomicroscope for photodynamic thrombosis. The light source was changed from white light to argon laser, which made it possible to perform fluorescein angiography (FAG) simultaneously during photodynamic thrombosis. We irradiated with a continuous diode laser to occlude three retinal veins in a rat after PAD-S31 injection. The breakdown of BRB was quantitated by measuring extravasated Evans blue dye in albino and pigmented rats. We compared hypertensive rats (SHR) to normotensive rats (WKY) and sodium iodate-treated rats to normal rats. Results. High photosensitivity of PAD-S31 made it possible to occlude any retinal veins within 120 seconds at a low dose of 10 mg/kg without retinal thermal burn at the occlusion site. Simultaneous FAG enabled us to observe the formation of thrombus during diode laser irradiation. Our measured value of intraretinal Evans blue correlated with the range of serous retinal detachment. Both albino and pigmented rats demonstrated stable and constant values of Evans blue. SHR recovered from the breakdown of BRB after venous occlusion more slowly than WKY. Sodium iodate-treated rats had smaller breakdowns of BRB and recovered earlier than normal rats. Conclusions. In this study, we established the stable and constant rat model of RVO efficiently by using a new photosensitizer. Our simultaneous FAG method was considered to have an advantage of several potential clinical applications. Our rat model of RVO allows us to study factors associated with the recovery from damage by RVO.