Successful application of lorlatinib in a 23-year-old patient with anaplastic lymphoma kinase (ALK)-positive lung cancer and multiple brain metastases.

BACKGROUND: Anaplastic lymphoma kinase (ALK)-positive lung cancer has a better long-term prognosis with ALK-inhibitor than other lung cancers. However, resistance to ALK-inhibitors and the control of metastases in the central nervous system (CNS) remain to be a challenge in the management of ALK-positive lung cancer. CASE: We present the case of a 23-year-old man who developed multiple brain metastases while receiving alectinib treatment for ALK-positive lung cancer. After 3 months of lorlatinib initiation, brain metastases disappeared, and complete response (CR) was maintained. CONCLUSION: While lorlatinib can be used as first line therapy, this drug may be considered as second line or later option for patients with multiple brain metastases if the patient has already been treated with other ALK-inhibitors since lorlatinib is thought to have good CNS penetration. This treatment option should be verified by further research.

A case of atrial septal defect with right-to-left shunting without pulmonary hypertension.

We report a case of a 54-year-old man with atrial septal defect who presented with oxygen desaturation on pulse oximetry. Cardiac magnetic resonance imaging and transesophageal echocardiography showed right-to-left shunting through an atrial septal defect, which was confirmed by superior vena cavography and suggested Eisenmenger syndrome. However, cardiac catheterization revealed a normal pulmonary arterial pressure. Simultaneous measurement of interatrial pressure identified two transient interatrial pressure gradient points, where the right atrial pressure was higher than the left atrial pressure. The patient was finally diagnosed with atrial septal defect without pulmonary hypertension. Right-to-left shunting was primarily caused by a transient interatrial pressure gradient due to a time delay in both initial atrial contraction and completion of passive ventricular filling between the right and left sides of the heart. Surgical closure of the atrial septal defect was performed, and hypoxemia improved. This is the first report of right-to-left shunting without pulmonary hypertension caused by a transient interatrial pressure gradient due to a time delay between the right and left cardiac cycles. Precise assessment of the simultaneous interatrial pressure in addition to diagnostic imaging played a pivotal role in clarifying the etiology of this rare condition. Learning objective: Atrial septal defect with right-to-left shunting without Eisenmenger syndrome is a rare condition. We identified transient interatrial pressure gradients associated with a time delay in both initial atrial contraction and completion of the passive ventricular filling phase, which we considered as the primary mechanism underpinning right-to-left shunting. Simultaneous measurement of interatrial pressure played a pivotal role in elucidating the hemodynamics and abnormal shunt flow mechanism.

Navigation Method Enhancing Music Listening Experience by Stimulating Both Neck Sides With Modulated Musical Vibration.

We propose a method that stimulates musical vibration (generated from and synchronized with musical signals), modulated by the direction and distance to the target, on both sides of a user's neck with Hapbeat, a necklace-type haptic device. We conducted three experiments to confirm that the proposed method can achieve both haptic navigation and enhance the music-listening experience. Experiment 1 consisted of conducting a questionnaire survey to examine the effect of stimulating musical vibrations. Experiment 2 evaluated the accuracy (deg) of users' ability to adjust their direction toward a target using the proposed method. Experiment 3 examined the ability of four different navigation methods by performing navigation tasks in a virtual environment. The results of the experiments showed that stimulating musical vibration enhanced the music-listening experience, and that the proposed method is able to provide sufficient information to guide the users: accuracy in identifying directions was about 20 °, participants reached the target in all navigation tasks, and in about 80% of all trials participants reached the target using the shortest route. Furthermore, the proposed method succeeded in conveying distance information, and Hapbeat can be combined with conventional navigation methods without interfering with music listening.

Essential thrombocythemia complicated with simultaneous two-vessel acute myocardial infarction in the subacute phase of takotsubo cardiomyopathy: A case report.

We report the case of a 79-year-old woman with essential thrombocythemia who presented with simultaneous two-vessel acute myocardial infarction (AMI) in the subacute phase of takotsubo cardiomyopathy. Despite sufficient anticoagulation therapy with warfarin to prevent thrombus formation in the left ventricle, the patient developed simultaneous two-vessel AMI in the right and left circumflex coronary arteries 16 days after the onset of takotsubo cardiomyopathy. Thromboembolism from the left ventricle associated with takotsubo cardiomyopathy was considered a potential cause of this event. However, macroscopic and pathological findings of the aspirated thrombi revealed that the primary cause of AMI was non-organized white platelet thrombi associated with essential thrombocythemia. In addition to oral anticoagulation therapy with warfarin, low-dose aspirin was started. The patient was discharged without any symptoms, and the clinical course has been uneventful for >5 years. This case highlights the potential risk of fatal complications associated with essential thrombocythemia, including simultaneous multivessel AMI. Additionally, pathological findings of the thrombi may play a crucial role in clarifying the etiology in such complicated cases. Appropriate antithrombotic therapy should be selected according to the pathogenesis of the condition. Learning objective: We describe a 79-year-old woman with essential thrombocythemia complicated with simultaneous two-vessel acute myocardial infarction (AMI) in the subacute phase of takotsubo cardiomyopathy. Although patients with essential thrombocythemia are highly predisposed to thrombotic events including AMI, the appropriate antithrombotic regimen remains controversial. The macroscopic and pathological findings of the thrombi play a pivotal role in clarifying the etiology, which may lead to the appropriate antithrombotic therapy.

Implementation of Tension-Based Compact Necklace-Type Haptic Device Achieving Widespread Transmission of Low-Frequency Vibrations.

The haptic sensation of low-frequency vibration plays a vital role in the music listening experience, but it can be enjoyed only in certain facilities and environments. Many haptic devices have been proposed to convey music audio-induced vibration for various situations. Such devices require powerful, low-frequency vibration output and transmission over a wide area. Making such devices small and user-friendly is difficult, hindering their popularity. To promote haptic devices for music listening, this paper describes a method for developing a practical device using motors and a thread and evaluates this method's effectiveness. The proposed necklace-type device is small (about 55 × 58 × 15 mm), lightweight (58.5 g), and easy to wear, making it suitable for use during everyday travel. In addition, it can transmit low-frequency (20 Hz) vibrations, whose amplitude exceeds airborne vibration in a nightclub, to a wide area across the chest and neck, with a total power consumption of approximately 2 W. Our proposed method will contribute to the development of practical and high-performance haptic devices for music listening.

Heat-Resistant Black Insulative Thin Films for Flat-Panel Displays in Al-Doped Ag-Fe-O Systems.

Multilayer antireflection (AR) coatings require a material with a large and constant absorption coefficient over the whole visible range and thermal stability. Coatings for use in touch panel displays are also required to be electrically insulative. In this study, 60 mol % Ag-40 mol % (Fe1-xAlx)-O (x = 0, 0.25, 0.50, 0.75, and 1.0) thin films are prepared by pulsed laser deposition, and their optical properties, electric resistance, and thermal stability are clarified by combining the experimental data and density functional theory (DFT) calculations. Over the visible range, large and constant absorption coefficients are obtained for all compositions. The standard deviations of the absorption coefficients of the x = 0.75 and 1.0 samples are found to be smaller than those of conventional materials like graphite and CrOx. High sheet resistance (Rsheet > 107 Ω·sq-1) is also confirmed. It is determined that nanometer-sized Ag dispersed into a matrix, which was confirmed to be ionic Ag in the matrix phase, is responsible for the absorption at a shorter visible light range and insulative nature even at high Ag content. The films with high Al content are stable up to 500 °C. The potential of these black insulative Ag-Al-Fe-O thin films for use as black AR coatings is confirmed by optical simulations with multilayer stacks.

Temporal trends in tolvaptan use after revision of national heart failure guidelines in Japan.

Within no definite diuretic protocol for acute heart failure (AHF) patients and its variation in regional clinical guidelines, the latest national guidelines in Japan commends use of tolvaptan in diuretic-resistant patients. This study aimed to examine trends in tolvaptan usage and associated outcomes of AHF patients requiring hospitalization. Between April, 2018 and October, 2019, 1343 consecutive AHF patients (median 78 [69-85] year-old) were enrolled in a prospective, multicenter registry in Japan. Trends over time in tolvaptan usage, along with the severity of heart failure status based on the Get With The Guideline-Heart Failure [GWTG-HF] risk score, and in-hospital outcomes were investigated. During the study period, tolvaptan usage has increased from 13.0 to 28.7% over time (p for trend = 0.07), and 49.4% started tolvaptan within 3 days after admission. The GWTG-HF risk score in the tolvaptan group has significantly decreased over time, while that in the non-tolvaptan group has unchanged. There were no differences in the in-hospital mortality rate between the patients with and without tolvaptan (6.7% vs. 5.8%). After revision of the Japanese clinical practice guidelines for AHF in March 2018, tolvaptan usage for AHF patients has steadily increased. However, in-hospital outcomes including mortality do not seem to be affected.

[Japan Marrow Donor Program and its coordinating process: current situations].

We evaluated 18,487 patients and 223,842 cases of donor coordination among patients enrolled in the Japan Marrow Donor Program (JMDP) from January 2004 to December 2013. For patients who underwent stem cell transplantation from a JMDP donor [unrelated bone marrow transplantation (UBMT)], the median number of coordination and days from registration to transplantation were 11 and 146, respectively. Among enrolled patients, 40% did not undergo UBMT. With the increased estimated number of human leukocyte antigen 6/6-matched donors, the probability of undergoing UBMT was higher, and in those who underwent UBMT, the duration of coordination was shorter. Regarding the reasons for the termination of coordination, those attributable to the donors varied depending on the age and sex of the donors. Male donors in their 20s had lower and higher termination rates because of health conditions and inconvenience, respectively, compared with donors of different age and female sex. Among donors who experienced coordination more than once, the donation rate was higher if the precedent coordination ended because of reasons attributable to the patient compared with the donation rate because of other reasons. Using the results of our study, strategies to achieve a more efficient and rapid coordination process are warranted.

Asymmetric Strecker Reaction Arising from the Molecular Orientation of an Achiral Imine at the Single-Crystal Face: Enantioenriched l- and d-Amino Acids.

Strecker synthesis has long been considered one of the prebiotic reactions for the synthesis of α-amino acids. However, the correlation between the origin of chirality and highly enantioenriched α-amino acids through this method remains a puzzle. In the reaction, it may be conceivable that the handedness of amino acids has been determined at the formation stage of the chiral intermediate α-aminonitrile, that is, the enantioselective addition of hydrogen cyanide to an imine. Herein, an enantiotopic crystal surface of an achiral imine acted as an origin of chirality for the enantioselective formation of α-aminonitriles by the addition of HCN. In conjunction with the amplification of the enantiomeric excess and multiplication of enantioenriched aminonitrile, a large amount of near enantiopure α-amino acids, with the l- and d-handedness corresponding to the molecular orientation of the imine, is reported.

Isolation of growth inhibitors of the snow rot pathogen Pythium iwayamai from an arctic strain of Trichoderma polysporum.

Growth inhibitors were isolated from an arctic strain of Trichoderma polysporum, and the structures were elucidated and the in vitro inhibitory effects of these compounds against Pythium iwayamai were investigated. Eleven compounds were isolated; four showed a concentration-dependent growth-inhibitory effect against P. iwayamai. None of these compounds have been reported previously as substances with antimicrobial activity against P. iwayamai. One of these four compounds inhibited the growth of the pathogen at 33 µg ml(-1) concentration during a 15-day incubation at 20 °C. This effect was comparable to that of chloroneb (1: 1,4-dichloro-2,5-dimethoxybenzene), a fungicide with activity against P. iwayamai. Thus, the results of the present study show that the arctic strain of T. polysporum can be an effective source of antibiotics with activity against the snow rot pathogen, P. iwayamai.

Synthesis and N-H reductive elimination study of dinuclear ruthenium imido dihydride complexes.

Diruthenium imido dihydride complexes [(Cp*Ru)(2)(µ-NAr)(µ-H)(2)] (Ar = Ph (2a), p-MeOC(6)H(4) (2b), p-ClC(6)H(4) (2c), 2,6-Me(2)C(6)H(3) (2d); Cp* = η(5)-C(5)Me(5)) have been synthesized by hydrogenation of the corresponding bis(amido) complexes [Cp*Ru(µ-NHAr)](2) (1a-d). Reductive elimination of the N-H bond from 2a-c in the presence of arene yields the amido hydride complexes [(Cp*Ru)(2)(µ-NHAr)(µ-H)(µ-η(2):η(2)-arene)] containing a π-bound arene. The rate and kinetic isotope effect for this reaction are consistent with a mechanism involving initial rate-determining reductive elimination of an N-H bond to produce the coordinatively unsaturated amido hydride species {(Cp*Ru)(2)(µ-NHAr)(µ-H)} (A) followed by rapid trapping of this species by an arene. The existence of A is also supported by the reversible interconversion of [(Cp*Ru)(2)(µ-NHPh)(µ-H)(µ-η(2):η(2)-C(7)H(8))] with the tetranuclear complex [(Cp*Ru)(4)(µ(4)-NHPh)(µ-NHPh)(µ-H)(2)] (4), a dimerization product of A through a µ(4)-NHPh bridge. DFT calculations provide structures of A and transition states for the N-H reductive elimination. Two distinct reaction pathways are found for the N-H reductive elimination, one of which involves direct migration of a µ-hydride to the µ-NAr ligand, and the other involves formation of a transient terminal hydride species.